Author: "Kahn, RS" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Kahn, RS"' showing total 1,202 results

Start Over Author "Kahn, RS"

1,202 results on '"Kahn, RS"'

1. Brain charts for the human lifespan

Author: Bethlehem, RAI, Seidlitz, J, White, SR, Vogel, JW, Anderson, KM, Adamson, C, Adler, S, Alexopoulos, GS, Anagnostou, E, Areces-Gonzalez, A, Astle, DE, Auyeung, B, Ayub, M, Bae, J, Ball, G, Baron-Cohen, S, Beare, R, Bedford, SA, Benegal, V, Beyer, F, Blangero, J, Blesa Cábez, M, Boardman, JP, Borzage, M, Bosch-Bayard, JF, Bourke, N, Calhoun, VD, Chakravarty, MM, Chen, C, Chertavian, C, Chetelat, G, Chong, YS, Cole, JH, Corvin, A, Costantino, M, Courchesne, E, Crivello, F, Cropley, VL, Crosbie, J, Crossley, N, Delarue, M, Delorme, R, Desrivieres, S, Devenyi, GA, Di Biase, MA, Dolan, R, Donald, KA, Donohoe, G, Dunlop, K, Edwards, AD, Elison, JT, Ellis, CT, Elman, JA, Eyler, L, Fair, DA, Feczko, E, Fletcher, PC, Fonagy, P, Franz, CE, Galan-Garcia, L, Gholipour, A, Giedd, J, Gilmore, JH, Glahn, DC, Goodyer, IM, Grant, PE, Groenewold, NA, Gunning, FM, Gur, RE, Gur, RC, Hammill, CF, Hansson, O, Hedden, T, Heinz, A, Henson, RN, Heuer, K, Hoare, J, Holla, B, Holmes, AJ, Holt, R, Huang, H, Im, K, Ipser, J, Jack, CR, Jackowski, AP, Jia, T, Johnson, KA, Jones, PB, Jones, DT, Kahn, RS, Karlsson, H, Karlsson, L, Kawashima, R, Kelley, EA, Kern, S, Kim, KW, Kitzbichler, MG, Kremen, WS, Lalonde, F, and Landeau, B
Subjects: Biological Psychology, Psychology, Aging, Clinical Research, Neurosciences, Brain Disorders, Biomedical Imaging, Neurological, Mental health, Body Height, Brain, Humans, Longevity, Magnetic Resonance Imaging, Neuroimaging, 3R-BRAIN, AIBL, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s Disease Repository Without Borders Investigators, CALM Team, Cam-CAN, CCNP, COBRE, cVEDA, ENIGMA Developmental Brain Age Working Group, Developing Human Connectome Project, FinnBrain, Harvard Aging Brain Study, IMAGEN, KNE96, Mayo Clinic Study of Aging, NSPN, POND, PREVENT-AD Research Group, VETSA, General Science & Technology
Abstract: Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
Published: 2022

2. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author: Kelly, S, Jahanshad, N, Zalesky, A, Kochunov, P, Agartz, I, Alloza, C, Andreassen, OA, Arango, C, Banaj, N, Bouix, S, Bousman, CA, Brouwer, RM, Bruggemann, J, Bustillo, J, Cahn, W, Calhoun, V, Cannon, D, Carr, V, Catts, S, Chen, J, Chen, J-X, Chen, X, Chiapponi, C, Cho, Kl K, Ciullo, V, Corvin, AS, Crespo-Facorro, B, Cropley, V, De Rossi, P, Diaz-Caneja, CM, Dickie, EW, Ehrlich, S, Fan, F-M, Faskowitz, J, Fatouros-Bergman, H, Flyckt, L, Ford, JM, Fouche, J-P, Fukunaga, M, Gill, M, Glahn, DC, Gollub, R, Goudzwaard, ED, Guo, H, Gur, RE, Gur, RC, Gurholt, TP, Hashimoto, R, Hatton, SN, Henskens, FA, Hibar, DP, Hickie, IB, Hong, LE, Horacek, J, Howells, FM, Hulshoff Pol, HE, Hyde, CL, Isaev, D, Jablensky, A, Jansen, PR, Janssen, J, Jönsson, EG, Jung, LA, Kahn, RS, Kikinis, Z, Liu, K, Klauser, P, Knöchel, C, Kubicki, M, Lagopoulos, J, Langen, C, Lawrie, S, Lenroot, RK, Lim, KO, Lopez-Jaramillo, C, Lyall, A, Magnotta, V, Mandl, RCW, Mathalon, DH, McCarley, RW, McCarthy-Jones, S, McDonald, C, McEwen, S, McIntosh, A, Melicher, T, Mesholam-Gately, RI, Michie, PT, Mowry, B, Mueller, BA, Newell, DT, O'Donnell, P, Oertel-Knöchel, V, Oestreich, L, Paciga, SA, Pantelis, C, Pasternak, O, Pearlson, G, Pellicano, GR, Pereira, A, and Pineda Zapata, J
Subjects: Neurosciences, Brain Disorders, Mental Health, Serious Mental Illness, Biomedical Imaging, Schizophrenia, Clinical Research, Mental health, Adult, Aged, Aged, 80 and over, Brain, Cohort Studies, Corpus Callosum, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, White Matter, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
Published: 2018

3. Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

Author: Walton, E, Hibar, DP, van Erp, TGM, Potkin, SG, Roiz-Santiañez, R, Crespo-Facorro, B, Suarez-Pinilla, P, van Haren, NEM, de Zwarte, SMC, Kahn, RS, Cahn, W, Doan, NT, Jørgensen, KN, Gurholt, TP, Agartz, I, Andreassen, OA, Westlye, LT, Melle, I, Berg, AO, Morch-Johnsen, L, Færden, A, Flyckt, L, Fatouros-Bergman, H, Karolinska Schizophrenia Project Consortium (KaSP), Jönsson, EG, Hashimoto, R, Yamamori, H, Fukunaga, M, Jahanshad, N, De Rossi, P, Piras, F, Banaj, N, Spalletta, G, Gur, RE, Gur, RC, Wolf, DH, Satterthwaite, TD, Beard, LM, Sommer, IE, Koops, S, Gruber, O, Richter, A, Krämer, B, Kelly, S, Donohoe, G, McDonald, C, Cannon, DM, Corvin, A, Gill, M, Di Giorgio, A, Bertolino, A, Lawrie, S, Nickson, T, Whalley, HC, Neilson, E, Calhoun, VD, Thompson, PM, Turner, JA, and Ehrlich, S
Subjects: Karolinska Schizophrenia Project Consortium, Prefrontal Cortex, Humans, Magnetic Resonance Imaging, Linear Models, Schizophrenia, Psychiatric Status Rating Scales, Schizophrenic Psychology, Internationality, Image Processing, Computer-Assisted, Adult, Female, Male, Functional Laterality, Cortical thickness, ENIGMA, FreeSurfer, MRI, PANSS, SANS, medial orbitofrontal cortex, negative symptoms, schizophrenia, Image Processing, Computer-Assisted, Psychiatry, Psychology, Public Health and Health Services, Neurosciences
Abstract: BackgroundOur understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.MethodsThis study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).ResultsMeta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.ConclusionsUsing an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Published: 2018

4. Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.

Author: Witt, SH, Streit, F, Jungkunz, M, Frank, J, Awasthi, S, Reinbold, CS, Treutlein, J, Degenhardt, F, Forstner, AJ, Heilmann-Heimbach, S, Dietl, L, Schwarze, CE, Schendel, D, Strohmaier, J, Abdellaoui, A, Adolfsson, R, Air, TM, Akil, H, Alda, M, Alliey-Rodriguez, N, Andreassen, OA, Babadjanova, G, Bass, NJ, Bauer, M, Baune, BT, Bellivier, F, Bergen, S, Bethell, A, Biernacka, JM, Blackwood, DHR, Boks, MP, Boomsma, DI, Børglum, AD, Borrmann-Hassenbach, M, Brennan, P, Budde, M, Buttenschøn, HN, Byrne, EM, Cervantes, P, Clarke, T-K, Craddock, N, Cruceanu, C, Curtis, D, Czerski, PM, Dannlowski, U, Davis, T, de Geus, EJC, Di Florio, A, Djurovic, S, Domenici, E, Edenberg, HJ, Etain, B, Fischer, SB, Forty, L, Fraser, C, Frye, MA, Fullerton, JM, Gade, K, Gershon, ES, Giegling, I, Gordon, SD, Gordon-Smith, K, Grabe, HJ, Green, EK, Greenwood, TA, Grigoroiu-Serbanescu, M, Guzman-Parra, J, Hall, LS, Hamshere, M, Hauser, J, Hautzinger, M, Heilbronner, U, Herms, S, Hitturlingappa, S, Hoffmann, P, Holmans, P, Hottenga, J-J, Jamain, S, Jones, I, Jones, LA, Juréus, A, Kahn, RS, Kammerer-Ciernioch, J, Kirov, G, Kittel-Schneider, S, Kloiber, S, Knott, SV, Kogevinas, M, Landén, M, Leber, M, Leboyer, M, Li, QS, Lissowska, J, Lucae, S, Martin, NG, Mayoral-Cleries, F, McElroy, SL, McIntosh, AM, McKay, JD, and McQuillin, A
Subjects: Bipolar Disorders Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Humans, Genetic Predisposition to Disease, Case-Control Studies, Bipolar Disorder, Depressive Disorder, Major, Borderline Personality Disorder, Schizophrenia, Genotype, Multifactorial Inheritance, Adolescent, Adult, Aged, Middle Aged, Female, Male, Genome-Wide Association Study, Young Adult, Depressive Disorder, Major, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10-7) and PKP4 (P=8.67 × 10-7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10-3]), SCZ (rg=0.34 [P=4.37 × 10-5]) and MDD (rg=0.57 [P=1.04 × 10-3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
Published: 2017

5. Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium

Author: Walton, E, Hibar, DP, Erp, TGM, Potkin, SG, Roiz‐Santiañez, R, Crespo‐Facorro, B, Suarez‐Pinilla, P, Van Haren, NEM, Zwarte, SMC, Kahn, RS, Cahn, W, Doan, NT, Jørgensen, KN, Gurholt, TP, Agartz, I, Andreassen, OA, Westlye, LT, Melle, I, Berg, AO, Mørch‐Johnsen, L, Færden, A, Flyckt, L, Fatouros‐Bergman, H, Consortium, Karolinska Schizophrenia Project, Jönsson, EG, Hashimoto, R, Yamamori, H, Fukunaga, M, Preda, A, De Rossi, P, Piras, F, Banaj, N, Ciullo, V, Spalletta, G, Gur, RE, Gur, RC, Wolf, DH, Satterthwaite, TD, Beard, LM, Sommer, IE, Koops, S, Gruber, O, Richter, A, Krämer, B, Kelly, S, Donohoe, G, McDonald, C, Cannon, DM, Corvin, A, Gill, M, Di Giorgio, A, Bertolino, A, Lawrie, S, Nickson, T, Whalley, HC, Neilson, E, Calhoun, VD, Thompson, PM, Turner, JA, and Ehrlich, S
Subjects: Schizophrenia, Mental Health, Brain Disorders, Mental health, Good Health and Well Being, Adult, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Prospective Studies, Psychiatric Status Rating Scales, Schizophrenic Psychology, Temporal Lobe, schizophrenia, positive symptoms, superior temporal gyrus, cortical thickness, ENIGMA, FreeSurfer, MRI, scale for the assessment of positive symptoms, positive and negative syndrome scale, Karolinska Schizophrenia Project Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: ObjectiveBased on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia.MethodThis prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness.ResultsPositive symptom severity was negatively related to STG thickness in both hemispheres (left: βstd = -0.052; P = 0.021; right: βstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness.ConclusionOur findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.
Published: 2017

6. Peripheral blood gene expression profiles linked to monoamine metabolite levels in cerebrospinal fluid.

Author: Luykx, JJ, Olde Loohuis, LM, Neeleman, M, Strengman, E, Bakker, SC, Lentjes, E, Borgdorff, P, van Dongen, EPA, Bruins, P, Kahn, RS, Horvath, S, de Jong, S, and Ophoff, RA
Subjects: Brain, Humans, Methoxyhydroxyphenylglycol, Biogenic Monoamines, Serotonin, Homovanillic Acid, Hydroxyindoleacetic Acid, RNA, Messenger, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Reference Values, Adolescent, Adult, Aged, Middle Aged, Female, Male, Young Adult, Endophenotypes, RNA, Messenger, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: The blood-brain barrier separates circulating blood from the central nervous system (CNS). The scope of this barrier is not fully understood which limits our ability to relate biological measurements from peripheral to central phenotypes. For example, it is unknown to what extent gene expression levels in peripheral blood are reflective of CNS metabolism. In this study, we examine links between central monoamine metabolite levels and whole-blood gene expression to better understand the connection between peripheral systems and the CNS. To that end, we correlated the prime monoamine metabolites in cerebrospinal fluid (CSF) with whole-genome gene expression microarray data from blood (N=240 human subjects). We additionally applied gene-enrichment analysis and weighted gene co-expression network analyses (WGCNA) to identify modules of co-expressed genes in blood that may be involved with monoamine metabolite levels in CSF. Transcript levels of two genes were significantly associated with CSF serotonin metabolite levels after Bonferroni correction for multiple testing: THAP7 (P=2.8 × 10-8, β=0.08) and DDX6 (P=2.9 × 10-7, β=0.07). Differentially expressed genes were significantly enriched for genes expressed in the brain tissue (P=6.0 × 10-52). WGCNA revealed significant correlations between serotonin metabolism and hub genes with known functions in serotonin metabolism, for example, HTR2A and COMT. We conclude that gene expression levels in whole blood are associated with monoamine metabolite levels in the human CSF. Our results, including the strong enrichment of brain-expressed genes, illustrate that gene expression profiles in peripheral blood can be relevant for quantitative metabolic phenotypes in the CNS.
Published: 2016

7. Subcortical volumetric abnormalities in bipolar disorder.

Author: Hibar, DP, Westlye, LT, van Erp, TGM, Rasmussen, J, Leonardo, CD, Faskowitz, J, Haukvik, UK, Hartberg, CB, Doan, NT, Agartz, I, Dale, AM, Gruber, O, Krämer, B, Trost, S, Liberg, B, Abé, C, Ekman, CJ, Ingvar, M, Landén, M, Fears, SC, Freimer, NB, Bearden, CE, Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar Endophenotypes, Sprooten, E, Glahn, DC, Pearlson, GD, Emsell, L, Kenney, J, Scanlon, C, McDonald, C, Cannon, DM, Almeida, J, Versace, A, Caseras, X, Lawrence, NS, Phillips, ML, Dima, D, Delvecchio, G, Frangou, S, Satterthwaite, TD, Wolf, D, Houenou, J, Henry, C, Malt, UF, Bøen, E, Elvsåshagen, T, Young, AH, Lloyd, AJ, Goodwin, GM, Mackay, CE, Bourne, C, Bilderbeck, A, Abramovic, L, Boks, MP, van Haren, NEM, Ophoff, RA, Kahn, RS, Bauer, M, Pfennig, A, Alda, M, Hajek, T, Mwangi, B, Soares, JC, Nickson, T, Dimitrova, R, Sussmann, JE, Hagenaars, S, Whalley, HC, McIntosh, AM, Thompson, PM, and Andreassen, OA
Subjects: Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar Endophenotypes, Brain, Humans, Magnetic Resonance Imaging, Organ Size, Case-Control Studies, Retrospective Studies, Bipolar Disorder, Adult, Middle Aged, Female, Male, Clinical Research, Mental Health, Brain Disorders, Serious Mental Illness, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Mental health, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.
Published: 2016

8. Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis

Author: Haas, SS, Ge, R, Agartz, I, Amminger, GP, Andreassen, OA, Bachman, P, Baeza, I, Choi, S, Colibazzi, T, Cropley, VL, de la Fuente-Sandoval, C, Ebdrup, BH, Fortea, A, Fusar-Poli, P, Glenthoj, BY, Glenthoj, LB, Haut, KM, Hayes, RA, Heekeren, K, Hooker, CI, Hwang, WJ, Jahanshad, N, Kaess, M, Kasai, K, Katagiri, N, Kim, M, Kindler, J, Koike, S, Kristensen, TD, Kwon, JS, Lawrie, SM, Lebedeva, I, Lee, J, Lemmers-Jansen, ILJ, Lin, A, Ma, X, Mathalon, DH, McGuire, P, Michel, C, Mizrahi, R, Mizuno, M, Moller, P, Mora-Duran, R, Nelson, B, Nemoto, T, Nordentoft, M, Nordholm, D, Omelchenko, MA, Pantelis, C, Pariente, JC, Raghava, J, Reyes-Madrigal, F, Rossberg, JI, Rossler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Smigielski, L, Sugranyes, G, Suzuki, M, Takahashi, T, Tamnes, CK, Theodoridou, A, Thomopoulos, SI, Thompson, PM, Tomyshev, AS, Uhlhaas, PJ, Vaernes, TG, van Amelsvoort, TAMJ, van Erp, TGM, Waltz, JA, Wenneberg, C, Westlye, LT, Wood, SJ, Zhou, JH, Hernaus, D, Jalbrzikowski, M, Kahn, RS, Corcoran, CM, Frangou, S, Haas, SS, Ge, R, Agartz, I, Amminger, GP, Andreassen, OA, Bachman, P, Baeza, I, Choi, S, Colibazzi, T, Cropley, VL, de la Fuente-Sandoval, C, Ebdrup, BH, Fortea, A, Fusar-Poli, P, Glenthoj, BY, Glenthoj, LB, Haut, KM, Hayes, RA, Heekeren, K, Hooker, CI, Hwang, WJ, Jahanshad, N, Kaess, M, Kasai, K, Katagiri, N, Kim, M, Kindler, J, Koike, S, Kristensen, TD, Kwon, JS, Lawrie, SM, Lebedeva, I, Lee, J, Lemmers-Jansen, ILJ, Lin, A, Ma, X, Mathalon, DH, McGuire, P, Michel, C, Mizrahi, R, Mizuno, M, Moller, P, Mora-Duran, R, Nelson, B, Nemoto, T, Nordentoft, M, Nordholm, D, Omelchenko, MA, Pantelis, C, Pariente, JC, Raghava, J, Reyes-Madrigal, F, Rossberg, JI, Rossler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Smigielski, L, Sugranyes, G, Suzuki, M, Takahashi, T, Tamnes, CK, Theodoridou, A, Thomopoulos, SI, Thompson, PM, Tomyshev, AS, Uhlhaas, PJ, Vaernes, TG, van Amelsvoort, TAMJ, van Erp, TGM, Waltz, JA, Wenneberg, C, Westlye, LT, Wood, SJ, Zhou, JH, Hernaus, D, Jalbrzikowski, M, Kahn, RS, Corcoran, CM, and Frangou, S
Abstract: IMPORTANCE: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. OBJECTIVE: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. DESIGN, SETTING, AND PARTICIPANTS: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. MAIN OUTCOMES AND MEASURES: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. RESULTS: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD
Published: 2024

9. Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS

Author: Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Marcy, PJ, Allott, K, Amminger, P, Arango, C, Broome, MR, Cadenhead, KS, Chen, EYH, Choi, J, Conus, P, Cornblatt, BA, Glenthoj, LB, Horton, LE, Kambeitz, J, Kapur, T, Keshavan, MS, Koutsouleris, N, Langbein, K, Lavoie, S, Diaz-Caneja, CM, Mathalon, DH, Mittal, VA, Nordentoft, M, Pasternak, O, Pearlson, GD, Gaspar, PA, Shah, JL, Smesny, S, Stone, WS, Strauss, GP, Wang, J, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, Clark, SR, Lewandowski, KE, Torous, J, Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Marcy, PJ, Allott, K, Amminger, P, Arango, C, Broome, MR, Cadenhead, KS, Chen, EYH, Choi, J, Conus, P, Cornblatt, BA, Glenthoj, LB, Horton, LE, Kambeitz, J, Kapur, T, Keshavan, MS, Koutsouleris, N, Langbein, K, Lavoie, S, Diaz-Caneja, CM, Mathalon, DH, Mittal, VA, Nordentoft, M, Pasternak, O, Pearlson, GD, Gaspar, PA, Shah, JL, Smesny, S, Stone, WS, Strauss, GP, Wang, J, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, Clark, SR, Lewandowski, KE, and Torous, J
Abstract: AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSIONS: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.
Published: 2024

10. Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

Author: Wannan, CMJ, Nelson, B, Addington, J, Allott, K, Anticevic, A, Arango, C, Baker, JT, Bearden, CE, Billah, T, Bouix, S, Broome, MR, Buccilli, K, Cadenhead, KS, Calkins, ME, Cannon, TD, Cecci, G, Chen, EYH, Cho, KIK, Choi, J, Clark, SR, Coleman, MJ, Conus, P, Corcoran, CM, Cornblatt, BA, Diaz-Caneja, CM, Dwyer, D, Ebdrup, BH, Ellman, LM, Fusar-Poli, P, Galindo, L, Gaspar, PA, Gerber, C, Glenthoj, LB, Glynn, R, Harms, MP, Horton, LE, Kahn, RS, Kambeitz, J, Kambeitz-Ilankovic, L, Kane, JM, Kapur, T, Keshavan, MS, Kim, S-W, Koutsouleris, N, Kubicki, M, Kwon, JS, Langbein, K, Lewandowski, KE, Light, GA, Mamah, D, Marcy, PJ, Mathalon, DH, McGorry, PD, Mittal, VA, Nordentoft, M, Nunez, A, Pasternak, O, Pearlson, GD, Perez, J, Perkins, DO, Powers, AR, Roalf, DR, Sabb, FW, Schiffman, J, Shah, JL, Smesny, S, Spark, J, Stone, WS, Strauss, GP, Tamayo, Z, Torous, J, Upthegrove, R, Vangel, M, Verma, S, Wang, J, Winter-van Rossum, I, Wolf, DH, Wolff, P, Wood, SJ, Yung, AR, Agurto, C, Alvarez-Jimenez, M, Amminger, P, Armando, M, Asgari-Targhi, A, Cahill, J, Carrion, RE, Castro, E, Cetin-Karayumak, S, Chakravarty, MM, Cho, YT, Cotter, D, D'Alfonso, S, Ennis, M, Fadnavis, S, Fonteneau, C, Gao, C, Gupta, T, Gur, RE, Gur, RC, Hamilton, HK, Hoftman, GD, Jacobs, GR, Jarcho, J, Ji, JL, Kohler, CG, Lalousis, PA, Lavoie, S, Lepage, M, Liebenthal, E, Mervis, J, Murty, V, Nicholas, SC, Ning, L, Penzel, N, Poldrack, R, Polosecki, P, Pratt, DN, Rabin, R, Eichi, HR, Rathi, Y, Reichenberg, A, Reinen, J, Rogers, J, Ruiz-Yu, B, Scott, I, Seitz-Holland, J, Srihari, VH, Srivastava, A, Thompson, A, Turetsky, BI, Walsh, BC, Whitford, T, Wigman, JTW, Yao, B, Yuen, HP, Ahmed, U, Byun, AJS, Chung, Y, Do, K, Hendricks, L, Huynh, K, Jeffries, C, Lane, E, Langholm, C, Lin, E, Mantua, V, Santorelli, G, Ruparel, K, Zoupou, E, Adasme, T, Addamo, L, Adery, L, Ali, M, Auther, A, Aversa, S, Baek, S-H, Bates, K, Bathery, A, Bayer, JMM, Beedham, R, Bilgrami, Z, Birch, S, Bonoldi, I, Borders, O, Borgatti, R, Brown, L, Bruna, A, Carrington, H, Castillo-Passi, RI, Chen, J, Cheng, N, Ching, AE, Clifford, C, Colton, B-L, Contreras, P, Corral, S, Damiani, S, Done, M, Estrade, A, Etuka, BA, Formica, M, Furlan, R, Geljic, M, Germano, C, Getachew, R, Goncalves, M, Haidar, A, Hartmann, J, Jo, A, John, O, Kerins, S, Kerr, M, Kesselring, I, Kim, H, Kim, N, Kinney, K, Krcmar, M, Kotler, E, Lafanechere, M, Lee, C, Llerena, J, Markiewicz, C, Matnejl, P, Maturana, A, Mavambu, A, Mayol-Troncoso, R, McDonnell, A, McGowan, A, McLaughlin, D, McIlhenny, R, McQueen, B, Mebrahtu, Y, Mensi, M, Hui, CLM, Suen, YN, Wong, SMY, Morrell, N, Omar, M, Partridge, A, Phassouliotis, C, Pichiecchio, A, Politi, P, Porter, C, Provenzani, U, Prunier, N, Raj, J, Ray, S, Rayner, V, Reyes, M, Reynolds, K, Rush, S, Salinas, C, Shetty, J, Snowball, C, Tod, S, Turra-Farina, G, Valle, D, Veale, S, Whitson, S, Wickham, A, Youn, S, Zamorano, F, Zavaglia, E, Zinberg, J, Woods, SW, Shenton, ME, Wannan, CMJ, Nelson, B, Addington, J, Allott, K, Anticevic, A, Arango, C, Baker, JT, Bearden, CE, Billah, T, Bouix, S, Broome, MR, Buccilli, K, Cadenhead, KS, Calkins, ME, Cannon, TD, Cecci, G, Chen, EYH, Cho, KIK, Choi, J, Clark, SR, Coleman, MJ, Conus, P, Corcoran, CM, Cornblatt, BA, Diaz-Caneja, CM, Dwyer, D, Ebdrup, BH, Ellman, LM, Fusar-Poli, P, Galindo, L, Gaspar, PA, Gerber, C, Glenthoj, LB, Glynn, R, Harms, MP, Horton, LE, Kahn, RS, Kambeitz, J, Kambeitz-Ilankovic, L, Kane, JM, Kapur, T, Keshavan, MS, Kim, S-W, Koutsouleris, N, Kubicki, M, Kwon, JS, Langbein, K, Lewandowski, KE, Light, GA, Mamah, D, Marcy, PJ, Mathalon, DH, McGorry, PD, Mittal, VA, Nordentoft, M, Nunez, A, Pasternak, O, Pearlson, GD, Perez, J, Perkins, DO, Powers, AR, Roalf, DR, Sabb, FW, Schiffman, J, Shah, JL, Smesny, S, Spark, J, Stone, WS, Strauss, GP, Tamayo, Z, Torous, J, Upthegrove, R, Vangel, M, Verma, S, Wang, J, Winter-van Rossum, I, Wolf, DH, Wolff, P, Wood, SJ, Yung, AR, Agurto, C, Alvarez-Jimenez, M, Amminger, P, Armando, M, Asgari-Targhi, A, Cahill, J, Carrion, RE, Castro, E, Cetin-Karayumak, S, Chakravarty, MM, Cho, YT, Cotter, D, D'Alfonso, S, Ennis, M, Fadnavis, S, Fonteneau, C, Gao, C, Gupta, T, Gur, RE, Gur, RC, Hamilton, HK, Hoftman, GD, Jacobs, GR, Jarcho, J, Ji, JL, Kohler, CG, Lalousis, PA, Lavoie, S, Lepage, M, Liebenthal, E, Mervis, J, Murty, V, Nicholas, SC, Ning, L, Penzel, N, Poldrack, R, Polosecki, P, Pratt, DN, Rabin, R, Eichi, HR, Rathi, Y, Reichenberg, A, Reinen, J, Rogers, J, Ruiz-Yu, B, Scott, I, Seitz-Holland, J, Srihari, VH, Srivastava, A, Thompson, A, Turetsky, BI, Walsh, BC, Whitford, T, Wigman, JTW, Yao, B, Yuen, HP, Ahmed, U, Byun, AJS, Chung, Y, Do, K, Hendricks, L, Huynh, K, Jeffries, C, Lane, E, Langholm, C, Lin, E, Mantua, V, Santorelli, G, Ruparel, K, Zoupou, E, Adasme, T, Addamo, L, Adery, L, Ali, M, Auther, A, Aversa, S, Baek, S-H, Bates, K, Bathery, A, Bayer, JMM, Beedham, R, Bilgrami, Z, Birch, S, Bonoldi, I, Borders, O, Borgatti, R, Brown, L, Bruna, A, Carrington, H, Castillo-Passi, RI, Chen, J, Cheng, N, Ching, AE, Clifford, C, Colton, B-L, Contreras, P, Corral, S, Damiani, S, Done, M, Estrade, A, Etuka, BA, Formica, M, Furlan, R, Geljic, M, Germano, C, Getachew, R, Goncalves, M, Haidar, A, Hartmann, J, Jo, A, John, O, Kerins, S, Kerr, M, Kesselring, I, Kim, H, Kim, N, Kinney, K, Krcmar, M, Kotler, E, Lafanechere, M, Lee, C, Llerena, J, Markiewicz, C, Matnejl, P, Maturana, A, Mavambu, A, Mayol-Troncoso, R, McDonnell, A, McGowan, A, McLaughlin, D, McIlhenny, R, McQueen, B, Mebrahtu, Y, Mensi, M, Hui, CLM, Suen, YN, Wong, SMY, Morrell, N, Omar, M, Partridge, A, Phassouliotis, C, Pichiecchio, A, Politi, P, Porter, C, Provenzani, U, Prunier, N, Raj, J, Ray, S, Rayner, V, Reyes, M, Reynolds, K, Rush, S, Salinas, C, Shetty, J, Snowball, C, Tod, S, Turra-Farina, G, Valle, D, Veale, S, Whitson, S, Wickham, A, Youn, S, Zamorano, F, Zavaglia, E, Zinberg, J, Woods, SW, and Shenton, ME
Abstract: This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.
Published: 2024

11. A naturalistic cohort study of first-episode schizophrenia spectrum disorder: A description of the early phase of illness in the PSYSCAN cohort.

Author: Slot, MIE, van Hell, HH, Rossum, IW-V, Dazzan, P, Maat, A, de Haan, L, Crespo-Facorro, B, Glenthøj, B, Lawrie, SM, McDonald, C, Gruber, O, van Amelsvoort, T, Arango, C, Kircher, T, Nelson, B, Galderisi, S, Weiser, M, Sachs, G, Maatz, A, Bressan, RA, Kwon, JS, Mizrahi, R, PSYSCAN Consortium, McGuire, P, Kahn, RS, Slot, MIE, van Hell, HH, Rossum, IW-V, Dazzan, P, Maat, A, de Haan, L, Crespo-Facorro, B, Glenthøj, B, Lawrie, SM, McDonald, C, Gruber, O, van Amelsvoort, T, Arango, C, Kircher, T, Nelson, B, Galderisi, S, Weiser, M, Sachs, G, Maatz, A, Bressan, RA, Kwon, JS, Mizrahi, R, PSYSCAN Consortium, McGuire, P, and Kahn, RS
Abstract: BACKGROUND: We examined the course of illness over a 12-month period in a large, international multi-center cohort of people with a first-episode schizophrenia spectrum disorder (FES) in a naturalistic, prospective study (PSYSCAN). METHOD: Patients with a first episode of schizophrenia, schizoaffective disorder (depressive type) or schizophreniform disorder were recruited at 16 institutions in Europe, Israel and Australia. Participants (N = 304) received clinical treatment as usual throughout the study. RESULTS: The mean age of the cohort was 24.3 years (SD = 5.6), and 67 % were male. At baseline, participants presented with a range of intensities of psychotic symptoms, 80 % were taking antipsychotic medication, 68 % were receiving psychological treatment, with 46.5 % in symptomatic remission. The mean duration of untreated psychosis was 6.2 months (SD = 17.0). After one year, 67 % were in symptomatic remission and 61 % were in functional remission, but 31 % had been readmitted to hospital at some time after baseline. In the cohort as a whole, depressive symptoms remained stable over the follow-up period. In patients with a current depressive episode at baseline, depressive symptoms slightly improved. Alcohol, tobacco and cannabis were the most commonly used substances, with daily users of cannabis ranging between 9 and 11 % throughout the follow-up period. CONCLUSIONS: This study provides valuable insight into the early course of a broad range of clinical and functional aspects of illness in FES patients in routine clinical practice.
Published: 2024

12. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium

Author: van Erp, TGM, Hibar, DP, Rasmussen, JM, Glahn, DC, Pearlson, GD, Andreassen, OA, Agartz, I, Westlye, LT, Haukvik, UK, Dale, AM, Melle, I, Hartberg, CB, Gruber, O, Kraemer, B, Zilles, D, Donohoe, G, Kelly, S, McDonald, C, Morris, DW, Cannon, DM, Corvin, A, Machielsen, MWJ, Koenders, L, de Haan, L, Veltman, DJ, Satterthwaite, TD, Wolf, DH, Gur, RC, Gur, RE, Potkin, SG, Mathalon, DH, Mueller, BA, Preda, A, Macciardi, F, Ehrlich, S, Walton, E, Hass, J, Calhoun, VD, Bockholt, HJ, Sponheim, SR, Shoemaker, JM, van Haren, NEM, Pol, HEH, Ophoff, RA, Kahn, RS, Roiz-Santiañez, R, Crespo-Facorro, B, Wang, L, Alpert, KI, Jönsson, EG, Dimitrova, R, Bois, C, Whalley, HC, McIntosh, AM, Lawrie, SM, Hashimoto, R, Thompson, PM, and Turner, JA
Subjects: Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Serious Mental Illness, Brain Disorders, Schizophrenia, Clinical Research, Neurosciences, Mental Health, Biomedical Imaging, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Adult, Brain, Brain Mapping, Case-Control Studies, Female, Functional Laterality, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Prospective Studies, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.
Published: 2016

13. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.

Author: Stringer, S, Minică, CC, Verweij, KJH, Mbarek, H, Bernard, M, Derringer, J, van Eijk, KR, Isen, JD, Loukola, A, Maciejewski, DF, Mihailov, E, van der Most, PJ, Sánchez-Mora, C, Roos, L, Sherva, R, Walters, R, Ware, JJ, Abdellaoui, A, Bigdeli, TB, Branje, SJT, Brown, SA, Bruinenberg, M, Casas, M, Esko, T, Garcia-Martinez, I, Gordon, SD, Harris, JM, Hartman, CA, Henders, AK, Heath, AC, Hickie, IB, Hickman, M, Hopfer, CJ, Hottenga, JJ, Huizink, AC, Irons, DE, Kahn, RS, Korhonen, T, Kranzler, HR, Krauter, K, van Lier, PAC, Lubke, GH, Madden, PAF, Mägi, R, McGue, MK, Medland, SE, Meeus, WHJ, Miller, MB, Montgomery, GW, Nivard, MG, Nolte, IM, Oldehinkel, AJ, Pausova, Z, Qaiser, B, Quaye, L, Ramos-Quiroga, JA, Richarte, V, Rose, RJ, Shin, J, Stallings, MC, Stiby, AI, Wall, TL, Wright, MJ, Koot, HM, Paus, T, Hewitt, JK, Ribasés, M, Kaprio, J, Boks, MP, Snieder, H, Spector, T, Munafò, MR, Metspalu, A, Gelernter, J, Boomsma, DI, Iacono, WG, Martin, NG, Gillespie, NA, Derks, EM, and Vink, JM
Subjects: Humans, Marijuana Abuse, Carrier Proteins, Potassium Channels, Cell Adhesion Molecules, Membrane Proteins, Marijuana Smoking, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Young Adult, CD56 Antigen, Potassium Channels, Sodium-Activated, and over, Sodium-Activated, Antigens, CD56, Genetics, Tobacco, Substance Abuse, Human Genome, Drug Abuse, Brain Disorders, Pediatric Research Initiative, Tobacco Smoke and Health, Prevention, Biotechnology, Clinical Research, 2.1 Biological and endogenous factors, Mental Health, Psychology, Clinical Sciences, Public Health and Health Services
Abstract: Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P
Published: 2016

14. Seasonal variation of serotonin turnover in human cerebrospinal fluid, depressive symptoms and the role of the 5-HTTLPR.

Author: Luykx, JJ, Bakker, SC, van Geloven, N, Eijkemans, MJC, Horvath, S, Lentjes, E, Boks, MPM, Strengman, E, DeYoung, J, Buizer-Voskamp, JE, Cantor, RM, Lu, A, van Dongen, EPA, Borgdorff, P, Bruins, P, Kahn, RS, and Ophoff, RA
Subjects: Humans, Serotonin, Homovanillic Acid, Hydroxyindoleacetic Acid, Regression Analysis, Longitudinal Studies, Depression, Seasons, Polymorphism, Genetic, Alleles, Adult, Middle Aged, Female, Male, Serotonin Plasma Membrane Transport Proteins, cerebrospinal fluid, depression, 5-HTTLPR, monoamine, season, serotonin, Polymorphism, Genetic, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: Studying monoaminergic seasonality is likely to improve our understanding of neurobiological mechanisms underlying season-associated physiological and pathophysiological behavior. Studies of monoaminergic seasonality and the influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on serotonin seasonality have yielded conflicting results, possibly due to lack of power and absence of multi-year analyses. We aimed to assess the extent of seasonal monoamine turnover and examined the possible involvement of the 5-HTTLPR. To determine the influence of seasonality on monoamine turnover, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the cerebrospinal fluid of 479 human subjects collected during a 3-year period. Cosine and non-parametric seasonal modeling were applied to both metabolites. We computed serotonin (5-HT) seasonality values and performed an association analysis with the s/l alleles of the 5-HTTLPR. Depressive symptomatology was assessed using the Beck Depression Inventory-II. Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074). Season of sampling explained 5.4% (P=1.57 × 10(-7)) of the variance in 5-HIAA concentrations. The 5-HTTLPR s-allele was associated with increased 5-HIAA seasonality (standardized regression coefficient=0.12, P=0.020, N=393). 5-HIAA seasonality correlated with depressive symptoms (Spearman's rho=0.13, P=0.018, N=345). In conclusion, we highlight a dose-dependent association of the 5-HTTLPR with 5-HIAA seasonality and a positive correlation between 5-HIAA seasonality and depressive symptomatology. The presented data set the stage for follow-up in clinical populations with a role for seasonality, such as affective disorders.
Published: 2013

15. “Forward Genetics” as a Method to Maximize Power and Cost-Efficiency in Studies of Human Complex Traits

Author: Boks, MPM, Derks, EM, Dolan, CV, Kahn, RS, and Ophoff, RA
Subjects: Health Sciences, Genetics, Human Genome, Aetiology, 2.5 Research design and methodologies (aetiology), Computational Biology, Genetics, Population, Genome-Wide Association Study, Genotype, Humans, Models, Genetic, Phenotype, Quantitative Trait, Heritable, Power, Forward genetics, Complex traits, Selective sampling, Phenomics, Zoology, Neurosciences, Psychology, Genetics & Heredity, Biomedical and clinical sciences, Health sciences
Abstract: There is increasing interest in methods to disentangle the relationship between genotype and (endo)phenotypes in human complex traits. We present a population-based method of increasing the power and cost-efficiency of studies by selecting random individuals with a particular genotype and then assessing the accompanying quantitative phenotypes. Using statistical derivations, power- and cost graphs we show that such a "forward genetics" approach can lead to a marked reduction in sample size and costs. This approach is particularly apt for implementing in epidemiological studies for which DNA is already available but the phenotyping costs are high.
Published: 2010

16. Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS.

Author: Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, Accelerating Medicines Partnership Schizophrenia, Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, and Accelerating Medicines Partnership Schizophrenia
Abstract: AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and partial harmonization for CHR-P criteria. The semi-structured interview, named P ositive SY mptoms and Diagnostic Criteria for the C AARMS H armonized with the S IPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSION: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.
Published: 2023

17. Extreme deviations from the normative model reveal cortical heterogeneity and associations with negative symptom severity in first-episode psychosis from the OPTiMiSE and GAP studies

Author: Worker, A, Berthert, P, Lawrence, AJ, Kia, SM, Arango, C, Dinga, R, Galderisi, S, Glenthoj, B, Kahn, RS, Leslie, A, Murray, RM, Pariante, CM, Pantelis, C, Weiser, M, Winter-van Rossum, I, Mcguire, P, Dazzan, P, Marquand, AF, Worker, A, Berthert, P, Lawrence, AJ, Kia, SM, Arango, C, Dinga, R, Galderisi, S, Glenthoj, B, Kahn, RS, Leslie, A, Murray, RM, Pariante, CM, Pantelis, C, Weiser, M, Winter-van Rossum, I, Mcguire, P, Dazzan, P, and Marquand, AF
Abstract: There is currently no quantifiable method to predict long-term clinical outcomes in patients presenting with a first episode of psychosis. A major barrier to developing useful markers for this is biological heterogeneity, where many different pathological mechanisms may underly the same set of symptoms in different individuals. Normative modelling has been used to quantify this heterogeneity in established psychotic disorders by identifying regions of the cortex which are thinner than expected based on a normative healthy population range. These brain atypicalities are measured at the individual level and therefore potentially useful in a clinical setting. However, it is still unclear whether alterations in individual brain structure can be detected at the time of the first psychotic episode, and whether they are associated with subsequent clinical outcomes. We applied normative modelling of cortical thickness to a sample of first-episode psychosis patients, with the aim of quantifying heterogeneity and to use any pattern of cortical atypicality to predict symptoms and response to antipsychotic medication at timepoints from baseline up to 95 weeks (median follow-ups = 4). T1-weighted brain magnetic resonance images from the GAP and OPTiMiSE samples were processed with Freesurfer V6.0.0 yielding 148 cortical thickness features. An existing normative model of cortical thickness (n = 37,126) was adapted to integrate data from each clinical site and account for effects of gender and site. Our test sample consisted of control participants (n = 149, mean age = 26, SD = 6.7) and patient data (n = 295, mean age = 26, SD = 6.7), this sample was used for estimating deviations from the normative model and subsequent statistical analysis. For each individual, the 148 cortical thickness features were mapped to centiles of the normative distribution and converted to z-scores reflecting the distance from the population mean. Individual cortical thickness metrics of +/- 2.6 standar
Published: 2023

18. Large- scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author: Schijven, D, Postema, MC, Fukunaga, M, Matsumoto, J, Miura, K, de Zwarte, SMC, van Haren, NEM, Cahn, W, Pol, HEH, Kahn, RS, Ayesa-Arriola, R, de la Foz, VO-G, Tordesillas-Gutierrez, D, Vazquez-Bourgon, J, Crespo-Facorro, B, Alnaes, D, Dahl, A, Westlye, LT, Agartz, I, Andreassen, OA, Jonsson, EG, Kochunov, P, Bruggemann, JM, Catts, SV, Michie, PT, Mowry, BJ, Quide, Y, Rasser, PE, Schall, U, Scott, RJ, Carr, VJ, Green, MJ, Henskens, FA, Loughland, CM, Pantelis, C, Weickert, CS, Weickert, TW, De Haan, L, Brosch, K, Pfarr, J-K, Ringwald, KG, Stein, F, Jansen, A, Kircher, TTJ, Nenadic, I, Kramer, B, Gruber, O, Satterthwaite, TD, Bustillo, J, Mathalon, DH, Preda, A, Calhoun, VD, Ford, JM, Potkin, SG, Chen, J, Tan, Y, Wang, Z, Xiang, H, Fan, F, Bernardoni, F, Ehrlich, S, Fuentes-Claramonte, P, Garcia-Leon, MA, Guerrero-Pedraza, A, Salvador, R, Sarro, S, Pomarol-Clotet, E, Ciullo, V, Piras, F, Vecchio, D, Banaj, N, Spalletta, G, Michielse, S, van Amelsvoort, T, Dickie, EW, Voineskos, AN, Sim, K, Ciufolini, S, Dazzan, P, Murray, RM, Kim, W-S, Chung, Y-C, Andreou, C, Schmidt, A, Borgwardt, S, McIntosh, AM, Whalley, HC, Lawrie, SM, Du Plessis, S, Luckhoff, HK, Scheffler, F, Emsley, R, Grotegerd, D, Lencer, R, Dannlowski, U, Edmond, JT, Rootes-Murdy, K, Stephen, JM, Mayer, AR, Antonucci, LA, Fazio, L, Pergola, G, Bertolino, A, Diaz-Caneja, CM, Janssen, J, Lois, NG, Arango, C, Tomyshev, AS, Lebedeva, I, Cervenkav, S, Sellgrenv, CM, Georgiadis, F, Kirschner, M, Kaiser, S, Hajek, T, Skoch, A, Spaniel, F, Kim, M, Bin Kwak, Y, Oh, S, Kwon, JS, James, A, Bakker, G, Knochel, C, Stablein, M, Oertel, V, Uhlmann, A, Howells, FM, Stein, DJ, Temmingh, HS, Diaz-Zuluaga, AM, Pineda-Zapata, JA, Lopez-Jaramillo, C, Homan, S, Ji, E, Surbeck, W, Homan, P, Fishera, SE, Franke, B, Glahn, DC, Gur, RC, Hashimoto, R, Jahanshad, N, Luders, E, Medland, SE, Thompson, PM, Turner, JA, van Erp, TGM, Francks, C, Schijven, D, Postema, MC, Fukunaga, M, Matsumoto, J, Miura, K, de Zwarte, SMC, van Haren, NEM, Cahn, W, Pol, HEH, Kahn, RS, Ayesa-Arriola, R, de la Foz, VO-G, Tordesillas-Gutierrez, D, Vazquez-Bourgon, J, Crespo-Facorro, B, Alnaes, D, Dahl, A, Westlye, LT, Agartz, I, Andreassen, OA, Jonsson, EG, Kochunov, P, Bruggemann, JM, Catts, SV, Michie, PT, Mowry, BJ, Quide, Y, Rasser, PE, Schall, U, Scott, RJ, Carr, VJ, Green, MJ, Henskens, FA, Loughland, CM, Pantelis, C, Weickert, CS, Weickert, TW, De Haan, L, Brosch, K, Pfarr, J-K, Ringwald, KG, Stein, F, Jansen, A, Kircher, TTJ, Nenadic, I, Kramer, B, Gruber, O, Satterthwaite, TD, Bustillo, J, Mathalon, DH, Preda, A, Calhoun, VD, Ford, JM, Potkin, SG, Chen, J, Tan, Y, Wang, Z, Xiang, H, Fan, F, Bernardoni, F, Ehrlich, S, Fuentes-Claramonte, P, Garcia-Leon, MA, Guerrero-Pedraza, A, Salvador, R, Sarro, S, Pomarol-Clotet, E, Ciullo, V, Piras, F, Vecchio, D, Banaj, N, Spalletta, G, Michielse, S, van Amelsvoort, T, Dickie, EW, Voineskos, AN, Sim, K, Ciufolini, S, Dazzan, P, Murray, RM, Kim, W-S, Chung, Y-C, Andreou, C, Schmidt, A, Borgwardt, S, McIntosh, AM, Whalley, HC, Lawrie, SM, Du Plessis, S, Luckhoff, HK, Scheffler, F, Emsley, R, Grotegerd, D, Lencer, R, Dannlowski, U, Edmond, JT, Rootes-Murdy, K, Stephen, JM, Mayer, AR, Antonucci, LA, Fazio, L, Pergola, G, Bertolino, A, Diaz-Caneja, CM, Janssen, J, Lois, NG, Arango, C, Tomyshev, AS, Lebedeva, I, Cervenkav, S, Sellgrenv, CM, Georgiadis, F, Kirschner, M, Kaiser, S, Hajek, T, Skoch, A, Spaniel, F, Kim, M, Bin Kwak, Y, Oh, S, Kwon, JS, James, A, Bakker, G, Knochel, C, Stablein, M, Oertel, V, Uhlmann, A, Howells, FM, Stein, DJ, Temmingh, HS, Diaz-Zuluaga, AM, Pineda-Zapata, JA, Lopez-Jaramillo, C, Homan, S, Ji, E, Surbeck, W, Homan, P, Fishera, SE, Franke, B, Glahn, DC, Gur, RC, Hashimoto, R, Jahanshad, N, Luders, E, Medland, SE, Thompson, PM, Turner, JA, van Erp, TGM, and Francks, C
Abstract: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023

19. Psychosis Endophenotypes:A Gene-Set-Specific Polygenic Risk Score Analysis

Author: Wang, BH, Irizar, H, Thygesen, JH, Zartaloudi, E, Austin-Zimmerman, I, Bhat, A, Harju-Seppaenen, J, Pain, O, Bass, N, Gkofa, V, Alizadeh, BZ, van Amelsvoort, T, Arranz, MJ, Bender, S, Cahn, W, Calafato, MS, Crespo-Facorro, B, Di Forti, M, Giegling, I, de Haan, L, Hall, J, Hall, MH, van Haren, N, Iyegbe, C, Kahn, RS, Kravariti, E, Lawrie, SM, Lin, K, Luykx, JJ, Mata, I, McDonald, C, McIntosh, AM, Murray, RM, Picchioni, M, Powell, J, Prata, DP, Rujescu, D, Rutten, BPF, Shaikh, M, Simons, CJP, Toulopoulou, T, Weisbrod, M, van Winkel, R, Kuchenbaecker, K, McQuillin, A, Bramon, E, Wang, BH, Irizar, H, Thygesen, JH, Zartaloudi, E, Austin-Zimmerman, I, Bhat, A, Harju-Seppaenen, J, Pain, O, Bass, N, Gkofa, V, Alizadeh, BZ, van Amelsvoort, T, Arranz, MJ, Bender, S, Cahn, W, Calafato, MS, Crespo-Facorro, B, Di Forti, M, Giegling, I, de Haan, L, Hall, J, Hall, MH, van Haren, N, Iyegbe, C, Kahn, RS, Kravariti, E, Lawrie, SM, Lin, K, Luykx, JJ, Mata, I, McDonald, C, McIntosh, AM, Murray, RM, Picchioni, M, Powell, J, Prata, DP, Rujescu, D, Rutten, BPF, Shaikh, M, Simons, CJP, Toulopoulou, T, Weisbrod, M, van Winkel, R, Kuchenbaecker, K, McQuillin, A, and Bramon, E
Abstract: Background and Hypothesis: Endophenotypes can help to bridge the gap between psychosis and its genetic predispositions, but their underlying mechanisms remain largely unknown. This study aims to identify biological mechanisms that are relevant to the endophenotypes for psychosis, by partitioning polygenic risk scores into specific gene sets and testing their associations with endophenotypes. Study Design: We computed polygenic risk scores for schizophrenia and bipolar disorder restricted to brain-related gene sets retrieved from public databases and previous publications. Three hundred and seventy-eight gene-set-specific polygenic risk scores were generated for 4506 participants. Seven endophenotypes were also measured in the sample. Linear mixed-effects models were fitted to test associations between each endophenotype and each gene-set-specific polygenic risk score. Study Results: After correction for multiple testing, we found that a reduced P300 amplitude was associated with a higher schizophrenia polygenic risk score of the forebrain regionalization gene set (mean difference per SD increase in the polygenic risk score: −1.15 µV; 95% CI: −1.70 to −0.59 µV; P = 6 × 10−5). The schizophrenia polygenic risk score of forebrain regionalization also explained more variance of the P300 amplitude (R2 = 0.032) than other polygenic risk scores, including the genome-wide polygenic risk scores. Conclusions: Our finding on reduced P300 amplitudes suggests that certain genetic variants alter early brain development thereby increasing schizophrenia risk years later. Gene-set-specific polygenic risk scores are a useful tool to elucidate biological mechanisms of psychosis and endophenotypes, offering leads for experimental validation in cellular and animal models.
Published: 2023

20. Evidence of discontinuity between psychosis-risk and non-clinical samples in the neuroanatomical correlates of social function

Author: Haas, SS, Doucet, GE, Antoniades, M, Modabbernia, A, Corcoran, CM, Kahn, RS, Kambeitz, J, Kambeitz-Ilankovic, L, Borgwardt, S, Brambilla, P, Upthegrove, R, Wood, SJ, Salokangas, RKR, Hietala, J, Meisenzahl, E, Koutsouleris, N, Frangou, S, Haas, SS, Doucet, GE, Antoniades, M, Modabbernia, A, Corcoran, CM, Kahn, RS, Kambeitz, J, Kambeitz-Ilankovic, L, Borgwardt, S, Brambilla, P, Upthegrove, R, Wood, SJ, Salokangas, RKR, Hietala, J, Meisenzahl, E, Koutsouleris, N, and Frangou, S
Abstract: OBJECTIVE: Social dysfunction is a major feature of clinical-high-risk states for psychosis (CHR-P). Prior research has identified a neuroanatomical pattern associated with impaired social function outcome in CHR-P. The aim of the current study was to test whether social dysfunction in CHR-P is neurobiologically distinct or in a continuum with the lower end of the normal distribution of individual differences in social functioning. METHODS: We used a machine learning classifier to test for the presence of a previously validated brain structural pattern associated with impaired social outcome in CHR-P (CHR-outcome-neurosignature) in the neuroimaging profiles of individuals from two non-clinical samples (total n = 1763) and examined its association with social function, psychopathology and cognition. RESULTS: Although the CHR-outcome-neurosignature could be detected in a subset of the non-clinical samples, it was not associated was adverse social outcomes or higher psychopathology levels. However, participants whose neuroanatomical profiles were highly aligned with the CHR-outcome-neurosignature manifested subtle disadvantage in fluid (PFDR = 0.004) and crystallized intelligence (PFDR = 0.01), cognitive flexibility (PFDR = 0.02), inhibitory control (PFDR = 0.01), working memory (PFDR = 0.0005), and processing speed (PFDR = 0.04). CONCLUSIONS: We provide evidence of divergence in brain structural underpinnings of social dysfunction derived from a psychosis-risk enriched population when applied to non-clinical samples. This approach appears promising in identifying brain mechanisms bound to psychosis through comparisons of patient populations to non-clinical samples with the same neuroanatomical profiles.
Published: 2022

21. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author: Mullins, N, Kang, J, Campos, A, Coleman, JR, Edwards, AC, Galfalvy, H, Levey, DF, Lori, A, Shabalin, A, Starnawska, A, Su, M-H, Watson, HJ, Adams, M, Awasthi, S, Ganda, M, Hafferty, JD, Hishimoto, A, Kim, M, Okazaki, S, Otsuka, I, Ripke, S, Ware, EB, Bergen, AW, Berrettini, WH, Bohus, M, Brandt, H, Chang, X, Chen, WJ, Chen, H-C, Crawford, S, Crow, S, DiBlasi, E, Duriez, P, Fernandez-Aranda, F, Fichter, MM, Gallinger, S, Glatt, SJ, Gorwood, P, Guo, Y, Hakonarson, H, Halmi, KA, Hwu, H-G, Jain, S, Jamain, S, Jimenez-Murcia, S, Johnson, C, Kaplan, AS, Kaye, WH, Keel, PK, Kennedy, JL, Klump, KL, Li, D, Liao, S-C, Lieb, K, Lilenfeld, L, Liu, C-M, Magistretti, PJ, Marshall, CR, Mitchell, JE, Monson, ET, Myers, RM, Pinto, D, Powers, A, Ramoz, N, Roepke, S, Rozanov, V, Scherer, SW, Schmahl, C, Sokolowski, M, Strober, M, Thornton, LM, Treasure, J, Tsuang, MT, Witt, SH, Woodside, DB, Yilmaz, Z, Zillich, L, Adolfsson, R, Agartz, I, Air, TM, Alda, M, Alfredsson, L, Andreassen, OA, Anjorin, A, Appadurai, V, Artigas, MS, Van der Auwera, S, Azevedo, MH, Bass, N, Bau, CHD, Baune, BT, Bellivier, F, Berger, K, Biernacka, JM, Bigdeli, TB, Binder, EB, Boehnke, M, Boks, MP, Bosch, R, Braff, DL, Bryant, R, Budde, M, Byrne, EM, Cahn, W, Casas, M, Castelao, E, Cervilla, JA, Chaumette, B, Cichon, S, Corvin, A, Craddock, N, Craig, D, Degenhardt, F, Djurovic, S, Edenberg, HJ, Fanous, AH, Foo, JC, Forstner, AJ, Frye, M, Fullerton, JM, Gatt, JM, Gejman, P, Giegling, I, Grabe, HJ, Green, MJ, Grevet, EH, Grigoroiu-Serbanescu, M, Gutierrez, B, Guzman-Parra, J, Hamilton, SP, Hamshere, ML, Hartmann, A, Hauser, J, Heilmann-Heimbach, S, Hoffmann, P, Ising, M, Jones, I, Jones, LA, Jonsson, L, Kahn, RS, Kelsoe, JR, Kendler, KS, Kloiber, S, Koenen, KC, Kogevinas, M, Konte, B, Krebs, M-O, Lander, M, Lawrence, J, Leboyer, M, Lee, PH, Levinson, DF, Liao, C, Lissowska, J, Lucae, S, Mayoral, F, McElroy, SL, McGrath, P, McGuffin, P, McQuillin, A, Medland, SE, Mehta, D, Melle, I, Milaneschi, Y, Mitchell, PB, Molina, E, Morken, G, Mortensen, PB, Mueller-Myhsok, B, Nievergelt, C, Nimgaonkar, V, Noethen, MM, O'Donovan, MC, Ophoff, RA, Owen, MJ, Pato, C, Pato, MT, Penninx, BWJH, Pimm, J, Pistis, G, Potash, JB, Power, RA, Preisig, M, Quested, D, Ramos-Quiroga, JA, Reif, A, Ribases, M, Richarte, V, Rietschel, M, Rivera, M, Roberts, A, Roberts, G, Rouleau, GA, Rovaris, DL, Rujescu, D, Sanchez-Mora, C, Sanders, AR, Schofield, PR, Schulze, TG, Scott, LJ, Serretti, A, Shi, J, Shyn, S, Sirignano, L, Sklar, P, Smeland, OB, Smoller, JW, Sonuga-Barke, EJS, Spalletta, G, Strauss, JS, Swiatkowska, B, Trzaskowski, M, Turecki, G, Vilar-Ribo, L, Vincent, JB, Voelzke, H, Walters, JTR, Weickert, CS, Weickert, TW, Weissman, MM, Williams, LM, Wray, NR, Zai, CC, Ashley-Koch, AE, Beckham, JC, Hauser, ER, Hauser, MA, Kimbrel, NA, Lindquist, JH, McMahon, B, Oslin, DW, Qin, X, Agerbo, E, Borglum, AD, Breen, G, Erlangsen, A, Esko, T, Gelernter, J, Hougaard, DM, Kessler, RC, Kranzler, HR, Li, QS, Martin, NG, McIntosh, AM, Mors, O, Nordentoft, M, Olsen, CM, Porteous, D, Ursano, RJ, Wasserman, D, Werge, T, Whiteman, DC, Bulik, CM, Coon, H, Demontis, D, Docherty, AR, Kuo, P-H, Lewis, CM, Mann, JJ, Renteria, ME, Smith, DJ, Stahl, EA, Stein, MB, Streit, F, Willour, V, Ruderfer, DM, Mullins, N, Kang, J, Campos, A, Coleman, JR, Edwards, AC, Galfalvy, H, Levey, DF, Lori, A, Shabalin, A, Starnawska, A, Su, M-H, Watson, HJ, Adams, M, Awasthi, S, Ganda, M, Hafferty, JD, Hishimoto, A, Kim, M, Okazaki, S, Otsuka, I, Ripke, S, Ware, EB, Bergen, AW, Berrettini, WH, Bohus, M, Brandt, H, Chang, X, Chen, WJ, Chen, H-C, Crawford, S, Crow, S, DiBlasi, E, Duriez, P, Fernandez-Aranda, F, Fichter, MM, Gallinger, S, Glatt, SJ, Gorwood, P, Guo, Y, Hakonarson, H, Halmi, KA, Hwu, H-G, Jain, S, Jamain, S, Jimenez-Murcia, S, Johnson, C, Kaplan, AS, Kaye, WH, Keel, PK, Kennedy, JL, Klump, KL, Li, D, Liao, S-C, Lieb, K, Lilenfeld, L, Liu, C-M, Magistretti, PJ, Marshall, CR, Mitchell, JE, Monson, ET, Myers, RM, Pinto, D, Powers, A, Ramoz, N, Roepke, S, Rozanov, V, Scherer, SW, Schmahl, C, Sokolowski, M, Strober, M, Thornton, LM, Treasure, J, Tsuang, MT, Witt, SH, Woodside, DB, Yilmaz, Z, Zillich, L, Adolfsson, R, Agartz, I, Air, TM, Alda, M, Alfredsson, L, Andreassen, OA, Anjorin, A, Appadurai, V, Artigas, MS, Van der Auwera, S, Azevedo, MH, Bass, N, Bau, CHD, Baune, BT, Bellivier, F, Berger, K, Biernacka, JM, Bigdeli, TB, Binder, EB, Boehnke, M, Boks, MP, Bosch, R, Braff, DL, Bryant, R, Budde, M, Byrne, EM, Cahn, W, Casas, M, Castelao, E, Cervilla, JA, Chaumette, B, Cichon, S, Corvin, A, Craddock, N, Craig, D, Degenhardt, F, Djurovic, S, Edenberg, HJ, Fanous, AH, Foo, JC, Forstner, AJ, Frye, M, Fullerton, JM, Gatt, JM, Gejman, P, Giegling, I, Grabe, HJ, Green, MJ, Grevet, EH, Grigoroiu-Serbanescu, M, Gutierrez, B, Guzman-Parra, J, Hamilton, SP, Hamshere, ML, Hartmann, A, Hauser, J, Heilmann-Heimbach, S, Hoffmann, P, Ising, M, Jones, I, Jones, LA, Jonsson, L, Kahn, RS, Kelsoe, JR, Kendler, KS, Kloiber, S, Koenen, KC, Kogevinas, M, Konte, B, Krebs, M-O, Lander, M, Lawrence, J, Leboyer, M, Lee, PH, Levinson, DF, Liao, C, Lissowska, J, Lucae, S, Mayoral, F, McElroy, SL, McGrath, P, McGuffin, P, McQuillin, A, Medland, SE, Mehta, D, Melle, I, Milaneschi, Y, Mitchell, PB, Molina, E, Morken, G, Mortensen, PB, Mueller-Myhsok, B, Nievergelt, C, Nimgaonkar, V, Noethen, MM, O'Donovan, MC, Ophoff, RA, Owen, MJ, Pato, C, Pato, MT, Penninx, BWJH, Pimm, J, Pistis, G, Potash, JB, Power, RA, Preisig, M, Quested, D, Ramos-Quiroga, JA, Reif, A, Ribases, M, Richarte, V, Rietschel, M, Rivera, M, Roberts, A, Roberts, G, Rouleau, GA, Rovaris, DL, Rujescu, D, Sanchez-Mora, C, Sanders, AR, Schofield, PR, Schulze, TG, Scott, LJ, Serretti, A, Shi, J, Shyn, S, Sirignano, L, Sklar, P, Smeland, OB, Smoller, JW, Sonuga-Barke, EJS, Spalletta, G, Strauss, JS, Swiatkowska, B, Trzaskowski, M, Turecki, G, Vilar-Ribo, L, Vincent, JB, Voelzke, H, Walters, JTR, Weickert, CS, Weickert, TW, Weissman, MM, Williams, LM, Wray, NR, Zai, CC, Ashley-Koch, AE, Beckham, JC, Hauser, ER, Hauser, MA, Kimbrel, NA, Lindquist, JH, McMahon, B, Oslin, DW, Qin, X, Agerbo, E, Borglum, AD, Breen, G, Erlangsen, A, Esko, T, Gelernter, J, Hougaard, DM, Kessler, RC, Kranzler, HR, Li, QS, Martin, NG, McIntosh, AM, Mors, O, Nordentoft, M, Olsen, CM, Porteous, D, Ursano, RJ, Wasserman, D, Werge, T, Whiteman, DC, Bulik, CM, Coon, H, Demontis, D, Docherty, AR, Kuo, P-H, Lewis, CM, Mann, JJ, Renteria, ME, Smith, DJ, Stahl, EA, Stein, MB, Streit, F, Willour, V, and Ruderfer, DM
Abstract: BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
Published: 2022

22. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author: Brouwer, RM, Klein, M, Grasby, KL, Schnack, HG, Jahanshad, N, Teeuw, J, Thomopoulos, SI, Sprooten, E, Franz, CE, Gogtay, N, Kremen, WS, Panizzon, MS, Olde Loohuis, LM, Whelan, CD, Aghajani, M, Alloza, C, Alanaes, D, Artiges, E, Ayesa-Arriola, R, Barker, GJ, Bastin, ME, Blok, E, Boen, E, Breukelaar, IA, Bright, JK, Buimer, EEL, Bulow, R, Cannon, DM, Ciufolini, S, Crossley, NA, Damatac, CG, Dazzan, P, de Mol, CL, de Zwarte, SMC, Desrivieres, S, Diaz-Caneja, CM, Doan, NT, Dohm, K, Froehner, JH, Goltermann, J, Grigis, A, Grotegerd, D, Han, LKM, Harris, MA, Hartman, CA, Heany, SJ, Heindel, W, Heslenfeld, DJ, Hohmann, S, Ittermann, B, Jansen, PR, Janssen, J, Jia, T, Jiang, J, Jockwitz, C, Karali, T, Keeser, D, Koevoets, MGJC, Lenroot, RK, Malchow, B, Mandl, RCW, Medel, V, Meinert, S, Morgan, CA, Muehleisen, TW, Nabulsi, L, Opel, N, de la Foz, VO-G, Overs, BJ, Paillere Martinot, M-L, Redlich, R, Marques, TR, Repple, J, Roberts, G, Roshchupkin, GV, Setiaman, N, Shumskaya, E, Stein, F, Sudre, G, Takahashi, S, Thalamuthu, A, Tordesillas-Gutierrez, D, van der Lugt, A, van Haren, NEM, Wardlaw, JM, Wen, W, Westeneng, H-J, Wittfeld, K, Zhu, AH, Zugman, A, Armstrong, NJ, Bonfiglio, G, Bralten, J, Dalvie, S, Davies, G, Di Forti, M, Ding, L, Donohoe, G, Forstner, AJ, Gonzalez-Penas, J, Guimaraes, JPOFT, Homuth, G, Hottenga, J-J, Knol, MJ, Kwok, JBJ, Le Hellard, S, Mather, KA, Milaneschi, Y, Morris, DW, Noethen, MM, Papiol, S, Rietschel, M, Santoro, ML, Steen, VM, Stein, JL, Streit, F, Tankard, RM, Teumer, A, van 't Ent, D, van der Meer, D, van Eijk, KR, Vassos, E, Vazquez-Bourgon, J, Witt, SH, Adams, HHH, Agartz, I, Ames, D, Amunts, K, Andreassen, OA, Arango, C, Banaschewski, T, Baune, BT, Belangero, SI, Bokde, ALW, Boomsma, DI, Bressan, RA, Brodaty, H, Buitelaar, JK, Cahn, W, Caspers, S, Cichon, S, Crespo-Facorro, B, Cox, SR, Dannlowski, U, Elvsashagen, T, Espeseth, T, Falkai, PG, Fisher, SE, Flor, H, Fullerton, JM, Garavan, H, Gowland, PA, Grabe, HJ, Hahn, T, Heinz, A, Hillegers, M, Hoare, J, Hoekstra, PJ, Ikram, MA, Jackowski, AP, Jansen, A, Jonsson, EG, Kahn, RS, Kircher, T, Korgaonkar, MS, Krug, A, Lemaitre, H, Malt, UF, Martinot, J-L, McDonald, C, Mitchell, PB, Muetzel, RL, Murray, RM, Nees, F, Nenadic, I, Oosterlaan, J, Ophoff, RA, Pan, PM, Penninx, BWJH, Poustka, L, Sachdev, PS, Salum, GA, Schofield, PR, Schumann, G, Shaw, P, Sim, K, Smolka, MN, Stein, DJ, Trollor, JN, van den Berg, LH, Veldink, JH, Walter, H, Westlye, LT, Whelan, R, White, T, Wright, MJ, Medland, SE, Franke, B, Thompson, PM, Hulshoff Pol, HE, Brouwer, RM, Klein, M, Grasby, KL, Schnack, HG, Jahanshad, N, Teeuw, J, Thomopoulos, SI, Sprooten, E, Franz, CE, Gogtay, N, Kremen, WS, Panizzon, MS, Olde Loohuis, LM, Whelan, CD, Aghajani, M, Alloza, C, Alanaes, D, Artiges, E, Ayesa-Arriola, R, Barker, GJ, Bastin, ME, Blok, E, Boen, E, Breukelaar, IA, Bright, JK, Buimer, EEL, Bulow, R, Cannon, DM, Ciufolini, S, Crossley, NA, Damatac, CG, Dazzan, P, de Mol, CL, de Zwarte, SMC, Desrivieres, S, Diaz-Caneja, CM, Doan, NT, Dohm, K, Froehner, JH, Goltermann, J, Grigis, A, Grotegerd, D, Han, LKM, Harris, MA, Hartman, CA, Heany, SJ, Heindel, W, Heslenfeld, DJ, Hohmann, S, Ittermann, B, Jansen, PR, Janssen, J, Jia, T, Jiang, J, Jockwitz, C, Karali, T, Keeser, D, Koevoets, MGJC, Lenroot, RK, Malchow, B, Mandl, RCW, Medel, V, Meinert, S, Morgan, CA, Muehleisen, TW, Nabulsi, L, Opel, N, de la Foz, VO-G, Overs, BJ, Paillere Martinot, M-L, Redlich, R, Marques, TR, Repple, J, Roberts, G, Roshchupkin, GV, Setiaman, N, Shumskaya, E, Stein, F, Sudre, G, Takahashi, S, Thalamuthu, A, Tordesillas-Gutierrez, D, van der Lugt, A, van Haren, NEM, Wardlaw, JM, Wen, W, Westeneng, H-J, Wittfeld, K, Zhu, AH, Zugman, A, Armstrong, NJ, Bonfiglio, G, Bralten, J, Dalvie, S, Davies, G, Di Forti, M, Ding, L, Donohoe, G, Forstner, AJ, Gonzalez-Penas, J, Guimaraes, JPOFT, Homuth, G, Hottenga, J-J, Knol, MJ, Kwok, JBJ, Le Hellard, S, Mather, KA, Milaneschi, Y, Morris, DW, Noethen, MM, Papiol, S, Rietschel, M, Santoro, ML, Steen, VM, Stein, JL, Streit, F, Tankard, RM, Teumer, A, van 't Ent, D, van der Meer, D, van Eijk, KR, Vassos, E, Vazquez-Bourgon, J, Witt, SH, Adams, HHH, Agartz, I, Ames, D, Amunts, K, Andreassen, OA, Arango, C, Banaschewski, T, Baune, BT, Belangero, SI, Bokde, ALW, Boomsma, DI, Bressan, RA, Brodaty, H, Buitelaar, JK, Cahn, W, Caspers, S, Cichon, S, Crespo-Facorro, B, Cox, SR, Dannlowski, U, Elvsashagen, T, Espeseth, T, Falkai, PG, Fisher, SE, Flor, H, Fullerton, JM, Garavan, H, Gowland, PA, Grabe, HJ, Hahn, T, Heinz, A, Hillegers, M, Hoare, J, Hoekstra, PJ, Ikram, MA, Jackowski, AP, Jansen, A, Jonsson, EG, Kahn, RS, Kircher, T, Korgaonkar, MS, Krug, A, Lemaitre, H, Malt, UF, Martinot, J-L, McDonald, C, Mitchell, PB, Muetzel, RL, Murray, RM, Nees, F, Nenadic, I, Oosterlaan, J, Ophoff, RA, Pan, PM, Penninx, BWJH, Poustka, L, Sachdev, PS, Salum, GA, Schofield, PR, Schumann, G, Shaw, P, Sim, K, Smolka, MN, Stein, DJ, Trollor, JN, van den Berg, LH, Veldink, JH, Walter, H, Westlye, LT, Whelan, R, White, T, Wright, MJ, Medland, SE, Franke, B, Thompson, PM, and Hulshoff Pol, HE
Abstract: Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.
Published: 2022

23. Brain charts for the human lifespan (vol 604, pg 525, 2022)

Author: Bethlehem, RAI, Seidlitz, J, White, SR, Vogel, JW, Anderson, KM, Adamson, C, Adler, S, Alexopoulos, GS, Anagnostou, E, Areces-Gonzalez, A, Astle, DE, Auyeung, B, Ayub, M, Bae, J, Ball, G, Baron-Cohen, S, Beare, R, Bedford, SA, Benegal, V, Beyer, F, Blangero, J, Blesa Cabez, M, Boardman, JP, Borzage, M, Bosch-Bayard, JF, Bourke, N, Calhoun, VD, Chakravarty, MM, Chen, C, Chertavian, C, Chetelat, G, Chong, YS, Cole, JH, Corvin, A, Costantino, M, Courchesne, E, Crivello, F, Cropley, VL, Crosbie, J, Crossley, N, Delarue, M, Delorme, R, Desrivieres, S, Devenyi, GA, Di Biase, MA, Dolan, R, Donald, KA, Donohoe, G, Dunlop, K, Edwards, AD, Elison, JT, Ellis, CT, Elman, JA, Eyler, L, Fair, DA, Feczko, E, Fletcher, PC, Fonagy, P, Franz, CE, Galan-Garcia, L, Gholipour, A, Giedd, J, Gilmore, JH, Glahn, DC, Goodyer, IM, Grant, PE, Groenewold, NA, Gunning, FM, Gur, RE, Gur, RC, Hammill, CF, Hansson, O, Hedden, T, Heinz, A, Henson, RN, Heuer, K, Hoare, J, Holla, B, Holmes, AJ, Holt, R, Huang, H, Im, K, Ipser, J, Jack, CR, Jackowski, AP, Jia, T, Johnson, KA, Jones, PB, Jones, DT, Kahn, RS, Karlsson, H, Karlsson, L, Kawashima, R, Kelley, EA, Kern, S, Kim, KW, Kitzbichler, MG, Kremen, WS, Lalonde, F, Landeau, B, Lee, S, Lerch, J, Lewis, JD, Li, J, Liao, W, Liston, C, Lombardo, MV, Lv, J, Lynch, C, Mallard, TT, Marcelis, M, Markello, RD, Mathias, SR, Mazoyer, B, McGuire, P, Meaney, MJ, Mechelli, A, Medic, N, Misic, B, Morgan, SE, Mothersill, D, Nigg, J, Ong, MQW, Ortinau, C, Ossenkoppele, R, Ouyang, M, Palaniyappan, L, Paly, L, Pan, PM, Pantelis, C, Park, MM, Paus, T, Pausova, Z, Paz-Linares, D, Pichet Binette, A, Pierce, K, Qian, X, Qiu, J, Qiu, A, Raznahan, A, Rittman, T, Rodrigue, A, Rollins, CK, Romero-Garcia, R, Ronan, L, Rosenberg, MD, Rowitch, DH, Salum, GA, Satterthwaite, TD, Schaare, HL, Schachar, RJ, Schultz, AP, Schumann, G, Scholl, M, Sharp, D, Shinohara, RT, Skoog, I, Smyser, CD, Sperling, RA, Stein, DJ, Stolicyn, A, Suckling, J, Sullivan, G, Taki, Y, Thyreau, B, Toro, R, Traut, N, Tsvetanov, KA, Turk-Browne, NB, Tuulari, JJ, Tzourio, C, Vachon-Presseau, E, Valdes-Sosa, MJ, Valdes-Sosa, PA, Valk, SL, van Amelsvoort, T, Vandekar, SN, Vasung, L, Victoria, LW, Villeneuve, S, Villringer, A, Vertes, PE, Wagstyl, K, Wang, YS, Warfield, SK, Warrier, V, Westman, E, Westwater, ML, Whalley, HC, Witte, AV, Yang, N, Yeo, B, Yun, H, Zalesky, A, Zar, HJ, Zettergren, A, Zhou, JH, Ziauddeen, H, Zugman, A, Zuo, XN, Bullmore, ET, Alexander-Bloch, AF, Bethlehem, RAI, Seidlitz, J, White, SR, Vogel, JW, Anderson, KM, Adamson, C, Adler, S, Alexopoulos, GS, Anagnostou, E, Areces-Gonzalez, A, Astle, DE, Auyeung, B, Ayub, M, Bae, J, Ball, G, Baron-Cohen, S, Beare, R, Bedford, SA, Benegal, V, Beyer, F, Blangero, J, Blesa Cabez, M, Boardman, JP, Borzage, M, Bosch-Bayard, JF, Bourke, N, Calhoun, VD, Chakravarty, MM, Chen, C, Chertavian, C, Chetelat, G, Chong, YS, Cole, JH, Corvin, A, Costantino, M, Courchesne, E, Crivello, F, Cropley, VL, Crosbie, J, Crossley, N, Delarue, M, Delorme, R, Desrivieres, S, Devenyi, GA, Di Biase, MA, Dolan, R, Donald, KA, Donohoe, G, Dunlop, K, Edwards, AD, Elison, JT, Ellis, CT, Elman, JA, Eyler, L, Fair, DA, Feczko, E, Fletcher, PC, Fonagy, P, Franz, CE, Galan-Garcia, L, Gholipour, A, Giedd, J, Gilmore, JH, Glahn, DC, Goodyer, IM, Grant, PE, Groenewold, NA, Gunning, FM, Gur, RE, Gur, RC, Hammill, CF, Hansson, O, Hedden, T, Heinz, A, Henson, RN, Heuer, K, Hoare, J, Holla, B, Holmes, AJ, Holt, R, Huang, H, Im, K, Ipser, J, Jack, CR, Jackowski, AP, Jia, T, Johnson, KA, Jones, PB, Jones, DT, Kahn, RS, Karlsson, H, Karlsson, L, Kawashima, R, Kelley, EA, Kern, S, Kim, KW, Kitzbichler, MG, Kremen, WS, Lalonde, F, Landeau, B, Lee, S, Lerch, J, Lewis, JD, Li, J, Liao, W, Liston, C, Lombardo, MV, Lv, J, Lynch, C, Mallard, TT, Marcelis, M, Markello, RD, Mathias, SR, Mazoyer, B, McGuire, P, Meaney, MJ, Mechelli, A, Medic, N, Misic, B, Morgan, SE, Mothersill, D, Nigg, J, Ong, MQW, Ortinau, C, Ossenkoppele, R, Ouyang, M, Palaniyappan, L, Paly, L, Pan, PM, Pantelis, C, Park, MM, Paus, T, Pausova, Z, Paz-Linares, D, Pichet Binette, A, Pierce, K, Qian, X, Qiu, J, Qiu, A, Raznahan, A, Rittman, T, Rodrigue, A, Rollins, CK, Romero-Garcia, R, Ronan, L, Rosenberg, MD, Rowitch, DH, Salum, GA, Satterthwaite, TD, Schaare, HL, Schachar, RJ, Schultz, AP, Schumann, G, Scholl, M, Sharp, D, Shinohara, RT, Skoog, I, Smyser, CD, Sperling, RA, Stein, DJ, Stolicyn, A, Suckling, J, Sullivan, G, Taki, Y, Thyreau, B, Toro, R, Traut, N, Tsvetanov, KA, Turk-Browne, NB, Tuulari, JJ, Tzourio, C, Vachon-Presseau, E, Valdes-Sosa, MJ, Valdes-Sosa, PA, Valk, SL, van Amelsvoort, T, Vandekar, SN, Vasung, L, Victoria, LW, Villeneuve, S, Villringer, A, Vertes, PE, Wagstyl, K, Wang, YS, Warfield, SK, Warrier, V, Westman, E, Westwater, ML, Whalley, HC, Witte, AV, Yang, N, Yeo, B, Yun, H, Zalesky, A, Zar, HJ, Zettergren, A, Zhou, JH, Ziauddeen, H, Zugman, A, Zuo, XN, Bullmore, ET, and Alexander-Bloch, AF
Published: 2022

24. Dosing frequency and adherence in chronic psychiatric disease: systematic review and meta-analysis

Author: Medic G, Higashi K, Littlewood KJ, Diez T, Granström O, and Kahn RS
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Goran Medic,1 Kyoko Higashi,1 Kavi J Littlewood,1 Teresa Diez,2 Ola Granström,3 René S Kahn41MAPI Consultancy, Houten, The Netherlands; 2AstraZeneca, Zaventem, Belgium; 3AstraZeneca, Södertälje, Sweden; 4Division of Neuroscience at the Utrecht University Medical Center, Utrecht, The NetherlandsBackground: The purpose of this study was to investigate the impact of dosing frequency on adherence in severe chronic psychiatric and neurological diseases.Methods: A systematic literature review was conducted for articles in English from medical databases. Diseases were schizophrenia, psychosis, epilepsy, bipolar disorder, and major depressive disorder.Results: Of 1420 abstracts screened, 12 studies were included. Adherence measures included Medication Event Monitoring System (MEMS®), medication possession ratio, medication persistence, and refill adherence. Three schizophrenia and one epilepsy study used MEMS, and all showed a trend towards higher adherence rates with less frequent dosing regimens. Three depression and one schizophrenia study used the medication possession ratio; the pooled odds ratio of being adherent was 89% higher (ie, 1.89, 95% credibility limits 1.71–2.09) on once-daily versus twice-daily dosing. Two studies in depression and one in all bupropion patients assessed medication persistence and refill adherence. The pooled odds ratio for the two depression studies using medication persistence was 2.10 (95% credibility limits 1.86–2.37) for once-daily versus twice-daily dosing. For refill adherence after 9 months, 65%–75% of patients on once-daily versus 56% on twice-daily dosing had at least one refill. In all but one of the studies using other measures of adherence, adherence rates were higher with once-daily dosing compared with more frequent dosing regimens. No relevant studies were identified for bipolar disorder or psychosis.Conclusion: Differences in study design and adherence measures used across the studies were too large to allow pooling of all results. Despite these differences, there was a consistent trend of better adherence with less frequent dosing.Keywords: adherence, dosing frequency, schizophrenia, epilepsy, depression
Published: 2013

25. Stratification and prediction of remission in first-episode psychosis patients: the OPTiMiSE cohort study

Author: Martinuzzi, E, Barbosa, S, Daoudlarian, D, Bel Haj Ali, W, Gilet, C, Fillatre, L, Khalfallah, O, Troudet, R, Jamain, S, Fond, G, Sommer, I, Leucht, S, Dazzan, P, McGuire, P, Arango, C, Diaz-Caneja, CM, Fleischhacker, W, Rujescu, D, Glenthøj, B, Winter, I, Kahn, RS, Yolken, R, Lewis, S, Drake, R, Davidovic, L, Leboyer, M, Glaichenhaus, N, OPTiMiSE Study Group, De Hert, Marc, Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia-Antipolis (I3S) / Equipe IMAGES-CREATIVE, Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia-Antipolis (I3S) / Projet MEDIACODING, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), INSERM U955, équipe 15, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Brain Centre Rudolf Magnus [Utrecht], University Medical Center [Utrecht], Psychological Medicine, Psychiatry Department, Adolescent Unit, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Stanley Laboratory of Developmental Neurovirology, Johns Hopkins University Medical Center, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Immunologie des muqueuses et inflammation, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: 0301 basic medicine, Male, Pediatrics, SYMPTOMS, Internationality, ComputerSystemsOrganization_COMPUTERSYSTEMIMPLEMENTATION, Physiology, [SDV]Life Sciences [q-bio], law.invention, Cohort Studies, 0302 clinical medicine, Randomized controlled trial, law, 1234567890(), ComputingMilieux_MISCELLANEOUS, Inflammation/metabolism, NONSTEROIDAL ANTIINFLAMMATORY DRUGS, ASSOCIATION, ddc, 3. Good health, Psychiatry and Mental health, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Cytokines, Female, Biological psychiatry, Antipsychotic Agents, Cohort study, Adult, medicine.medical_specialty, Treatment response, TheoryofComputation_COMPUTATIONBYABSTRACTDEVICES, Adolescent, MEDLINE, 1ST EPISODE, SCHIZOPHRENIA-PATIENTS, Cytokines/blood, Article, lcsh:RC321-571, CYTOKINE ALTERATIONS, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, First episode psychosis, MENTAL-DISORDERS, medicine, Humans, AGENTS, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Nicolas Glaichenhaus 1234567890(), Biological Psychiatry, TREATMENT RESPONSE, Inflammation, Psychiatric Status Rating Scales, INTERLEUKIN-15, business.industry, Correction, Psychotic Disorders/blood, 030104 developmental biology, Logistic Models, Psychotic Disorders, Multicenter study, Marion Leboyer, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Psychiatric status rating scales, business, Biomarkers, 030217 neurology & neurosurgery, Antipsychotic Agents/therapeutic use, Biomarkers/blood
Abstract: Early response to first-line antipsychotic treatments is strongly associated with positive long-term symptomatic and functional outcome in psychosis. Unfortunately, attempts to identify reliable predictors of treatment response in first-episode psychosis (FEP) patients have not yet been successful. One reason for this could be that FEP patients are highly heterogeneous in terms of symptom expression and underlying disease biological mechanisms, thereby impeding the identification of one-size-fits-all predictors of treatment response. We have used a clustering approach to stratify 325 FEP patients into four clinical subtypes, termed C1A, C1B, C2A and C2B, based on their symptoms assessed using the Positive and Negative Syndrome Scale (PANSS) scale. Compared to C1B, C2A and C2B patients, those from the C1A subtype exhibited the most severe symptoms and were the most at risk of being non-remitters when treated with the second-generation antipsychotic drug amisulpride. Before treatment, C1A patients exhibited higher serum levels of several pro-inflammatory cytokines and inflammation-associated biomarkers therefore validating our stratification approach on external biological measures. Most importantly, in the C1A subtype, but not others, lower serum levels of interleukin (IL)-15, higher serum levels of C-X-C motif chemokine 12 (CXCL12), previous exposure to cytomegalovirus (CMV), use of recreational drugs and being younger were all associated with higher odds of being non-remitters 4 weeks after treatment. The predictive value of this model was good (mean area under the curve (AUC) = 0.73 ± 0.10), and its specificity and sensitivity were 45 ± 0.09% and 83 ± 0.03%, respectively. Further validation and replication of these results in clinical trials would pave the way for the development of a blood-based assisted clinical decision support system in psychosis. ispartof: Translational Psychiatry vol:9 issue:1 pages:1-20 ispartof: location:United States status: published
Published: 2019
Full Text: View/download PDF

26. Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Author: Velthorst, E, Mollon, J, Murray, RM, de Haan, L, Germeys, IM, Glahn, DC, Arango, C, van der Ven, E, Di Forti, M, Bernardo, M, Guloksuz, S, Delespaul, P, Mezquida, G, Amoretti, S, Bobes, J, Saiz, PA, Garcia-Portilla, MP, Santos, JL, Jimenez-Lopez, E, Sanjuan, J, Aguilar, EJ, Arrojo, M, Carracedo, A, Lopez, G, Gonzalez-Penas, J, Parellada, M, Atbasoglu, C, Saka, MC, Ucok, A, Alptekin, K, Akdede, B, Binbay, T, Altinyazar, V, Ulas, H, Yalincetin, B, Gumus-Akay, G, Beyaz, BC, Soygur, H, Cankurtaran, ES, Kaymak, SU, Maric, NP, Mihaljevic, MM, Petrovic, SA, Mirjanic, T, Del-Ben, CM, Ferraro, L, Gayer-Anderson, C, Jones, PB, Jongsma, HE, Kirkbride, JB, La Cascia, C, Lasalvia, A, Tosato, S, Llorca, P-M, Menezes, PR, Morgan, C, Quattrone, D, Menchetti, M, Selten, J-P, Szoke, A, Tarricone, I, Tortelli, A, McGuire, P, Valmaggia, L, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, McGorry, P, Pantelis, C, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, AA, Bruggeman, R, van Beveren, NJ, Luykx, JJ, Cahn, W, Simons, CJP, Kahn, RS, Schirmbeck, F, van Winkel, R, Reichenberg, A, Velthorst, E, Mollon, J, Murray, RM, de Haan, L, Germeys, IM, Glahn, DC, Arango, C, van der Ven, E, Di Forti, M, Bernardo, M, Guloksuz, S, Delespaul, P, Mezquida, G, Amoretti, S, Bobes, J, Saiz, PA, Garcia-Portilla, MP, Santos, JL, Jimenez-Lopez, E, Sanjuan, J, Aguilar, EJ, Arrojo, M, Carracedo, A, Lopez, G, Gonzalez-Penas, J, Parellada, M, Atbasoglu, C, Saka, MC, Ucok, A, Alptekin, K, Akdede, B, Binbay, T, Altinyazar, V, Ulas, H, Yalincetin, B, Gumus-Akay, G, Beyaz, BC, Soygur, H, Cankurtaran, ES, Kaymak, SU, Maric, NP, Mihaljevic, MM, Petrovic, SA, Mirjanic, T, Del-Ben, CM, Ferraro, L, Gayer-Anderson, C, Jones, PB, Jongsma, HE, Kirkbride, JB, La Cascia, C, Lasalvia, A, Tosato, S, Llorca, P-M, Menezes, PR, Morgan, C, Quattrone, D, Menchetti, M, Selten, J-P, Szoke, A, Tarricone, I, Tortelli, A, McGuire, P, Valmaggia, L, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, McGorry, P, Pantelis, C, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, AA, Bruggeman, R, van Beveren, NJ, Luykx, JJ, Cahn, W, Simons, CJP, Kahn, RS, Schirmbeck, F, van Winkel, R, and Reichenberg, A
Abstract: Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.
Published: 2021

27. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author: Mullins, N, Forstner, AJ, O'Connell, KS, Coombes, B, Coleman, JR, Qiao, Z, Als, TD, Bigdeli, TB, Borte, S, Bryois, J, Charney, AW, Drange, OK, Gandal, MJ, Hagenaars, SP, Ikeda, M, Kamitaki, N, Kim, M, Krebs, K, Panagiotaropoulou, G, Schilder, BM, Sloofman, LG, Steinberg, S, Trubetskoy, V, Winsvold, BS, Won, H-H, Abramova, L, Adorjan, K, Agerbo, E, Al Eissa, M, Albani, D, Alliey-Rodriguez, N, Anjorin, A, Antilla, V, Antoniou, A, Awasthi, S, Baek, JH, Baekvad-Hansen, M, Bass, N, Bauer, M, Beins, EC, Bergen, SE, Birner, A, Pedersen, CB, Boen, E, Boks, MP, Bosch, R, Brum, M, Brumpton, BM, Brunkhorst-Kanaan, N, Budde, M, Bybjerg-Grauholm, J, Byerley, W, Cairns, M, Casas, M, Cervantes, P, Clarke, T-K, Cruceanu, C, Cuellar-Barboza, A, Cunningham, J, Curtis, D, Czerski, PM, Dale, AM, Dalkner, N, David, FS, Degenhardt, F, Djurovic, S, Dobbyn, AL, Douzenis, A, Elvsashagen, T, Escott-Price, V, Ferrier, IN, Fiorentino, A, Foroud, TM, Forty, L, Frank, J, Frei, O, Freimer, NB, Frisen, L, Gade, K, Garnham, J, Gelernter, J, Pedersen, MG, Gizer, IR, Gordon, SD, Gordon-Smith, K, Greenwood, TA, Grove, J, Guzman-Parra, J, Ha, K, Haraldsson, M, Hautzinger, M, Heilbronner, U, Hellgren, D, Herms, S, Hoffmann, P, Holmans, PA, Huckins, L, Jamain, S, Johnson, JS, Kalman, JL, Kamatani, Y, Kennedy, JL, Kittel-Schneider, S, Knowles, JA, Kogevinas, M, Koromina, M, Kranz, TM, Kranzler, HR, Kubo, M, Kupka, R, Kushner, SA, Lavebratt, C, Lawrence, J, Leber, M, Lee, H-J, Lee, PH, Levy, SE, Lewis, C, Liao, C, Lucae, S, Lundberg, M, MacIntyre, DJ, Maier, W, Maihofer, A, Malaspina, D, Maratou, E, Martinsson, L, Mattheisen, M, McCarroll, SA, McGregor, NW, McGuffin, P, McKay, JD, Medeiros, H, Medland, SE, Millischer, V, Montgomery, GW, Moran, JL, Morris, DW, Muhleisen, TW, O'Brien, N, O'Donovan, C, Loohuis, LMO, Oruc, L, Papiol, S, Pardinas, AF, Perry, A, Pfennig, A, Porichi, E, Potash, JB, Quested, D, Raj, T, Rapaport, MH, DePaulo, JR, Regeer, EJ, Rice, JP, Rivas, F, Rivera, M, Roth, J, Roussos, P, Ruderfer, DM, Sanchez-Mora, C, Schulte, EC, Senner, F, Sharp, S, Shilling, PD, Sigurdsson, E, Sirignano, L, Slaney, C, Smeland, OB, Sobell, JL, Hansen, CS, Artigas, MS, Spijker, AT, Stein, DJ, Strauss, JS, Swiatkowska, B, Terao, C, Thorgeirsson, TE, Toma, C, Tooney, P, Tsermpini, E-E, Vawter, MP, Vedder, H, Walters, JTR, Witt, SH, Xi, S, Xu, W, Yang, JMK, Young, AH, Young, H, Zandi, PP, Zhou, H, Zillich, L, Adolfsson, R, Agartz, I, Alda, M, Alfredsson, L, Babadjanova, G, Backlund, L, Baune, BT, Bellivier, F, Bengesser, S, Berrettini, WH, Blackwood, DHR, Boehnke, M, Borglum, AD, Breen, G, Carr, VJ, Catts, S, Corvin, A, Craddock, N, Dannlowski, U, Dikeos, D, Esko, T, Etain, B, Ferentinos, P, Frye, M, Fullerton, JM, Gawlik, M, Gershon, ES, Goes, F, Green, MJ, Grigoroiu-Serbanescu, M, Hauser, J, Henskens, F, Hillert, J, Hong, KS, Hougaard, DM, Hultman, CM, Hveem, K, Iwata, N, Jablensky, A, Jones, I, Jones, LA, Kahn, RS, Kelsoe, JR, Kirov, G, Landen, M, Leboyer, M, Lewis, CM, Li, QS, Lissowska, J, Lochner, C, Loughland, C, Martin, NG, Mathews, CA, Mayoral, F, McElroy, SL, McIntosh, AM, McMahon, FJ, Melle, I, Michie, P, Milani, L, Mitchell, PB, Morken, G, Mors, O, Mortensen, PB, Mowry, B, Muller-Myhsok, B, Myers, RM, Neale, BM, Nievergelt, CM, Nordentoft, M, Nothen, MM, ODonovan, MC, Oedegaard, KJ, Olsson, T, Owen, MJ, Paciga, SA, Pantelis, C, Pato, C, Pato, MT, Patrinos, GP, Perlis, RH, Posthuma, D, Ramos-Quiroga, JA, Reif, A, Reininghaus, EZ, Ribases, M, Rietschel, M, Ripke, S, Rouleau, GA, Saito, T, Schall, U, Schalling, M, Schofield, PR, Schulze, TG, Scott, LJ, Scott, RJ, Serretti, A, Weickert, CS, Smoller, JW, Stefansson, H, Stefansson, K, Stordal, E, Streit, F, Sullivan, PF, Turecki, G, Vaaler, AE, Vieta, E, Vincent, JB, Waldman, ID, Weickert, TW, Werge, T, Wray, NR, Zwart, J, Biernacka, JM, Nurnberger, J, Cichon, S, Edenberg, HJ, Stahl, EA, McQuillin, A, Di Florio, A, Ophoff, RA, Andreassen, OA, Mullins, N, Forstner, AJ, O'Connell, KS, Coombes, B, Coleman, JR, Qiao, Z, Als, TD, Bigdeli, TB, Borte, S, Bryois, J, Charney, AW, Drange, OK, Gandal, MJ, Hagenaars, SP, Ikeda, M, Kamitaki, N, Kim, M, Krebs, K, Panagiotaropoulou, G, Schilder, BM, Sloofman, LG, Steinberg, S, Trubetskoy, V, Winsvold, BS, Won, H-H, Abramova, L, Adorjan, K, Agerbo, E, Al Eissa, M, Albani, D, Alliey-Rodriguez, N, Anjorin, A, Antilla, V, Antoniou, A, Awasthi, S, Baek, JH, Baekvad-Hansen, M, Bass, N, Bauer, M, Beins, EC, Bergen, SE, Birner, A, Pedersen, CB, Boen, E, Boks, MP, Bosch, R, Brum, M, Brumpton, BM, Brunkhorst-Kanaan, N, Budde, M, Bybjerg-Grauholm, J, Byerley, W, Cairns, M, Casas, M, Cervantes, P, Clarke, T-K, Cruceanu, C, Cuellar-Barboza, A, Cunningham, J, Curtis, D, Czerski, PM, Dale, AM, Dalkner, N, David, FS, Degenhardt, F, Djurovic, S, Dobbyn, AL, Douzenis, A, Elvsashagen, T, Escott-Price, V, Ferrier, IN, Fiorentino, A, Foroud, TM, Forty, L, Frank, J, Frei, O, Freimer, NB, Frisen, L, Gade, K, Garnham, J, Gelernter, J, Pedersen, MG, Gizer, IR, Gordon, SD, Gordon-Smith, K, Greenwood, TA, Grove, J, Guzman-Parra, J, Ha, K, Haraldsson, M, Hautzinger, M, Heilbronner, U, Hellgren, D, Herms, S, Hoffmann, P, Holmans, PA, Huckins, L, Jamain, S, Johnson, JS, Kalman, JL, Kamatani, Y, Kennedy, JL, Kittel-Schneider, S, Knowles, JA, Kogevinas, M, Koromina, M, Kranz, TM, Kranzler, HR, Kubo, M, Kupka, R, Kushner, SA, Lavebratt, C, Lawrence, J, Leber, M, Lee, H-J, Lee, PH, Levy, SE, Lewis, C, Liao, C, Lucae, S, Lundberg, M, MacIntyre, DJ, Maier, W, Maihofer, A, Malaspina, D, Maratou, E, Martinsson, L, Mattheisen, M, McCarroll, SA, McGregor, NW, McGuffin, P, McKay, JD, Medeiros, H, Medland, SE, Millischer, V, Montgomery, GW, Moran, JL, Morris, DW, Muhleisen, TW, O'Brien, N, O'Donovan, C, Loohuis, LMO, Oruc, L, Papiol, S, Pardinas, AF, Perry, A, Pfennig, A, Porichi, E, Potash, JB, Quested, D, Raj, T, Rapaport, MH, DePaulo, JR, Regeer, EJ, Rice, JP, Rivas, F, Rivera, M, Roth, J, Roussos, P, Ruderfer, DM, Sanchez-Mora, C, Schulte, EC, Senner, F, Sharp, S, Shilling, PD, Sigurdsson, E, Sirignano, L, Slaney, C, Smeland, OB, Sobell, JL, Hansen, CS, Artigas, MS, Spijker, AT, Stein, DJ, Strauss, JS, Swiatkowska, B, Terao, C, Thorgeirsson, TE, Toma, C, Tooney, P, Tsermpini, E-E, Vawter, MP, Vedder, H, Walters, JTR, Witt, SH, Xi, S, Xu, W, Yang, JMK, Young, AH, Young, H, Zandi, PP, Zhou, H, Zillich, L, Adolfsson, R, Agartz, I, Alda, M, Alfredsson, L, Babadjanova, G, Backlund, L, Baune, BT, Bellivier, F, Bengesser, S, Berrettini, WH, Blackwood, DHR, Boehnke, M, Borglum, AD, Breen, G, Carr, VJ, Catts, S, Corvin, A, Craddock, N, Dannlowski, U, Dikeos, D, Esko, T, Etain, B, Ferentinos, P, Frye, M, Fullerton, JM, Gawlik, M, Gershon, ES, Goes, F, Green, MJ, Grigoroiu-Serbanescu, M, Hauser, J, Henskens, F, Hillert, J, Hong, KS, Hougaard, DM, Hultman, CM, Hveem, K, Iwata, N, Jablensky, A, Jones, I, Jones, LA, Kahn, RS, Kelsoe, JR, Kirov, G, Landen, M, Leboyer, M, Lewis, CM, Li, QS, Lissowska, J, Lochner, C, Loughland, C, Martin, NG, Mathews, CA, Mayoral, F, McElroy, SL, McIntosh, AM, McMahon, FJ, Melle, I, Michie, P, Milani, L, Mitchell, PB, Morken, G, Mors, O, Mortensen, PB, Mowry, B, Muller-Myhsok, B, Myers, RM, Neale, BM, Nievergelt, CM, Nordentoft, M, Nothen, MM, ODonovan, MC, Oedegaard, KJ, Olsson, T, Owen, MJ, Paciga, SA, Pantelis, C, Pato, C, Pato, MT, Patrinos, GP, Perlis, RH, Posthuma, D, Ramos-Quiroga, JA, Reif, A, Reininghaus, EZ, Ribases, M, Rietschel, M, Ripke, S, Rouleau, GA, Saito, T, Schall, U, Schalling, M, Schofield, PR, Schulze, TG, Scott, LJ, Scott, RJ, Serretti, A, Weickert, CS, Smoller, JW, Stefansson, H, Stefansson, K, Stordal, E, Streit, F, Sullivan, PF, Turecki, G, Vaaler, AE, Vieta, E, Vincent, JB, Waldman, ID, Weickert, TW, Werge, T, Wray, NR, Zwart, J, Biernacka, JM, Nurnberger, J, Cichon, S, Edenberg, HJ, Stahl, EA, McQuillin, A, Di Florio, A, Ophoff, RA, and Andreassen, OA
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
Published: 2021

28. Neuroharmony: A new tool for harmonizing volumetric MRI data from unseen scanners

Author: Garcia-Dias, R, Scarpazza, C, Baecker, L, Vieira, S, Pinaya, WHL, Corvin, A, Redolfi, A, Nelson, B, Crespo-Facorro, B, McDonald, C, Tordesillas-Gutierrez, D, Cannon, D, Mothersill, D, Hernaus, D, Morris, D, Setien-Suero, E, Donohoe, G, Frisoni, G, Tronchin, G, Sato, J, Marcelis, M, Kempton, M, van Haren, NEM, Gruber, O, McGorry, P, Amminger, P, McGuire, P, Gong, Q, Kahn, RS, Ayesa-Arriola, R, van Amelsvoort, T, de la Foz, VO-G, Calhoun, V, Cahn, W, Mechelli, A, Garcia-Dias, R, Scarpazza, C, Baecker, L, Vieira, S, Pinaya, WHL, Corvin, A, Redolfi, A, Nelson, B, Crespo-Facorro, B, McDonald, C, Tordesillas-Gutierrez, D, Cannon, D, Mothersill, D, Hernaus, D, Morris, D, Setien-Suero, E, Donohoe, G, Frisoni, G, Tronchin, G, Sato, J, Marcelis, M, Kempton, M, van Haren, NEM, Gruber, O, McGorry, P, Amminger, P, McGuire, P, Gong, Q, Kahn, RS, Ayesa-Arriola, R, van Amelsvoort, T, de la Foz, VO-G, Calhoun, V, Cahn, W, and Mechelli, A
Abstract: • We present Neuroharmony, a harmonization tool for images from unseen scanners. • We developed Neuroharmony using a total of 15,026 sMRI images. • The tool was able to reduce scanner-related bias from unseen scans. • Neuroharmony represents a significant step towards imaging-based clinical tools. • Neuroharmony is available at https://github.com/garciadias/Neuroharmony.
Published: 2020

29. The genetic architecture of the human cerebral cortex

Author: Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnaes, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bulow, R, Burger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Nhat, TD, Dohm, K, Ehrlich, S, Engelbrecht, H-R, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, J-J, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Kramer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Mirza-Schreiber, N, Moreira, JCV, Muhleisen, TW, Mueller-Myhsok, B, Najt, P, Nakahara, S, Nho, K, Loohuis, LMO, Orfanos, DP, Pearson, JF, Pitcher, TL, Putz, B, Quide, Y, Ragothaman, A, Rashid, FM, Reay, WR, Redlich, R, Reinbold, CS, Repple, J, Richard, G, Riedel, BC, Risacher, SL, Rocha, CS, Mota, NR, Salminen, L, Saremi, A, Saykin, AJ, Schlag, F, Schmaal, L, Schofield, PR, Secolin, R, Shapland, CY, Shen, L, Shin, J, Shumskaya, E, Sonderby, IE, Sprooten, E, Tansey, KE, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Turner, JA, Uhlmann, A, Vallerga, CL, van der Meer, D, van Donkelaar, MMJ, van Eijk, L, van Erp, TGM, van Haren, NEM, van Rooij, D, van Tol, M-J, Veldink, JH, Verhoef, E, Walton, E, Wang, M, Wang, Y, Wardlaw, JM, Wen, W, Westlye, LT, Whelan, CD, Witt, SH, Wittfeld, K, Wolf, C, Wolfers, T, Wu, JQ, Yasuda, CL, Zaremba, D, Zhang, Z, Zwiers, MP, Artiges, E, Assareh, AA, Ayesa-Arriola, R, Belger, A, Brandt, CL, Brown, GG, Cichon, S, Curran, JE, Davies, GE, Degenhardt, F, Dennis, MF, Dietsche, B, Djurovic, S, Doherty, CP, Espiritu, R, Garijo, D, Gil, Y, Gowland, PA, Green, RC, Hausler, AN, Heindel, W, Ho, B-C, Hoffmann, WU, Holsboer, F, Homuth, G, Hosten, N, Jack, CR, Jang, M, Jansen, A, Kimbrel, NA, Kolskar, K, Koops, S, Krug, A, Lim, KO, Luykx, JJ, Mathalon, DH, Mather, KA, Mattay, VS, Matthews, S, Van Son, JM, McEwen, SC, Melle, I, Morris, DW, Mueller, BA, Nauck, M, Nordvik, JE, Noethen, MM, O'Leary, DS, Opel, N, Martinot, M-LP, Pike, GB, Preda, A, Quinlan, EB, Rasser, PE, Ratnakar, V, Reppermund, S, Steen, VM, Tooney, PA, Torres, FR, Veltman, DJ, Voyvodic, JT, Whelan, R, White, T, Yamamori, H, Adams, HHH, Bis, JC, Debette, S, Decarli, C, Fornage, M, Gudnason, V, Hofer, E, Ikram, MA, Launer, L, Longstreth, WT, Lopez, OL, Mazoyer, B, Mosley, TH, Roshchupkin, GV, Satizabal, CL, Schmidt, R, Seshadri, S, Yang, Q, Alvim, MKM, Ames, D, Anderson, TJ, Andreassen, OA, Arias-Vasquez, A, Bastin, ME, Baune, BT, Beckham, JC, Blangero, J, Boomsma, DI, Brodaty, H, Brunner, HG, Buckner, RL, Buitelaar, JK, Bustillo, JR, Cahn, W, Cairns, MJ, Calhoun, V, Carr, VJ, Caseras, X, Caspers, S, Cavalleri, GL, Cendes, F, Corvin, A, Crespo-Facorro, B, Dalrymple-Alford, JC, Dannlowski, U, de Geus, EJC, Deary, IJ, Delanty, N, Depondt, C, Desrivieres, S, Donohoe, G, Espeseth, T, Fernandez, G, Fisher, SE, Flor, H, Forstner, AJ, Francks, C, Franke, B, Glahn, DC, Gollub, RL, Grabe, HJ, Gruber, O, Haberg, AK, Hariri, AR, Hartman, CA, Hashimoto, R, Heinz, A, Henskens, FA, Hillegers, MHJ, Hoekstra, PJ, Holmes, AJ, Hong, LE, Hopkins, WD, Pol, HEH, Jernigan, TL, Jonsson, EG, Kahn, RS, Kennedy, MA, Kircher, TTJ, Kochunov, P, Kwok, JBJ, Le Hellard, S, Loughland, CM, Martin, NG, Martinot, J-L, McDonald, C, McMahon, KL, Meyer-Lindenberg, A, Michie, PT, Morey, RA, Mowry, B, Nyberg, L, Oosterlaan, J, Ophoff, RA, Pantelis, C, Paus, T, Pausova, Z, Penninx, BWJH, Polderman, TJC, Posthuma, D, Rietschel, M, Roffman, JL, Rowland, LM, Sachdev, PS, Samann, PG, Schall, U, Schumann, G, Scott, RJ, Sim, K, Sisodiya, SM, Smoller, JW, Sommer, IE, St Pourcain, B, Stein, DJ, Toga, AW, Trollor, JN, Van der Wee, NJA, van't Ent, D, Volzke, H, Walter, H, Weber, B, Weinberger, DR, Wright, MJ, Zhou, J, Stein, JL, Thompson, PM, Medland, SE, Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnaes, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bulow, R, Burger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Nhat, TD, Dohm, K, Ehrlich, S, Engelbrecht, H-R, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, J-J, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Kramer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Mirza-Schreiber, N, Moreira, JCV, Muhleisen, TW, Mueller-Myhsok, B, Najt, P, Nakahara, S, Nho, K, Loohuis, LMO, Orfanos, DP, Pearson, JF, Pitcher, TL, Putz, B, Quide, Y, Ragothaman, A, Rashid, FM, Reay, WR, Redlich, R, Reinbold, CS, Repple, J, Richard, G, Riedel, BC, Risacher, SL, Rocha, CS, Mota, NR, Salminen, L, Saremi, A, Saykin, AJ, Schlag, F, Schmaal, L, Schofield, PR, Secolin, R, Shapland, CY, Shen, L, Shin, J, Shumskaya, E, Sonderby, IE, Sprooten, E, Tansey, KE, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Turner, JA, Uhlmann, A, Vallerga, CL, van der Meer, D, van Donkelaar, MMJ, van Eijk, L, van Erp, TGM, van Haren, NEM, van Rooij, D, van Tol, M-J, Veldink, JH, Verhoef, E, Walton, E, Wang, M, Wang, Y, Wardlaw, JM, Wen, W, Westlye, LT, Whelan, CD, Witt, SH, Wittfeld, K, Wolf, C, Wolfers, T, Wu, JQ, Yasuda, CL, Zaremba, D, Zhang, Z, Zwiers, MP, Artiges, E, Assareh, AA, Ayesa-Arriola, R, Belger, A, Brandt, CL, Brown, GG, Cichon, S, Curran, JE, Davies, GE, Degenhardt, F, Dennis, MF, Dietsche, B, Djurovic, S, Doherty, CP, Espiritu, R, Garijo, D, Gil, Y, Gowland, PA, Green, RC, Hausler, AN, Heindel, W, Ho, B-C, Hoffmann, WU, Holsboer, F, Homuth, G, Hosten, N, Jack, CR, Jang, M, Jansen, A, Kimbrel, NA, Kolskar, K, Koops, S, Krug, A, Lim, KO, Luykx, JJ, Mathalon, DH, Mather, KA, Mattay, VS, Matthews, S, Van Son, JM, McEwen, SC, Melle, I, Morris, DW, Mueller, BA, Nauck, M, Nordvik, JE, Noethen, MM, O'Leary, DS, Opel, N, Martinot, M-LP, Pike, GB, Preda, A, Quinlan, EB, Rasser, PE, Ratnakar, V, Reppermund, S, Steen, VM, Tooney, PA, Torres, FR, Veltman, DJ, Voyvodic, JT, Whelan, R, White, T, Yamamori, H, Adams, HHH, Bis, JC, Debette, S, Decarli, C, Fornage, M, Gudnason, V, Hofer, E, Ikram, MA, Launer, L, Longstreth, WT, Lopez, OL, Mazoyer, B, Mosley, TH, Roshchupkin, GV, Satizabal, CL, Schmidt, R, Seshadri, S, Yang, Q, Alvim, MKM, Ames, D, Anderson, TJ, Andreassen, OA, Arias-Vasquez, A, Bastin, ME, Baune, BT, Beckham, JC, Blangero, J, Boomsma, DI, Brodaty, H, Brunner, HG, Buckner, RL, Buitelaar, JK, Bustillo, JR, Cahn, W, Cairns, MJ, Calhoun, V, Carr, VJ, Caseras, X, Caspers, S, Cavalleri, GL, Cendes, F, Corvin, A, Crespo-Facorro, B, Dalrymple-Alford, JC, Dannlowski, U, de Geus, EJC, Deary, IJ, Delanty, N, Depondt, C, Desrivieres, S, Donohoe, G, Espeseth, T, Fernandez, G, Fisher, SE, Flor, H, Forstner, AJ, Francks, C, Franke, B, Glahn, DC, Gollub, RL, Grabe, HJ, Gruber, O, Haberg, AK, Hariri, AR, Hartman, CA, Hashimoto, R, Heinz, A, Henskens, FA, Hillegers, MHJ, Hoekstra, PJ, Holmes, AJ, Hong, LE, Hopkins, WD, Pol, HEH, Jernigan, TL, Jonsson, EG, Kahn, RS, Kennedy, MA, Kircher, TTJ, Kochunov, P, Kwok, JBJ, Le Hellard, S, Loughland, CM, Martin, NG, Martinot, J-L, McDonald, C, McMahon, KL, Meyer-Lindenberg, A, Michie, PT, Morey, RA, Mowry, B, Nyberg, L, Oosterlaan, J, Ophoff, RA, Pantelis, C, Paus, T, Pausova, Z, Penninx, BWJH, Polderman, TJC, Posthuma, D, Rietschel, M, Roffman, JL, Rowland, LM, Sachdev, PS, Samann, PG, Schall, U, Schumann, G, Scott, RJ, Sim, K, Sisodiya, SM, Smoller, JW, Sommer, IE, St Pourcain, B, Stein, DJ, Toga, AW, Trollor, JN, Van der Wee, NJA, van't Ent, D, Volzke, H, Walter, H, Weber, B, Weinberger, DR, Wright, MJ, Zhou, J, Stein, JL, Thompson, PM, and Medland, SE
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Published: 2020

30. Lithium Use during Pregnancy and the Risk of Miscarriage

Author: Poels, Eline, Kamperman, Astrid, Vreeker, Annabel, Gilden, Janneke, Boks, M P, Kahn, RS, Ophoff, Roel, Bergink, Veerle, Poels, Eline, Kamperman, Astrid, Vreeker, Annabel, Gilden, Janneke, Boks, M P, Kahn, RS, Ophoff, Roel, and Bergink, Veerle
Published: 2020

31. Changes in the intracranial volume from early adulthood to the sixth decade of life: A longitudinal study

Author: Caspi, Y, Brouwer, RM, Schnack, HG, van de Nieuwenhuijzen, ME, Cahn, W, Kahn, RS, Niessen, Wiro, van der Lugt, Aad, Pol, HH, Caspi, Y, Brouwer, RM, Schnack, HG, van de Nieuwenhuijzen, ME, Cahn, W, Kahn, RS, Niessen, Wiro, van der Lugt, Aad, and Pol, HH
Published: 2020

32. Polygenic risk score for schizophrenia was not associated with glycemic level (HbA1c) in patients with non-affective psychosis: Genetic Risk and Outcome of Psychosis (GROUP) cohort study

Author: Habtewold, TD, Islam, MA, Liemburg, E J, Bartels-Velthuis, AA, Beveren, JM, Cahn, W, de Haan, L, Delespaul, P, Meijer, CJ, Myin-Germeys, I, Kahn, RS, Schirmbeck, F, Simons, CJP, van Amelsvoort, T, Haren, NEM, van Os, J, van Winkel, R, Bruggeman, R, Alizadeh, BZ, Habtewold, TD, Islam, MA, Liemburg, E J, Bartels-Velthuis, AA, Beveren, JM, Cahn, W, de Haan, L, Delespaul, P, Meijer, CJ, Myin-Germeys, I, Kahn, RS, Schirmbeck, F, Simons, CJP, van Amelsvoort, T, Haren, NEM, van Os, J, van Winkel, R, Bruggeman, R, and Alizadeh, BZ
Published: 2020

33. Brain structure, IQ, and psychopathology in young offspring of patients with schizophrenia or bipolar disorder

Author: van Haren, Neeltje, Setiaman, Nikita, Koevoets, MGJC, Baalbergen, H, Kahn, RS, Hillegers, Manon, van Haren, Neeltje, Setiaman, Nikita, Koevoets, MGJC, Baalbergen, H, Kahn, RS, and Hillegers, Manon
Published: 2020

34. Shared vulnerability for connectome alterations across psychiatric and neurological brain disorders

Author: de Lange SC, Scholtens LH, Alzheimer’s Disease Neuroimaging Initiative, van den Berg LH, Boks MP, Bozzali M, Cahn W, Dannlowski U, Durston S, Geuze E, van Haren NEM, Hillegers MHJ, Koch K, Jurado MA, Mancini M, Marqués-Iturria I, Meinert S, Ophoff RA, Reess TJ, Repple J, Kahn RS, and van den Heuvel MP
Subjects: Behavioral Neuroscience, Social Psychology, Journal Article, Experimental and Cognitive Psychology
Abstract: Macroscale white matter pathways are the infrastructure for large-scale communication in the human brain and a prerequisite for healthy brain function. Disruptions in the brain's connectivity architecture play an important role in many psychiatric and neurological brain disorders. Here we show that connections important for global communication and network integration are particularly vulnerable to brain alterations across multiple brain disorders. We report on a cross-disorder connectome study comprising in total 1,033 patients and 1,154 matched controls across 8 psychiatric and 4 neurological disorders. We extracted disorder connectome fingerprints for each of these 12 disorders and combined them into a 'cross-disorder disconnectivity involvement map' describing the level of cross-disorder involvement of each white matter pathway of the human brain network. Network analysis revealed connections central to global network communication and integration to display high disturbance across disorders, suggesting a general cross-disorder involvement and the importance of these pathways in normal function.
Published: 2019

35. Targeted Sequencing of 10,198 Samples Confirms Abnormalities in Neuronal Activity and Implicates Voltage-Gated Sodium Channels in Schizophrenia Pathogenesis

Author: Rees, E, Carrera, N, Morgan, J, Hambridge, K, Escott-Price, V, Pocklington, AJ, Richards, AL, Pardinas, AF, McDonald, C, Donohoe, G, Morris, DW, Kenny, E, Kelleher, E, Gill, M, Corvin, A, Kirov, G, Walters, JTR, Holmans, P, Owen, MJ, O'Donovan, MC, Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, AA, Beveren, JM, Bruggeman, R, Cahn, W, de Haan, L, Delespaul, P, Meijer, CJ, Myin-Germeys, I, Kahn, RS, Schirmbeck, F, Simons, CJP, van Haren, NE, van Os, J, van Winkel, R, Luykx, JJ, APH - Mental Health, ANS - Complex Trait Genetics, Adult Psychiatry, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), Neurosciences, and Psychiatry
Subjects: Psychiatry, RISK, Science & Technology, DISORDERS, Neurosciences, OF-FUNCTION VARIANTS, SUSCEPTIBILITY, FRAMEWORK, ARC, NMDAR, INDIVIDUALS, DE-NOVO MUTATIONS, mental disorders, SETD1A, Genetics, Schizophrenia, Sequencing, Neurosciences & Neurology, GENOME-WIDE ASSOCIATION, Voltage-gated sodium channels, BURDEN, Life Sciences & Biomedicine, Biological Psychiatry
Abstract: BACKGROUND: Sequencing studies have pointed to the involvement in schizophrenia of rare coding variants in neuronally expressed genes, including activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-D-aspartate receptor (NMDAR) complexes; however, larger samples are required to reveal novel genes and specific biological mechanisms. METHODS: We sequenced 187 genes, selected for prior evidence of association with schizophrenia, in a new dataset of 5207 cases and 4991 controls. Included among these genes were members of ARC and NMDAR postsynaptic protein complexes, as well as voltage-gated sodium and calcium channels. We performed a rare variant meta-analysis with published sequencing data for a total of 11,319 cases, 15,854 controls, and 1136 trios. RESULTS: While no individual gene was significantly associated with schizophrenia after genome-wide correction for multiple testing, we strengthen the evidence that rare exonic variants in the ARC (p = 4.0 × 10-4) and NMDAR (p = 1.7 × 10-5) synaptic complexes are risk factors for schizophrenia. In addition, we found that loss-of-function variants and missense variants at paralog-conserved sites were enriched in voltage-gated sodium channels, particularly the alpha subunits (p = 8.6 × 10-4). CONCLUSIONS: In one of the largest sequencing studies of schizophrenia to date, we provide novel evidence that multiple voltage-gated sodium channels are involved in schizophrenia pathogenesis and confirm the involvement of ARC and NMDAR postsynaptic complexes. ispartof: BIOLOGICAL PSYCHIATRY vol:85 issue:7 pages:554-562 ispartof: location:United States status: published
Published: 2019

36. The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder

Author: de Zwarte, SMC, Brouwer, RM, Agartz, I, Alda, M, Aleman, A, Alpert, KI, Bearden, CE, Bertolino, A, Bois, C, Bonvino, A, Bramon, E, Buimer, EEL, Cahn, W, Cannon, DM, Cannon, TD, Caseras, X, Castro-Fornieles, J, Chen, Q, Chung, Y, De la Serna, E, Di Giorgio, A, Doucet, GE, Eker, MC, Erk, S, Fears, SC, Foley, SF, Frangou, S, Frankland, A, Fullerton, JM, Glahn, DC, Goghari, VM, Goldman, AL, Gonul, AS, Gruber, O, de Haan, L, Hajek, T, Hawkins, EL, Heinz, A, Hillegers, MHJ, Hulshoff Pol, HE, Hultman, CM, Ingvar, M, Johansson, V, Jönsson, EG, Kane, F, Kempton, MJ, Koenis, MMG, Kopecek, M, Krabbendam, L, Krämer, B, Lawrie, SM, Lenroot, RK, Marcelis, M, Marsman, JBC, Mattay, VS, McDonald, C, Meyer-Lindenberg, A, Michielse, S, Mitchell, PB, Moreno, D, Murray, RM, Mwangi, B, Najt, P, Neilson, E, Newport, J, van Os, J, Overs, B, Ozerdem, A, Picchioni, MM, Richter, A, Roberts, G, Aydogan, AS, Schofield, PR, Simsek, F, Soares, JC, Sugranyes, G, Toulopoulou, T, Tronchin, G, Walter, H, Wang, L, Weinberger, DR, Whalley, HC, Yalin, N, Andreassen, OA, Ching, CRK, van Erp, TGM, Turner, JA, Jahanshad, N, Thompson, PM, Kahn, RS, van Haren, NEM, de Zwarte, SMC, Brouwer, RM, Agartz, I, Alda, M, Aleman, A, Alpert, KI, Bearden, CE, Bertolino, A, Bois, C, Bonvino, A, Bramon, E, Buimer, EEL, Cahn, W, Cannon, DM, Cannon, TD, Caseras, X, Castro-Fornieles, J, Chen, Q, Chung, Y, De la Serna, E, Di Giorgio, A, Doucet, GE, Eker, MC, Erk, S, Fears, SC, Foley, SF, Frangou, S, Frankland, A, Fullerton, JM, Glahn, DC, Goghari, VM, Goldman, AL, Gonul, AS, Gruber, O, de Haan, L, Hajek, T, Hawkins, EL, Heinz, A, Hillegers, MHJ, Hulshoff Pol, HE, Hultman, CM, Ingvar, M, Johansson, V, Jönsson, EG, Kane, F, Kempton, MJ, Koenis, MMG, Kopecek, M, Krabbendam, L, Krämer, B, Lawrie, SM, Lenroot, RK, Marcelis, M, Marsman, JBC, Mattay, VS, McDonald, C, Meyer-Lindenberg, A, Michielse, S, Mitchell, PB, Moreno, D, Murray, RM, Mwangi, B, Najt, P, Neilson, E, Newport, J, van Os, J, Overs, B, Ozerdem, A, Picchioni, MM, Richter, A, Roberts, G, Aydogan, AS, Schofield, PR, Simsek, F, Soares, JC, Sugranyes, G, Toulopoulou, T, Tronchin, G, Walter, H, Wang, L, Weinberger, DR, Whalley, HC, Yalin, N, Andreassen, OA, Ching, CRK, van Erp, TGM, Turner, JA, Jahanshad, N, Thompson, PM, Kahn, RS, and van Haren, NEM
Abstract: Background: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. Methods: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. Results: FDRs-BD had significantly larger ICV (d = +0.16, q <.05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = −0.12, q <.05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < −0.09, q <.05 corrected); and third ventricle was larger (d = +0.15, q <.05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. Conclusions: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
Published: 2019

37. Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness

Author: Bigdeli, T. B, Ripke, S, Bacanu, Sa, Lee, S. H, Wray, Nr, Gejman, P. V, Rietschel, M, Cichon, S, St Clair, D, Corvin, A, Kirov, G, Mcquillin, A, Gurling, H, Rujescu, D, Andreassen, O. A, Werge, T, Blackwood, D. H. R, Pato, C. N, Pato, M. T, Malhotra, A. K, O'Donovan, M. C, Kendler, K. S, Fanous, A. H, Neale, Bm, Walters, Jt, Farh, Kh, Holmans, Pa, Lee, P, Bulik Sullivan, B, Collier, Da, Huang, H, Pers, Th, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Begemann, M, Belliveau, Ra, Bene, J, Bergen, Se, Bevilacqua, E, Bigdeli, Tb, Black, Dw, Børglum, Ad, Bruggeman, R, Buccola, Ng, Buckner, Rl, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, Rm, Carr, Vj, Carrera, N, Catts, Sv, Chambert, Kd, Chan, Rc, Chen, Ry, Chen, Ey, Cheng, W, Cheung, Ef, Chong, Sa, Cloninger, C, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, Jj, Curtis, D, Davidson, M, Davis, Kl, Degenhardt, F, Del, Favero, J, Delisi, Le, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott Price, V, Essioux, L, Fanous, Ah, Farrell, Ms, Frank, J, Franke, L, Freedman, R, Freimer, Nb, Friedl, M, Friedman, Ji, Fromer, M, Genovese, G, Georgieva, L, Gershon, Es, Giegling, I, Giusti Rodríguez, P, Godard, S, Goldstein, Ji, Golimbet, V, Gopal, S, Gratten, J, Grove, J, Haan, De, L, Hammer, C, Hamshere, Ml, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, Am, Henskens, Fa, Herms, S, Hirschhorn, Jn, Hoffmann, P, Hofman, A, Hollegaard, Mv, Hougaard, Dm, Ikeda, M, Joa, I, Julìa, A, Kahn, Rs, Kalaydjieva, L, Karachanak Yankova, S, Karjalainen, J, Kavanagh, D, Keller, Mc, Kelly, Bj, Kennedy, Jl, Khrunin, A, Kim, Y, Klovins, J, Knowles, Ja, Konte, B, Kucinskas, V, Kucinskiene, Za, Kuzelova Ptackova, H, Kähler, Ak, Laurent, C, Keong, Jl, Lee, S, Legge, Se, Lerer, B, Li, M, Li, T, Liang, Ky, Lieberman, J, Limborska, S, Loughland, Cm, Lubinski, J, Lönnqvist, J, Macek, M, Magnusson, Pk, Maher, Bs, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, Mccarley, Rw, Mcdonald, C, Mcintosh, Am, Meier, S, Meijer, Cj, Melegh, B, Melle, I, Mesholam Gately, Ri, Metspalu, A, Michie, Pt, Milani, L, Milanova, V, Mokrab, Y, Morris, Dw, Mors, O, Mortensen, Pb, Murphy, Kc, Murray, Rm, Myin Germeys, I, Müller Myhsok, B, Nelis, M, Nenadic, I, Nertney, Da, Nestadt, G, Nicodemus, Kk, Nikitina Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, F, Sy, Oh, Olincy, A, Olsen, L, Jv, Os, Pantelis, C, Papadimitriou, Gn, Papiol, S, Parkhomenko, E, Pato, Mt, Paunio, T, Pejovic Milovancevic, M, Perkins, Do, Pietiläinen, O, Pimm, J, Pocklington, Aj, Powell, J, Price, A, Pulver, Ae, Purcell, Sm, Quested, D, Rasmussen, Hb, Reichenberg, A, Reimers, Ma, Richards, Al, Roffman, Jl, Roussos, P, Ruderfer, Dm, Salomaa, V, Sanders, Ar, Schall, U, Schubert, Cr, Schulze, Tg, Schwab, Sg, Scolnick, Em, Scott, Rj, Seidman, Lj, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, Jm, Sim, K, Slominsky, P, Smoller, Jw, Hc, So, Spencer, Cc, Stahl, Ea, Stefansson, H, Steinberg, S, Stogmann, E, Straub, Re, Strengman, E, Strohmaier, J, Stroup, T, Subramaniam, M, Suvisaari, J, Svrakic, Dm, Szatkiewicz, Jp, Söderman, E, Thirumalai, S, Toncheva, D, Tooney, Pa, Tosato, Sarah, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, Bt, Weiser, M, Wildenauer, Db, Williams, Nm, Williams, S, Witt, Sh, Wolen, Ar, Wong, Eh, Wormley, Bk, Jq, Wu, Hs, Xi, Zai, Cc, Zheng, X, Zimprich, F, Stefansson, K, Visscher, Pm, Adolfsson, R, Andreassen, Oa, Blackwood, Dh, Bramon, E, Buxbaum, Jd, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, Pv, Gill, M, Hultman, Cm, Iwata, N, Jablensky, Av, Jönsson, Eg, Kendler, Ks, Knight, J, Lencz, T, Levinson, Df, Qs, Li, Liu, J, Malhotra, Ak, Mccarroll, Sa, Moran, Jl, Mowry, Bj, Nöthen, Mm, Ophoff, Ra, Owen, Mj, Palotie, A, Pato, Cn, Petryshen, Tl, Posthuma, D, Riley, Bp, Sham, Pc, Sklar, P, Clair, Ds, Weinberger, Dr, Wendland, Jr, Daly, Mj, Sullivan, Pf, O'Donovan, Mc, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Bigdeli, Tim B, Ripke, Stephan, Bacanu, Silviu-Alin, Lee, Sang Hong, Fanous, Ayman H, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Psychosis Endophenotype International Consortium, Wellcome Trust Case-Control Consortium 2, Other departments, Adult Psychiatry, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and Del-Favero, Jurgen
Subjects: 0301 basic medicine, Multifactorial Inheritance, Bipolar Disorder, Inheritance Patterns, Genome-wide association study, Single-nucleotide polymorphism, polygenic, heritability, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, medicine, Humans, SNP, GWAS, Family, Genetic Predisposition to Disease, Family history, Allele, Genetics (clinical), Genetic association, Genetics & Heredity, Psychiatry, Genetics, Depressive Disorder, Major, family history, Models, Genetic, Case-control study, medicine.disease, 3. Good health, schizophrenia, Psychiatry and Mental health, 030104 developmental biology, Schizophrenia, Case-Control Studies, Human medicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N=978), cases reporting no such family history (N=4,503), and unscreened controls (N=8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke's R-2=0.0021; P=0.00331; P-value threshold
Published: 2016
Full Text: View/download PDF

38. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

Author: van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Bustillo, JR, Clark, VP, Agartz, I, Mueller, BA, Cahn, W, de Zwarte, SMC, Hulshoff Pol, HE, Kahn, RS, Ophoff, RA, van Haren, NEM, Andreassen, OA, Dale, AM, Doan, NT, Gurholt, TP, Hartberg, CB, Haukvik, UK, Jørgensen, KN, Lagerberg, TV, Melle, I, Westlye, LT, Gruber, O, Kraemer, B, Richter, A, Zilles, D, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Carr, VJ, Catts, S, Cropley, VL, Fullerton, JM, Green, MJ, Henskens, FA, Jablensky, A, Lenroot, RK, Mowry, BJ, Michie, PT, Pantelis, C, Quidé, Y, Schall, U, and Scott, RJ
Abstract: © 2018 Society of Biological Psychiatry Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. Methods: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11–78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10–87 years; 53% male) assessed with standardized methods at 39 centers worldwide. Results: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = −0.530/−0.516) and smaller surface area (left/right hemisphere: Cohen's d = −0.251/−0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. Conclusions: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.
Published: 2018
Full Text: View/download PDF

39. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 26, 2018)

Author: Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Di Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Consortium, GG, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
Published: 2018

40. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 765, 2017)

Author: Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
Published: 2018

41. Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group

Author: Hibar, DP, Westlye, LT, Doan, NT, Jahanshad, N, Cheung, JW, Ching, CRK, Versace, A, Bilderbeck, AC, Uhlmann, A, Mwangi, B, Kraemer, B, Overs, B, Hartberg, CB, Abe, C, Dima, D, Grotegerd, D, Sprooten, E, Boen, E, Jimenez, E, Howells, FM, Delvecchio, G, Temmingh, H, Starke, J, Almeida, JRC, Goikolea, JM, Houenou, J, Beard, LM, Rauer, L, Abramovic, L, Bonnin, M, Ponteduro, MF, Keil, M, Rive, MM, Yao, N, Yalin, N, Najt, P, Rosa, PG, Redlich, R, Trost, S, Hagenaars, S, Fears, SC, Alonso-Lana, S, van Erp, TGM, Nickson, T, Chaim-Avancini, TM, Meier, TB, Elvsashagen, T, Haukvik, UK, Lee, WH, Schene, AH, Lloyd, AJ, Young, AH, Nugent, A, Dale, AM, Pfennig, A, McIntosh, AM, Lafer, B, Baune, BT, Ekman, CJ, Zarate, CA, Bearden, CE, Henry, C, Simhandl, C, McDonald, C, Bourne, C, Stein, DJ, Wolf, DH, Cannon, DM, Glahn, DC, Veltman, DJ, Pomarol-Clotet, E, Vieta, E, Canales-Rodriguez, EJ, Nery, FG, Duran, FLS, Busatto, GF, Roberts, G, Pearlson, GD, Goodwin, GM, Kugel, H, Whalley, HC, Ruhe, HG, Soares, JC, Fullerton, JM, Rybakowski, JK, Savitz, J, Chaim, KT, Fatjo-Vilas, M, Soeiro-de-Souza, MG, Boks, MP, Zanetti, MV, Otaduy, MCG, Schaufelberger, MS, Alda, M, Ingvar, M, Phillips, ML, Kempton, MJ, Bauer, M, Landen, M, Lawrence, NS, van Haren, NEM, Horn, NR, Freimer, NB, Gruber, O, Schofield, PR, Mitchell, PB, Kahn, RS, Lenroot, R, Machado-Vieira, R, Ophoff, RA, Sarro, S, Frangou, S, Satterthwaite, TD, Hajek, T, Dannlowski, U, Malt, UF, Arolt, V, Gattaz, WF, Drevets, WC, Caseras, X, Agartz, I, Thompson, PM, Andreassen, OA, Hibar, DP, Westlye, LT, Doan, NT, Jahanshad, N, Cheung, JW, Ching, CRK, Versace, A, Bilderbeck, AC, Uhlmann, A, Mwangi, B, Kraemer, B, Overs, B, Hartberg, CB, Abe, C, Dima, D, Grotegerd, D, Sprooten, E, Boen, E, Jimenez, E, Howells, FM, Delvecchio, G, Temmingh, H, Starke, J, Almeida, JRC, Goikolea, JM, Houenou, J, Beard, LM, Rauer, L, Abramovic, L, Bonnin, M, Ponteduro, MF, Keil, M, Rive, MM, Yao, N, Yalin, N, Najt, P, Rosa, PG, Redlich, R, Trost, S, Hagenaars, S, Fears, SC, Alonso-Lana, S, van Erp, TGM, Nickson, T, Chaim-Avancini, TM, Meier, TB, Elvsashagen, T, Haukvik, UK, Lee, WH, Schene, AH, Lloyd, AJ, Young, AH, Nugent, A, Dale, AM, Pfennig, A, McIntosh, AM, Lafer, B, Baune, BT, Ekman, CJ, Zarate, CA, Bearden, CE, Henry, C, Simhandl, C, McDonald, C, Bourne, C, Stein, DJ, Wolf, DH, Cannon, DM, Glahn, DC, Veltman, DJ, Pomarol-Clotet, E, Vieta, E, Canales-Rodriguez, EJ, Nery, FG, Duran, FLS, Busatto, GF, Roberts, G, Pearlson, GD, Goodwin, GM, Kugel, H, Whalley, HC, Ruhe, HG, Soares, JC, Fullerton, JM, Rybakowski, JK, Savitz, J, Chaim, KT, Fatjo-Vilas, M, Soeiro-de-Souza, MG, Boks, MP, Zanetti, MV, Otaduy, MCG, Schaufelberger, MS, Alda, M, Ingvar, M, Phillips, ML, Kempton, MJ, Bauer, M, Landen, M, Lawrence, NS, van Haren, NEM, Horn, NR, Freimer, NB, Gruber, O, Schofield, PR, Mitchell, PB, Kahn, RS, Lenroot, R, Machado-Vieira, R, Ophoff, RA, Sarro, S, Frangou, S, Satterthwaite, TD, Hajek, T, Dannlowski, U, Malt, UF, Arolt, V, Gattaz, WF, Drevets, WC, Caseras, X, Agartz, I, Thompson, PM, and Andreassen, OA
Abstract: Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.
Published: 2018

42. The role of cognitive functioning in the relationship between childhood trauma and a mixed phenotype of affective-anxious-psychotic symptoms in psychotic disorders

Author: Mansueto, G, van Nierop, M, Schruers, K, Alizadeh, BZ, Bartels-Velthuis, AA, Beveren, JM, Bruggeman, R, Cahn, W, de Haan, L, Delespaul, P, Meijer, CJ, Myin-Germeys, I, Kahn, RS, Schirmbeck, F, Simons, CJP, van Haren, Neeltje, van Os, J, van Winkel, R, Mansueto, G, van Nierop, M, Schruers, K, Alizadeh, BZ, Bartels-Velthuis, AA, Beveren, JM, Bruggeman, R, Cahn, W, de Haan, L, Delespaul, P, Meijer, CJ, Myin-Germeys, I, Kahn, RS, Schirmbeck, F, Simons, CJP, van Haren, Neeltje, van Os, J, and van Winkel, R
Published: 2018

43. Age at first birth in women is genetically associated with increased risk of schizophrenia

Author: Ni, G, Gratten, J, Wray, NR, Lee, SH, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Haan, L de, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Juliá, A, Kahn, RS, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kähler, AK, Laurent, C, Keong, JLC, Legge, SE, Lerer, B, Li, M, Li, T, Liang, KY, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lönnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Müller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, SY, Olincy, A, Olsen, L, van Os, JV, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietiläinen, O, Pimm, J, Pocklington, AJ, Powell, J, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, HC, Spencer, CCA, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Söderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, Xuebin, Zimprich, F, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Bramon, E, Buxbaum, JD, Børglum, AD, Cichon, S, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jönsson, EG, Kendler, KS, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Nöthen, MM, Ophoff, RA, Owen, MJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, Daniëlle, Rietschel, M, Riley, BP, Rujescu, D, Sham, PC, Clair, DS, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF, O'Donovan, MC, Ni, G, Gratten, J, Wray, NR, Lee, SH, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Haan, L de, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Juliá, A, Kahn, RS, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kähler, AK, Laurent, C, Keong, JLC, Legge, SE, Lerer, B, Li, M, Li, T, Liang, KY, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lönnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Müller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, SY, Olincy, A, Olsen, L, van Os, JV, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietiläinen, O, Pimm, J, Pocklington, AJ, Powell, J, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, HC, Spencer, CCA, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Söderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, Xuebin, Zimprich, F, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Bramon, E, Buxbaum, JD, Børglum, AD, Cichon, S, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jönsson, EG, Kendler, KS, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Nöthen, MM, Ophoff, RA, Owen, MJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, Daniëlle, Rietschel, M, Riley, BP, Rujescu, D, Sham, PC, Clair, DS, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF, and O'Donovan, MC
Published: 2018

44. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

Author: McLaughlin, RL, Schijven, D, Van Rheenen, W, Van Eijk, KR, O'Brien, M, Kahn, RS, Ophoff, RA, Goris, A, Bradley, DG, Al-Chalabi, A, Van Den Berg, LH, Luykx, JJ, Hardiman, O, Veldink, JH, Shatunov, A, Dekker, AM, Diekstra, FP, Pulit, SL, Van Der Spek, RAA, Van Doormaal, PTC, Sproviero, W, Jones, AR, Nicholson, GA, Rowe, DB, Pamphlett, R, Kiernan, MC, Bauer, D, Kahlke, T, Williams, K, Eftimov, F, Fogh, I, Ticozzi, N, Lin, K, Millecamps, S, Salachas, F, Meininger, V, Carvalho, MD, Pinto, S, Mora, JS, Rojas-Garcyá, R, Polak, M, Chandran, S, Colville, S, Swingler, R, Morrison, KE, Shaw, PJ, Hardy, J, Orrell, RW, Pittman, A, Sidle, K, Fratta, P, Malaspina, A, Petri, S, Abdulla, S, Drepper, C, Sendtner, M, Meyer, T, Wiedau-Pazos, M, Lomen-Hoerth, C, Deerlin, VMV, Trojanowski, JQ, Elman, L, McCluskey, L, Basak, N, Meitinger, T, Lichtner, P, Blagojevic-Radivojkov, M, Andres, CR, Maurel, C, Bensimon, G, Landwehrmeyer, B, Brice, A, Payan, CAM, Saker-Delye, S, Durr, A, Wood, N, Tittmann, L, Lieb, W, Franke, A, Rietschel, M, Cichon, S, Nothen, MM, Amouyel, P, Tzourio, C, Dartigues, JF, Uitterlinden, AG, Rivadeneira, F, Estrada, K, Hofman, A, Curtis, C, Derkooi, AJV, De Visser, M, Weber, M, Shaw, CE, Smith, BN, Pansarasa, O, Cereda, C, Bo, RD, Comi, GP, and D'Alfonso, S
Subjects: Multifactorial Inheritance, Amyotrophic Lateral Sclerosis, European Continental Ancestry Group, Comorbidity, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Cohort Studies, Case-Control Studies, mental disorders, Linear Models, Odds Ratio, Schizophrenia, Humans, Genetic Predisposition to Disease, Family, Genome-Wide Association Study
Abstract: © 2017 The Author(s). We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.
Published: 2017

45. Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases

Author: Gusev, A, Lee, Sh, SWE SCZ, Consortium, O'Dushlaine, Cgusev, Trynka, G, Finucane, H, Vilhjálmsson, Bj, Xu, H, Zang, C, Ripke, S, Bulik Sullivan, B, Stahl, E, Schizophrenia, Working, Neale, Bm, Corvin, A, Walters, Jt, Farh, Kh, Holmans, Pa, Lee, P, Collier, Da, Huang, H, Pers, Th, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, Sa, Begemann, M, Belliveau, Ra, Bene, J, Bergen, Se, Bevilacqua, E, Bigdeli, Tb, Black, Dw, Børglum, Ad, Bruggeman, R, Buccola, Ng, Buckner, Rl, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, Rm, Carr, Vj, Carrera, N, Catts, Sv, Chambert, Kd, Chan, Rc, Chen, Ry, Chen, Ey, Cheng, W, Cheung, Ef, Chong, Sa, Cloninger, Cr, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, Jj, Curtis, D, Davidson, M, Davis, Kl, Degenhardt, F, Del, Favero, Delisi, Le, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott Price, V, Essioux, L, Fanous, Ah, Farrell, Ms, Frank, J, Franke, L, Freedman, R, Freimer, Nb, Friedl, M, Friedman, Ji, Fromer, M, Genovese, G, Georgieva, L, Gershon, Es, Giegling, I, Giusti Rodrguez, P, Godard, S, Goldstein, Ji, Golimbet, V, Gopal, S, Gratten, J, Grove, J, Haan, De, Hammer, C, Hamshere, Ml, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, Am, Henskens, Fa, Herms, S, Hirschhorn, Jn, Hoffmann, P, Hofman, A, Hollegaard, Mv, Hougaard, Dm, Ikeda, M, Joa, I, Julià, A, Kahn, Rs, Kalaydjieva, L, Karachanak Yankova, S, Karjalainen, J, Kavanagh, D, Keller, Mc, Kelly, Bj, Kennedy, Jl, Khrunin, A, Kim, Y, Klovins, J, Knowles, Ja, Konte, B, Kucinskas, V, Kucinskiene, Za, Kuzelova Ptackova, H, Kähler, Ak, Laurent, C, Keong, Jl, Legge, Se, Lerer, B, Li, M, Li, T, Liang, Ky, Lieberman, J, Limborska, S, Loughland, Cm, Lubinski, J, Lnnqvist, J, Macek, M, Magnusson, Pk, Maher, Bs, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, Mccarley, Rw, Mcdonald, C, Mcintosh, Am, Meier, S, Meijer, Cj, Melegh, B, Melle, I, Mesholam Gately, Ri, Metspalu, A, Michie, Pt, Milani, L, Milanova, V, Mokrab, Y, Morris, Dw, Mors, O, Mortensen, Pb, Murphy, Kc, Murray, Rm, Myin Germeys, I, Mller Myhsok, B, Nelis, M, Nenadic, I, Nertney, Da, Nestadt, G, Nicodemus, Kk, Nikitina Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, Fa, Sy, Oh, Olincy, A, Olsen, L, Van, Os, Pantelis, C, Papadimitriou, Gn, Papiol, S, Parkhomenko, E, Pato, Mt, Paunio, T, Pejovic Milovancevic, M, Perkins, Do, Pietilinen, O, Pimm, J, Pocklington, Aj, Powell, J, Price, A, Pulver, Ae, Purcell, Sm, Quested, D, Rasmussen, Hb, Reichenberg, A, Reimers, Ma, Richards, Al, Roffman, Jl, Roussos, P, Ruderfer, Dm, Salomaa, V, Sanders, Ar, Schall, U, Schubert, Cr, Schulze, Tg, Schwab, Sg, Scolnick, Em, Scott, Rj, Seidman, Lj, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, Jm, Sim, K, Slominsky, P, Smoller, Jw, Hc, So, Spencer, Cc, Stahl, Ea, Stefansson, H, Steinberg, S, Stogmann, E, Straub, Re, Strengman, E, Strohmaier, J, Stroup, Ts, Subramaniam, M, Suvisaari, J, Svrakic, Dm, Szatkiewicz, Jp, Sderman, E, Thirumalai, S, Toncheva, D, Tooney, Pa, Tosato, Sarah, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, Bt, Weiser, M, Wildenauer, Db, Williams, Nm, Williams, S, Witt, Sh, Wolen, Ar, Wong, Eh, Wormley, Bk, Jq, Wu, Hs, Xi, Zai, Cc, Zheng, X, Zimprich, F, Wray, Nr, Stefansson, K, Visscher, Pm, Adolfsson, R, Andreassen, Oa, Blackwood, Dh, Bramon, E, Buxbaum, Jd, Brglum, Ad, Cichon, S, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, Pv, Gill, M, Gurling, H, Hultman, Cm, Iwata, N, Jablensky, Av, Jönsson, Eg, Kendler, Ks, Kirov, G, Knight, J, Lencz, T, Levinson, Df, Qs, Li, Liu, J, Malhotra, Ak, Mccarroll, Sa, Mcquillin, A, Moran, Jl, Mowry, Bj, Nthen, Mm, Ophoff, Ra, Owen, Mj, Palotie, A, Pato, Cn, Petryshen, Tl, Posthuma, D, Rietschel, M, Riley, Bp, Rujescu, D, Sham, Pc, Sklar, P, Clair, St, Weinberger, Dr, Wendland, Jr, Werge, T, Daly, Mj, Sullivan, Pf, O'Donovan, Mc, Chambert, K, Akterin, S, Bergen, S, Ruderfer, D, Scolnick, E, Purcell, S, Mccarroll, S, Daly, M, Pasaniuc, B, Raychaudhuri, S, Price, Al, Gusev, Alexander, Lee, S Hong, Trynka, Gosia, Finucane, Hilary K, Price, Alkes L, Schizophrenia Working Group of the Psychiatric Genomics Consortium, SWE-SCZ Consortium, ANS - Amsterdam Neuroscience, Adult Psychiatry, Other departments, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Complex Trait Genetics, Functional Genomics, and Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease
Subjects: Linkage disequilibrium, GWAS, schizophrenia, SNP, trait heritability, disease architecture, Inheritance Patterns, Single-nucleotide polymorphism, Genome-wide association study, Biology, Article, Open Reading Frames, SDG 3 - Good Health and Well-being, Genetic, Models, Genotype, Genetics, Humans, Genetics(clinical), Computer Simulation, Regulatory Elements, Transcriptional, Exome, Genetics (clinical), genotype imputation, Genetic association, Genetics & Heredity, genome-wide association study, Models, Genetic, Genetic Diseases, Inborn, Genetic Variation, Heritability, exome chips, Regulatory Elements, Inborn, Genetic Diseases, Transcriptional, coding variants, Genome-Wide Association Study
Abstract: Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (h(g)(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of h(g)(2) from imputed SNPs (5.1 x enrichment; p = 3.7 x 10(-17)) and 38% (SE = 4%) of h(g)(2) from genotyped SNPs (1.6 x enrichment, p = 1.0 x 10(-4)). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained
Published: 2014
Full Text: View/download PDF

46. Variability in Working Memory Performance Explained by Epistasis vs Polygenic Scores in the ZNF804A Pathway

Author: Nicodemus, Kk, Hargreaves, A, Morris, D, Anney, R, Gill, M, Corvin, A, Donohoe, G, Ripke, S, Sanders, Ar, Kendler, Ks, Levinson, Df, Sklar, P, Holmans, Pa, Lin, Dy, Duan, J, Ophoff, Ra, Andreassen, Oa, Scolnick, E, Cichon, S, Clair, St, D, Gurling, H, Werge, T, Rujescu, D, Blackwood, Dh, Pato, Cn, Malhotra, Ak, Purcell, S, Dudbridge, F, Neale, Bm, Rossin, L, Visscher, Pm, Posthuma, D, Ruderfer, Dm, Fanous, A, Stefansson, H, Steinberg, S, Mowry, Bj, Golimbet, V, Hert, De, M, Jönsson, Eg, Bitter, I, Pietiläinen, Op, Collier, Da, Tosato, Sarah, Agartz, I, Albus, M, Alexander, M, Amdur, Rl, Amin, F, Bass, N, Bergen, Se, Black, Dw, Børglum, Ad, Brown, Ma, Bruggeman, R, Buccola, Ng, Byerley, Wf, Cahn, W, Cantor, Rm, Carr, Vj, Catts, Sv, Choudhury, K, Cloninger, C, Cormican, P, Craddock, N, Danoy, Pa, Datta, S, Haan, De, L, Demontis, D, Dikeos, D, Djurovic, S, Donnelly, P, Duong, L, Dwyer, S, Fink Jensen, A, Freedman, R, Freimer, Nb, Friedl, M, Georgieva, L, Giegling, I, Glenthøj, B, Godard, S, Hamshere, M, Hansen, M, Hansen, T, Hartmann, Am, Henskens, Fa, Hougaard, Dm, Hultman, Cm, Ingason, A, Jablensky, Av, Jakobsen, Kd, Jay, M, Jürgens, G, Kahn, Rs, Keller, Mc, Kenis, G, Kenny, E, Kim, Y, Kirov, Gk, Konnerth, H, Konte, B, Krabbendam, L, Krasucki, R, Lasseter, Vk, Laurent, C, Lawrence, J, Lencz, T, Lerer, F, Liang, Ky, Lichtenstein, P, Lieberman, Ja, Linszen, Dh, Lönnqvist, J, Loughland, Cm, Maclean, Aw, Maher, Bs, Maier, W, Mallet, J, Malloy, P, Mattheisen, M, Mattingsdal, M, Mcghee, Ka, Mcgrath, Jj, Mcintosh, A, Mclean, De, Mcquillin, A, Melle, I, Michie, Pt, Milanova, V, Morris, Dw, Mors, O, Mortensen, Pb, Moskvina, V, Muglia, P, Myin Germeys, I, Nertney, Da, Nestadt, G, Nielsen, J, Nikolov, I, Nordentoft, M, Norton, N, Nöthen, Mm, O'Dushlaine, Ct, Olincy, A, Olsen, L, O'Neill, F, Ørntoft, Tf, Owen, Mj, Pantelis, C, Papadimitriou, G, Pato, Mt, Peltonen, L, Petursson, H, Pickard, B, Pimm, J, Pulver, Ae, Puri, V, Quested, D, Quinn, Em, Rasmussen, Hb, Réthelyi, Jm, Ribble, R, Rietschel, M, Riley, Bp, Ruggeri, Mirella, Schall, U, Schulze, Tg, Schwab, Sg, Scott, Rj, Shi, J, Sigurdsson, E, Silverman, Jm, Spencer, Cc, Stefansson, K, Strange, A, Strengman, E, Stroup, T, Suvisaari, J, Terenius, L, Thirumalai, S, Thygesen, Jh, Timm, S, Toncheva, D, Van, Den, Oord, E, Van, Os, Van, J, Winkel, R, Veldink, J, Walsh, D, Wang, Ag, Wiersma, D, Wildenauer, Db, Williams, Hj, Williams, Nm, Wormley, B, Zammit, S, Sullivan, Pf, O'Donovan, Mc, Daly, Mj, Gejman, P., Functional Genomics, Complex Trait Genetics, De Hert, Marc, Myin-Germeys, Inez, van Winkel, Ruud, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Amsterdam Neuroscience, and Adult Psychiatry
Subjects: epistasis, Male, Multifactorial Inheritance, polygenic, Neuropsychological Tests, involvement, 0302 clinical medicine, Neural Pathways, 2.1 Biological and endogenous factors, Psychology, schizophrenia risk, psychosis variant, Aetiology, 0303 health sciences, susceptibility gene znf804a, medicine.diagnostic_test, phenotypes, Zinc Fingers, Neuropsychological test, Single Nucleotide, Middle Aged, Serious Mental Illness, Psychiatry and Mental health, Memory, Short-Term, Mental Health, Schizophrenia, Major depressive disorder, Female, Cognitive Sciences, social and economic factors, Adult, medicine.medical_specialty, Psychosis, working memory, schizophrenia, IQ, Schizoaffective disorder, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Gene interaction, Genetic, Social cognition, Memory, Clinical Research, 2.3 Psychological, Behavioral and Social Science, medicine, Genetics, Humans, Genetic Predisposition to Disease, Bipolar disorder, Polymorphism, Psychiatry, 030304 developmental biology, Other Medical and Health Sciences, Prevention, Wellcome Trust Case Control Consortium 2, Neurosciences, Genetic Variation, Epistasis, Genetic, Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium, medicine.disease, attention, Brain Disorders, deficits, Short-Term, Psychotic Disorders, genome-wide association, Epistasis, healthy controls, identification, Cognition Disorders, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: IMPORTANCE We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. OBJECTIVES To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. DESIGN, SETTING, AND PARTICIPANTS Patients with psychosis (n = 424)were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition.We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). MAIN OUTCOMES AND MEASURES Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. RESULTS Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1%to 3%of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2%using the polygenic score only to 4.8%(P = .11 and .001, respectively) but did not explain additional variation in control participants. CONCLUSIONS AND RELEVANCE These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score. © 2014 American Medical Association. All rights reserved.
Published: 2014
Full Text: View/download PDF

47. Schizophrenia genetic variants are not associated with intelligence

Author: van Scheltinga, Af, Bakker, Sc, van Haren, Ne, Derks, Em, Buizer Voskamp, Je, Cahn, W, Ripke, S, Sanders, A, Kendler, K, Levinson, D, Sklar, P, Holmans, P, Lin, D., Duan, J, Ophoff, R, Andreassen, O, Scolnick, E, Cichon, S, St Clair, D, Corvin, A, Gurling, H, Werge, T, Rujescu, D, Blackwood, D, Pato, C, Malhotra, A, Purcell, S, Dudbridge, F, Neale, B, Rossin, L, Visscher, P, Posthuma, D, Ruderfer, D, Fanous, A, Stefansson, H, Steinberg, S, Mowry, B, Golimbet, V, Hert, De, M, Jonsson, E, Bitter, I, Pietilainen, O, Collier, D, Tosato, Sarah, Agartz, I, Albus, M, Alexander, M, Amdur, R, Amin, F, Bass, N, Bergen, S, Black, D, Børglum, A, Brown, M, Bruggeman, R, Buccola, N, Byerley, W, Cantor, R, Carr, V, Catts, S, Choudhury, K, Cloninger, C, Cormican, P, Craddock, N, Danoy, P, Datta, S, Haan, De, L, Demontis, D, Dikeos, D, Djurovic, S, Donnelly, P, Donohoe, G, Duong, L, Dwyer, S, Fink Jensen, A, Freedman, R, Freimer, N, Friedl, M, Georgieva, L, Giegling, I, Gill, M, Glenthøj, B, Godard, S, Hamshere, M, Hansen, M, Hansen, T, Hartmann, A, Henskens, F, Hougaard, D, Hultman, C, Ingason, A, Jablensky, A, Jakobsen, K, Jay, M, Jurgens, G, Kahn, R, Keller, M, Kenis, G, Kenny, E, Kim, Y, Kirov, G, Konnerth, H, Konte, B, Krabbendam, L, Krasucki, R, Lasseter, V, Laurent, C, Lawrence, J, Lencz, T, Lerer, F, Liang, K, Lichtenstein, P, Lieberman, J, Linszen, D, Lonnqvist, J, Loughland, C, Maclean, A, Maher, B, Maier, W, Mallet, J, Malloy, P, Mattheisen, M, Mattingsdal, M, Mcghee, K, Mcgrath, J, Mcintosh, A, Mclean, D, Mcquillin, A, Melle, I, Michie, P, Milanova, V, Morris, D, Mors, O, Mortensen, P, Moskvina, V, Muglia, P, Myin Germeys, I, Nertney, D, Nestadt, G, Nielsen, J, Nikolov, I, Nordentoft, M, Norton, N, Nothen, M, O'Dushlaine, C, Olincy, A, Olsen, L, O'Neill, F, Ørntoft, T, Owen, M, Pantelis, C, Papadimitriou, G, Pato, M, Peltonen, L, Petursson, H, Pickard, B, Pimm, J, Pulver, A, Puri, V, Quested, D, Quinn, E, Rasmussen, H, Rethelyi, Jm, Ribble, R, Rietschel, M, Riley, B, Ruggeri, Mirella, Schall, U, Schulze, T, Schwab, S, Scott, R, Shi, J, Sigurdsson, E, Silverman, J, Spencer, C, Stefansson, K, Strange, A, Strengman, E, Stroup, T, Suvisaari, J, Terenius, L, Thirumalai, S, Thygesen, J, Timm, S, Toncheva, D, van den Oord, E, van Os, J, van Winkel, R, Veldink, J, Walsh, D, Wang, A, Wiersma, D, Wildenauer, D, Williams, H, Williams, N, Wormley, B, Zammit, S, Sullivan, P, O'Donovan, M, Daly, M, Gejman, P), Ophoff, Ra, Kahn, Rs, Functional Genomics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, and Adult Psychiatry
Subjects: Oncology, Adult, Male, Psychosis, medicine.medical_specialty, Multifactorial Inheritance, DNA Copy Number Variations, Endophenotypes, Schizophrenia (object-oriented programming), Intelligence, SNP, Single-nucleotide polymorphism, Genome-wide association study, polygenic, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, Cognition, Internal medicine, mental disorders, medicine, Humans, Genetic Predisposition to Disease, deletion, Cognitive decline, Applied Psychology, Genetic association, Genetics, Wechsler Scales, Wechsler Adult Intelligence Scale, medicine.disease, endophenotype, Psychiatry and Mental health, duplication, IQ, Endophenotype, Schizophrenia, Female, Psychology, cognition, schizophrenia, Genome-Wide Association Study
Abstract: BackgroundSchizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits. Therefore, we hypothesized that genetic variants associated with schizophrenia, including copy number variants (CNVs) and a polygenic schizophrenia (risk) score (PSS), may influence intelligence.MethodIQ was estimated with the Wechsler Adult Intelligence Scale (WAIS). CNVs were determined from single nucleotide polymorphism (SNP) data using the QuantiSNP and PennCNV algorithms. For the PSS, odds ratios for genome-wide SNP data were calculated in a sample collected by the Psychiatric Genome-Wide Association Study (GWAS) Consortium (8690 schizophrenia patients and 11 831 controls). These were used to calculate individual PSSs in our independent sample of 350 schizophrenia patients and 322 healthy controls.ResultsAlthough significantly more genes were disrupted by deletions in schizophrenia patients compared to controls (p = 0.009), there was no effect of CNV measures on IQ. The PSS was associated with disease status (R2 = 0.055, p = 2.1 × 10−7) and with IQ in the entire sample (R2 = 0.018, p = 0.0008) but the effect on IQ disappeared after correction for disease status.ConclusionsOur data suggest that rare and common schizophrenia-associated variants do not explain the variation in IQ in healthy subjects or in schizophrenia patients. Thus, reductions in IQ in schizophrenia patients may be secondary to other processes related to schizophrenia risk.
Published: 2013
Full Text: View/download PDF

48. Multi-center MRI prediction models: Predicting sex and illness course in first episode psychosis patients

Author: Nieuwenhuis, M, Schnack, HG, van Haren, NE, Kahn, RS, Lappin, J, Dazzan, P, Morgan, C, Reinders, AA, Gutierrez-Tordesillas, D, Roiz-Santiañez, R, Crespo-Facorro, B, Schaufelberger, MS, Rosa, PG, Zanetti, MV, Busatto, GF, McGorry, PD, Velakoulis, D, Pantelis, C, Wood, SJ, Mourao-Miranda, J, Nieuwenhuis, M, Schnack, HG, van Haren, NE, Kahn, RS, Lappin, J, Dazzan, P, Morgan, C, Reinders, AA, Gutierrez-Tordesillas, D, Roiz-Santiañez, R, Crespo-Facorro, B, Schaufelberger, MS, Rosa, PG, Zanetti, MV, Busatto, GF, McGorry, PD, Velakoulis, D, Pantelis, C, Wood, SJ, and Mourao-Miranda, J
Abstract: Structural Magnetic Resonance Imaging (MRI) studies have attempted to use brain measures obtained at the first-episode of psychosis to predict subsequent outcome, with inconsistent results. Thus, there is a real need to validate the utility of brain measures in the prediction of outcome using large datasets, from independent samples, obtained with different protocols and from different MRI scanners. This study had three main aims: 1) to investigate whether structural MRI data from multiple centers can be combined to create a machine-learning model able to predict a strong biological variable like sex; 2) to replicate our previous finding that an MRI scan obtained at first episode significantly predicts subsequent illness course in other independent datasets; and finally, 3) to test whether these datasets can be combined to generate multicenter models with better accuracy in the prediction of illness course. The multi-center sample included brain structural MRI scans from 256 males and 133 females patients with first episode psychosis, acquired in five centers: University Medical Center Utrecht (The Netherlands) (n = 67); Institute of Psychiatry, Psychology and Neuroscience, London (United Kingdom) (n = 97); University of São Paulo (Brazil) (n = 64); University of Cantabria, Santander (Spain) (n = 107); and University of Melbourne (Australia) (n = 54). All images were acquired on 1.5-Tesla scanners and all centers provided information on illness course during a follow-up period ranging 3 to 7 years. We only included in the analyses of outcome prediction patients for whom illness course was categorized as either “continuous” (n = 94) or “remitting” (n = 118). Using structural brain scans from all centers, sex was predicted with significant accuracy (89%; p < 0.001). In the single- or multi-center models, illness course could not be predicted with significant accuracy. However, when reducing heterogeneity by restricting the analyses to male patients only, classificatio
Published: 2017

49. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

Author: Guadalupe, T, Mathias, SR, vanErp, TGM, Whelan, CD, Zwiers, MP, Abe, Y, Abramovic, L, Agartz, I, Andreassen, OA, Arias-Vásquez, A, Aribisala, BS, Armstrong, NJ, Arolt, V, Artiges, E, Ayesa-Arriola, R, Baboyan, VG, Banaschewski, T, Barker, G, Bastin, ME, Baune, BT, Blangero, J, Bokde, ALW, Boedhoe, PSW, Bose, A, Brem, S, Brodaty, H, Bromberg, U, Brooks, S, Büchel, C, Buitelaar, J, Calhoun, VD, Cannon, DM, Cattrell, A, Cheng, Y, Conrod, PJ, Conzelmann, A, Corvin, A, Crespo-Facorro, B, Crivello, F, Dannlowski, U, de Zubicaray, GI, de Zwarte, SMC, Deary, IJ, Desrivières, S, Doan, NT, Donohoe, G, Dørum, ES, Ehrlich, S, Espeseth, T, Fernández, G, Flor, H, Fouche, J-P, Frouin, V, Fukunaga, M, Gallinat, J, Garavan, H, Gill, M, Suarez, AG, Gowland, P, Grabe, HJ, Grotegerd, D, Gruber, O, Hagenaars, S, Hashimoto, R, Hauser, TU, Heinz, A, Hibar, DP, Hoekstra, PJ, Hoogman, M, Howells, FM, Hu, H, Hulshoff Pol, HE, Huyser, C, Ittermann, B, Jahanshad, N, Jönsson, EG, Jurk, S, Kahn, RS, Kelly, S, Kraemer, B, Kugel, H, Kwon, JS, Lemaitre, H, Lesch, K-P, Lochner, C, Luciano, M, Marquand, AF, Martin, NG, Martínez-Zalacaín, I, Martinot, J-L, Mataix-Cols, D, Mather, K, McDonald, C, McMahon, KL, Medland, SE, Menchón, JM, Morris, DW, Mothersill, O, Maniega, SM, Mwangi, B, Nakamae, T, Nakao, T, Narayanaswaamy, JC, Nees, F, Nordvik, JE, Onnink, AMH, Opel, N, Ophoff, R, Paillère Martinot, M-L, Papadopoulos Orfanos, D, Pauli, P, Paus, T, Poustka, L, Reddy, JY, Renteria, ME, Roiz-Santiáñez, R, Roos, A, Royle, NA, Sachdev, P, Sánchez-Juan, P, Schmaal, L, Schumann, G, Shumskaya, E, Smolka, MN, Soares, JC, Soriano-Mas, C, Stein, DJ, Strike, LT, Toro, R, Turner, JA, Tzourio-Mazoyer, N, Uhlmann, A, Hernández, MV, van den Heuvel, OA, van der Meer, D, van Haren, NEM, Veltman, DJ, Venkatasubramanian, G, Vetter, NC, Vuletic, D, Walitza, S, Walter, H, Walton, E, Wang, Z, Wardlaw, J, Wen, W, Westlye, LT, Whelan, R, Wittfeld, K, Wolfers, T, Wright, MJ, Xu, J, Xu, X, Yun, J-Y, Zhao, J, Franke, B, Thompson, PM, Glahn, DC, Mazoyer, B, Fisher, SE, Francks, C, Guadalupe, T, Mathias, SR, vanErp, TGM, Whelan, CD, Zwiers, MP, Abe, Y, Abramovic, L, Agartz, I, Andreassen, OA, Arias-Vásquez, A, Aribisala, BS, Armstrong, NJ, Arolt, V, Artiges, E, Ayesa-Arriola, R, Baboyan, VG, Banaschewski, T, Barker, G, Bastin, ME, Baune, BT, Blangero, J, Bokde, ALW, Boedhoe, PSW, Bose, A, Brem, S, Brodaty, H, Bromberg, U, Brooks, S, Büchel, C, Buitelaar, J, Calhoun, VD, Cannon, DM, Cattrell, A, Cheng, Y, Conrod, PJ, Conzelmann, A, Corvin, A, Crespo-Facorro, B, Crivello, F, Dannlowski, U, de Zubicaray, GI, de Zwarte, SMC, Deary, IJ, Desrivières, S, Doan, NT, Donohoe, G, Dørum, ES, Ehrlich, S, Espeseth, T, Fernández, G, Flor, H, Fouche, J-P, Frouin, V, Fukunaga, M, Gallinat, J, Garavan, H, Gill, M, Suarez, AG, Gowland, P, Grabe, HJ, Grotegerd, D, Gruber, O, Hagenaars, S, Hashimoto, R, Hauser, TU, Heinz, A, Hibar, DP, Hoekstra, PJ, Hoogman, M, Howells, FM, Hu, H, Hulshoff Pol, HE, Huyser, C, Ittermann, B, Jahanshad, N, Jönsson, EG, Jurk, S, Kahn, RS, Kelly, S, Kraemer, B, Kugel, H, Kwon, JS, Lemaitre, H, Lesch, K-P, Lochner, C, Luciano, M, Marquand, AF, Martin, NG, Martínez-Zalacaín, I, Martinot, J-L, Mataix-Cols, D, Mather, K, McDonald, C, McMahon, KL, Medland, SE, Menchón, JM, Morris, DW, Mothersill, O, Maniega, SM, Mwangi, B, Nakamae, T, Nakao, T, Narayanaswaamy, JC, Nees, F, Nordvik, JE, Onnink, AMH, Opel, N, Ophoff, R, Paillère Martinot, M-L, Papadopoulos Orfanos, D, Pauli, P, Paus, T, Poustka, L, Reddy, JY, Renteria, ME, Roiz-Santiáñez, R, Roos, A, Royle, NA, Sachdev, P, Sánchez-Juan, P, Schmaal, L, Schumann, G, Shumskaya, E, Smolka, MN, Soares, JC, Soriano-Mas, C, Stein, DJ, Strike, LT, Toro, R, Turner, JA, Tzourio-Mazoyer, N, Uhlmann, A, Hernández, MV, van den Heuvel, OA, van der Meer, D, van Haren, NEM, Veltman, DJ, Venkatasubramanian, G, Vetter, NC, Vuletic, D, Walitza, S, Walter, H, Walton, E, Wang, Z, Wardlaw, J, Wen, W, Westlye, LT, Whelan, R, Wittfeld, K, Wolfers, T, Wright, MJ, Xu, J, Xu, X, Yun, J-Y, Zhao, J, Franke, B, Thompson, PM, Glahn, DC, Mazoyer, B, Fisher, SE, and Francks, C
Abstract: The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.
Published: 2017

50. Novel genetic loci associated with hippocampal volume

Author: Hibar, DP, Adams, HHH, Jahanshad, N, Chauhan, G, Stein, JL, Hofer, E, Renteria, ME, Bis, JC, Arias-Vasquez, A, Ikram, MK, Desrivieres, S, Vernooij, MW, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beecham, AH, Beiser, A, Bernard, M, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chen, Q, Ching, CRK, Chouraki, V, Cuellar-Partida, G, Crivello, F, Den Braber, A, Nhat, TD, Ehrlich, S, Giddaluru, S, Goldman, AL, Gottesman, RF, Grimm, O, Griswold, ME, Guadalupe, T, Gutman, BA, Hass, J, Haukvik, UK, Hoehn, D, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Jorgensen, KN, Karbalai, N, Kasperaviciute, D, Kim, S, Klein, M, Kraemer, B, Lee, PH, Liewald, DCM, Lopez, LM, Luciano, M, Macare, C, Marquand, AF, Matarin, M, Mather, KA, Mattheisen, M, McKay, DR, Milaneschi, Y, Maniega, SM, Nho, K, Nugent, AC, Nyquist, P, Loohuis, LMO, Oosterlaan, J, Papmeyer, M, Pirpamer, L, Puetz, B, Ramasamy, A, Richards, JS, Risacher, SL, Roiz-Santianez, R, Rommelse, N, Ropele, S, Rose, EJ, Royle, NA, Rundek, T, Saemann, PG, Saremi, A, Satizabal, CL, Schmaal, L, Schork, AJ, Shen, L, Shin, J, Shumskaya, E, Smith, AV, Sprooten, E, Strike, LT, Teumer, A, Tordesillas-Gutierrez, D, Toro, R, Trabzuni, D, Trompet, S, Vaidya, D, Van der Grond, J, Van der Lee, SJ, Van der Meer, D, Van Donkelaar, MMJ, Van Eijk, KR, Van Erp, TGM, Van Rooij, D, Walton, E, Westlye, LT, Whelan, CD, Windham, BG, Winkler, AM, Wittfeld, K, Woldehawariat, G, Wolf, C, Wolfers, T, Yanek, LR, Yang, J, Zijdenbos, A, Zwiers, MP, Agartz, I, Almasy, L, Ames, D, Amouyel, P, Andreassen, OA, Arepalli, S, Assareh, AA, Barral, S, Bastin, ME, Becker, DM, Becker, JT, Bennett, DA, Blangero, J, van Bokhoven, H, Boomsma, DI, Brodaty, H, Brouwer, RM, Brunner, HG, Buckner, RL, Buitelaar, JK, Bulayeva, KB, Cahn, W, Calhoun, VD, Cannon, DM, Cavalleri, GL, Cheng, C-Y, Cichon, S, Cookson, MR, Corvin, A, Crespo-Facorro, B, Curran, JE, Czisch, M, Dale, AM, Davies, GE, De Craen, AJM, De Geus, EJC, De Jager, PL, De Zubicaray, GI, Deary, IJ, Debette, S, DeCarli, C, Delanty, N, Depondt, C, DeStefano, A, Dillman, A, Djurovic, S, Donohoe, G, Drevets, WC, Duggirala, R, Dyer, TD, Enzinger, C, Erk, S, Espeseth, T, Fedko, IO, Fernandez, G, Ferrucci, L, Fisher, SE, Fleischman, DA, Ford, I, Fornage, M, Foroud, TM, Fox, PT, Francks, C, Fukunaga, M, Gibbs, JR, Glahn, DC, Gollub, RL, Goring, HHH, Green, RC, Gruber, O, Gudnason, V, Guelfi, S, Haberg, AK, Hansell, NK, Hardy, J, Hartman, CA, Hashimoto, R, Hegenscheid, K, Heinz, A, Le Hellard, S, Hernandez, DG, Heslenfeld, DJ, Ho, B-C, Hoekstra, PJ, Hoffmann, W, Hofman, A, Holsboer, F, Homuth, G, Hosten, N, Hottenga, J-J, Huentelman, M, Pol, HEH, Ikeda, M, Jack, CR, Jenkinson, M, Johnson, R, Joensson, EG, Jukema, JW, Kahn, RS, Kanai, R, Kloszewska, I, Knopman, DS, Kochunov, P, Kwok, JB, Lawrie, SM, Lemaitre, H, Liu, X, Longo, DL, Lopez, OL, Lovestone, S, Martinez, O, Martinot, J-L, Mattay, VS, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Mecocci, P, Melle, I, Meyer-Lindenberg, A, Mohnke, S, Montgomery, GW, Morris, DW, Mosley, TH, Muhleisen, TW, Mueller-Myhsok, B, Nalls, MA, Nauck, M, Nichols, TE, Niessen, WJ, Nothen, MM, Nyberg, L, Ohi, K, Olvera, RL, Ophoff, RA, Pandolfo, M, Paus, T, Pausova, Z, Penninx, BWJH, Pike, GB, Potkin, SG, Psaty, BM, Reppermund, S, Rietschel, M, Roffman, JL, Romanczuk-Seiferth, N, Rotter, JI, Ryten, M, Sacco, RL, Sachdev, PS, Saykin, AJ, Schmidt, R, Schmidt, H, Schofield, PR, Sigursson, S, Simmons, A, Singleton, A, Sisodiya, SM, Smith, C, Smoller, JW, Soininen, H, Steen, VM, Stott, DJ, Sussmann, JE, Thalamuthu, A, Toga, AW, Traynor, BJ, Troncoso, J, Tsolaki, M, Tzourio, C, Uitterlinden, AG, Hernandez, MCV, Van der Brug, M, van der Lugt, A, van der Wee, NJA, Van Haren, NEM, van't Ent, D, Van Tol, M-J, Vardarajan, BN, Vellas, B, Veltman, DJ, Voelzke, H, Walter, H, Wardlaw, JM, Wassink, TH, Weale, ME, Weinberger, DR, Weiner, MW, Wen, W, Westman, E, White, T, Wong, TY, Wright, CB, Zielke, RH, Zonderman, AB, Martin, NG, Van Duijn, CM, Wright, MJ, Longstreth, WT, Schumann, G, Grabe, HJ, Franke, B, Launer, LJ, Medland, SE, Seshadri, S, Thompson, PM, Ikram, MA, Hibar, DP, Adams, HHH, Jahanshad, N, Chauhan, G, Stein, JL, Hofer, E, Renteria, ME, Bis, JC, Arias-Vasquez, A, Ikram, MK, Desrivieres, S, Vernooij, MW, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beecham, AH, Beiser, A, Bernard, M, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chen, Q, Ching, CRK, Chouraki, V, Cuellar-Partida, G, Crivello, F, Den Braber, A, Nhat, TD, Ehrlich, S, Giddaluru, S, Goldman, AL, Gottesman, RF, Grimm, O, Griswold, ME, Guadalupe, T, Gutman, BA, Hass, J, Haukvik, UK, Hoehn, D, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Jorgensen, KN, Karbalai, N, Kasperaviciute, D, Kim, S, Klein, M, Kraemer, B, Lee, PH, Liewald, DCM, Lopez, LM, Luciano, M, Macare, C, Marquand, AF, Matarin, M, Mather, KA, Mattheisen, M, McKay, DR, Milaneschi, Y, Maniega, SM, Nho, K, Nugent, AC, Nyquist, P, Loohuis, LMO, Oosterlaan, J, Papmeyer, M, Pirpamer, L, Puetz, B, Ramasamy, A, Richards, JS, Risacher, SL, Roiz-Santianez, R, Rommelse, N, Ropele, S, Rose, EJ, Royle, NA, Rundek, T, Saemann, PG, Saremi, A, Satizabal, CL, Schmaal, L, Schork, AJ, Shen, L, Shin, J, Shumskaya, E, Smith, AV, Sprooten, E, Strike, LT, Teumer, A, Tordesillas-Gutierrez, D, Toro, R, Trabzuni, D, Trompet, S, Vaidya, D, Van der Grond, J, Van der Lee, SJ, Van der Meer, D, Van Donkelaar, MMJ, Van Eijk, KR, Van Erp, TGM, Van Rooij, D, Walton, E, Westlye, LT, Whelan, CD, Windham, BG, Winkler, AM, Wittfeld, K, Woldehawariat, G, Wolf, C, Wolfers, T, Yanek, LR, Yang, J, Zijdenbos, A, Zwiers, MP, Agartz, I, Almasy, L, Ames, D, Amouyel, P, Andreassen, OA, Arepalli, S, Assareh, AA, Barral, S, Bastin, ME, Becker, DM, Becker, JT, Bennett, DA, Blangero, J, van Bokhoven, H, Boomsma, DI, Brodaty, H, Brouwer, RM, Brunner, HG, Buckner, RL, Buitelaar, JK, Bulayeva, KB, Cahn, W, Calhoun, VD, Cannon, DM, Cavalleri, GL, Cheng, C-Y, Cichon, S, Cookson, MR, Corvin, A, Crespo-Facorro, B, Curran, JE, Czisch, M, Dale, AM, Davies, GE, De Craen, AJM, De Geus, EJC, De Jager, PL, De Zubicaray, GI, Deary, IJ, Debette, S, DeCarli, C, Delanty, N, Depondt, C, DeStefano, A, Dillman, A, Djurovic, S, Donohoe, G, Drevets, WC, Duggirala, R, Dyer, TD, Enzinger, C, Erk, S, Espeseth, T, Fedko, IO, Fernandez, G, Ferrucci, L, Fisher, SE, Fleischman, DA, Ford, I, Fornage, M, Foroud, TM, Fox, PT, Francks, C, Fukunaga, M, Gibbs, JR, Glahn, DC, Gollub, RL, Goring, HHH, Green, RC, Gruber, O, Gudnason, V, Guelfi, S, Haberg, AK, Hansell, NK, Hardy, J, Hartman, CA, Hashimoto, R, Hegenscheid, K, Heinz, A, Le Hellard, S, Hernandez, DG, Heslenfeld, DJ, Ho, B-C, Hoekstra, PJ, Hoffmann, W, Hofman, A, Holsboer, F, Homuth, G, Hosten, N, Hottenga, J-J, Huentelman, M, Pol, HEH, Ikeda, M, Jack, CR, Jenkinson, M, Johnson, R, Joensson, EG, Jukema, JW, Kahn, RS, Kanai, R, Kloszewska, I, Knopman, DS, Kochunov, P, Kwok, JB, Lawrie, SM, Lemaitre, H, Liu, X, Longo, DL, Lopez, OL, Lovestone, S, Martinez, O, Martinot, J-L, Mattay, VS, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Mecocci, P, Melle, I, Meyer-Lindenberg, A, Mohnke, S, Montgomery, GW, Morris, DW, Mosley, TH, Muhleisen, TW, Mueller-Myhsok, B, Nalls, MA, Nauck, M, Nichols, TE, Niessen, WJ, Nothen, MM, Nyberg, L, Ohi, K, Olvera, RL, Ophoff, RA, Pandolfo, M, Paus, T, Pausova, Z, Penninx, BWJH, Pike, GB, Potkin, SG, Psaty, BM, Reppermund, S, Rietschel, M, Roffman, JL, Romanczuk-Seiferth, N, Rotter, JI, Ryten, M, Sacco, RL, Sachdev, PS, Saykin, AJ, Schmidt, R, Schmidt, H, Schofield, PR, Sigursson, S, Simmons, A, Singleton, A, Sisodiya, SM, Smith, C, Smoller, JW, Soininen, H, Steen, VM, Stott, DJ, Sussmann, JE, Thalamuthu, A, Toga, AW, Traynor, BJ, Troncoso, J, Tsolaki, M, Tzourio, C, Uitterlinden, AG, Hernandez, MCV, Van der Brug, M, van der Lugt, A, van der Wee, NJA, Van Haren, NEM, van't Ent, D, Van Tol, M-J, Vardarajan, BN, Vellas, B, Veltman, DJ, Voelzke, H, Walter, H, Wardlaw, JM, Wassink, TH, Weale, ME, Weinberger, DR, Weiner, MW, Wen, W, Westman, E, White, T, Wong, TY, Wright, CB, Zielke, RH, Zonderman, AB, Martin, NG, Van Duijn, CM, Wright, MJ, Longstreth, WT, Schumann, G, Grabe, HJ, Franke, B, Launer, LJ, Medland, SE, Seshadri, S, Thompson, PM, and Ikram, MA
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

1,202 results on '"Kahn, RS"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources