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1,404 results on '"Faraone SV"'

1. Longitudinal course of deficient emotional self-regulation CBCL profile in youth with ADHD: prospective controlled study

Author

Biederman J, Spencer TJ, Petty C, Hyder LL, O'Connor KB, Surman CBH, and Faraone SV

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Joseph Biederman,1,2 Thomas J Spencer,1,2 Carter Petty,1 Laran L Hyder,1 Katherine B O’Connor,1 Craig BH Surman,1,2 Stephen V Faraone31Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Pediatric Psychopharmacology Unit, Yawkey Center for Outpatient Care, Boston, MA, 2Department of Psychiatry, Harvard Medical School, Cambridge, MA, 3Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NYBackground: While symptoms of deficient emotional self-regulation (DESR) have been long associated with attention-deficit/hyperactivity disorder (ADHD), there has been limited investigation of this aspect of the clinical picture of the disorder. The main aim of this study was to examine the predictive utility of DESR in moderating the course of ADHD children into adolescence.Methods: Subjects comprised 177 children with and 204 children without ADHD followed for an average of 4 years (aged 6–18 years at baseline, 54% male). Subjects were assessed with structured diagnostic interviews and measures of psychosocial functioning. DESR was defined by the presence (n = 79) or absence (n = 98) of Child Behavior Checklist (CBCL)-DESR profile (score ≥ 180 < 210 total of Attention, Aggression, and Anxious/Depressed subscales) at the baseline assessment.Results: Of subjects with DESR at baseline, 57% had DESR at follow-up. Persistent ADHD was significantly associated with DESR at follow-up (χ2(1) = 15.37, P < 0.001). At follow-up, ADHD + DESR subjects had significantly more comorbidities (z = 2.55, P = 0.01), a higher prevalence of oppositional defiant disorder (z = 3.01, P = 0.003), and more impaired CBCL social problems t-score (t(227) = 2.41, P = 0.02) versus ADHD subjects.Conclusion: This work suggests that a positive CBCL-DESR profile predicts subsequent psychopathology and functional impairments in children with ADHD suggesting that it has the potential to help identify children with ADHD at high risk for compromised outcomes.Keywords: attention-deficit/hyperactivity disorder, emotion, regulation, longitudinal, youth

Published
2012

2. Behavioral and genetic evidence for a novel animal model of Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Subtype

Author

Zhang-James Y, DasBanerjee T, Sagvolden T, Middleton FA, and Faraone SV

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background According to DSM-IV there are three subtypes of Attention-Deficit/Hyperactivity Disorder, namely: ADHD predominantly inattentive type (ADHD-PI), ADHD predominantly Hyperactive-Impulsive Type (ADHD-HI), and ADHD combined type (ADHD-C). These subtypes may represent distinct neurobehavioral disorders of childhood onset with separate etiologies. The diagnosis of ADHD is behaviorally based; therefore, investigations into its possible etiologies should be based in behavior. Animal models of ADHD demonstrate construct validity when they accurately reproduce elements of the etiology, biochemistry, symptoms, and treatment of the disorder. Spontaneously hypertensive rats (SHR) fulfill many of the validation criteria and compare well with clinical cases of ADHD-C. The present study describes a novel rat model of the predominantly inattentive subtype (ADHD-PI). Methods ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. Several strains with varied genetic background were needed to determine what constitutes a normal comparison. Five groups of rats were used: SHR/NCrl spontaneously hypertensive and WKY/NCrl Wistar/Kyoto rats from Charles River; SD/NTac Sprague Dawley and WH/HanTac Wistar rats from Taconic Europe; and WKY/NHsd Wistar/Kyoto rats from Harlan. DNA was analyzed to determine background differences in the strains by PCR genotyping of eight highly polymorphic microsatellite markers and 2625 single nucleotide polymorphisms (SNPs). Results Compared to appropriate comparison strains (WKY/NHsd and SD/NTac rats), SHR/NCrl showed ADHD-C-like behavior: striking overactivity and poor sustained attention. Compared to WKY/NHsd rats, WKY/NCrl rats showed inattention, but no overactivity or impulsiveness. WH/HanTac rats deviated significantly from the other control groups by being more active and less attentive than the WKY/NHsd and SD/NTac rats. We also found substantial genomic differences between the WKY/NCrl and WKY/NHsd rats for eight short tandem repeat loci and 2625 SNPs. About 33.5 percent of the genome differs between the two WKY rat substrains, with large stretches of divergence on each chromosome. Discussion These data provide solid behavioral and genetic evidence that the WKY/NCrl and WKY/NHsd rats should be considered as separate substrains. Moreover, the behavioral features of the WKY/NCrl rat indicate that it should be a useful model for ADHD-PI, the primarily inattentive subtype of ADHD. The SD/NTac and the WH/HanTac rats show significant genetic and/or behavioral differences from WKY/NHsd rats and appear not to be appropriate controls in studies using the SHR/NCrl. The present results support the conclusion that SHR/NCrl is the best validated animal model of ADHD-C. The overactivity, impulsiveness and deficient sustained attention of the SHR/NCrl strain are independent behaviors. Thus, overactivity does not account for this strain's impulsiveness and deficient sustained attention. Finally, the present study shows that great care has to be exercised to select the model and comparison groups.

Published
2008
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4. Psychiatric gene discoveries shape evidence on ADHD’s biology

Author

Thapar, A, Martin, J, Mick, E, Arias Vásquez, A, Langley, K, Scherer, SW, Schachar, R, Crosbie, J, Williams, N, Franke, B, Elia, J, Glessner, J, Hakonarson, H, Owen, MJ, Faraone, SV, O'Donovan, MC, and Holmans, P

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Pediatric, Neurosciences, Attention Deficit Hyperactivity Disorder (ADHD), Autism, Biotechnology, Genetics, Schizophrenia, Brain Disorders, Mental Health, Human Genome, Intellectual and Developmental Disabilities (IDD), 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Adolescent, Attention Deficit Disorder with Hyperactivity, Autistic Disorder, Biological Psychiatry, Canada, Child, Child, Preschool, DNA Copy Number Variations, Databases, Nucleic Acid, Europe, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Ireland, Male, Neurodevelopmental Disorders, Polymorphism, Single Nucleotide, United Kingdom, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

A strong motivation for undertaking psychiatric gene discovery studies is to provide novel insights into unknown biology. Although attention-deficit hyperactivity disorder (ADHD) is highly heritable, and large, rare copy number variants (CNVs) contribute to risk, little is known about its pathogenesis and it remains commonly misunderstood. We assembled and pooled five ADHD and control CNV data sets from the United Kingdom, Ireland, United States of America, Northern Europe and Canada. Our aim was to test for enrichment of neurodevelopmental gene sets, implicated by recent exome-sequencing studies of (a) schizophrenia and (b) autism as a means of testing the hypothesis that common pathogenic mechanisms underlie ADHD and these other neurodevelopmental disorders. We also undertook hypothesis-free testing of all biological pathways. We observed significant enrichment of individual genes previously found to harbour schizophrenia de novo non-synonymous single-nucleotide variants (SNVs; P=5.4 × 10(-4)) and targets of the Fragile X mental retardation protein (P=0.0018). No enrichment was observed for activity-regulated cytoskeleton-associated protein (P=0.23) or N-methyl-D-aspartate receptor (P=0.74) post-synaptic signalling gene sets previously implicated in schizophrenia. Enrichment of ADHD CNV hits for genes impacted by autism de novo SNVs (P=0.019 for non-synonymous SNV genes) did not survive Bonferroni correction. Hypothesis-free testing yielded several highly significantly enriched biological pathways, including ion channel pathways. Enrichment findings were robust to multiple testing corrections and to sensitivity analyses that excluded the most significant sample. The findings reveal that CNVs in ADHD converge on biologically meaningful gene clusters, including ones now established as conferring risk of other neurodevelopmental disorders.

Published
2016

5. ADHD medication discontinuation and persistence across the lifespan: a retrospective observational study using population-based databases

Author

Brikell, I, Yao, H, Li, L, Astrup, A, Gao, L, Gillies, MB ; https://orcid.org/0000-0001-9038-8050, Xie, T, Zhang-James, Y, Dalsgaard, S, Engeland, A, Faraone, SV, Haavik, J, Hartman, C, Ip, P, Jakobsdóttir Smári, U, Larsson, H, Man, KK, de Oliveira Costa, J ; https://orcid.org/0000-0002-8355-023X, Pearson, SA ; https://orcid.org/0000-0001-7137-6855, Hostrup Nielsen, NP, Snieder, H, Wimberley, T, Wong, IC, Zhang, L, Zoega, H ; https://orcid.org/0000-0003-0761-9028, Klungsøyr, K, Chang, Z, Brikell, I, Yao, H, Li, L, Astrup, A, Gao, L, Gillies, MB ; https://orcid.org/0000-0001-9038-8050, Xie, T, Zhang-James, Y, Dalsgaard, S, Engeland, A, Faraone, SV, Haavik, J, Hartman, C, Ip, P, Jakobsdóttir Smári, U, Larsson, H, Man, KK, de Oliveira Costa, J ; https://orcid.org/0000-0002-8355-023X, Pearson, SA ; https://orcid.org/0000-0001-7137-6855, Hostrup Nielsen, NP, Snieder, H, Wimberley, T, Wong, IC, Zhang, L, Zoega, H ; https://orcid.org/0000-0003-0761-9028, Klungsøyr, K, and Chang, Z

Abstract

Background: Although often intended for long-term treatment, discontinuation of medication for ADHD is common. However, cross-national estimates of discontinuation are missing due to the absence of standardised measures. The aim of this study was to determine the rate of ADHD treatment discontinuation across the lifespan and to describe similarities and differences across countries to guide clinical practice. Methods: We did a retrospective, observational study using population-based databases from eight countries and one Special Administrative Region (Australia, Denmark, Hong Kong, Iceland, the Netherlands, Norway, Sweden, the UK, and the USA). We used a common analytical protocol approach and extracted prescription data to identify new users of ADHD medication. Eligible individuals were aged 3 years or older who had initiated ADHD medication between 2010 and 2020. We estimated treatment discontinuation and persistence in the 5 years after treatment initiation, stratified by age at initiation (children [age 4–11 years], adolescents [age 12–17 years], young adults [age 18–24 years], and adults [age ≥25 years]) and sex. Ethnicity data were not available. Findings: 1 229 972 individuals (735 503 [60%] males, 494 469 females [40%]; median age 8–21 years) were included in the study. Across countries, treatment discontinuation 1–5 years after initiation was lowest in children, and highest in young adults and adolescents. Within 1 year of initiation, 65% (95% CI 60–70) of children, 47% (43–51) of adolescents, 39% (36–42) of young adults, and 48% (44–52) of adults remained on treatment. The proportion of patients discontinuing was highest between age 18 and 19 years. Treatment persistence for up to 5 years was higher across countries when accounting for reinitiation of medication; at 5 years of follow-up, 50–60% of children and 30–40% of adolescents and adults were covered by treatment in most countries. Patterns were similar across sex. Interpretation: Early medication di

Published
2024

7. Polygenic resilience scores capture protective genetic effects for Alzheimer’s disease

Author

Hou, J, Hess, JL, Armstrong, N, Bis, JC, Grenier-Boley, B, Karlsson, IK, Leonenko, G, Numbers, K ; https://orcid.org/0000-0002-7009-2401, O’Brien, EK, Shadrin, A, Thalamuthu, A ; https://orcid.org/0000-0002-7114-1260, Yang, Q, Andreassen, OA, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Gatz, M, Kochan, NA ; https://orcid.org/0000-0002-8630-6398, Lambert, JC, Laws, SM, Masters, CL, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Pedersen, NL, Posthuma, D, Sachdev, PS ; https://orcid.org/0000-0002-9595-3220, Williams, J, Fan, CC, Faraone, SV, Fennema-Notestine, C, Lin, SJ, Escott-Price, V, Holmans, P, Seshadri, S, Tsuang, MT, Kremen, WS, Glatt, SJ, Hou, J, Hess, JL, Armstrong, N, Bis, JC, Grenier-Boley, B, Karlsson, IK, Leonenko, G, Numbers, K ; https://orcid.org/0000-0002-7009-2401, O’Brien, EK, Shadrin, A, Thalamuthu, A ; https://orcid.org/0000-0002-7114-1260, Yang, Q, Andreassen, OA, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Gatz, M, Kochan, NA ; https://orcid.org/0000-0002-8630-6398, Lambert, JC, Laws, SM, Masters, CL, Mather, KA ; https://orcid.org/0000-0003-4143-8941, Pedersen, NL, Posthuma, D, Sachdev, PS ; https://orcid.org/0000-0002-9595-3220, Williams, J, Fan, CC, Faraone, SV, Fennema-Notestine, C, Lin, SJ, Escott-Price, V, Holmans, P, Seshadri, S, Tsuang, MT, Kremen, WS, and Glatt, SJ

Published
2022

8. Physical Health, Media Use, and Mental Health in Children and Adolescents With ADHD During the COVID-19 Pandemic in Australia

Author

Sciberras, Emma, Patel, P, Stokes, Mark, Coghill, D, Middeldorp, CM, Bellgrove, MA, Becker, SP, Efron, D, Stringaris, A, Faraone, SV, Bellows, Susannah, Quach, J, Banaschewski, T, McGillivray, Jane, Hutchinson, Delyse, Silk, Tim, Melvin, Glenn, Wood, Amanda, Jackson, A, Loram, George Frederick Arthur, Engel, Lidia, Montgomery, A, Westrupp, Elizabeth, Sciberras, Emma, Patel, P, Stokes, Mark, Coghill, D, Middeldorp, CM, Bellgrove, MA, Becker, SP, Efron, D, Stringaris, A, Faraone, SV, Bellows, Susannah, Quach, J, Banaschewski, T, McGillivray, Jane, Hutchinson, Delyse, Silk, Tim, Melvin, Glenn, Wood, Amanda, Jackson, A, Loram, George Frederick Arthur, Engel, Lidia, Montgomery, A, and Westrupp, Elizabeth

Abstract

Objective: To examine the impact of COVID-19 restrictions among children with attention-deficit/hyperactivity disorder (ADHD). Methods: Parents of 213 Australian children (5–17 years) with ADHD completed a survey in May 2020 when COVID-19 restrictions were in place (i.e., requiring citizens to stay at home except for essential reasons). Results: Compared to pre-pandemic, children had less exercise (Odds Ratio (OR) = 0.4; 95% CI 0.3–0.6), less outdoor time (OR = 0.4; 95% 0.3–0.6), and less enjoyment in activities (OR = 6.5; 95% CI 4.0–10.4), while television (OR = 4.0; 95% CI 2.5–6.5), social media (OR = 2.4; 95% CI 1.3–4.5), gaming (OR = 2.0; 95% CI 1.3–3.0), sad/depressed mood (OR = 1.8; 95% CI 1.2–2.8), and loneliness (OR = 3.6; 95% CI 2.3–5.5) were increased. Child stress about COVID-19 restrictions was associated with poorer functioning across most domains. Most parents (64%) reported positive changes for their child including more family time. Conclusions: COVID-19 restrictions were associated with both negative and positive impacts among children with ADHD.

Published
2022

9. Reproducibility in the absence of selective reporting: An illustration from large-scale brain asymmetry research

Author

Kong, XZ, Francks, C, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Asherson, P, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Cannon, DM, Caparelli, EC, Castellanos, FX, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dannlowski, U, de Bruttopilo, SA, de Zeeuw, P, Deary, IJ, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Flint, C, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, JM, Garavan, H, do Santos Garcia, D, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, del Carmen Valdés Hernández, M, Kong, XZ, Francks, C, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Asherson, P, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Cannon, DM, Caparelli, EC, Castellanos, FX, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dannlowski, U, de Bruttopilo, SA, de Zeeuw, P, Deary, IJ, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Flint, C, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, JM, Garavan, H, do Santos Garcia, D, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, and del Carmen Valdés Hernández, M

Published
2022

10. International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder

Author

Ozgen, H, Spijkerman, R, Noack, M, Holtmann, M, Schellekens, ASA, van de Glind, G, Banaschewski, T, Barta, C, Begeman, A, Casas, M, Crunelle, CL, Daigre Blanco, C, Dalsgaard, S, Demetrovics, Z, den Boer, J, Dom, G, Eapen, V, Faraone, SV, Franck, J, Gonzalez, RA, Grau-Lopez, L, Groenman, AP, Hemphala, M, Icick, R, Johnson, B, Kaess, M, Kapitany-Foveny, M, Kasinathan, JG, Kaye, SS, Kiefer, F, Konstenius, M, Levin, FR, Luderer, M, Martinotti, G, Matthys, FIA, Meszaros, G, Moggi, F, Munasur-Naidoo, AP, Post, M, Rabinovitz, S, Ramos-Quiroga, JA, Sala, R, Shafi, A, Slobodin, O, Staal, WG, Thomasius, R, Truter, I, van Kernebeek, MW, Velez-Pastrana, MC, Vollstadt-Klein, S, Vorspan, F, Young, JT, Yule, A, van den Brink, W, Hendriks, V, Ozgen, H, Spijkerman, R, Noack, M, Holtmann, M, Schellekens, ASA, van de Glind, G, Banaschewski, T, Barta, C, Begeman, A, Casas, M, Crunelle, CL, Daigre Blanco, C, Dalsgaard, S, Demetrovics, Z, den Boer, J, Dom, G, Eapen, V, Faraone, SV, Franck, J, Gonzalez, RA, Grau-Lopez, L, Groenman, AP, Hemphala, M, Icick, R, Johnson, B, Kaess, M, Kapitany-Foveny, M, Kasinathan, JG, Kaye, SS, Kiefer, F, Konstenius, M, Levin, FR, Luderer, M, Martinotti, G, Matthys, FIA, Meszaros, G, Moggi, F, Munasur-Naidoo, AP, Post, M, Rabinovitz, S, Ramos-Quiroga, JA, Sala, R, Shafi, A, Slobodin, O, Staal, WG, Thomasius, R, Truter, I, van Kernebeek, MW, Velez-Pastrana, MC, Vollstadt-Klein, S, Vorspan, F, Young, JT, Yule, A, van den Brink, W, and Hendriks, V

Abstract

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder Abstract. Background: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. Objective: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. Method: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. Results: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should pr

Published
2022

11. Physical Health, Media Use, and Mental Health in Children and Adolescents With ADHD During the COVID-19 Pandemic in Australia

Author

Sciberras, E, Patel, P, Stokes, MA, Coghill, D, Middeldorp, CM, Bellgrove, MA, Becker, SP, Efron, D, Stringaris, A, Faraone, SV, Bellows, ST, Quach, J, Banaschewski, T, McGillivray, J, Hutchinson, D, Silk, TJ, Melvin, G, Wood, AG, Jackson, A, Loram, G, Engel, L, Montgomery, A, Westrupp, E, Sciberras, E, Patel, P, Stokes, MA, Coghill, D, Middeldorp, CM, Bellgrove, MA, Becker, SP, Efron, D, Stringaris, A, Faraone, SV, Bellows, ST, Quach, J, Banaschewski, T, McGillivray, J, Hutchinson, D, Silk, TJ, Melvin, G, Wood, AG, Jackson, A, Loram, G, Engel, L, Montgomery, A, and Westrupp, E

Abstract

OBJECTIVE: To examine the impact of COVID-19 restrictions among children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Parents of 213 Australian children (5-17 years) with ADHD completed a survey in May 2020 when COVID-19 restrictions were in place (i.e., requiring citizens to stay at home except for essential reasons). RESULTS: Compared to pre-pandemic, children had less exercise (Odds Ratio (OR) = 0.4; 95% CI 0.3-0.6), less outdoor time (OR = 0.4; 95% 0.3-0.6), and less enjoyment in activities (OR = 6.5; 95% CI 4.0-10.4), while television (OR = 4.0; 95% CI 2.5-6.5), social media (OR = 2.4; 95% CI 1.3-4.5), gaming (OR = 2.0; 95% CI 1.3-3.0), sad/depressed mood (OR = 1.8; 95% CI 1.2-2.8), and loneliness (OR = 3.6; 95% CI 2.3-5.5) were increased. Child stress about COVID-19 restrictions was associated with poorer functioning across most domains. Most parents (64%) reported positive changes for their child including more family time. CONCLUSIONS: COVID-19 restrictions were associated with both negative and positive impacts among children with ADHD.

Published
2022

12. Toward Precision Medicine in ADHD.

Author

Buitelaar, J, Bölte, S, Brandeis, D, Caye, A, Christmann, N, Cortese, S, Coghill, D, Faraone, SV, Franke, B, Gleitz, M, Greven, CU, Kooij, S, Leffa, DT, Rommelse, N, Newcorn, JH, Polanczyk, GV, Rohde, LA, Simonoff, E, Stein, M, Vitiello, B, Yazgan, Y, Roesler, M, Doepfner, M, Banaschewski, T, Buitelaar, J, Bölte, S, Brandeis, D, Caye, A, Christmann, N, Cortese, S, Coghill, D, Faraone, SV, Franke, B, Gleitz, M, Greven, CU, Kooij, S, Leffa, DT, Rommelse, N, Newcorn, JH, Polanczyk, GV, Rohde, LA, Simonoff, E, Stein, M, Vitiello, B, Yazgan, Y, Roesler, M, Doepfner, M, and Banaschewski, T

Abstract

Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.

Published
2022

13. Non-mental diseases associated with ADHD across the lifespan: Fidgety Philipp and Pippi Longstocking at risk of multimorbidity?

Author

Kittel-Schneider S, Arteaga-Henriquez G, Vasquez AA, Asherson P, Banaschewski T, Brikell I, Buitelaar J, Cormand B, Faraone SV, Freitag CM, Ginsberg Y, Haavik J, Hartman CA, Kuntsi J, Larsson H, Matura S, McNeill RV, Antoni Ramos-Quiroga J, Ribases M, Romanos M, Vainieri I, Franke B, and Reif A

Subjects
Epilepsy, Elimination disorders, Diabetes mellitus type II, Attention-deficit, hyperactivity disorder, Obesity, Somatic disorders, Non-mental disease, Asthma, Migraine
Abstract

Several non-mental diseases seem to be associated with an increased risk of ADHD and ADHD seems to be associated with increased risk for non-mental diseases. The underlying trajectories leading to such brain-body co occurrences are often unclear are there direct causal relationships from one disorder to the other, or does the sharing of genetic and/or environmental risk factors lead to their occurring together more frequently or both? Our goal with this narrative review was to provide a conceptual synthesis of the associations between ADHD and non-mental disease across the lifespan. We discuss potential shared pathologic mechanisms, genetic background and treatments in co-occurring diseases. For those co-occurrences for which published studies with sufficient sample sizes exist, meta-analyses have been published by others and we discuss those in detail. We conclude that non-mental diseases are common in ADHD and vice versa and add to the disease burden of the patient across the lifespan. Insufficient attention to such co-occurring conditions may result in missed diagnoses and suboptimal treatment in the affected individuals.

Published
2022

14. Eye Vergence Responses During an Attention Task in Adults With ADHD and Clinical Controls

Author

Jiménez EC, Avella-Garcia C, Kustow J, Cubbin S, Corrales M, Richarte V, Esposito FL, Morata I, Perera A, Varela P, Cañete J, Faraone SV, Super H, and Ramos-Quiroga JA

Subjects
diagnosis, genetic structures, binocular, mental disorders, biomarker, eye vergence, ADHD, behavioral disciplines and activities, adults
Abstract

Objective: ADHD patients show poor oculomotor control and recent studies show that attention-related eye vergence is weak in ADHD children. We aimed to assess vergence as a potential diagnostic biomarker for ADHD in adults. Method: We assessed the modulation in the angle of vergence while performing an attention task (N = 144), comparing the results for adults previously diagnosed with ADHD (N = 108) with age-matched clinical controls (N = 36). Results: Significant differences in eye vergence response modulation between clinical controls and ADHD patients were documented. Diagnostic test accuracy was 79%. Conclusion: In combination with an attention task, eye vergence responses could be used as an objective marker to support the clinical diagnosis of adult ADHD.

Published
2021

15. Virtual histology of cortical thickness and shared neurobiology in 6 psychiatric disorders

Author

Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abé, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargalló, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, Del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bülow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodríguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjó-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, Silk, Timothy, Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abé, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargalló, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, Del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bülow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodríguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjó-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, and Silk, Timothy

Published
2021

16. Characterizing neuroanatomic heterogeneity in people with and without ADHD based on subcortical brain volumes

Author

Li, T, van Rooij, D, Roth Mota, N, Buitelaar, JK, Hoogman, M, Arias Vasquez, A, Franke, B, Ambrosino, S, Banaschewski, T, Bandeira, CE, Bau, CHD, Baumeister, S, Baur-Streubel, R, Bellgrove, MA, Biederman, J, Bralten, J, Bramati, IE, Brandeis, D, Berm, S, Busatto, GF, Calvo, A, Castellanos, FX, Cercignani, M, Chantiluke, KC, Christakou, A, Coghill, D, Conzelmann, A, Cubillo, AI, Cupertino, RB, de Zeeuw, P, Durston, S, Earl, EA, Epstein, JN, Ethofer, T, Fallgatter, AJ, Fair, DA, Faraone, SV, Frodl, T, Gabel, MC, Gogberashvili, T, Grevet, EH, Haavik, J, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hoekstra, PJ, Høvik, MF, Jahanshad, N, Kardatzki, B, Karkashadze, G, Kelly, C, Kohls, G, Konrad, K, Kuntsi, J, Lazaro, L, Lera-Miguel, S, Lesch, KP, Louza, MR, Lundervold, AJ, Malpas, CB, Mattos, P, McCarthy, H, Nicolau, R, Nigg, JT, O'Gorman Tuura, RL, Oosterlaan, J, Oranje, B, Paloyelis, Y, Pauli, P, Picon, FA, Plessen, KJ, Ramos-Quiroga, JA, Reif, A, Reneman, L, Rosa, PGP, Rubia, K, Schrantee, A, Schweren, LJS, Seitz, J, Shaw, P, Silk, Tim, Skokauskas, N, Carlos Soliva Vila, J, Soloveva, A, Stevens, MC, Sudre, G, Tamm, L, Thompson, PM, Tovar-Moll, F, van Erp, TGM, Vance, A, Vilarroya, O, Vives-Gilabert, Y, von Polier, GG, Walitza, S, Yoncheva, YN, Zanetti, MV, Ziegler, GC, Anikin, A, Asherson, P, Li, T, van Rooij, D, Roth Mota, N, Buitelaar, JK, Hoogman, M, Arias Vasquez, A, Franke, B, Ambrosino, S, Banaschewski, T, Bandeira, CE, Bau, CHD, Baumeister, S, Baur-Streubel, R, Bellgrove, MA, Biederman, J, Bralten, J, Bramati, IE, Brandeis, D, Berm, S, Busatto, GF, Calvo, A, Castellanos, FX, Cercignani, M, Chantiluke, KC, Christakou, A, Coghill, D, Conzelmann, A, Cubillo, AI, Cupertino, RB, de Zeeuw, P, Durston, S, Earl, EA, Epstein, JN, Ethofer, T, Fallgatter, AJ, Fair, DA, Faraone, SV, Frodl, T, Gabel, MC, Gogberashvili, T, Grevet, EH, Haavik, J, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hoekstra, PJ, Høvik, MF, Jahanshad, N, Kardatzki, B, Karkashadze, G, Kelly, C, Kohls, G, Konrad, K, Kuntsi, J, Lazaro, L, Lera-Miguel, S, Lesch, KP, Louza, MR, Lundervold, AJ, Malpas, CB, Mattos, P, McCarthy, H, Nicolau, R, Nigg, JT, O'Gorman Tuura, RL, Oosterlaan, J, Oranje, B, Paloyelis, Y, Pauli, P, Picon, FA, Plessen, KJ, Ramos-Quiroga, JA, Reif, A, Reneman, L, Rosa, PGP, Rubia, K, Schrantee, A, Schweren, LJS, Seitz, J, Shaw, P, Silk, Tim, Skokauskas, N, Carlos Soliva Vila, J, Soloveva, A, Stevens, MC, Sudre, G, Tamm, L, Thompson, PM, Tovar-Moll, F, van Erp, TGM, Vance, A, Vilarroya, O, Vives-Gilabert, Y, von Polier, GG, Walitza, S, Yoncheva, YN, Zanetti, MV, Ziegler, GC, Anikin, A, and Asherson, P

Published
2021

17. Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets

Author

Postema, MC, Hoogman, M, Ambrosino, S, Asherson, P, Banaschewski, T, Bandeira, CE, Baranov, A, Bau, CHD, Baumeister, S, Baur-Streubel, R, Bellgrove, MA, Biederman, J, Bralten, J, Brandeis, D, Brem, S, Buitelaar, JK, Busatto, GF, Castellanos, FX, Cercignani, M, Chaim-Avancini, TM, Chantiluke, KC, Christakou, A, Coghill, D, Conzelmann, A, Cubillo, AI, Cupertino, RB, de Zeeuw, P, Doyle, AE, Durston, S, Earl, EA, Epstein, JN, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Frodl, T, Gabel, MC, Gogberashvili, T, Grevet, EH, Haavik, J, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hoekstra, PJ, Hohmann, S, Høvik, MF, Jernigan, TL, Kardatzki, B, Karkashadze, G, Kelly, C, Kohls, G, Konrad, K, Kuntsi, J, Lazaro, L, Lera-Miguel, S, Lesch, KP, Louza, MR, Lundervold, AJ, Malpas, CB, Mattos, P, McCarthy, H, Namazova-Baranova, L, Nicolau, R, Nigg, JT, Novotny, SE, Oberwelland Weiss, E, O'Gorman Tuura, RL, Oosterlaan, J, Oranje, B, Paloyelis, Y, Pauli, P, Picon, FA, Plessen, KJ, Ramos-Quiroga, JA, Reif, A, Reneman, L, Rosa, PGP, Rubia, K, Schrantee, A, Schweren, LJS, Seitz, J, Shaw, P, Silk, Tim, Skokauskas, N, Soliva Vila, JC, Stevens, MC, Sudre, G, Tamm, L, Tovar-Moll, F, van Erp, TGM, Vance, A, Vilarroya, O, Vives-Gilabert, Y, von Polier, GG, Walitza, S, Yoncheva, YN, Zanetti, MV, Ziegler, GC, Glahn, DC, Jahanshad, N, Postema, MC, Hoogman, M, Ambrosino, S, Asherson, P, Banaschewski, T, Bandeira, CE, Baranov, A, Bau, CHD, Baumeister, S, Baur-Streubel, R, Bellgrove, MA, Biederman, J, Bralten, J, Brandeis, D, Brem, S, Buitelaar, JK, Busatto, GF, Castellanos, FX, Cercignani, M, Chaim-Avancini, TM, Chantiluke, KC, Christakou, A, Coghill, D, Conzelmann, A, Cubillo, AI, Cupertino, RB, de Zeeuw, P, Doyle, AE, Durston, S, Earl, EA, Epstein, JN, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Frodl, T, Gabel, MC, Gogberashvili, T, Grevet, EH, Haavik, J, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hoekstra, PJ, Hohmann, S, Høvik, MF, Jernigan, TL, Kardatzki, B, Karkashadze, G, Kelly, C, Kohls, G, Konrad, K, Kuntsi, J, Lazaro, L, Lera-Miguel, S, Lesch, KP, Louza, MR, Lundervold, AJ, Malpas, CB, Mattos, P, McCarthy, H, Namazova-Baranova, L, Nicolau, R, Nigg, JT, Novotny, SE, Oberwelland Weiss, E, O'Gorman Tuura, RL, Oosterlaan, J, Oranje, B, Paloyelis, Y, Pauli, P, Picon, FA, Plessen, KJ, Ramos-Quiroga, JA, Reif, A, Reneman, L, Rosa, PGP, Rubia, K, Schrantee, A, Schweren, LJS, Seitz, J, Shaw, P, Silk, Tim, Skokauskas, N, Soliva Vila, JC, Stevens, MC, Sudre, G, Tamm, L, Tovar-Moll, F, van Erp, TGM, Vance, A, Vilarroya, O, Vives-Gilabert, Y, von Polier, GG, Walitza, S, Yoncheva, YN, Zanetti, MV, Ziegler, GC, Glahn, DC, and Jahanshad, N

Published
2021

18. Structural brain imaging studies offer clues about the effects of the shared genetic etiology among neuropsychiatric disorders

Author

Radonjic, NV, Hess, JL, Rovira, P, Andreassen, O, Buitelaar, JK, Ching, CRK, Franke, B, Hoogman, M, Jahanshad, N, McDonald, C, Schmaal, L, Sisodiya, SM, Stein, DJ, van den Heuvel, OA, van Erp, TGM, van Rooij, D, Veltman, DJ, Thompson, P, Faraone, SV, Radonjic, NV, Hess, JL, Rovira, P, Andreassen, O, Buitelaar, JK, Ching, CRK, Franke, B, Hoogman, M, Jahanshad, N, McDonald, C, Schmaal, L, Sisodiya, SM, Stein, DJ, van den Heuvel, OA, van Erp, TGM, van Rooij, D, Veltman, DJ, Thompson, P, and Faraone, SV

Abstract

Genomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. From the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, we acquired standardized mean differences (SMDs) in regional brain volume and cortical thickness between cases and controls. We had data on 41 brain regions for: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD), and schizophrenia (SCZ). These data had been derived from 24,360 patients and 37,425 controls. The SMDs were significantly correlated between SCZ and BD, OCD, MDD, and ASD. MDD was positively correlated with BD and OCD. BD was positively correlated with OCD and negatively correlated with ADHD. These pairwise correlations among disorders were correlated with the corresponding pairwise correlations among disorders derived from genomewide association studies (r = 0.494). Our results show substantial similarities in sMRI phenotypes among neuropsychiatric disorders and suggest that these similarities are accounted for, in part, by corresponding similarities in common genetic variant architectures.

Published
2021

19. Variants of the Aggression-Related RBFOX1 Gene in a Population Representative Birth Cohort Study: Aggressiveness, Personality, and Alcohol Use Disorder

Author

Vaht M, Laas K, Fernandez N, Kurrikoff T, Kanarik M, Faraone SV, Tooding LM, Veidebaum T, Franke B, Reif A, Cormand B, and Harro J

Subjects
A2BP1, extraversion, gender, neuroticism, aggressiveness, alcohol use disorder, RBFOX1
Abstract

Background: Recently, RBFOX1, a gene encoding an RNA binding protein, has consistently been associated with aggressive and antisocial behavior. Several loci in the gene have been nominally associated with aggression in genome-wide association studies, the risk alleles being more frequent in the general population. We have hence examined the association of four RBFOX1 single nucleotide polymorphisms, previously found related to aggressive traits, with aggressiveness, personality, and alcohol use disorder in birth cohort representative samples. Methods: We used both birth cohorts of the Estonian Children Personality Behavior and Health Study (ECPBHS; original n = 1,238). Aggressiveness was assessed using the Buss-Perry Aggression Questionnaire and the Lifetime History of Aggressiveness structured interview at age 25 (younger cohort) or 33 (older cohort). Big Five personality at age 25 was measured with self-reports and the lifetime occurrence of alcohol use disorder assessed with the MINI interview. RBFOX1 polymorphisms rs809682, rs8062784, rs12921846, and rs6500744 were genotyped in all participants. Given the restricted size of the sample, correction for multiple comparisons was not applied. Results: Aggressiveness was not significantly associated with the RBFOX1 genotype. RBFOX1 rs8062784 was associated with neuroticism and rs809682 with extraversion. Two out of four analyzed RBFOX1 variants, rs8062784 and rs12921846, were associated with the occurrence of alcohol use disorder. Conclusions: In the birth cohort representative sample of the ECPBHS, no association of RBFOX1 with aggressiveness was found, but RBFOX1 variants affected basic personality traits and the prevalence of alcohol use disorder. Future studies on RBFOX1 should consider the moderating role of personality and alcohol use patterns in aggressiveness.

Published
2020

21. Shared genetic background between children and adults with attention deficit/hyperactivity disorder

Author

Rovira P, Demontis D, Sánchez-Mora C, Zayats T, Klein M, Mota NR, Weber H, Garcia-Martínez I, Pagerols M, Vilar L, Arribas L, Richarte V, Corrales M, Fadeuilhe C, Bosch R, Martin GE, Almos P, Doyle AE, Grevet EH, Grimm O, Halmøy A, Hoogman M, Hutz M, Jacob CP, Kittel-Schneider S, Knappskog PM, Lundervold AJ, Rivero O, Rovaris DL, Salatino-Oliveira A, da Silva BS, Svirin E, Sprooten E, Strekalova T, ADHD Working Group of the Psychiatric Genomics Consortium, 23andMe Research team, Arias-Vasquez A, Sonuga-Barke EJS, Asherson P, Bau CHD, Buitelaar JK, Cormand B, Faraone SV, Haavik J, Johansson SE, Kuntsi J, Larsson H, Lesch KP, Reif A, Rohde LA, Casas M, Børglum AD, Franke B, Ramos-Quiroga JA, Artigas MS, and Ribasés M

Subjects
mental disorders, behavioral disciplines and activities
Abstract

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.

Published
2020

22. RBFOX1, encoding a splicing regulator, is a candidate gene for aggressive behavior

Author

Fernandez N, Gan G, van Donkelaar MMJ, Vaht M, Weber H, Retz W, Meyer-Lindenberg A, Franke B, Harro J, Reif A, Faraone SV, and Cormand B

Subjects
Epigenetics, Neuroimaging, Aggression, RBFOX1, Animal models, Genetics, Transcriptomics, A2BP1
Abstract

The RBFOX1 gene (or A2BP1) encodes a splicing factor important for neuronal development that has been related to autism spectrum disorder and other neurodevelopmental phenotypes. Evidence from complementary sources suggests that this gene contributes to aggressive behavior. Suggestive associations with RBFOX1 have been identified in genome-wide association studies (GWAS) of anger, conduct disorder, and aggressive behavior. Nominal association signals in RBFOX1 were also found in an epigenome-wide association study (EWAS) of aggressive behavior. Also, variants in this gene affect temporal lobe volume, a brain area that is altered in several aggression-related phenotypes. In animals, this gene has been shown to modulate aggressive behavior in Drosophila. RBFOX1 has also been associated with canine aggression and is upregulated in mice that show increased aggression after frustration of an expected reward. Associated common genetic variants as well as rare duplications and deletions affecting RBFOX1 have been identified in several psychiatric and neurodevelopmental disorders that are often comorbid with aggressive behaviors. In this paper, we comprehensively review the cumulative evidence linking RBFOX1 to aggression behavior and provide new results implicating RBFOX1 in this phenotype. Most of these studies (genetic and epigenetic analyses in humans, neuroimaging genetics, gene expression and animal models) are hypothesis-free, which strengthens the validity of the findings, although all the evidence is nominal and should therefore be taken with caution. Further studies are required to clarify in detail the role of this gene in this complex phenotype.

Published
2020

23. ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

Author

Thompson, PM, Jahanshad, N, Ching, CRK, Salminen, LE, Thomopoulos, SI, Bright, J, Baune, BT, Bertolin, S, Bralten, J, Bruin, WB, Buelow, R, Chen, J, Chye, Y, Dannlowski, U, de Kovel, CGF, Donohoe, G, Eyler, LT, Faraone, SV, Favre, P, Filippi, CA, Frodl, T, Garijo, D, Gil, Y, Grabe, HJ, Grasby, KL, Hajek, T, Han, LKM, Hatton, SN, Hilbert, K, Ho, TC, Holleran, L, Homuth, G, Hosten, N, Houenou, J, Ivanov, I, Jia, T, Kelly, S, Klein, M, Kwon, JS, Laansma, MA, Leerssen, J, Lueken, U, Nunes, A, Neill, JO, Opel, N, Piras, F, Postema, MC, Pozzi, E, Shatokhina, N, Soriano-Mas, C, Spalletta, G, Sun, D, Teumer, A, Tilot, AK, Tozzi, L, van der Merwe, C, Van Someren, EJW, van Wingen, GA, Voelzke, H, Walton, E, Wang, L, Winkler, AM, Wittfeld, K, Wright, MJ, Yun, J-Y, Zhang, G, Zhang-James, Y, Adhikari, BM, Agartz, I, Aghajani, M, Aleman, A, Althoff, RR, Altmann, A, Andreassen, OA, Baron, DA, Bartnik-Olson, BL, Bas-Hoogendam, J, Baskin-Sommers, AR, Bearden, CE, Berner, LA, Boedhoe, PSW, Brouwer, RM, Buitelaar, JK, Caeyenberghs, K, Cecil, CAM, Cohen, RA, Cole, JH, Conrod, PJ, De Brito, SA, de Zwarte, SMC, Dennis, EL, Desrivieres, S, Dima, D, Ehrlich, S, Esopenko, C, Fairchild, G, Fisher, SE, Fouche, J-P, Francks, C, Frangou, S, Franke, B, Garavan, HP, Glahn, DC, Groenewold, NA, Gurholt, TP, Gutman, BA, Hahn, T, Harding, IH, Hernaus, D, Hibar, DP, Hillary, FG, Hoogman, M, Pol, HE, Jalbrzikowski, M, Karkashadze, GA, Klapwijk, ET, Knickmeyer, RC, Kochunov, P, Koerte, IK, Kong, X-Z, Liew, S-L, Lin, AP, Logue, MW, Luders, E, Macciardi, F, Mackey, S, Mayer, AR, McDonald, CR, McMahon, AB, Medland, SE, Modinos, G, Morey, RA, Mueller, SC, Mukherjee, P, Namazova-Baranova, L, Nir, TM, Olsen, A, Paschou, P, Pine, DS, Pizzagalli, F, Renteria, ME, Rohrer, JD, Saemann, PG, Schmaal, L, Schumann, G, Shiroishi, MS, Sisodiya, SM, Smit, DJA, Sonderby, IE, Stein, DJ, Stein, JL, Tahmasian, M, Tate, DF, Turner, JA, van den Heuvel, OA, van der Wee, NJA, van der Werf, YD, van Erp, TGM, van Haren, NEM, van Rooij, D, van Velzen, LS, Veer, IM, Veltman, DJ, Villalon-Reina, JE, Walter, H, Whelan, CD, Wilde, EA, Zarei, M, Zelman, V, Thompson, PM, Jahanshad, N, Ching, CRK, Salminen, LE, Thomopoulos, SI, Bright, J, Baune, BT, Bertolin, S, Bralten, J, Bruin, WB, Buelow, R, Chen, J, Chye, Y, Dannlowski, U, de Kovel, CGF, Donohoe, G, Eyler, LT, Faraone, SV, Favre, P, Filippi, CA, Frodl, T, Garijo, D, Gil, Y, Grabe, HJ, Grasby, KL, Hajek, T, Han, LKM, Hatton, SN, Hilbert, K, Ho, TC, Holleran, L, Homuth, G, Hosten, N, Houenou, J, Ivanov, I, Jia, T, Kelly, S, Klein, M, Kwon, JS, Laansma, MA, Leerssen, J, Lueken, U, Nunes, A, Neill, JO, Opel, N, Piras, F, Postema, MC, Pozzi, E, Shatokhina, N, Soriano-Mas, C, Spalletta, G, Sun, D, Teumer, A, Tilot, AK, Tozzi, L, van der Merwe, C, Van Someren, EJW, van Wingen, GA, Voelzke, H, Walton, E, Wang, L, Winkler, AM, Wittfeld, K, Wright, MJ, Yun, J-Y, Zhang, G, Zhang-James, Y, Adhikari, BM, Agartz, I, Aghajani, M, Aleman, A, Althoff, RR, Altmann, A, Andreassen, OA, Baron, DA, Bartnik-Olson, BL, Bas-Hoogendam, J, Baskin-Sommers, AR, Bearden, CE, Berner, LA, Boedhoe, PSW, Brouwer, RM, Buitelaar, JK, Caeyenberghs, K, Cecil, CAM, Cohen, RA, Cole, JH, Conrod, PJ, De Brito, SA, de Zwarte, SMC, Dennis, EL, Desrivieres, S, Dima, D, Ehrlich, S, Esopenko, C, Fairchild, G, Fisher, SE, Fouche, J-P, Francks, C, Frangou, S, Franke, B, Garavan, HP, Glahn, DC, Groenewold, NA, Gurholt, TP, Gutman, BA, Hahn, T, Harding, IH, Hernaus, D, Hibar, DP, Hillary, FG, Hoogman, M, Pol, HE, Jalbrzikowski, M, Karkashadze, GA, Klapwijk, ET, Knickmeyer, RC, Kochunov, P, Koerte, IK, Kong, X-Z, Liew, S-L, Lin, AP, Logue, MW, Luders, E, Macciardi, F, Mackey, S, Mayer, AR, McDonald, CR, McMahon, AB, Medland, SE, Modinos, G, Morey, RA, Mueller, SC, Mukherjee, P, Namazova-Baranova, L, Nir, TM, Olsen, A, Paschou, P, Pine, DS, Pizzagalli, F, Renteria, ME, Rohrer, JD, Saemann, PG, Schmaal, L, Schumann, G, Shiroishi, MS, Sisodiya, SM, Smit, DJA, Sonderby, IE, Stein, DJ, Stein, JL, Tahmasian, M, Tate, DF, Turner, JA, van den Heuvel, OA, van der Wee, NJA, van der Werf, YD, van Erp, TGM, van Haren, NEM, van Rooij, D, van Velzen, LS, Veer, IM, Veltman, DJ, Villalon-Reina, JE, Walter, H, Whelan, CD, Wilde, EA, Zarei, M, and Zelman, V

Abstract

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

Published
2020

24. Genome wide meta-analysis identifies genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders

Author

Phil Lee, Richard Anney, Pieter J. Hoekstra, Barbara Franke, Geschwind Dh, Michael C. Neale, Yen-Chen Anne Feng, Edwin H. Cook, Anttila, E Stahl, Borglum Ad, Kenneth S. Kendler, Santangelo Sl, Wray Nr, Danielle Posthuma, Carol A. Mathews, Sintia Iole Belangero, Amanda B Zheutlin, Cynthia M. Bulik, Jeremiah M. Scharf, Laramie E. Duncan, Luis Augusto Rohde, Jacob Rosenthal, Anna Keski-Rahkonen, Stein Mb, Fanous Ah, Zhaozhong Zhu, Karen S. Mitchell, J Kaprio, Breen G, Michel G. Nivard, G. Kirov, John I. Nurnberger, Patrick F. Sullivan, Daly Mj, Michael Conlon O'Donovan, Andreassen Oa, Hyejung Won, Wang Mm, Faraone Sv, Mattheisen M, Benjamin M. Neale, Gelernter J, Smoller Jw, Henry R. Kranzler, Thornton Lm, Clement C. Zai, Ripke S, Elliot M. Tucker-Drob, Howard J. Edenberg, Lewis Cm, McIntosh Am, Tobias Banaschewski, Dongmei Yu, Andrew D. Grotzinger, Walters Jt, Raymond K. Walters, Giovanni Coppola, and Jurjen J. Luykx

Subjects
0303 health sciences, medicine.medical_specialty, Biology, medicine.disease, Genome, Tourette syndrome, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Pleiotropy, Anorexia nervosa (differential diagnoses), Autism spectrum disorder, Schizophrenia, medicine, Bipolar disorder, Psychiatry, 030217 neurology & neurosurgery, Depression (differential diagnoses), 030304 developmental biology
Abstract

SummaryGenetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed a meta-analysis of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders identifying three groups of inter-related disorders. We detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning in the second trimester prenatally, and play prominent roles in a suite of neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

Published
2019
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25. Exploring genetic variation that influences brain methylation in attention-deficit/hyperactivity disorder

Author

Pineda L, Shivalikanjli A, Cabana J, Demontis D, Rajagopal VM, Børglum AD, Faraone SV, Cormand B, and Fernandez N

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder caused by an interplay of genetic and environmental factors. Epigenetics is crucial to lasting changes in gene expression in the brain. Recent studies suggest a role for DNA methylation in ADHD. We explored the contribution to ADHD of allele-specific methylation (ASM), an epigenetic mechanism that involves SNPs correlating with differential levels of DNA methylation at CpG sites. We selected 3896 tagSNPs reported to influence methylation in human brain regions and performed a case-control association study using the summary statistics from the largest GWAS meta-analysis of ADHD, comprising 20,183 cases and 35,191 controls. We observed that genetic risk variants for ADHD are enriched in ASM SNPs and identified associations with eight tagSNPs that were significant at a 5% false discovery rate (FDR). These SNPs correlated with methylation of CpG sites lying in the promoter regions of six genes. Since methylation may affect gene expression, we inspected these ASM SNPs together with 52 ASM SNPs in high LD with them for eQTLs in brain tissues and observed that the expression of three of those genes was affected by them. ADHD risk alleles correlated with increased expression (and decreased methylation) of ARTN and PIDD1 and with a decreased expression (and increased methylation) of C2orf82. Furthermore, these three genes were predicted to have altered expression in ADHD, and genetic variants in C2orf82 correlated with brain volumes. In summary, we followed a systematic approach to identify risk variants for ADHD that correlated with differential cis-methylation, identifying three novel genes contributing to the disorder.

Published
2019

26. The association between Attention-Deficit/Hyperactivity Disorder (ADHD) and asthma: systematic review with meta-analysis and new data from a Swedish population-based study: systematic review with meta-analysis and new data from a Swedish population-based study

Author

Cortese, Samuele, Sun, Shihua, Zhang, Junhua, Sharma, Esha, Chang, Zheng, Kuja-Halkola, Ralf, Almqvist, Catarina, Larsson, Henrik, and Faraone, SV

Abstract

BackgroundSeveral studies have assessed the possible association between attention deficit hyperactivity disorder (ADHD) and asthma. However, existing evidence is inconclusive as to whether this association remains after controlling for possible important confounders. To fill this knowledge gap, we did a systematic review and meta-analysis, followed by a population-based study.MethodsFor the systematic review and meta-analysis, we searched PubMed, PsycINFO, Embase, Embase Classic, Ovid MEDLINE, and Web of Knowledge databases up to Oct 31, 2017, for observational studies allowing estimation of the association between asthma and ADHD. No restrictions to date, language, or article type were applied. Unpublished data were collected from authors of the identified studies. We extracted unadjusted and adjusted odds ratios (ORs) from the identified studies and calculated ORs when they were not reported. We assessed study quality using the Newcastle-Ottawa Scale and study heterogeneity using I2 statistics. A random-effects model was used to calculate pooled ORs. The systematic review is registered with PROSPERO (CRD42017073368). To address the fact that the ORs obtained in the meta-analysis were adjusted for confounders that inevitably varied across studies, we did a population-based study of individuals in multiple national registers in Sweden. We calculated an unadjusted OR and an OR that was simultaneously adjusted for all confounders identified in a directed acyclic graph based on the studies of asthma and ADHD identified in our systematic review.FindingsWe identified 2649 potentially eligible citations, from which we obtained 49 datasets including a total of 210 363 participants with ADHD and 3 115 168 without. The pooled unadjusted OR was 1·66 (95% CI 1·22–2·26; I2 =99·47) and the pooled adjusted OR was 1·53 (1·41–1·65; I2 =50·76), indicating a significant association between asthma and ADHD. Possible lack of representativeness of the study population was detected with the Newcastle-Ottawa Scale in 42 of 49 datasets. In the population-based study, we included 1 575 377 individuals born between Jan 1, 1992, and Dec 31, 2006, of whom 259 253 (16·5%) had asthma and 57 957 (3·7%) had ADHD. Asthma was significantly associated with ADHD (OR 1·60, 95% CI 1·57–1·63) in the crude model adjusting for sex and year of birth, and this association remained significant after simultaneous adjustment for all covariates (1·45, 1·41–1·48).InterpretationThe combined results of the meta-analysis and the population-based study support a significant association between asthma and ADHD, which remained even after simultaneously controlling for several possible confounders in the population-based study. Awareness of this association might help to reduce delay in the diagnosis of both ADHD and asthma.

Published
2018

27. A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder

Author

Martin, J, Walters, RK, Demontis, D, Mattheisen, M, Lee, SH, Robinson, E, Brikell, I, Ghirardi, L, Larsson, H, Lichtenstein, P, Eriksson, N, 23andMe Research Team, Psychiatric Genomics Consortium: ADHD Subgroup, iPSYCH–Broad ADHD Workgroup, Werge, T, Mortensen, PB, Pedersen, MG, Mors, O, Nordentoft, M, Hougaard, DM, Bybjerg-Grauholm, J, Wray, NR, Franke, B, Faraone, SV, O’Donovan, MC, Thapar, A, Børglum, AD, Neale, BM, Albayrak, Özgür (Beitragende*r), Föcker, Manuel (Beitragende*r), Hebebrand, Johannes (Beitragende*r), Hinney, Anke (Beitragende*r), Oades, Robert D. (Beitragende*r), Scherag, Andre (Beitragende*r), and von Schimmelmann, Benno (Beitragende*r)

Subjects
Medizin
Abstract

Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98–1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11–1.18], p = 1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence.

Published
2018

28. Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA consortium

Author

Kong, XZ, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Canive, JM, Cannon, DM, Caparelli, EC, Castellanos, FX, Cavalleri, GL, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dale, A, Dannlowski, U, De Bruttopilo, SA, De Zeeuw, P, Deary, IJ, Delanty, N, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, J ; https://orcid.org/0000-0003-4014-4490, Garavan, H, Garcia, DDS, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, Hernández, MDCV, Mitchell, Philip ; https://orcid.org/0000-0002-7954-5235, Roberts, Gloria ; https://orcid.org/0000-0002-1966-5120, Lenroot, Rhoshel ; https://orcid.org/0000-0002-0949-5121, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Wen, Wei ; https://orcid.org/0000-0003-2753-3870, Fisher, Simon, Kong, XZ, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H ; https://orcid.org/0000-0001-9487-6617, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Canive, JM, Cannon, DM, Caparelli, EC, Castellanos, FX, Cavalleri, GL, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dale, A, Dannlowski, U, De Bruttopilo, SA, De Zeeuw, P, Deary, IJ, Delanty, N, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, J ; https://orcid.org/0000-0003-4014-4490, Garavan, H, Garcia, DDS, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, Hernández, MDCV, Mitchell, Philip ; https://orcid.org/0000-0002-7954-5235, Roberts, Gloria ; https://orcid.org/0000-0002-1966-5120, Lenroot, Rhoshel ; https://orcid.org/0000-0002-0949-5121, Sachdev, Perminder ; https://orcid.org/0000-0002-9595-3220, Wen, Wei ; https://orcid.org/0000-0003-2753-3870, and Fisher, Simon

Abstract

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

Published
2018

29. Genetics of aggressive behavior: An overview

Author

Veroude K, Zhang-James Y, Fernandez N, Bakker MJ, Cormand B, and Faraone SV

Subjects
GWAS, aggression, candidate genes, genetics, mutations, twin
Abstract

The Research Domain Criteria (RDoC) address three types of aggression: frustrative non-reward, defensive aggression and offensive/proactive aggression. This review sought to present the evidence for genetic underpinnings of aggression and to determine to what degree prior studies have examined phenotypes that fit into the RDoC framework. Although the constructs of defensive and offensive aggression have been widely used in the animal genetics literature, the human literature is mostly agnostic with regard to all the RDoC constructs. We know from twin studies that about half the variance in behavior may be explained by genetic risk factors. This is true for both dimensional, trait-like, measures of aggression and categorical definitions of psychopathology. The non-shared environment seems to have a moderate influence with the effects of shared environment being unclear. Human molecular genetic studies of aggression are in an early stage. The most promising candidates are in the dopaminergic and serotonergic systems along with hormonal regulators. Genome-wide association studies have not yet achieved genome-wide significance, but current samples are too small to detect variants having the small effects one would expect for a complex disorder. The strongest molecular evidence for a genetic basis for aggression comes from animal models comparing aggressive and non-aggressive strains or documenting the effects of gene knockouts. Although we have learned much from these prior studies, future studies should improve the measurement of aggression by using a systematic method of measurement such as that proposed by the RDoC initiative.

Published
2016

31. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Author

O’dushlaine, C, Rossin, L, Lee, PH, Duncan, L, Parikshak, NN, Newhouse, S, Ripke, S, Neale, BM, Purcell, SM, Posthuma, D, Nurnberger, JI, Lee, SH, Faraone, SV, Perlis, RH, Mowry, BJ, Thapar, A, Goddard, ME, Witte, JS, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, OA, Anjorin, A, Anney, R, Anttila, V, Arking, DE, Asherson, P, Azevedo, MH, Backlund, L, Badner, JA, Bailey, AJ, Banaschewski, T, Barchas, JD, Barnes, MR, Barrett, TB, Bass, N, Battaglia, A, Bauer, M, Bayés, M, Bellivier, F, Bergen, SE, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, EB, Black, DW, Blackwood, DHR, Bloss, CS, Boehnke, M, Boomsma, DI, Breuer, R, Bruggeman, R, Cormican, P, Buccola, NG, Buitelaar, JK, Bunney, WE, Buxbaum, JD, Byerley, WF, Byrne, EM, Caesar, S, Cahn, W, Cantor, RM, Casas, M, Chakravarti, A, Chambert, K, Choudhury, K, and Cichon, S

Abstract

© 2015 Nature America, Inc. All rights reserved. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

Published
2015
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33. Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3

Author

Williams, NM, Franke, B, Mick, E, Anney, RJL, Freitag, CM, Gill, M, Thapar, A, O'Donovan, MC, Owen, MJ, Holmans, P, Kent, L, Middleton, F, Zhang-James, Y, Liu, L, Meyer, J, Nguyen, TT, Romanos, J, Romanos, M, Seitz, C, Renner, TJ, Walitza, S, Warnke, A, Palmason, H, Buitelaar, J, Rommelse, N, Vasquez, AA, Hawi, Z, Langley, K, Sergeant, J, Steinhausen, HC, Roeyers, Herbert, Biederman, J, Zaharieva, I, Hakonarson, H, Elia, J, Lionel, AC, Crosbie, J, Marshall, CR, Schachar, R, Scherer, SW, Todorov, A, Smalley, SL, Loo, S, Nelson, S, Shtir, C, Asherson, P, Reif, A, Lesch, KP, Faraone, SV, Psychiatrie & Neuropsychologie, Farmacologie en Toxicologie, and RS: CARIM School for Cardiovascular Diseases

Subjects
CANDIDATE GENE, Canada, Adolescent, alpha7 Nicotinic Acetylcholine Receptor, Genetics and epigenetic pathways of disease [NCMLS 6], DCN MP - Plasticity and memory, Gene Dosage, Inheritance Patterns, Social Sciences, ASSOCIATION SCAN, DCN PAC - Perception action and control, Nicotinic, MICRODUPLICATIONS, Medical and Health Sciences, Mental health [NCEBP 9], Fluorescence, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], MOLECULAR-GENETICS, SCHIZOPHRENIA, Receptors, mental disorders, ADHD, Humans, Genetic Predisposition to Disease, DCN PAC - Perception action and control NCEBP 9 - Mental health, Polymorphism, Child, Preschool, QH426, CHROMOSOMAL DELETIONS, In Situ Hybridization, Psychiatry, AUTISM SPECTRUM DISORDER, Psychology and Cognitive Sciences, Single Nucleotide, Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3], R1, United States, United Kingdom, NICOTINIC RECEPTOR, Causality, Segmental Duplications, Attention Deficit Disorder with Hyperactivity, Genomic, RC0321, Female, DEFICIT/HYPERACTIVITY DISORDER, Genome-Wide Association Study
Abstract

Item does not contain fulltext OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology. METHOD: The authors performed a genome-wide analysis of large, rare CNVs (100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder. CONCLUSIONS: These findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5-3.6), this locus could be an important contributor to ADHD etiology. 01 februari 2012

Published
2012
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34. Risk Factors for Borderline Personality Disorder in Treatment Seeking Patients with a Substance Use Disorder: An International Multicenter Study

Author

Wapp, M, van de Glind, G, van Emmerik-van Oortmerssen, K, Dom, G, Verspreet, S, Carpentier, PJ, Ramos-Quiroga, JA, Skutle, A, Bu, E-T, Franck, J, Konstenius, M, Kaye, S, Demetrovics, Z, Barta, C, Fatseas, M, Auriacombe, M, Johnson, B, Faraone, SV, Levin, FR, Allsop, S, Carruthers, S, Schoevers, RA, Koeter, MWJ, van den Brink, W, Moggi, F, Wapp, M, van de Glind, G, van Emmerik-van Oortmerssen, K, Dom, G, Verspreet, S, Carpentier, PJ, Ramos-Quiroga, JA, Skutle, A, Bu, E-T, Franck, J, Konstenius, M, Kaye, S, Demetrovics, Z, Barta, C, Fatseas, M, Auriacombe, M, Johnson, B, Faraone, SV, Levin, FR, Allsop, S, Carruthers, S, Schoevers, RA, Koeter, MWJ, van den Brink, W, and Moggi, F

Abstract

Borderline personality disorder (BPD) and substance use disorders (SUDs) often co-occur, partly because they share risk factors. In this international multicenter study, risk factors for BPD were examined for SUD patients. In total, 1,205 patients were comprehensively examined by standardized interviews and questionnaires on psychiatric diagnosis and risk factors, and it was found that 1,033 (85.7%) had SUDs without BPD (SUD) and 172 (14.3%) had SUD with BPD (SUD + BPD). SUD + BPD patients were significantly younger, more often females and more often diagnosed with comorbid adult attention deficit/hyperactivity disorder. SUD + BPD patients did not differ from SUD patients on most risk factors typical for SUD such as maternal use of drugs during pregnancy or parents having any SUD. However, SUD + BPD patients did have a higher risk of having experienced emotional and physical abuse, neglect, or family violence in childhood compared to SUD patients, suggesting that child abuse and family violence are BPD-specific risk factors in patients with SUDs.

Published
2015

38. Severity of the aggression/anxiety-depression/attention child behavior checklist profile discriminates between different levels of deficits in emotional regulation in youth with attention-deficit hyperactivity disorder.

Author

Biederman J, Petty CR, Day H, Goldin RL, Spencer T, Faraone SV, Surman CB, Wozniak J, Biederman, Joseph, Petty, Carter R, Day, Helen, Goldin, Rachel L, Spencer, Thomas, Faraone, Stephen V, Surman, Craig B H, and Wozniak, Janet

Published
2012
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42. Interpreting ADHD rating scale scores: linking ADHD rating scale scores and CGI levels in two randomized controlled trials of lisdexamfetamine dimesylate in ADHD.

Author

Goodman D, Faraone SV, Adler LA, Dirks B, Hamdani M, and Weisler R

Abstract

Objective: To provide additional understanding of the clinical significance of Attention-Deficit/Hyperactivity Disorder Rating Scale, Version IV (ADHD-RS-IV) total and change scores in relation to Clinical Global Impressions-Severity or -Improvement (CGI-S/-I) levels. Methods: Using two similarly designed pivotal trials of lisdexamfetamine dimesylate (Vyvanse, Shire US Inc), equipementile linking was used to identify scores on the ADHD-RS-IV and CGI that have the same percentile rank. Results: As assessed by CGI-S levels, moderately, markedly, severely, and extremely ill adults had mean (SD) baseline ADHD-RS-IV scores of 36.2 (4.9), 42.1 (6.1), 45.4 (5.1), and 53.0, respectively, A similar relationship was observed in children. At endpoint, children categorized as minimally, much. or very much improved by CGI-I demonstrated mean (SD) ADHD-RS-IV changes from baseline of -9.9 (6.8), -25.5 (7.2). and -33.2 (9.3), respectively, Adults demonstrated a similar relationship between ADHD-RS-IV change scores and CGI-I ratings. Based on equipercentile link function, a change from baseline in ADHD-RS-IV total score of 10-15 points or 25% to 30% corresponded to a change of 1 level in CGI-I score. Conclusion: This analysis makes possible the establishment of a clinical impression of severity of illness from total ADHD-RS-IV scores and may facilitate the clinical interpretation of improvement of ADHD-RS-IV change scores. [ABSTRACT FROM AUTHOR]

Published
2010

43. Effects of lisdexamfetamine dimesylate treatment for ADHD on growth.

Author

Faraone SV, Spencer TJ, Kollins SH, Glatt SJ, Faraone, Stephen V, Spencer, Thomas J, Kollins, Scott H, and Glatt, Stephen J

Abstract

Objective: To complete an exploratory uncontrolled study of the effects of lisdexamfetamine dimesylate (LDX) on growth of children treated for attention-deficit/hyperactivity disorder (ADHD).Method: Height, weight, and body mass index (BMI) from 281 children ages 6 to 13 years from longitudinal assessments up to 15 months were compared to norms from the Centers for Disease Control.Results: At study entry, children were taller and heavier than average. Growth delays were largest for weight and BMI, and there was a 13 percentile point decrease in height. Children continued to grow in terms of height while treated with LDX; we found no increase in raw weight or BMI during the study period. LDX treatment was significantly associated with diminished gains in height, weight, and BMI compared to levels that would be expected based on age-appropriate standards from the Centers for Disease Control. Growth delays were greatest for the heaviest and tallest children, for those who had not previously received stimulant therapy, and for those with a greater cumulative exposure to LDX. More work is needed to determine effects on ultimate adult height.Conclusions: Consistent with prior studies of stimulants, treatment with LDX leads to statistically significant reductions in expected height, weight, and BMI. Growth of patients with ADHD treated with LDX should be closely monitored and corrective action taken should growth delays be observed. [ABSTRACT FROM AUTHOR]

Published
2010
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46. Using Meta-analysis to Compare the Efficacy of Medications for Attention-Deficit/Hyperactivity Disorder in Youths.

Author

Faraone SV and Faraone, Stephen V

Abstract

Medications used to treat attention-deficit/hyperactivity disorder (ADHD) have been well researched, but comparisons among agents are hindered by the absence of head-to-head clinical trials. By using meta-analysis, we sought to compare the efficacy of these medications for the symptoms of ADHD. We analyzed published literature on the pharmacotherapy of ADHD to describe the variability of drug-placebo effect sizes and conducted a literature search to identify double-blind, placebo-controlled studies of youths with ADHD that were published after 1979. Meta-analysis regression was used to assess the influence of the medication type on drug effects. We also assessed for publication bias.Thirty-two trials met our criteria and were included in this meta-analysis. These trials involved 16 drugs using 20 different outcome measures of ADHD behaviors. The effect sizes for immediate-release stimulants and long-acting stimulants were similar and were greater than the effect sizes for non-stimulants. There was no evidence of publication bias.Although nearly all of the ADHD medications had significant effects, we found substantial variability. When translated into the costs of treating large numbers of patients, these effect sizes have implications for formulary medication choices. [ABSTRACT FROM AUTHOR]

Published
2009

47. Estimating the size of treatment effects: moving beyond P values.

Author

McGough JJ and Faraone SV

Abstract

Objective: To increase understanding of effect size calculations among clinicians who over-rely on interpretations of P values in their assessment of the medical literature. Design: We review five methods of calculating effect sizes: Cohen's d (also known as the standardized mean difference)-used in studies that report efficacy in terms of a continuous measurement and calculated from two mean values and their standard deviations; relative risk-the ratio of patients responding to treatment divided by the ratio of patients responding to a different treatment (or placebo), which is particularly useful in prospective clinical trials to assess differences between treatments; odds ratio- used to interpret results of retrospective case-control studies and provide estimates of the risk of side effects by comparing the probability (odds) of an outcome occurring in the presence or absence of a specified condition; number needed to treat-the number of subjects one would expect to treat with agent A to have one more success (or one less failure) than if the same number were treated with agent B; and area under the curve (also known as the drug-placebo response curve)-a six-step process that can be used to assess the effects of medication on both worsening and improvement and the probability that a medication-treated subject will have a better outcome than a placebo-treated subject. Conclusion: Effect size statistics provide a better estimate of treatment effects than P values alone. [ABSTRACT FROM AUTHOR]

Published
2009

48. Sleep in children with attention-deficit/hyperactivity disorder: meta-analysis of subjective and objective studies.

Author

Cortese S, Faraone SV, Konofal E, Lecendreux M, Cortese, Samuele, Faraone, Stephen V, Konofal, Eric, and Lecendreux, Michel

Abstract

Objective: To perform a meta-analysis of subjective (i.e., based on questionnaires) and objective (i.e., using polysomnography or actigraphy) studies comparing sleep in children with attention-deficit/hyperactivity disorder (ADHD) versus controls.Method: We searched for subjective and objective sleep studies (1987-2008) in children with ADHD (diagnosed according to standardized criteria). Studies including subjects pharmacologically treated or with comorbid anxiety/depressive disorders were excluded.Results: Sixteen studies, providing 9 subjective and 15 objective parameters and including a total pooled sample of 722 children with ADHD versus 638 controls, were retained. With regard to subjective items, the meta-analysis indicated that children with ADHD had significantly higher bedtime resistance (z = 6.94, p <.001), more sleep onset difficulties (z = 9.38, p <.001), night awakenings (z = 2.15, p =.031), difficulties with morning awakenings (z = 5.19, p <.001), sleep disordered breathing (z = 2.05, p =.040), and daytime sleepiness (z = 1.96, p =.050) compared with the controls. As for objective parameters, sleep onset latency (on actigraphy), the number of stage shifts/hour sleep, and the apnea-hypopnea index were significantly higher in the children with ADHD compared with the controls (z = 3.44, p =.001; z = 2.43, p =.015; z = 3.47, p =.001, respectively). The children with ADHD also had significantly lower sleep efficiency on polysomnography (z = 2.26, p =.024), true sleep time on actigraphy (z = 2.85, p =.004), and average times to fall asleep for the Multiple Sleep Latency Test (z = 6.37, p <.001) than the controls.Conclusions: The children with ADHD are significantly more impaired than the controls in most of the subjective and some of the objective sleep measures. These results lay the groundwork for future evidence-based guidelines on the management of sleep disturbances in children with ADHD. [ABSTRACT FROM AUTHOR]

Published
2009
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49. Parsing the associations between prenatal exposure to nicotine and offspring psychopathology in a nonreferred sample.

Author

Biederman J, Monuteaux MC, Faraone SV, and Mick E

Abstract

PURPOSE: Several studies have suggested an association between maternal smoking during pregnancy and both attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) in the offspring of women who smoke during pregnancy. However, it is unclear whether one or both of the documented links are spurious, given the considerable comorbidity between these disorders. The main aim of this study was to disentangle the association between maternal smoking during pregnancy with psychopathological outcomes, adjusting for possible confounders. METHODS: Two large, identically designed, longitudinal, case-control family studies of male and female probands with and without ADHD were combined. We used data from the nonreferred siblings of the probands from both studies (n = 536). All subjects were blindly assessed with structured diagnostic interviews. Logistic regression analysis was used to determine the adjusted effect of exposure to maternal smoking during pregnancy. RESULTS: Among all siblings, maternal smoking during pregnancy was significantly associated with ADHD, independent of CD and other covariates. In contrast, maternal smoking during pregnancy was a risk factor for CD only in siblings of control probands, after adjusting for covariates. CONCLUSIONS: These results support the hypothesis that maternal smoking during pregnancy is a risk factor for both ADHD and CD, independently of each other. However, the risk for CD appears to be conditional on family risk status. [ABSTRACT FROM AUTHOR]

Published
2009
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