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2. Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Author

Trubetskoy, Vassily, Pardiñas, Antonio F, Qi, Ting, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Bigdeli, Tim B, Bryois, Julien, Chen, Chia-Yen, Dennison, Charlotte A, Hall, Lynsey S, Lam, Max, Watanabe, Kyoko, Frei, Oleksandr, Ge, Tian, Harwood, Janet C, Koopmans, Frank, Magnusson, Sigurdur, Richards, Alexander L, Sidorenko, Julia, Wu, Yang, Zeng, Jian, Grove, Jakob, Kim, Minsoo, Li, Zhiqiang, Voloudakis, Georgios, Zhang, Wen, Adams, Mark, Agartz, Ingrid, Atkinson, Elizabeth G, Agerbo, Esben, Al Eissa, Mariam, Albus, Margot, Alexander, Madeline, Alizadeh, Behrooz Z, Alptekin, Köksal, Als, Thomas D, Amin, Farooq, Arolt, Volker, Arrojo, Manuel, Athanasiu, Lavinia, Azevedo, Maria Helena, Bacanu, Silviu A, Bass, Nicholas J, Begemann, Martin, Belliveau, Richard A, Bene, Judit, Benyamin, Beben, Bergen, Sarah E, Blasi, Giuseppe, Bobes, Julio, Bonassi, Stefano, Braun, Alice, Bressan, Rodrigo Affonseca, Bromet, Evelyn J, Bruggeman, Richard, Buckley, Peter F, Buckner, Randy L, Bybjerg-Grauholm, Jonas, Cahn, Wiepke, Cairns, Murray J, Calkins, Monica E, Carr, Vaughan J, Castle, David, Catts, Stanley V, Chambert, Kimberley D, Chan, Raymond CK, Chaumette, Boris, Cheng, Wei, Cheung, Eric FC, Chong, Siow Ann, Cohen, David, Consoli, Angèle, Cordeiro, Quirino, Costas, Javier, Curtis, Charles, Davidson, Michael, Davis, Kenneth L, de Haan, Lieuwe, Degenhardt, Franziska, DeLisi, Lynn E, Demontis, Ditte, Dickerson, Faith, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Duan, Jubao, Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G, Fañanás, Lourdes, Faraone, Stephen V, Fiorentino, Alessia, Forstner, Andreas, Frank, Josef, Freimer, Nelson B, Fromer, Menachem, Frustaci, Alessandra, Gadelha, Ary, Genovese, Giulio, and Gershon, Elliot S

Subjects
Brain Disorders, Human Genome, Mental Health, Schizophrenia, Serious Mental Illness, Biotechnology, Neurosciences, Genetics, Aetiology, 2.1 Biological and endogenous factors, Alleles, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Polymorphism, Single Nucleotide, Indonesia Schizophrenia Consortium, PsychENCODE, Psychosis Endophenotypes International Consortium, SynGO Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, General Science & Technology
Abstract

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

Published
2022

3. Rare coding variants in ten genes confer substantial risk for schizophrenia.

Author

Singh, Tarjinder, Poterba, Timothy, Curtis, David, Akil, Huda, Al Eissa, Mariam, Barchas, Jack D, Bass, Nicholas, Bigdeli, Tim B, Breen, Gerome, Bromet, Evelyn J, Buckley, Peter F, Bunney, William E, Bybjerg-Grauholm, Jonas, Byerley, William F, Chapman, Sinéad B, Chen, Wei J, Churchhouse, Claire, Craddock, Nicholas, Cusick, Caroline M, DeLisi, Lynn, Dodge, Sheila, Escamilla, Michael A, Eskelinen, Saana, Fanous, Ayman H, Faraone, Stephen V, Fiorentino, Alessia, Francioli, Laurent, Gabriel, Stacey B, Gage, Diane, Gagliano Taliun, Sarah A, Ganna, Andrea, Genovese, Giulio, Glahn, David C, Grove, Jakob, Hall, Mei-Hua, Hämäläinen, Eija, Heyne, Henrike O, Holi, Matti, Hougaard, David M, Howrigan, Daniel P, Huang, Hailiang, Hwu, Hai-Gwo, Kahn, René S, Kang, Hyun Min, Karczewski, Konrad J, Kirov, George, Knowles, James A, Lee, Francis S, Lehrer, Douglas S, Lescai, Francesco, Malaspina, Dolores, Marder, Stephen R, McCarroll, Steven A, McIntosh, Andrew M, Medeiros, Helena, Milani, Lili, Morley, Christopher P, Morris, Derek W, Mortensen, Preben Bo, Myers, Richard M, Nordentoft, Merete, O'Brien, Niamh L, Olivares, Ana Maria, Ongur, Dost, Ouwehand, Willem H, Palmer, Duncan S, Paunio, Tiina, Quested, Digby, Rapaport, Mark H, Rees, Elliott, Rollins, Brandi, Satterstrom, F Kyle, Schatzberg, Alan, Scolnick, Edward, Scott, Laura J, Sharp, Sally I, Sklar, Pamela, Smoller, Jordan W, Sobell, Janet L, Solomonson, Matthew, Stahl, Eli A, Stevens, Christine R, Suvisaari, Jaana, Tiao, Grace, Watson, Stanley J, Watts, Nicholas A, Blackwood, Douglas H, Børglum, Anders D, Cohen, Bruce M, Corvin, Aiden P, Esko, Tõnu, Freimer, Nelson B, Glatt, Stephen J, Hultman, Christina M, McQuillin, Andrew, Palotie, Aarno, Pato, Carlos N, Pato, Michele T, Pulver, Ann E, and St Clair, David

Subjects
Humans, Genetic Predisposition to Disease, Receptors, N-Methyl-D-Aspartate, Case-Control Studies, Schizophrenia, Mutation, Exome, Neurodevelopmental Disorders, Human Genome, Biotechnology, Mental Health, Neurosciences, Brain Disorders, Genetics, Serious Mental Illness, Aetiology, 2.1 Biological and endogenous factors, Mental health, Neurological, General Science & Technology
Abstract

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P

Published
2022

4. Age of onset and cumulative risk of mental disorders: a cross-national analysis of population surveys from 29 countries

Author

Aguilar-Gaxiola, Sergio, Al-Hamzawi, Ali, Alonso, Jordi, Altwaijri, Yasmin A., Andrade, Laura Helena, Atwoli, Lukoye, Benjet, Corina, Bromet, Evelyn J., Bruffaerts, Ronny, Bunting, Brendan, Caldas-de-Almeida, José Miguel, Cardoso, Graça, Chardoul, Stephanie, Cía, Alfredo H., Degenhardt, Louisa, De Girolamo, Giovanni, Gureje, Oye, Haro, Josep Maria, Harris, Meredith G., Hinkov, Hristo, Hu, Chi-yi, De Jonge, Peter, Karam, Aimee N., Karam, Elie G., Karam, Georges, Kazdin, Alan E., Kawakami, Norito, Kessler, Ronald C., Kiejna, Andrzej, Kovess-Masfety, Viviane, McGrath, John J., Medina-Mora, Maria Elena, Moskalewicz, Jacek, Navarro-Mateu, Fernando, Nishi, Daisuke, Piazza, Marina, Posada-Villa, José, Scott, Kate M., Stagnaro, Juan Carlos, Stein, Dan J., Ten Have, Margreet, Torres, Yolanda, Viana, Maria Carmen, Vigo, Daniel V., Vladescu, Cristian, Williams, David R., Woodruff, Peter, Wojtyniak, Bogdan, Xavier, Miguel, Zaslavsky, Alan M., McGrath, John J, Altwaijri, Yasmin, Andrade, Laura H, Bromet, Evelyn J, de Almeida, José Miguel Caldas, Chiu, Wai Tat, Demler, Olga V, Ferry, Finola, Karam, Elie G, Khaled, Salma M, Magno, Marta, Plana-Ripoll, Oleguer, Rapsey, Charlene, Sampson, Nancy A, Stein, Dan J, ten Have, Margreet, Woodruff, Peter W, Zarkov, Zahari, and Kessler, Ronald C

Published
2023
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6. Characterisation of age and polarity at onset in bipolar disorder.

Author

Kalman, Janos L, Olde Loohuis, Loes M, Vreeker, Annabel, McQuillin, Andrew, Stahl, Eli A, Ruderfer, Douglas, Grigoroiu-Serbanescu, Maria, Panagiotaropoulou, Georgia, Ripke, Stephan, Bigdeli, Tim B, Stein, Frederike, Meller, Tina, Meinert, Susanne, Pelin, Helena, Streit, Fabian, Papiol, Sergi, Adams, Mark J, Adolfsson, Rolf, Adorjan, Kristina, Agartz, Ingrid, Aminoff, Sofie R, Anderson-Schmidt, Heike, Andreassen, Ole A, Ardau, Raffaella, Aubry, Jean-Michel, Balaban, Ceylan, Bass, Nicholas, Baune, Bernhard T, Bellivier, Frank, Benabarre, Antoni, Bengesser, Susanne, Berrettini, Wade H, Boks, Marco P, Bromet, Evelyn J, Brosch, Katharina, Budde, Monika, Byerley, William, Cervantes, Pablo, Chillotti, Catina, Cichon, Sven, Clark, Scott R, Comes, Ashley L, Corvin, Aiden, Coryell, William, Craddock, Nick, Craig, David W, Croarkin, Paul E, Cruceanu, Cristiana, Czerski, Piotr M, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, Del Zompo, Maria, DePaulo, J Raymond, Djurovic, Srdjan, Edenberg, Howard J, Eissa, Mariam Al, Elvsåshagen, Torbjørn, Etain, Bruno, Fanous, Ayman H, Fellendorf, Frederike, Fiorentino, Alessia, Forstner, Andreas J, Frye, Mark A, Fullerton, Janice M, Gade, Katrin, Garnham, Julie, Gershon, Elliot, Gill, Michael, Goes, Fernando S, Gordon-Smith, Katherine, Grof, Paul, Guzman-Parra, Jose, Hahn, Tim, Hasler, Roland, Heilbronner, Maria, Heilbronner, Urs, Jamain, Stephane, Jimenez, Esther, Jones, Ian, Jones, Lisa, Jonsson, Lina, Kahn, Rene S, Kelsoe, John R, Kennedy, James L, Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Klöhn-Saghatolislam, Farah, Knowles, James A, Kranz, Thorsten M, Lagerberg, Trine Vik, Landen, Mikael, Lawson, William B, Leboyer, Marion, Li, Qingqin S, Maj, Mario, Malaspina, Dolores, Manchia, Mirko, and Mayoral, Fermin

Subjects
Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics, Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Humans, Bipolar Disorder, Depressive Disorder, Major, Age of Onset, Multifactorial Inheritance, Genome-Wide Association Study, Autism Spectrum Disorder, Bipolar disorder, GWAS, age at onset, polarity at onset, polygenic score, Genetics, Mental Health, Prevention, Brain Disorders, Serious Mental Illness, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundStudying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = -0.34 years, s.e. = 0.08), major depression (β = -0.34 years, s.e. = 0.08), schizophrenia (β = -0.39 years, s.e. = 0.08), and educational attainment (β = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Published
2021

7. World Trade Center responders in their own words: Predicting PTSD symptom trajectories with AI-based language analyses of interviews

Author

Son, Youngseo, Clouston, Sean A. P., Kotov, Roman, Eichstaedt, Johannes C., Bromet, Evelyn J., Luft, Benjamin J., and Schwartz, H Andrew

Subjects
Computer Science - Computation and Language
Abstract

Background: Oral histories from 9/11 responders to the World Trade Center (WTC) attacks provide rich narratives about distress and resilience. Artificial Intelligence (AI) models promise to detect psychopathology in natural language, but they have been evaluated primarily in non-clinical settings using social media. This study sought to test the ability of AI-based language assessments to predict PTSD symptom trajectories among responders. Methods: Participants were 124 responders whose health was monitored at the Stony Brook WTC Health and Wellness Program who completed oral history interviews about their initial WTC experiences. PTSD symptom severity was measured longitudinally using the PTSD Checklist (PCL) for up to 7 years post-interview. AI-based indicators were computed for depression, anxiety, neuroticism, and extraversion along with dictionary-based measures of linguistic and interpersonal style. Linear regression and multilevel models estimated associations of AI indicators with concurrent and subsequent PTSD symptom severity (significance adjusted by false discovery rate). Results: Cross-sectionally, greater depressive language (beta=0.32; p=0.043) and first-person singular usage (beta=0.31; p=0.044) were associated with increased symptom severity. Longitudinally, anxious language predicted future worsening in PCL scores (beta=0.31; p=0.031), whereas first-person plural usage (beta=-0.37; p=0.007) and longer words usage (beta=-0.36; p=0.007) predicted improvement. Conclusions: This is the first study to demonstrate the value of AI in understanding PTSD in a vulnerable population. Future studies should extend this application to other trauma exposures and to other demographic groups, especially under-represented minorities., Comment: 20 pages, 2 figures

Published
2020

8. Pathways from performance monitoring to negative symptoms and functional outcomes in psychotic disorders.

Author

Foti, Dan, Perlman, Greg, Bromet, Evelyn, Harvey, Philip, Hajcak, Greg, Mathalon, Daniel, and Kotov, Roman

Subjects
Cognition, ERN, ERP, executive function, psychosis, schizophrenia, Humans, Cross-Sectional Studies, Psychomotor Performance, Psychotic Disorders, Executive Function, Cohort Studies
Abstract

BACKGROUND: Performance monitoring entails rapid error detection to maintain task performance. Impaired performance monitoring is a candidate pathophysiological process in psychotic disorders, which may explain the broader deficit in executive function and its known associations with negative symptoms and poor functioning. The current study models cross-sectional pathways bridging neurophysiological measures of performance monitoring with executive function, symptoms, and functioning. METHODS: Data were from the 20-year assessment of the Suffolk County Mental Health Project. Individuals with psychotic disorders (N = 181) were originally recruited from inpatient psychiatric facilities. Data were also collected from a geographically and demographically matched group with no psychosis history (N = 242). Neural measures were the error-related negativity (ERN) and error positivity (Pe). Structural equation modeling tested mediation pathways. RESULTS: Blunted ERN and Pe in the clinical cohort related to impaired executive function (r = 0.26-0.35), negative symptom severity (r = 0.17-0.25), and poor real-world functioning (r = 0.17-0.19). Associations with executive function were consistent across groups. Multiple potential pathways were identified in the clinical cohort: reduced ERN to inexpressivity was mediated by executive function (β = 0.10); reduced Pe to global functioning was mediated by executive function and avolition (β = 0.10). CONCLUSIONS: This supports a transdiagnostic model of psychotic disorders by which poor performance monitoring contributes to impaired executive function, which contributes to negative symptoms and poor real-world functioning. If supported by future longitudinal research, these pathways could inform the development of targeted interventions to address cognitive and functional deficits that are central to psychotic disorders.

Published
2021

9. Predicting Long-Term Outcomes in First-Admission Psychosis: Does the Hierarchical Taxonomy of Psychopathology Aid DSM in Prognostication?

Author

Martin, Elizabeth A, Jonas, Katherine G, Lian, Wenxuan, Foti, Dan, Donaldson, Kayla R, Bromet, Evelyn J, and Kotov, Roman

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Schizophrenia, Brain Disorders, Mental Health, Behavioral and Social Science, Serious Mental Illness, Clinical Research, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Good Health and Well Being, Adolescent, Adult, Affective Disorders, Psychotic, Bipolar Disorder, Classification, Cognitive Dysfunction, Depressive Disorder, Major, Diagnostic and Statistical Manual of Mental Disorders, Female, Humans, Longitudinal Studies, Male, Middle Aged, Outcome Assessment, Health Care, Prognosis, Psychoses, Substance-Induced, Psychotic Disorders, Young Adult, nosology, DSM, schizophrenia, psychotic disorders, thought disorder, classification, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences
Abstract

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical, dimensional model of psychological symptoms and functioning. Its goals are to augment the use and address the limitations of traditional diagnoses, such as arbitrary thresholds of severity, within-disorder heterogeneity, and low reliability. HiTOP has made inroads to addressing these problems, but its prognostic validity is uncertain. The present study sought to test the prediction of long-term outcomes in psychotic disorders was improved when the HiTOP dimensional approach was considered along with traditional (ie, DSM) diagnoses. We analyzed data from the Suffolk County Mental Health Project (N = 316), an epidemiologic study of a first-admission psychosis cohort followed for 20 years. We compared 5 diagnostic groups (schizophrenia/schizoaffective, bipolar disorder with psychosis, major depressive disorder with psychosis, substance-induced psychosis, and other psychoses) and 5 dimensions derived from the HiTOP thought disorder spectrum (reality distortion, disorganization, inexpressivity, avolition, and functional impairment). Both nosologies predicted a significant amount of variance in most outcomes. However, except for cognitive functioning, HiTOP showed consistently greater predictive power across outcomes-it explained 1.7-fold more variance than diagnoses in psychiatric and physical health outcomes, 2.1-fold more variance in community functioning, and 3.4-fold more variance in neural responses. Even when controlling for diagnosis, HiTOP dimensions incrementally predicted almost all outcomes. These findings support a shift away from the exclusive use of categorical diagnoses and toward the incorporation of HiTOP dimensions for better prognostication and linkage with neurobiology.

Published
2021

14. Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR.

Author

Smith, Alicia K, Ratanatharathorn, Andrew, Maihofer, Adam X, Naviaux, Robert K, Aiello, Allison E, Amstadter, Ananda B, Ashley-Koch, Allison E, Baker, Dewleen G, Beckham, Jean C, Boks, Marco P, Bromet, Evelyn, Dennis, Michelle, Galea, Sandro, Garrett, Melanie E, Geuze, Elbert, Guffanti, Guia, Hauser, Michael A, Katrinli, Seyma, Kilaru, Varun, Kessler, Ronald C, Kimbrel, Nathan A, Koenen, Karestan C, Kuan, Pei-Fen, Li, Kefeng, Logue, Mark W, Lori, Adriana, Luft, Benjamin J, Miller, Mark W, Naviaux, Jane C, Nugent, Nicole R, Qin, Xuejun, Ressler, Kerry J, Risbrough, Victoria B, Rutten, Bart PF, Stein, Murray B, Ursano, Robert J, Vermetten, Eric, Vinkers, Christiaan H, Wang, Lin, Youssef, Nagy A, INTRuST Clinical Consortium, VA Mid-Atlantic MIRECC Workgroup, PGC PTSD Epigenetics Workgroup, Uddin, Monica, and Nievergelt, Caroline M

Subjects
INTRuST Clinical Consortium, VA Mid-Atlantic MIRECC Workgroup, PGC PTSD Epigenetics Workgroup, Humans, Wounds and Injuries, Kynurenine, Repressor Proteins, Case-Control Studies, Cohort Studies, Stress Disorders, Post-Traumatic, DNA Methylation, Epigenesis, Genetic, Military Personnel, Female, Male, Basic Helix-Loop-Helix Transcription Factors, Epigenome, Stress Disorders, Post-Traumatic, Epigenesis, Genetic
Abstract

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.

Published
2020

15. Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry

Author

Bigdeli, Tim B, Genovese, Giulio, Georgakopoulos, Penelope, Meyers, Jacquelyn L, Peterson, Roseann E, Iyegbe, Conrad O, Medeiros, Helena, Valderrama, Jorge, Achtyes, Eric D, Kotov, Roman, Stahl, Eli A, Abbott, Colony, Azevedo, Maria Helena, Belliveau, Richard A, Bevilacqua, Elizabeth, Bromet, Evelyn J, Byerley, William, Carvalho, Celia Barreto, Chapman, Sinéad B, DeLisi, Lynn E, Dumont, Ashley L, O’Dushlaine, Colm, Evgrafov, Oleg V, Fochtmann, Laura J, Gage, Diane, Kennedy, James L, Kinkead, Becky, Macedo, Antonio, Moran, Jennifer L, Morley, Christopher P, Dewan, Mantosh J, Nemesh, James, Perkins, Diana O, Purcell, Shaun M, Rakofsky, Jeffrey J, Scolnick, Edward M, Sklar, Brooke M, Sklar, Pamela, Smoller, Jordan W, Sullivan, Patrick F, Macciardi, Fabio, Marder, Stephen R, Gur, Ruben C, Gur, Raquel E, Braff, David L, Nicolini, Humberto, Escamilla, Michael A, Vawter, Marquis P, Sobell, Janet L, Malaspina, Dolores, Lehrer, Douglas S, Buckley, Peter F, Rapaport, Mark H, Knowles, James A, Fanous, Ayman H, Pato, Michele T, McCarroll, Steven A, and Pato, Carlos N

Subjects
Human Genome, Serious Mental Illness, Clinical Research, Schizophrenia, Brain Disorders, Genetics, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Black People, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Humans, Male, Polymorphism, Single Nucleotide, Consortium on the Genetics of Schizophrenia (COGS) Investigators, Genomic Psychiatry Cohort (GPC) Consortium, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke's R2 = 0.032; liability R2 = 0.017; P

Published
2020

16. The associations between traumatic experiences and subsequent onset of a substance use disorder: Findings from the World Health Organization World Mental Health surveys

Author

Aguilar-Gaxiola, Sergio, Al-Hamzawi, Ali, Al-Kaisy, Mohammed Salih, Alonso, Jordi, Altwaijri, Yasmin, Helena Andrade, Laura, Atwoli, Lukoye, Benjet, Corina, Borges, Guilherme, Bromet, Evelyn J., Bruffaerts, Ronny, Bunting, Brendan, Caldas-de-Almeida, Jose Miguel, Cardoso, Graça, Chatterji, Somnath, Cia, Alfredo H., Degenhardt, Louisa, Demyttenaere, Koen, Florescu, Silvia, Girolamo, Giovanni de, Gureje, Oye, Haro, Josep Maria, Harris, Meredith G., Hinkov, Hristo, Hu, Chi-yi, de Jonge, Peter, Karam, Aimee Nasser, Karam, Elie G., Kawakami, Norito, Kessler, Ronald C., Kiejna, Andrzej, Kovess-Masfety, Viviane, Lee, Sing, Lepine, Jean-Pierre, McGrath, John, Medina-Mora, Maria Elena, Mneimneh, Zeina, Moskalewicz, Jacek, Navarro-Mateu, Fernando, Piazza, Marina, Posada-Villa, Jose, Scott, Kate M., Slade, Tim, Stagnaro, Juan Carlos, Stein, Dan J., ten Have, Margreet, Torres, Yolanda, Viana, Maria Carmen, Vigo, Daniel V., Whiteford, Harvey, Williams, David R., Wojtyniak, Bogdan, Bharat, Chrianna, Glantz, Meyer D., de Girolamo, Giovanni, Karam, Georges, Makanjuola, Victor, Posada-Villa, José, Tachimori, Hisateru, and Tintle, Nathan

Published
2022
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18. Contribution of Rare Copy Number Variants to Bipolar Disorder Risk Is Limited to Schizoaffective Cases

Author

Charney, Alexander W, Stahl, Eli A, Green, Elaine K, Chen, Chia-Yen, Moran, Jennifer L, Chambert, Kimberly, Belliveau, Richard A, Forty, Liz, Gordon-Smith, Katherine, Lee, Phil H, Bromet, Evelyn J, Buckley, Peter F, Escamilla, Michael A, Fanous, Ayman H, Fochtmann, Laura J, Lehrer, Douglas S, Malaspina, Dolores, Marder, Stephen R, Morley, Christopher P, Nicolini, Humberto, Perkins, Diana O, Rakofsky, Jeffrey J, Rapaport, Mark H, Medeiros, Helena, Sobell, Janet L, Backlund, Lena, Bergen, Sarah E, Juréus, Anders, Schalling, Martin, Lichtenstein, Paul, Knowles, James A, Burdick, Katherine E, Jones, Ian, Jones, Lisa A, Hultman, Christina M, Perlis, Roy, Purcell, Shaun M, McCarroll, Steven A, Pato, Carlos N, Pato, Michele T, Di Florio, Ariana, Craddock, Nick, Landén, Mikael, Smoller, Jordan W, Ruderfer, Douglas M, and Sklar, Pamela

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Genetics, Serious Mental Illness, Bipolar Disorder, Mental Health, Prevention, Brain Disorders, Schizophrenia, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Case-Control Studies, Cohort Studies, DNA Copy Number Variations, Gene Duplication, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Psychotic Disorders, Bipolar disorder, Copy number variant, Polygenic risk score, Rare variant burden, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences, Psychology
Abstract

BackgroundGenetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.MethodsRare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.ResultsCNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p = .001), BD I (p = .0003), and BD II (p = .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p = .0007, PRS p = .004), and BD I without psychosis (CNV p = .0004, PRS p = 3.9 × 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .005) but not CNV burden.ConclusionsCNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.

Published
2019

19. Cognitive impairment and World Trade Centre-related exposures

Author

Clouston, Sean A. P., Hall, Charles B., Kritikos, Minos, Bennett, David A., DeKosky, Steven, Edwards, Jerri, Finch, Caleb, Kreisl, William C., Mielke, Michelle, Peskind, Elaine R., Raskind, Murray, Richards, Marcus, Sloan, Richard P., Spiro, III, Avron, Vasdev, Neil, Brackbill, Robert, Farfel, Mark, Horton, Megan, Lowe, Sandra, Lucchini, Roberto G., Prezant, David, Reibman, Joan, Rosen, Rebecca, Seil, Kacie, Zeig-Owens, Rachel, Deri, Yael, Diminich, Erica D., Fausto, Bernadette A., Gandy, Sam, Sano, Mary, Bromet, Evelyn J., and Luft, Benjamin J.

Published
2022
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23. Cognitive impact of exposure to airborne particles captured by brain imaging

Author

Azmoun, Somaiyeh, primary, Diaz, Yenny Fariñas, additional, Tang, Cheuk Y., additional, Horton, Megan, additional, Clouston, Sean A.P., additional, Luft, Ben J., additional, Bromet, Evelyn J., additional, Gandy, Sam, additional, Placidi, Donatella, additional, Ambrosi, Claudia, additional, Mascaro, Lorella, additional, Rodella, Carlo, additional, Paghera, Barbara, additional, Gasparotti, Roberto, additional, Chambers, Jeremy W., additional, Tieu, Kim, additional, and Lucchini, Roberto G., additional

Published
2022
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24. Perceived helpfulness of treatment for alcohol use disorders: Findings from the World Mental Health Surveys

Author

Al-Hamzawi, Ali, Al-Kaisy, Mohammed Salih, Alonso, Jordi, Altwaijri, Yasmin A., Andrade, Laura Helena, Atwoli, Lukoye, Benjet, Corina, Borges, Guilherme, Bromet, Evelyn J., Bruffaerts, Ronny, Bunting, Brendan, Caldas-de-Almeida, Jose Miguel, Cardoso, Graça, Chatterji, Somnath, Cia, Alfredo H., Degenhardt, Louisa, Demyttenaere, Koen, Florescu, Silvia, Giovanni de Girolamo, Gureje, Oye, Haro, Josep Maria, Harris, Meredith G., Hinkov, Hristo, Hu, Chi-yi, Peter de Jonge, Karam, Aimee Nasser, Karam, Elie G., Karam, Georges, Kawakami, Norito, Kessler, Ronald C., Kiejna, Andrzej, Kovess-Masfety, Viviane, Lee, Sing, Lepine, Jean-Pierre, McGrath, John J., Medina-Mora, Maria Elena, Mneimneh, Zeina, Moskalewicz, Jacek, Navarro-Mateu, Fernando, Piazza, Marina, Posada-Villa, Jose, Scott, Kate M., Slade, Tim, Stagnaro, Juan Carlos, Stein, Dan J., Margreet ten Have, Torres, Yolanda, Viana, Maria Carmen, Vigo, Daniel V., Whiteford, Harvey, Williams, David R., Wojtyniak, Bogdan, Bharat, Chrianna, Chiu, Wai Tat, Kazdin, Alan E., Sampson, Nancy A., de Girolamo, Giovanni, Hu, Chiyi, Karam, Aimee N., Makanjuola, Victor, Posada-Villa, José, Rapsey, Charlene, Tachimori, Hisateru, ten Have, Margreet, and Zarkov, Zahari

Published
2021
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30. Epigenome‐wide association of PTSD from heterogeneous cohorts with a common multi‐site analysis pipeline

Author

Ratanatharathorn, Andrew, Boks, Marco P, Maihofer, Adam X, Aiello, Allison E, Amstadter, Ananda B, Ashley‐Koch, Allison E, Baker, Dewleen G, Beckham, Jean C, Bromet, Evelyn, Dennis, Michelle, Garrett, Melanie E, Geuze, Elbert, Guffanti, Guia, Hauser, Michael A, Kilaru, Varun, Kimbrel, Nathan A, Koenen, Karestan C, Kuan, Pei‐Fen, Logue, Mark W, Luft, Benjamin J, Miller, Mark W, Mitchell, Colter, Nugent, Nicole R, Ressler, Kerry J, Rutten, Bart PF, Stein, Murray B, Vermetten, Eric, Vinkers, Christiaan H, Youssef, Nagy A, Workgroup, VA Mid‐Atlantic MIRECC, Workgroup, PGC PTSD Epigenetics, Uddin, Monica, Nievergelt, Caroline M, and Smith, Alicia K

Subjects
Human Genome, Genetics, Post-Traumatic Stress Disorder (PTSD), Mental Health, Anxiety Disorders, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Adult, Cohort Studies, DNA Methylation, Epigenomics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Male, Middle Aged, Phenotype, Stress Disorders, Post-Traumatic, EWAS, meta-analysis, stress, trauma, VA Mid-Atlantic MIRECC Workgroup, PGC PTSD Epigenetics Workgroup, Clinical Sciences, Neurosciences
Abstract

Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N = 1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive comparable data over the cohorts for meta-analysis. We propose methods to deal with ancestry population stratification and type I error inflation and discuss the advantages and disadvantages of applying robust error estimates. To evaluate our pipeline, we report results from an epigenome-wide association study (EWAS) of age, which is a well-characterized phenotype with known epigenetic associations. Overall, while EWAS are highly complex and subject to similar challenges as genome-wide association studies (GWAS), we demonstrate that an epigenetic meta-analysis with a relatively modest sample size can be well-powered to identify epigenetic associations. Our pipeline can be used as a framework for consortium efforts for EWAS.

Published
2017

31. Long-Term Course of Remission and Recovery in Psychotic Disorders.

Author

Tramazzo, Sara, Lian, Wenxuan, Ajnakina, Olesya, Carlson, Gabrielle, Bromet, Evelyn, Kotov, Roman, and Jonas, Katherine

Subjects
PSYCHOSES, SCHIZOPHRENIA, LONG-term health care, PEOPLE with schizophrenia, AUDITORY neuropathy, DISEASE progression
Abstract

Objective: Understanding prognosis is critical to anticipating public health needs and providing care to individuals with psychotic disorders. However, the long-term course of remission and recovery remains unclear. In this study, the most common trajectories of illness course are described for a cohort of individuals followed for 25 years since first admission for psychosis. Methods: Participants are from the Suffolk County Mental Health Project, an epidemiological study of first-admission psychosis. Data for the present study was collected from six follow-ups, with 311 individuals assessed at the 25-year follow-up. Common patterns of remission and recovery were assessed in the baseline cohort of 591 individuals and the subsample from the 25-year follow up. Results: In the baseline cohort and the 25-year subsample, the most common trajectory for individuals with schizophrenia spectrum disorders was no remission and no recovery. Among individuals with other psychotic disorders, in both the baseline and 25-year cohorts, the modal pattern was one of intermittent remission and recovery. Individuals with other psychotic disorders were more likely to experience stable remission (15.1%) and stable recovery (21.1%), outcomes that were rare among individuals with schizophrenia spectrum disorders (0% and 0.6%, respectively). Conclusions: The modal longitudinal pattern for individuals with other psychoses is one of multiple transitions into and out of symptomatic and functional recovery. Engagement in a long-term health care plan may help individuals detect and respond to these changes. Sustained remission and recovery are rare among people with schizophrenia spectrum disorders. Efforts should be directed toward developing more effective treatments for this population. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Age of onset and cumulative risk of mental disorders: a cross-national analysis of population surveys from 29 countries

Author

McGrath, John J, primary, Al-Hamzawi, Ali, additional, Alonso, Jordi, additional, Altwaijri, Yasmin, additional, Andrade, Laura H, additional, Bromet, Evelyn J, additional, Bruffaerts, Ronny, additional, de Almeida, José Miguel Caldas, additional, Chardoul, Stephanie, additional, Chiu, Wai Tat, additional, Degenhardt, Louisa, additional, Demler, Olga V, additional, Ferry, Finola, additional, Gureje, Oye, additional, Haro, Josep Maria, additional, Karam, Elie G, additional, Karam, Georges, additional, Khaled, Salma M, additional, Kovess-Masfety, Viviane, additional, Magno, Marta, additional, Medina-Mora, Maria Elena, additional, Moskalewicz, Jacek, additional, Navarro-Mateu, Fernando, additional, Nishi, Daisuke, additional, Plana-Ripoll, Oleguer, additional, Posada-Villa, José, additional, Rapsey, Charlene, additional, Sampson, Nancy A, additional, Stagnaro, Juan Carlos, additional, Stein, Dan J, additional, ten Have, Margreet, additional, Torres, Yolanda, additional, Vladescu, Cristian, additional, Woodruff, Peter W, additional, Zarkov, Zahari, additional, Kessler, Ronald C, additional, Aguilar-Gaxiola, Sergio, additional, Altwaijri, Yasmin A., additional, Andrade, Laura Helena, additional, Atwoli, Lukoye, additional, Benjet, Corina, additional, Bromet, Evelyn J., additional, Bunting, Brendan, additional, Caldas-de-Almeida, José Miguel, additional, Cardoso, Graça, additional, Cía, Alfredo H., additional, De Girolamo, Giovanni, additional, Harris, Meredith G., additional, Hinkov, Hristo, additional, Hu, Chi-yi, additional, De Jonge, Peter, additional, Karam, Aimee N., additional, Karam, Elie G., additional, Kazdin, Alan E., additional, Kawakami, Norito, additional, Kessler, Ronald C., additional, Kiejna, Andrzej, additional, McGrath, John J., additional, Piazza, Marina, additional, Scott, Kate M., additional, Stein, Dan J., additional, Ten Have, Margreet, additional, Viana, Maria Carmen, additional, Vigo, Daniel V., additional, Williams, David R., additional, Woodruff, Peter, additional, Wojtyniak, Bogdan, additional, Xavier, Miguel, additional, and Zaslavsky, Alan M., additional

Published
2023
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36. 65 The Impact of PTSD and Mild Cognitive Impairment on Resting State Brain Functional Connectivity in World Trade Center Responders

Author

Weisenbach, Sara L., primary, Clouston, Sean A. P., additional, Kaufman, Jack R., additional, Koppelmans, Vincent, additional, Langenecker, Scott A., additional, Pellecchia, Alison C., additional, Smith, Abigail J., additional, Carr, Melissa A., additional, Huang, Chuan, additional, Bromet, Evelyn J., additional, Palekar, Nikhil, additional, Welsh, Robert C., additional, and Luft, Benjamin J., additional

Published
2023
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43. The epidemiology of drug use disorders cross-nationally: Findings from the WHO’s World Mental Health Surveys

Author

Degenhardt, Louisa, Bharat, Chrianna, Glantz, Meyer D., Sampson, Nancy A., Scott, Kate, Lim, Carmen C.W., Aguilar-Gaxiola, Sergio, Al-Hamzawi, Ali, Alonso, Jordi, Andrade, Laura H., Bromet, Evelyn J., Bruffaerts, Ronny, Bunting, Brendan, de Girolamo, Giovanni, Gureje, Oye, Haro, Josep Maria, Harris, Meredith G., He, Yanling, de Jonge, Peter, Karam, Elie G., Karam, Georges E., Kiejna, Andrzej, Lee, Sing, Lepine, Jean-Pierre, Levinson, Daphna, Makanjuola, Victor, Medina-Mora, Maria Elena, Mneimneh, Zeina, Navarro-Mateu, Fernando, Posada-Villa, José, Stein, Dan J., Tachimori, Hisateru, Torres, Yolanda, Zarkov, Zahari, Chatterji, Somnath, and Kessler, Ronald C.

Published
2019
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47. The association between psychotic experiences and health-related quality of life: a cross-national analysis based on World Mental Health Surveys

Author

Alonso, Jordi, Saha, Sukanta, Lim, Carmen C.W., Aguilar-Gaxiola, Sergio, Al-Hamzawi, Ali, Benjet, Corina, Bromet, Evelyn J., Degenhardt, Louisa, de Girolamo, Giovanni, Esan, Oluyomi, Florescu, Silvia, Gureje, Oye, Haro, Josep M., Hu, Chiyi, Karam, Elie G., Karam, Georges, Kovess-Masfety, Viviane, Lepine, Jean-Pierre, Lee, Sing, Mneimneh, Zeina, Navarro-Mateu, Fernando, Posada-Villa, Jose, Sampson, Nancy A., Scott, Kate M., Stagnaro, Juan Carlos, ten Have, Margreet, Viana, Maria Carmen, Kessler, Ronald C., and McGrath, John J.

Published
2018
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48. Behavioral Impairments and Increased Risk of Cortical Atrophy Risk Scores Among World Trade Center Responders.

Author

Chen, Allen P. F., Ismail, Zahinoor, Mann, Frank D., Bromet, Evelyn J., Clouston, Sean A. P., and Luft, Benjamin J.

Subjects
CEREBRAL atrophy, DISEASE risk factors, ALZHEIMER'S disease, POST-traumatic stress disorder, FACTOR analysis, CEREBRAL amyloid angiopathy
Abstract

Objective: World Trade Center (WTC) responders are susceptible to both cognitive and neuropsychiatric impairments, particularly chronic posttraumatic stress disorder. The present study examined self-reported behavioral impairments in a sample of 732 WTC responders, 199 of whom were determined to have high risk of WTC-related cortical atrophy by an artificial neural network. Results: We found that responders at increased risk of cortical atrophy showed behavioral impairment across five domains: motivation, mood, disinhibition, empathy, and psychosis (14.6% vs 3.9% in the low-risk group; P = 3.90 × 10−7). Factor analysis models revealed that responders at high risk of cortical atrophy tended to have deficits generalized across all aspects of behavioral impairment with focal dysfunction in sensory psychosis. We additionally describe how relationships are modulated by exposure severity and pharmacological treatments. Discussion: Our findings suggest a potential link between sensory deficits and the development of cortical atrophy in WTC responders and may indicate symptoms consistent with a clinical portrait of parietal dominant Alzheimer's disease or a related dementia (ADRD). Results underscore the importance of investigating neuropsychiatric symptomatology in clinical evaluations of possible ADRD. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Mediterranean diet intervention among World Trade Center responders with post‐traumatic stress disorder: Feasibility and outcomes of a pilot randomized controlled trial.

Author

Arcan, Chrisa, Hou, Wei, Hoffman, Kathryn, Reichardt, Amanda, Yang, Xiaohua, Clouston, Sean A. P., Bromet, Evelyn J., and Luft, Benjamin

Subjects
POST-traumatic stress disorder, VIRTUAL reality therapy, MEDITERRANEAN diet, NUTRITION counseling, COUNSELING, BODY mass index, WAIST circumference
Abstract

Objective: Responders of the World Trade Center (WTC) disaster suffer from co‐morbidities. A Mediterranean Diet (MedDiet) nutrition intervention with physical activity was implemented among WTC responders with overweight/obesity and post‐traumatic stress disorder (PTSD). Methods: WTC Health Program members (N = 62), 45–65 years, males 87%, body mass index (BMI) 27–45 kg/m2 randomized to MedDiet (n = 31) or usual nutrition counseling (n = 31). The 10‐week intervention included online nutrition education, text messages, and group experiential cooking; both groups had three in‐person individual nutrition counseling. Anthropometrics, serum biomarkers, psychosocial factors, MedDiet score, and PTSD symptoms were assessed at baseline, post‐intervention, and 3‐months (follow‐up). The primary outcome was intervention feasibility and secondary outcomes were within‐ and between‐group changes of all measures at post‐intervention and follow‐up. Nonparametric Wilcoxon rank sum tests for between‐group comparisons and Wilcoxon signed rank tests for pre‐post within‐group comparisons. Results: A total of 58(94%) and 46(74%) participants completed the post‐intervention and follow‐up measurements, respectively. Both groups experienced significant improvements in anthropometrics, MedDiet score, oxidized low‐density lipoprotein, and PTSD symptoms. Baseline median (range) were weight 100.42 (73.66–135.17) kg, BMI 33.20 (27.50–41.75) kg/m2, and Waist circumference (WC) 109.22 (90.17–150.62) cm. Median % weight loss at post‐intervention was MedDiet: −3% (−11%–7%), p = 0.0002; Control: −1% (−13%–4%), p = 0.008 and at follow‐up MedDiet: −2% (−14%–12%), p = 0.07; Control: −2% (−20%–3%), p = 0.006. The overall BMI was reduced by −0.68 kg/m2 (−4.61–2.09) kg/m2p < 0.0001 at post‐intervention and by −0.60 kg/m2 (−6.91–3.39) kg/m2, p < 0.0009 at follow‐up. Overall, median WC was reduced (p < 0.0001); post‐intervention −3.81 cm (−33.00–3.30)cm and follow‐up −4.45(−38.10–4.57)cm. There were group differences in HbA1c (p = 0.019) and serum ω6/ω3 (p = 0.029) at post‐intervention. Conclusion: Online intervention with personal counseling was feasible in this population. Improvements in anthropometrics, MedDiet score, selected serum biomarkers and PTSD symptoms were found in both groups; group differences in HbA1c and serum ω6/ω3. A larger study with a delayed control is needed to better assess intervention effects. [ABSTRACT FROM AUTHOR]

Published
2024
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