Browsing by Author "Stein, Dan J"

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    ItemOpen Access
    A factor analysis of posttraumatic stress disorder symptoms using data pooled from two venlafaxine extended-release clinical trials.
    (Brain Behav, 2013-11) Stein, Dan J; Rothbaum, Barbara O; Baldwin, David S; Szumski, Annette; Pedersen, Ronald; Davidson, Jonathan RT
    BACKGROUND: Confirmatory factor analysis (CFA) of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) three-factor posttraumatic stress disorder (PTSD) diagnostic criteria was conducted to determine fit for this patient population. An exploratory factor analysis (EFA) of alternate symptom structures was planned to identify symptoms that cluster in this population. The response of symptom factors to treatment with venlafaxine extended release (ER) was explored. METHODS: Baseline 17-item Clinician-Administered PTSD Scale (CAPS-SX17) data were pooled from patients enrolled in two double-blind, randomized, placebo-controlled trials. The CFA was conducted using maximum likelihood and weighted, least-squares factor extraction methods. The EFA was performed using a polychoric correlation covariance matrix and Pearson correlation matrix. RESULTS: Data from a pooled population of 685 patients (venlafaxine ER: n = 339; placebo: n = 346) were analyzed. CFA rejected the DSM-IV three-factor structure. The EFA identified a different three-factor structure as the best fit: factor 1 included reexperiencing symptoms, factor 2 included symptoms of altered mood and cognition, whereas factor 3 comprised avoidance and arousal symptoms. All DSM-IV symptom factors and all factors in the identified three-factor model responded positively to venlafaxine ER treatment. CONCLUSIONS: Data are consistent with literature failing to confirm the three-factor structure of DSM-IV PTSD, and they support the DSM-5 inclusion of a symptom cluster addressing altered mood and cognition in PTSD. The efficacy of venlafaxine ER in reducing a range of symptom clusters in PTSD is consistent with its multiple mechanisms of action.
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    Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium.
    (Molecular psychiatry, 2021-08) Dennis, Emily L; Disner, Seth G; Fani, Negar; Salminen, Lauren E; Logue, Mark; Clarke, Emily K; Haswell, Courtney C; Averill, Christopher L; Baugh, Lee A; Bomyea, Jessica; Bruce, Steven E; Cha, Jiook; Choi, Kyle; Davenport, Nicholas D; Densmore, Maria; du Plessis, Stefan; Forster, Gina L; Frijling, Jessie L; Gonenc, Atilla; Gruber, Staci; Grupe, Daniel W; Guenette, Jeffrey P; Hayes, Jasmeet; Hofmann, David; Ipser, Jonathan; Jovanovic, Tanja; Kelly, Sinead; Kennis, Mitzy; Kinzel, Philipp; Koch, Saskia BJ; Koerte, Inga; Koopowitz, Sheri; Korgaonkar, Mayuresh; Krystal, John; Lebois, Lauren AM; Li, Gen; Magnotta, Vincent A; Manthey, Antje; May, Geoff J; Menefee, Deleene S; Nawijn, Laura; Nelson, Steven M; Neufeld, Richard WJ; Nitschke, Jack B; O'Doherty, Daniel; Peverill, Matthew; Ressler, Kerry J; Roos, Annerine; Sheridan, Margaret A; Sierk, Anika; Simmons, Alan; Simons, Raluca M; Simons, Jeffrey S; Stevens, Jennifer; Suarez-Jimenez, Benjamin; Sullivan, Danielle R; Théberge, Jean; Tran, Jana K; van den Heuvel, Leigh; van der Werff, Steven JA; van Rooij, Sanne JH; van Zuiden, Mirjam; Velez, Carmen; Verfaellie, Mieke; Vermeiren, Robert RJM; Wade, Benjamin SC; Wager, Tor; Walter, Henrik; Winternitz, Sherry; Wolff, Jonathan; York, Gerald; Zhu, Ye; Zhu, Xi; Abdallah, Chadi G; Bryant, Richard; Daniels, Judith K; Davidson, Richard J; Fercho, Kelene A; Franz, Carol; Geuze, Elbert; Gordon, Evan M; Kaufman, Milissa L; Kremen, William S; Lagopoulos, Jim; Lanius, Ruth A; Lyons, Michael J; McCauley, Stephen R; McGlinchey, Regina; McLaughlin, Katie A; Milberg, William; Neria, Yuval; Olff, Miranda; Seedat, Soraya; Shenton, Martha; Sponheim, Scott R; Stein, Dan J; Stein, Murray B; Straube, Thomas; Tate, David F; van der Wee, Nic JA; Veltman, Dick J; Wang, Li; Wilde, Elisabeth A; Thompson, Paul M; Kochunov, Peter; Jahanshad, Neda; Morey, Rajendra A
    A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.
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    ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.
    (Translational psychiatry, 2020-03) Thompson, Paul M; Jahanshad, Neda; Ching, Christopher RK; Salminen, Lauren E; Thomopoulos, Sophia I; Bright, Joanna; Baune, Bernhard T; Bertolín, Sara; Bralten, Janita; Bruin, Willem B; Bülow, Robin; Chen, Jian; Chye, Yann; Dannlowski, Udo; de Kovel, Carolien GF; Donohoe, Gary; Eyler, Lisa T; Faraone, Stephen V; Favre, Pauline; Filippi, Courtney A; Frodl, Thomas; Garijo, Daniel; Gil, Yolanda; Grabe, Hans J; Grasby, Katrina L; Hajek, Tomas; Han, Laura KM; Hatton, Sean N; Hilbert, Kevin; Ho, Tiffany C; Holleran, Laurena; Homuth, Georg; Hosten, Norbert; Houenou, Josselin; Ivanov, Iliyan; Jia, Tianye; Kelly, Sinead; Klein, Marieke; Kwon, Jun Soo; Laansma, Max A; Leerssen, Jeanne; Lueken, Ulrike; Nunes, Abraham; Neill, Joseph O'; Opel, Nils; Piras, Fabrizio; Piras, Federica; Postema, Merel C; Pozzi, Elena; Shatokhina, Natalia; Soriano-Mas, Carles; Spalletta, Gianfranco; Sun, Daqiang; Teumer, Alexander; Tilot, Amanda K; Tozzi, Leonardo; van der Merwe, Celia; Van Someren, Eus JW; van Wingen, Guido A; Völzke, Henry; Walton, Esther; Wang, Lei; Winkler, Anderson M; Wittfeld, Katharina; Wright, Margaret J; Yun, Je-Yeon; Zhang, Guohao; Zhang-James, Yanli; Adhikari, Bhim M; Agartz, Ingrid; Aghajani, Moji; Aleman, André; Althoff, Robert R; Altmann, Andre; Andreassen, Ole A; Baron, David A; Bartnik-Olson, Brenda L; Marie Bas-Hoogendam, Janna; Baskin-Sommers, Arielle R; Bearden, Carrie E; Berner, Laura A; Boedhoe, Premika SW; Brouwer, Rachel M; Buitelaar, Jan K; Caeyenberghs, Karen; Cecil, Charlotte AM; Cohen, Ronald A; Cole, James H; Conrod, Patricia J; De Brito, Stephane A; de Zwarte, Sonja MC; Dennis, Emily L; Desrivieres, Sylvane; Dima, Danai; Ehrlich, Stefan; Esopenko, Carrie; Fairchild, Graeme; Fisher, Simon E; Fouche, Jean-Paul; Francks, Clyde; Frangou, Sophia; Franke, Barbara; Garavan, Hugh P; Glahn, David C; Groenewold, Nynke A; Gurholt, Tiril P; Gutman, Boris A; Hahn, Tim; Harding, Ian H; Hernaus, Dennis; Hibar, Derrek P; Hillary, Frank G; Hoogman, Martine; Hulshoff Pol, Hilleke E; Jalbrzikowski, Maria; Karkashadze, George A; Klapwijk, Eduard T; Knickmeyer, Rebecca C; Kochunov, Peter; Koerte, Inga K; Kong, Xiang-Zhen; Liew, Sook-Lei; Lin, Alexander P; Logue, Mark W; Luders, Eileen; Macciardi, Fabio; Mackey, Scott; Mayer, Andrew R; McDonald, Carrie R; McMahon, Agnes B; Medland, Sarah E; Modinos, Gemma; Morey, Rajendra A; Mueller, Sven C; Mukherjee, Pratik; Namazova-Baranova, Leyla; Nir, Talia M; Olsen, Alexander; Paschou, Peristera; Pine, Daniel S; Pizzagalli, Fabrizio; Rentería, Miguel E; Rohrer, Jonathan D; Sämann, Philipp G; Schmaal, Lianne; Schumann, Gunter; Shiroishi, Mark S; Sisodiya, Sanjay M; Smit, Dirk JA; Sønderby, Ida E; Stein, Dan J; Stein, Jason L; Tahmasian, Masoud; Tate, David F; Turner, Jessica A; van den Heuvel, Odile A; van der Wee, Nic JA; van der Werf, Ysbrand D; van Erp, Theo GM; van Haren, Neeltje EM; van Rooij, Daan; van Velzen, Laura S; Veer, Ilya M; Veltman, Dick J; Villalon-Reina, Julio E; Walter, Henrik; Whelan, Christopher D; Wilde, Elisabeth A; Zarei, Mojtaba; Zelman, Vladimir; ENIGMA Consortium
    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.
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    ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide.
    (Neuroimage, 2017-01-15) Thompson, Paul M; Andreassen, Ole A; Arias-Vasquez, Alejandro; Bearden, Carrie E; Boedhoe, Premika S; Brouwer, Rachel M; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cannon, Dara M; Cohen, Ronald A; Conrod, Patricia J; Dale, Anders M; Deary, Ian J; Dennis, Emily L; de Reus, Marcel A; Desrivieres, Sylvane; Dima, Danai; Donohoe, Gary; Fisher, Simon E; Fouche, Jean-Paul; Francks, Clyde; Frangou, Sophia; Franke, Barbara; Ganjgahi, Habib; Garavan, Hugh; Glahn, David C; Grabe, Hans J; Guadalupe, Tulio; Gutman, Boris A; Hashimoto, Ryota; Hibar, Derrek P; Holland, Dominic; Hoogman, Martine; Hulshoff Pol, Hilleke E; Hosten, Norbert; Jahanshad, Neda; Kelly, Sinead; Kochunov, Peter; Kremen, William S; Lee, Phil H; Mackey, Scott; Martin, Nicholas G; Mazoyer, Bernard; McDonald, Colm; Medland, Sarah E; Morey, Rajendra A; Nichols, Thomas E; Paus, Tomas; Pausova, Zdenka; Schmaal, Lianne; Schumann, Gunter; Shen, Li; Sisodiya, Sanjay M; Smit, Dirk JA; Smoller, Jordan W; Stein, Dan J; Stein, Jason L; Toro, Roberto; Turner, Jessica A; van den Heuvel, Martijn P; van den Heuvel, Odile L; van Erp, Theo GM; van Rooij, Daan; Veltman, Dick J; Walter, Henrik; Wang, Yalin; Wardlaw, Joanna M; Whelan, Christopher D; Wright, Margaret J; Ye, Jieping; ENIGMA Consortium
    In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others(1), ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants - and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.
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    International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.
    (Nature communications, 2019-10) Nievergelt, Caroline M; Maihofer, Adam X; Klengel, Torsten; Atkinson, Elizabeth G; Chen, Chia-Yen; Choi, Karmel W; Coleman, Jonathan RI; Dalvie, Shareefa; Duncan, Laramie E; Gelernter, Joel; Levey, Daniel F; Logue, Mark W; Polimanti, Renato; Provost, Allison C; Ratanatharathorn, Andrew; Stein, Murray B; Torres, Katy; Aiello, Allison E; Almli, Lynn M; Amstadter, Ananda B; Andersen, Søren B; Andreassen, Ole A; Arbisi, Paul A; Ashley-Koch, Allison E; Austin, S Bryn; Avdibegovic, Esmina; Babić, Dragan; Bækvad-Hansen, Marie; Baker, Dewleen G; Beckham, Jean C; Bierut, Laura J; Bisson, Jonathan I; Boks, Marco P; Bolger, Elizabeth A; Børglum, Anders D; Bradley, Bekh; Brashear, Megan; Breen, Gerome; Bryant, Richard A; Bustamante, Angela C; Bybjerg-Grauholm, Jonas; Calabrese, Joseph R; Caldas-de-Almeida, José M; Dale, Anders M; Daly, Mark J; Daskalakis, Nikolaos P; Deckert, Jürgen; Delahanty, Douglas L; Dennis, Michelle F; Disner, Seth G; Domschke, Katharina; Dzubur-Kulenovic, Alma; Erbes, Christopher R; Evans, Alexandra; Farrer, Lindsay A; Feeny, Norah C; Flory, Janine D; Forbes, David; Franz, Carol E; Galea, Sandro; Garrett, Melanie E; Gelaye, Bizu; Geuze, Elbert; Gillespie, Charles; Uka, Aferdita Goci; Gordon, Scott D; Guffanti, Guia; Hammamieh, Rasha; Harnal, Supriya; Hauser, Michael A; Heath, Andrew C; Hemmings, Sian MJ; Hougaard, David Michael; Jakovljevic, Miro; Jett, Marti; Johnson, Eric Otto; Jones, Ian; Jovanovic, Tanja; Qin, Xue-Jun; Junglen, Angela G; Karstoft, Karen-Inge; Kaufman, Milissa L; Kessler, Ronald C; Khan, Alaptagin; Kimbrel, Nathan A; King, Anthony P; Koen, Nastassja; Kranzler, Henry R; Kremen, William S; Lawford, Bruce R; Lebois, Lauren AM; Lewis, Catrin E; Linnstaedt, Sarah D; Lori, Adriana; Lugonja, Bozo; Luykx, Jurjen J; Lyons, Michael J; Maples-Keller, Jessica; Marmar, Charles; Martin, Alicia R; Martin, Nicholas G; Maurer, Douglas; Mavissakalian, Matig R; McFarlane, Alexander; McGlinchey, Regina E; McLaughlin, Katie A; McLean, Samuel A; McLeay, Sarah; Mehta, Divya; Milberg, William P; Miller, Mark W; Morey, Rajendra A; Morris, Charles Phillip; Mors, Ole; Mortensen, Preben B; Neale, Benjamin M; Nelson, Elliot C; Nordentoft, Merete; Norman, Sonya B; O'Donnell, Meaghan; Orcutt, Holly K; Panizzon, Matthew S; Peters, Edward S; Peterson, Alan L; Peverill, Matthew; Pietrzak, Robert H; Polusny, Melissa A; Rice, John P; Ripke, Stephan; Risbrough, Victoria B; Roberts, Andrea L; Rothbaum, Alex O; Rothbaum, Barbara O; Roy-Byrne, Peter; Ruggiero, Ken; Rung, Ariane; Rutten, Bart PF; Saccone, Nancy L; Sanchez, Sixto E; Schijven, Dick; Seedat, Soraya; Seligowski, Antonia V; Seng, Julia S; Sheerin, Christina M; Silove, Derrick; Smith, Alicia K; Smoller, Jordan W; Sponheim, Scott R; Stein, Dan J; Stevens, Jennifer S; Sumner, Jennifer A; Teicher, Martin H; Thompson, Wesley K; Trapido, Edward; Uddin, Monica; Ursano, Robert J; van den Heuvel, Leigh Luella; Van Hooff, Miranda; Vermetten, Eric; Vinkers, Christiaan H; Voisey, Joanne; Wang, Yunpeng; Wang, Zhewu; Werge, Thomas; Williams, Michelle A; Williamson, Douglas E; Winternitz, Sherry; Wolf, Christiane; Wolf, Erika J; Wolff, Jonathan D; Yehuda, Rachel; Young, Ross McD; Young, Keith A; Zhao, Hongyu; Zoellner, Lori A; Liberzon, Israel; Ressler, Kerry J; Haas, Magali; Koenen, Karestan C
    The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.
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    Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium.
    (NeuroImage, 2023-12) Zhu, Xi; Kim, Yoojean; Ravid, Orren; He, Xiaofu; Suarez-Jimenez, Benjamin; Zilcha-Mano, Sigal; Lazarov, Amit; Lee, Seonjoo; Abdallah, Chadi G; Angstadt, Michael; Averill, Christopher L; Baird, C Lexi; Baugh, Lee A; Blackford, Jennifer U; Bomyea, Jessica; Bruce, Steven E; Bryant, Richard A; Cao, Zhihong; Choi, Kyle; Cisler, Josh; Cotton, Andrew S; Daniels, Judith K; Davenport, Nicholas D; Davidson, Richard J; DeBellis, Michael D; Dennis, Emily L; Densmore, Maria; deRoon-Cassini, Terri; Disner, Seth G; Hage, Wissam El; Etkin, Amit; Fani, Negar; Fercho, Kelene A; Fitzgerald, Jacklynn; Forster, Gina L; Frijling, Jessie L; Geuze, Elbert; Gonenc, Atilla; Gordon, Evan M; Gruber, Staci; Grupe, Daniel W; Guenette, Jeffrey P; Haswell, Courtney C; Herringa, Ryan J; Herzog, Julia; Hofmann, David Bernd; Hosseini, Bobak; Hudson, Anna R; Huggins, Ashley A; Ipser, Jonathan C; Jahanshad, Neda; Jia-Richards, Meilin; Jovanovic, Tanja; Kaufman, Milissa L; Kennis, Mitzy; King, Anthony; Kinzel, Philipp; Koch, Saskia BJ; Koerte, Inga K; Koopowitz, Sheri M; Korgaonkar, Mayuresh S; Krystal, John H; Lanius, Ruth; Larson, Christine L; Lebois, Lauren AM; Li, Gen; Liberzon, Israel; Lu, Guang Ming; Luo, Yifeng; Magnotta, Vincent A; Manthey, Antje; Maron-Katz, Adi; May, Geoffery; McLaughlin, Katie; Mueller, Sven C; Nawijn, Laura; Nelson, Steven M; Neufeld, Richard WJ; Nitschke, Jack B; O'Leary, Erin M; Olatunji, Bunmi O; Olff, Miranda; Peverill, Matthew; Phan, K Luan; Qi, Rongfeng; Quidé, Yann; Rektor, Ivan; Ressler, Kerry; Riha, Pavel; Ross, Marisa; Rosso, Isabelle M; Salminen, Lauren E; Sambrook, Kelly; Schmahl, Christian; Shenton, Martha E; Sheridan, Margaret; Shih, Chiahao; Sicorello, Maurizio; Sierk, Anika; Simmons, Alan N; Simons, Raluca M; Simons, Jeffrey S; Sponheim, Scott R; Stein, Murray B; Stein, Dan J; Stevens, Jennifer S; Straube, Thomas; Sun, Delin; Théberge, Jean; Thompson, Paul M; Thomopoulos, Sophia I; van der Wee, Nic JA; van der Werff, Steven JA; van Erp, Theo GM; van Rooij, Sanne JH; van Zuiden, Mirjam; Varkevisser, Tim; Veltman, Dick J; Vermeiren, Robert RJM; Walter, Henrik; Wang, Li; Wang, Xin; Weis, Carissa; Winternitz, Sherry; Xie, Hong; Zhu, Ye; Wall, Melanie; Neria, Yuval; Morey, Rajendra A

    Background

    Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group.

    Methods

    We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality.

    Results

    We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance.

    Conclusion

    These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.
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    Resilience as a predictor of treatment response in patients with posttraumatic stress disorder treated with venlafaxine extended release or placebo.
    (Journal of psychopharmacology (Oxford, England), 2012-06) Davidson, Jonathan; Stein, Dan J; Rothbaum, Barbara O; Pedersen, Ron; Szumski, Annette; Baldwin, David S
    This post-hoc analysis evaluated resilience as a predictor of treatment response in patients with posttraumatic stress disorder (PTSD). Data were pooled from two randomized, double-blind studies conducted with adult outpatients treated with flexible doses of venlafaxine extended release (ER) 37.5 to 300 mg/day or placebo. The 17-item Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS-SX(17)) was the primary outcome measure. Baseline Connor-Davidson Resilience Scale (CD-RISC) scores for the 25-, 10-, and 2-item versions were used to predict changes in PTSD symptom severity at week 12 and symptomatic remission (CAPS-SX(17) ≤ 20). Analyses were conducted for the overall population and separately for the individual treatment groups. In total, pretreatment resilience predicted a positive treatment response. For the overall population, all versions of the CD-RISC predicted CAPS-SX(17) change scores and remission after controlling for variables such as treatment group and baseline symptom severity. For venlafaxine ER-treated patients, all versions of the CD-RISC were predictive of remission, but only the 10-item version was predictive of CAPS-SX(17) change score. Our results suggest that higher pretreatment resilience is generally associated with a positive treatment response. Future research may be warranted to explore the relationship between response to active treatment and the spectrum of resiliency.
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    The genetic architecture of the human cerebral cortex.
    (Science (New York, N.Y.), 2020-03) Grasby, Katrina L; Jahanshad, Neda; Painter, Jodie N; Colodro-Conde, Lucía; Bralten, Janita; Hibar, Derrek P; Lind, Penelope A; Pizzagalli, Fabrizio; Ching, Christopher RK; McMahon, Mary Agnes B; Shatokhina, Natalia; Zsembik, Leo CP; Thomopoulos, Sophia I; Zhu, Alyssa H; Strike, Lachlan T; Agartz, Ingrid; Alhusaini, Saud; Almeida, Marcio AA; Alnæs, Dag; Amlien, Inge K; Andersson, Micael; Ard, Tyler; Armstrong, Nicola J; Ashley-Koch, Allison; Atkins, Joshua R; Bernard, Manon; Brouwer, Rachel M; Buimer, Elizabeth EL; Bülow, Robin; Bürger, Christian; Cannon, Dara M; Chakravarty, Mallar; Chen, Qiang; Cheung, Joshua W; Couvy-Duchesne, Baptiste; Dale, Anders M; Dalvie, Shareefa; de Araujo, Tânia K; de Zubicaray, Greig I; de Zwarte, Sonja MC; den Braber, Anouk; Doan, Nhat Trung; Dohm, Katharina; Ehrlich, Stefan; Engelbrecht, Hannah-Ruth; Erk, Susanne; Fan, Chun Chieh; Fedko, Iryna O; Foley, Sonya F; Ford, Judith M; Fukunaga, Masaki; Garrett, Melanie E; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Green, Melissa J; Groenewold, Nynke A; Grotegerd, Dominik; Gurholt, Tiril P; Gutman, Boris A; Hansell, Narelle K; Harris, Mathew A; Harrison, Marc B; Haswell, Courtney C; Hauser, Michael; Herms, Stefan; Heslenfeld, Dirk J; Ho, New Fei; Hoehn, David; Hoffmann, Per; Holleran, Laurena; Hoogman, Martine; Hottenga, Jouke-Jan; Ikeda, Masashi; Janowitz, Deborah; Jansen, Iris E; Jia, Tianye; Jockwitz, Christiane; Kanai, Ryota; Karama, Sherif; Kasperaviciute, Dalia; Kaufmann, Tobias; Kelly, Sinead; Kikuchi, Masataka; Klein, Marieke; Knapp, Michael; Knodt, Annchen R; Krämer, Bernd; Lam, Max; Lancaster, Thomas M; Lee, Phil H; Lett, Tristram A; Lewis, Lindsay B; Lopes-Cendes, Iscia; Luciano, Michelle; Macciardi, Fabio; Marquand, Andre F; Mathias, Samuel R; Melzer, Tracy R; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Moreira, Jose CV; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Najt, Pablo; Nakahara, Soichiro; Nho, Kwangsik; Olde Loohuis, Loes M; Orfanos, Dimitri Papadopoulos; Pearson, John F; Pitcher, Toni L; Pütz, Benno; Quidé, Yann; Ragothaman, Anjanibhargavi; Rashid, Faisal M; Reay, William R; Redlich, Ronny; Reinbold, Céline S; Repple, Jonathan; Richard, Geneviève; Riedel, Brandalyn C; Risacher, Shannon L; Rocha, Cristiane S; Mota, Nina Roth; Salminen, Lauren; Saremi, Arvin; Saykin, Andrew J; Schlag, Fenja; Schmaal, Lianne; Schofield, Peter R; Secolin, Rodrigo; Shapland, Chin Yang; Shen, Li; Shin, Jean; Shumskaya, Elena; Sønderby, Ida E; Sprooten, Emma; Tansey, Katherine E; Teumer, Alexander; Thalamuthu, Anbupalam; Tordesillas-Gutiérrez, Diana; Turner, Jessica A; Uhlmann, Anne; Vallerga, Costanza Ludovica; van der Meer, Dennis; van Donkelaar, Marjolein MJ; van Eijk, Liza; van Erp, Theo GM; van Haren, Neeltje EM; van Rooij, Daan; van Tol, Marie-José; Veldink, Jan H; Verhoef, Ellen; Walton, Esther; Wang, Mingyuan; Wang, Yunpeng; Wardlaw, Joanna M; Wen, Wei; Westlye, Lars T; Whelan, Christopher D; Witt, Stephanie H; Wittfeld, Katharina; Wolf, Christiane; Wolfers, Thomas; Wu, Jing Qin; Yasuda, Clarissa L; Zaremba, Dario; Zhang, Zuo; Zwiers, Marcel P; Artiges, Eric; Assareh, Amelia A; Ayesa-Arriola, Rosa; Belger, Aysenil; Brandt, Christine L; Brown, Gregory G; Cichon, Sven; Curran, Joanne E; Davies, Gareth E; Degenhardt, Franziska; Dennis, Michelle F; Dietsche, Bruno; Djurovic, Srdjan; Doherty, Colin P; Espiritu, Ryan; Garijo, Daniel; Gil, Yolanda; Gowland, Penny A; Green, Robert C; Häusler, Alexander N; Heindel, Walter; Ho, Beng-Choon; Hoffmann, Wolfgang U; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Jack, Clifford R; Jang, MiHyun; Jansen, Andreas; Kimbrel, Nathan A; Kolskår, Knut; Koops, Sanne; Krug, Axel; Lim, Kelvin O; Luykx, Jurjen J; Mathalon, Daniel H; Mather, Karen A; Mattay, Venkata S; Matthews, Sarah; Mayoral Van Son, Jaqueline; McEwen, Sarah C; Melle, Ingrid; Morris, Derek W; Mueller, Bryon A; Nauck, Matthias; Nordvik, Jan E; Nöthen, Markus M; O'Leary, Daniel S; Opel, Nils; Martinot, Marie-Laure Paillère; Pike, G Bruce; Preda, Adrian; Quinlan, Erin B; Rasser, Paul E; Ratnakar, Varun; Reppermund, Simone; Steen, Vidar M; Tooney, Paul A; Torres, Fábio R; Veltman, Dick J; Voyvodic, James T; Whelan, Robert; White, Tonya; Yamamori, Hidenaga; Adams, Hieab HH; Bis, Joshua C; Debette, Stephanie; Decarli, Charles; Fornage, Myriam; Gudnason, Vilmundur; Hofer, Edith; Ikram, M Arfan; Launer, Lenore; Longstreth, WT; Lopez, Oscar L; Mazoyer, Bernard; Mosley, Thomas H; Roshchupkin, Gennady V; Satizabal, Claudia L; Schmidt, Reinhold; Seshadri, Sudha; Yang, Qiong; Alzheimer’s Disease Neuroimaging Initiative; CHARGE Consortium; EPIGEN Consortium; IMAGEN Consortium; SYS Consortium; Parkinson’s Progression Markers Initiative; Alvim, Marina KM; Ames, David; Anderson, Tim J; Andreassen, Ole A; Arias-Vasquez, Alejandro; Bastin, Mark E; Baune, Bernhard T; Beckham, Jean C; Blangero, John; Boomsma, Dorret I; Brodaty, Henry; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bustillo, Juan R; Cahn, Wiepke; Cairns, Murray J; Calhoun, Vince; Carr, Vaughan J; Caseras, Xavier; Caspers, Svenja; Cavalleri, Gianpiero L; Cendes, Fernando; Corvin, Aiden; Crespo-Facorro, Benedicto; Dalrymple-Alford, John C; Dannlowski, Udo; de Geus, Eco JC; Deary, Ian J; Delanty, Norman; Depondt, Chantal; Desrivières, Sylvane; Donohoe, Gary; Espeseth, Thomas; Fernández, Guillén; Fisher, Simon E; Flor, Herta; Forstner, Andreas J; Francks, Clyde; Franke, Barbara; Glahn, David C; Gollub, Randy L; Grabe, Hans J; Gruber, Oliver; Håberg, Asta K; Hariri, Ahmad R; Hartman, Catharina A; Hashimoto, Ryota; Heinz, Andreas; Henskens, Frans A; Hillegers, Manon HJ; Hoekstra, Pieter J; Holmes, Avram J; Hong, L Elliot; Hopkins, William D; Hulshoff Pol, Hilleke E; Jernigan, Terry L; Jönsson, Erik G; Kahn, René S; Kennedy, Martin A; Kircher, Tilo TJ; Kochunov, Peter; Kwok, John BJ; Le Hellard, Stephanie; Loughland, Carmel M; Martin, Nicholas G; Martinot, Jean-Luc; McDonald, Colm; McMahon, Katie L; Meyer-Lindenberg, Andreas; Michie, Patricia T; Morey, Rajendra A; Mowry, Bryan; Nyberg, Lars; Oosterlaan, Jaap; Ophoff, Roel A; Pantelis, Christos; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda WJH; Polderman, Tinca JC; Posthuma, Danielle; Rietschel, Marcella; Roffman, Joshua L; Rowland, Laura M; Sachdev, Perminder S; Sämann, Philipp G; Schall, Ulrich; Schumann, Gunter; Scott, Rodney J; Sim, Kang; Sisodiya, Sanjay M; Smoller, Jordan W; Sommer, Iris E; St Pourcain, Beate; Stein, Dan J; Toga, Arthur W; Trollor, Julian N; Van der Wee, Nic JA; van 't Ent, Dennis; Völzke, Henry; Walter, Henrik; Weber, Bernd; Weinberger, Daniel R; Wright, Margaret J; Zhou, Juan; Stein, Jason L; Thompson, Paul M; Medland, Sarah E; Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group
    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.