Browsing by Author "Ressler, Kerry J"

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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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    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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    The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup: Posttraumatic Stress Disorder Enters the Age of Large-Scale Genomic Collaboration.
    (Neuropsychopharmacology, 2015-09) Logue, Mark W; Amstadter, Ananda B; Baker, Dewleen G; Duncan, Laramie; Koenen, Karestan C; Liberzon, Israel; Miller, Mark W; Morey, Rajendra A; Nievergelt, Caroline M; Ressler, Kerry J; Smith, Alicia K; Smoller, Jordan W; Stein, Murray B; Sumner, Jennifer A; Uddin, Monica
    The development of posttraumatic stress disorder (PTSD) is influenced by genetic factors. Although there have been some replicated candidates, the identification of risk variants for PTSD has lagged behind genetic research of other psychiatric disorders such as schizophrenia, autism, and bipolar disorder. Psychiatric genetics has moved beyond examination of specific candidate genes in favor of the genome-wide association study (GWAS) strategy of very large numbers of samples, which allows for the discovery of previously unsuspected genes and molecular pathways. The successes of genetic studies of schizophrenia and bipolar disorder have been aided by the formation of a large-scale GWAS consortium: the Psychiatric Genomics Consortium (PGC). In contrast, only a handful of GWAS of PTSD have appeared in the literature to date. Here we describe the formation of a group dedicated to large-scale study of PTSD genetics: the PGC-PTSD. The PGC-PTSD faces challenges related to the contingency on trauma exposure and the large degree of ancestral genetic diversity within and across participating studies. Using the PGC analysis pipeline supplemented by analyses tailored to address these challenges, we anticipate that our first large-scale GWAS of PTSD will comprise over 10 000 cases and 30 000 trauma-exposed controls. Following in the footsteps of our PGC forerunners, this collaboration-of a scope that is unprecedented in the field of traumatic stress-will lead the search for replicable genetic associations and new insights into the biological underpinnings of PTSD.