Search

Your search keyword '"Bryant, Richard A."' showing total 4,168 results
Start Over Author "Bryant, Richard A."
4,168 results on '"Bryant, Richard A."'

2. Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.

Author

Nievergelt, Caroline, Maihofer, Adam, Atkinson, Elizabeth, Chen, Chia-Yen, Choi, Karmel, Coleman, Jonathan, Daskalakis, Nikolaos, Duncan, Laramie, Polimanti, Renato, Aaronson, Cindy, Amstadter, Ananda, Andersen, Soren, Andreassen, Ole, Arbisi, Paul, Ashley-Koch, Allison, Austin, S, Avdibegoviç, Esmina, Babić, Dragan, Bacanu, Silviu-Alin, Baker, Dewleen, Batzler, Anthony, Beckham, Jean, Belangero, Sintia, Benjet, Corina, Bergner, Carisa, Bierer, Linda, Biernacka, Joanna, Bierut, Laura, Bisson, Jonathan, Boks, Marco, Bolger, Elizabeth, Brandolino, Amber, Breen, Gerome, Bressan, Rodrigo, Bryant, Richard, Bustamante, Angela, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Børglum, Anders, Børte, Sigrid, Cahn, Leah, Calabrese, Joseph, Caldas-de-Almeida, Jose, Chatzinakos, Chris, Cheema, Sheraz, Clouston, Sean, Colodro-Conde, Lucía, Coombes, Brandon, Cruz-Fuentes, Carlos, Dale, Anders, Dalvie, Shareefa, Davis, Lea, Deckert, Jürgen, Delahanty, Douglas, Dennis, Michelle, Desarnaud, Frank, DiPietro, Christopher, Disner, Seth, Docherty, Anna, Domschke, Katharina, Dyb, Grete, Kulenović, Alma, Edenberg, Howard, Evans, Alexandra, Fabbri, Chiara, Fani, Negar, Farrer, Lindsay, Feder, Adriana, Feeny, Norah, Flory, Janine, Forbes, David, Franz, Carol, Galea, Sandro, Garrett, Melanie, Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles, Goleva, Slavina, Gordon, Scott, Goçi, Aferdita, Grasser, Lana, Guindalini, Camila, Haas, Magali, Hagenaars, Saskia, Hauser, Michael, Heath, Andrew, Hemmings, Sian, Hesselbrock, Victor, Hickie, Ian, Hogan, Kelleigh, Hougaard, David, Huang, Hailiang, Huckins, Laura, Hveem, Kristian, Jakovljević, Miro, Javanbakht, Arash, Jenkins, Gregory, Johnson, Jessica, and Jones, Ian

Subjects
Humans, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Neurobiology, Polymorphism, Single Nucleotide, Stress Disorders, Post-Traumatic, White People, White, Black or African American, American Indian or Alaska Native
Abstract

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Published
2024

3. Mental health during the Covid-19 pandemic: An international comparison of gender-related home and work-related responsibilities, and social support

Author

Eugene, Dominique, Nöthling, Jani, Tarsitani, Lorenzo, Palantza, Christina, Papola, Davide, Barbui, Corrado, Bryant, Richard, Panter-Brick, Catherine, Hall, Brian J., Lam, Agnes Iok Fok, Huizink, Anja C., Fuhr, Daniela, Purba, Fredrick Dermawan, Mittendorfer-Rutz, Ellenor, Andriani, Dhini, van der Waerden, Judith, Acartürk, Ceren, Kurt, Gülşah, Burchert, Sebastian, Knaevelsrud, Christine, Witteveen, Anke B., Patane, Martina, Quero, Soledad, Díaz-García, Amanda, Morina, Naser, Pinucci, Irene, Sijbrandij, Marit, and Seedat, Soraya

Published
2024
Full Text
View/download PDF

4. First-in-man study of the PSMA Minibody IR800-IAB2M for molecularly targeted intraoperative fluorescence guidance during radical prostatectomy

Author

Hamdy, Freddie C., Lamb, Alastair D., Tullis, Iain D. C., Verrill, Clare, Rombach, Ines, Rao, Srinivasa R., Colling, Richard, Barber, Paul R., Volpi, Davide, Barbera-Martin, Luis, Lopez, J Francisco, Omer, Altan, Hewitt, Aimi, Lovell, Shelagh, Niederer, Jane, Lambert, Adam, Snoeck, Joke, Thomson, Claire, Leslie, Tom, Bryant, Richard J., Mascioni, Alessandro, Jia, Fang, Torgov, Michael, Wilson, Ian, Gudas, Jean, Wu, Anna M., Olafsen, Tove, and Vojnovic, Borivoj

Published
2024
Full Text
View/download PDF

8. Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole-genome sequencing with histopathological features

Author

Rao, Srinivasa, Verrill, Clare, Cerundolo, Lucia, Alham, Nasullah Khalid, Kaya, Zeynep, O’Hanlon, Miriam, Hayes, Alicia, Lambert, Adam, James, Martha, Tullis, Iain D. C., Niederer, Jane, Lovell, Shelagh, Omer, Altan, Lopez, Francisco, Leslie, Tom, Buffa, Francesca, Bryant, Richard J., Lamb, Alastair D., Vojnovic, Boris, Wedge, David C., Mills, Ian G., Woodcock, Dan J., Tomlinson, Ian, and Hamdy, Freddie C.

Published
2024
Full Text
View/download PDF

9. Correction: Effectiveness of a scalable, remotely delivered stepped-care intervention to reduce symptoms of psychological distress among Polish migrant workers in the Netherlands: study protocol for the RESPOND randomised controlled trial

Author

Roos, Rinske, Witteveen, Anke B, Ayuso-Mateos, José Luis, Barbui, Corrado, Bryant, Richard A., Felez-Nobrega, Mireia, Figueiredo, Natasha, Kalisch, Rafael, Haro, Josep Maria, McDaid, David, Mediavilla, Roberto, Melchior, Maria, Nicaise, Pablo, Park, A-La, Petri-Romão, Papoula, Purgato, Marianna, van Straten, Annemieke, Tedeschi, Federico, Underhill, James, and Sijbrandij, Marit

Published
2024
Full Text
View/download PDF

11. Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium.

Author

Zhu, Xi, Kim, Yoojean, Ravid, Orren, He, Xiaofu, Suarez-Jimenez, Benjamin, Zilcha-Mano, Sigal, Lazarov, Amit, Lee, Seonjoo, Abdallah, Chadi, Angstadt, Michael, Averill, Christopher, Baird, C, Baugh, Lee, Blackford, Jennifer, Bomyea, Jessica, Bruce, Steven, Bryant, Richard, Cao, Zhihong, Choi, Kyle, Cisler, Josh, Cotton, Andrew, Daniels, Judith, Davenport, Nicholas, Davidson, Richard, DeBellis, Michael, Dennis, Emily, Densmore, Maria, deRoon-Cassini, Terri, Disner, Seth, Hage, Wissam, Etkin, Amit, Fani, Negar, Fercho, Kelene, Fitzgerald, Jacklynn, Forster, Gina, Frijling, Jessie, Geuze, Elbert, Gonenc, Atilla, Gordon, Evan, Gruber, Staci, Grupe, Daniel, Guenette, Jeffrey, Haswell, Courtney, Herringa, Ryan, Herzog, Julia, Hofmann, David, Hosseini, Bobak, Hudson, Anna, Huggins, Ashley, Ipser, Jonathan, Jahanshad, Neda, Jia-Richards, Meilin, Jovanovic, Tanja, Kaufman, Milissa, Kennis, Mitzy, King, Anthony, Kinzel, Philipp, Koch, Saskia, Koerte, Inga, Koopowitz, Sheri, Korgaonkar, Mayuresh, Krystal, John, Lanius, Ruth, Larson, Christine, Lebois, Lauren, Li, Gen, Liberzon, Israel, Lu, Guang, Luo, Yifeng, Magnotta, Vincent, Manthey, Antje, Maron-Katz, Adi, May, Geoffery, McLaughlin, Katie, Mueller, Sven, Nawijn, Laura, Nelson, Steven, Neufeld, Richard, Nitschke, Jack, OLeary, Erin, Olatunji, Bunmi, Olff, Miranda, Peverill, Matthew, Phan, K, Qi, Rongfeng, Quidé, Yann, Rektor, Ivan, Ressler, Kerry, Riha, Pavel, Ross, Marisa, Rosso, Isabelle, Salminen, Lauren, Sambrook, Kelly, Schmahl, Christian, Shenton, Martha, Sheridan, Margaret, Shih, Chiahao, Sicorello, Maurizio, Sierk, Anika, and van Rooij, Sanne

Subjects
Classification, Deep learning, Machine learning, Multimodal MRI, Posttraumatic stress disorder, Humans, Stress Disorders, Post-Traumatic, Reproducibility of Results, Big Data, Neuroimaging, Magnetic Resonance Imaging, Brain
Abstract

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.

Published
2023

13. Rare copy number variation in posttraumatic stress disorder

Author

Maihofer, Adam X, Engchuan, Worrawat, Huguet, Guillaume, Klein, Marieke, MacDonald, Jeffrey R, Shanta, Omar, Thiruvahindrapuram, Bhooma, Jean-louis, Martineau, Saci, Zohra, Jacquemont, Sebastien, Scherer, Stephen W, Ketema, Elizabeth, Aiello, Allison E, Amstadter, Ananda B, Avdibegović, Esmina, Babic, Dragan, Baker, Dewleen G, Bisson, Jonathan I, Boks, Marco P, Bolger, Elizabeth A, Bryant, Richard A, Bustamante, Angela C, Caldas-de-Almeida, Jose Miguel, Cardoso, Graça, Deckert, Jurgen, Delahanty, Douglas L, Domschke, Katharina, Dunlop, Boadie W, Dzubur-Kulenovic, Alma, Evans, Alexandra, Feeny, Norah C, Franz, Carol E, Gautam, Aarti, Geuze, Elbert, Goci, Aferdita, Hammamieh, Rasha, Jakovljevic, Miro, Jett, Marti, Jones, Ian, Kaufman, Milissa L, Kessler, Ronald C, King, Anthony P, Kremen, William S, Lawford, Bruce R, Lebois, Lauren AM, Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D, Lugonja, Bozo, Luykx, Jurjen J, Lyons, Michael J, Mavissakalian, Matig R, McLaughlin, Katie A, McLean, Samuel A, Mehta, Divya, Mellor, Rebecca, Morris, Charles Phillip, Muhie, Seid, Orcutt, Holly K, Peverill, Matthew, Ratanatharathorn, Andrew, Risbrough, Victoria B, Rizzo, Albert, Roberts, Andrea L, Rothbaum, Alex O, Rothbaum, Barbara O, Roy-Byrne, Peter, Ruggiero, Kenneth J, Rutten, Bart PF, Schijven, Dick, Seng, Julia S, Sheerin, Christina M, Sorenson, Michael A, Teicher, Martin H, Uddin, Monica, Ursano, Robert J, Vinkers, Christiaan H, Voisey, Joanne, Weber, Heike, Winternitz, Sherry, Xavier, Miguel, Yang, Ruoting, McD Young, Ross, Zoellner, Lori A, Salem, Rany M, Shaffer, Richard A, Wu, Tianying, Ressler, Kerry J, Stein, Murray B, Koenen, Karestan C, Sebat, Jonathan, and Nievergelt, Caroline M

Subjects
Post-Traumatic Stress Disorder (PTSD), Mental Health, Human Genome, Genetics, Neurosciences, Brain Disorders, Mental health, Humans, DNA Copy Number Variations, Stress Disorders, Post-Traumatic, Genome, Brain, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Psychiatric Genomics Consortium PTSD Working Group, Psychiatric Genomics Consortium CNV Working Group, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q

Published
2022

14. Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder

Author

Mundy, Jessica, Hübel, Christopher, Gelernter, Joel, Levey, Daniel, Murray, Robin M, Skelton, Megan, Stein, Murray B, Maihofer, Adam X, Nievergelt, Caroline M, Baker, Dewlen G, Risborough, Victoria B, Calabrese, Joseph R, Galea, Sandro, Stein, Dan J, Koen, Nastassja, Dalvie, Shareefa, Aiello, Allison E, Roberts, Andrea L, Koenen, KC, Solovieff, Nadia, Kranzler, Henry R, Zhao, Hongyu, Farrer, Lindsay A, Johnson, Eric Otto, Rice, John P, Bierut, Laura J, Saccone, Nancy L, McFarlane, Alexander, Forbes, David, Silove, Derrick, O'Donnell, Meaghan, Bryant, Richard A, van Hooff, Miranda, Sponheim, Scott R, Disner, Seth G, Pietrzak, Robert H, Chen, Chia-Yen, Smoller, Jordan W, Ursano, Robert J, Kessler, Ronald C, Junglen, Angela G, Delahanty, Douglas L, Amstadter, Ananda B, Sheerin, Christina M, Ruggiero, Ken, McLaughlin, Katie A, Peverill, Matthew, Caldas-de-Almeida, JM, Austin, S Bryn, Gelaye, Bizu, Williams, Michelle A, Sanchez, Sixto E, Franz, Carol E, Panizzon, Matthew S, Lyons, Michael J, Kremen, William S, Andreassen, Ole A, Dale, Anders M, Rutten, Bart PF, Vinkers, Christiaan, Schijven, Dick, Geuze, Elbert, Vermetten, Eric, Luykx, Jurjen J, Boks, Marco P, Ashley-Koch, Allison E, Beckham, Jean C, Garrett, Melanie E, Hauser, Michael A, Dennis, Michelle F, Kimbrel, Nathan A, Qin, Xue-Jun, Karstoft, Karen-Inge, Andersen, Soren B, Borglum, Anders D, Hougaard, David Michael, Bybjerg-Grauholm, Jonas, Duncan, Laramie E, Bµkvad-Hansen, Marie, Nordentoft, Merete, Mors, Ole, Mortensen, PB, Werge, Thomas, Thompson, Wesley K, Wang, Yunpeng, Heath, Andrew C, Nelson, Elliot C, Martin, Nicholas G, Gordon, Scott D, Wolf, Erika J, Logue, Mark W, Miller, Mark W, McGlinchey, Regina E, Milberg, William, Erbes, Christopher R, Polusny, Melissa A, Arbisi, Paul A, and Peterson, Alan L

Subjects
Prevention, Clinical Research, Genetics, Serious Mental Illness, Depression, Post-Traumatic Stress Disorder (PTSD), Mental Health, Brain Disorders, Anxiety Disorders, Major Depressive Disorder, Human Genome, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Good Health and Well Being, Posttraumatic stress disorder, major depressive disorder, psychological trauma, genetics, genetic correlations, polygenic risk scores, Million Veteran Program, Post Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium, Neurosciences, Public Health and Health Services, Psychology, Psychiatry
Abstract

BackgroundPosttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD.MethodsGenetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals.ResultsGenetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01-1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ2 > 166, p < 0.001).ConclusionsOur findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.

Published
2022

16. A comparison of methods to harmonize cortical thickness measurements across scanners and sites

Author

Sun, Delin, Rakesh, Gopalkumar, Haswell, Courtney C, Logue, Mark, Baird, C Lexi, O'Leary, Erin N, Cotton, Andrew S, Xie, Hong, Tamburrino, Marijo, Chen, Tian, Dennis, Emily L, Jahanshad, Neda, Salminen, Lauren E, Thomopoulos, Sophia I, Rashid, Faisal, Ching, Christopher RK, Koch, Saskia BJ, Frijling, Jessie L, Nawijn, Laura, van Zuiden, Mirjam, Zhu, Xi, Suarez-Jimenez, Benjamin, Sierk, Anika, Walter, Henrik, Manthey, Antje, Stevens, Jennifer S, Fani, Negar, van Rooij, Sanne JH, Stein, Murray, Bomyea, Jessica, Koerte, Inga K, Choi, Kyle, van der Werff, Steven JA, Vermeiren, Robert RJM, Herzog, Julia, Lebois, Lauren AM, Baker, Justin T, Olson, Elizabeth A, Straube, Thomas, Korgaonkar, Mayuresh S, Andrew, Elpiniki, Zhu, Ye, Li, Gen, Ipser, Jonathan, Hudson, Anna R, Peverill, Matthew, Sambrook, Kelly, Gordon, Evan, Baugh, Lee, Forster, Gina, Simons, Raluca M, Simons, Jeffrey S, Magnotta, Vincent, Maron-Katz, Adi, du Plessis, Stefan, Disner, Seth G, Davenport, Nicholas, Grupe, Daniel W, Nitschke, Jack B, deRoon-Cassini, Terri A, Fitzgerald, Jacklynn M, Krystal, John H, Levy, Ifat, Olff, Miranda, Veltman, Dick J, Wang, Li, Neria, Yuval, De Bellis, Michael D, Jovanovic, Tanja, Daniels, Judith K, Shenton, Martha, van de Wee, Nic JA, Schmahl, Christian, Kaufman, Milissa L, Rosso, Isabelle M, Sponheim, Scott R, Hofmann, David Bernd, Bryant, Richard A, Fercho, Kelene A, Stein, Dan J, Mueller, Sven C, Hosseini, Bobak, Phan, K Luan, McLaughlin, Katie A, Davidson, Richard J, Larson, Christine L, May, Geoffrey, Nelson, Steven M, Abdallah, Chadi G, Gomaa, Hassaan, Etkin, Amit, Seedat, Soraya, Harpaz-Rotem, Ilan, Liberzon, Israel, van Erp, Theo GM, Quidé, Yann, Wang, Xin, Thompson, Paul M, and Morey, Rajendra A

Subjects
Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Child, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Stress Disorders, Post-Traumatic, Young Adult, Data Harmonization, Scanner Effects, Site Effects, Cortical Thickness, ComBat, ComBat-GAM, Linear Mixed-Effects Model, General Additive Model, PTSD, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.

Published
2022

22. Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Author

Maihofer, Adam X, Choi, Karmel W, Coleman, Jonathan RI, Daskalakis, Nikolaos P, Denckla, Christy A, Ketema, Elizabeth, Morey, Rajendra A, Polimanti, Renato, Ratanatharathorn, Andrew, Torres, Katy, Wingo, Aliza P, Zai, Clement C, Aiello, Allison E, Almli, Lynn M, Amstadter, Ananda B, Andersen, Soren B, Andreassen, Ole A, Arbisi, Paul A, Ashley-Koch, Allison E, Austin, S Bryn, Avdibegović, Esmina, Borglum, Anders D, Babić, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G, Beckham, Jean C, Bierut, Laura J, Bisson, Jonathan I, Boks, Marco P, Bolger, Elizabeth A, Bradley, Bekh, Brashear, Meghan, Breen, Gerome, Bryant, Richard A, Bustamante, Angela C, Bybjerg-Grauholm, Jonas, Calabrese, Joseph R, Caldas-de-Almeida, José M, Chen, Chia-Yen, Dale, Anders M, Dalvie, Shareefa, Deckert, Jürgen, Delahanty, Douglas L, Dennis, Michelle F, Disner, Seth G, Domschke, Katharina, Duncan, Laramie E, Džubur Kulenović, 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, Gautam, Aarti, Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles F, Goçi, Aferdita, Gordon, Scott D, Guffanti, Guia, Hammamieh, Rasha, Hauser, Michael A, Heath, Andrew C, Hemmings, Sian MJ, Hougaard, David Michael, Jakovljević, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue-Jun, 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, Liberzon, Israel, Linnstaedt, Sarah D, Logue, Mark W, Lori, Adriana, Lugonja, Božo, Luykx, Jurjen J, Lyons, Michael J, Maples-Keller, Jessica L, Marmar, Charles, Martin, Nicholas G, Maurer, Douglas, and Mavissakalian, Matig R

Subjects
Biological Sciences, Genetics, Anxiety Disorders, Mental Health, Brain Disorders, Post-Traumatic Stress Disorder (PTSD), Prevention, Human Genome, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Phenotype, Polymorphism, Single Nucleotide, Stress Disorders, Post-Traumatic, GWAS, Heritability, PTSD, PheWAS, Trauma, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences, Psychology
Abstract

BackgroundPosttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs).MethodsA GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms.ResultsGWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program.ConclusionsThrough using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.

Published
2022

25. Is Fear Extinction Impairment Central to Psychopathology?

Author

Bryant, Richard A., Geyer, Mark A., Series Editor, Marsden, Charles A., Series Editor, Ellenbroek, Bart A., Series Editor, Barnes, Thomas R. E., Series Editor, Andersen, Susan L., Series Editor, Paulus, Martin P., Series Editor, Olivier, Jocelien, Series Editor, Milad, Mohammed R., editor, and Norrholm, Seth D., editor

Published
2023
Full Text
View/download PDF

26. Five Essential Elements of Immediate and Mid–Term Mass Trauma Intervention: Empirical Evidence

Author

Hobfoll, Stevan E, Watson, Patricia, Bell, Carl C, Bryant, Richard A, Brymer, Melissa J, Friedman, Matthew J, Friedman, Merle, Gersons, Berthold PR, de Jong, Joop, Layne, Christopher M, Maguen, Shira, Neria, Yuval, Norwood, Ann E, Pynoos, Robert S, Reissman, Dori, Ruzek, Josef I, Shalev, Arieh Y, Solomon, Zahava, Steinberg, Alan M, and Ursano, Robert J

Subjects
Clinical Research, Behavioral and Social Science, Violence Research, Violence Against Women, Peace, Justice and Strong Institutions, Disasters, Humans, Violence, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract

Given the devastation caused by disasters and mass violence, it is critical that intervention policy be based on the most updated research findings. However, to date, no evidence-based consensus has been reached supporting a clear set of recommendations for intervention during the immediate and the mid-term post mass trauma phases. Because it is unlikely that there will be evidence in the near or mid-term future from clinical trials that cover the diversity of disaster and mass violence circumstances, we assembled a worldwide panel of experts on the study and treatment of those exposed to disaster and mass violence to extrapolate from related fields of research, and to gain consensus on intervention principles. We identified five empirically supported intervention principles that should be used to guide and inform intervention and prevention efforts at the early to mid-term stages. These are promoting: 1) a sense of safety, 2) calming, 3) a sense of self- and community efficacy, 4) connectedness, and 5) hope.

Published
2021

27. Efficacy and moderators of efficacy of cognitive behavioural therapies with a trauma focus in children and adolescents: an individual participant data meta-analysis of randomised trials

Author

de Haan, Anke, Meiser-Stedman, Richard, Landolt, Markus A, Kuhn, Isla, Black, Melissa J, Klaus, Kristel, Patel, Shivam D, Fisher, David J, Haag, Christina, Ukoumunne, Obioha C, Jones, Benjamin G, Flaiyah, Ashraf Muwafaq, Catani, Claudia, Dawson, Katie, Bryant, Richard A, de Roos, Carlijn, Ertl, Verena, Foa, Edna B, Ford, Julian D, Gilboa-Schechtman, Eva, Tutus, Dunja, Hermenau, Katharin, Hecker, Tobias, Hultmann, Ole, Axberg, Ulf, Jaberghaderi, Nasrin, Jensen, Tine K, Ormhaug, Silje M, Kenardy, Justin, Lindauer, Ramon J L, Diehle, Julia, Murray, Laura K, Kane, Jeremy C, Peltonen, Kirsi, Kangaslampi, Samuli, Robjant, Katy, Koebach, Anke, Rosner, Rita, Rossouw, Jaco, Smith, Patrick, Tonge, Bruce J, Hitchcock, Caitlin, and Dalgleish, Tim

Published
2024
Full Text
View/download PDF

30. Addressing mental health problems among persons without stable housing in the context of the COVID-19 pandemic: study protocol for a randomised trial. RESPOND – France

Author

Melchior, Maria, Figueiredo, Natasha, Roversi, Aurélia, Dubanchet, Alexandre, Bui, Eric, Vadell-Martínez, Julian, Barbui, Corrado, Purgato, Marianna, Ayuso-Mateos, José Luis, Mediavilla, Roberto, McDaid, David, Park, A-La, Petri-Romão, Papoula, Kalisch, Raffael, Nicaise, Pablo, Lorant, Vincent, Sijbrandij, Marit, Witteveen, Anke B., Bryant, Richard, Felez, Mireia, Underhill, James, Pollice, Giulia, and Tortelli, Andrea

Published
2023
Full Text
View/download PDF

31. Effectiveness of a scalable, remotely delivered stepped-care intervention to reduce symptoms of psychological distress among Polish migrant workers in the Netherlands: study protocol for the RESPOND randomised controlled trial

Author

Roos, Rinske, Witteveen, Anke B., Ayuso-Mateos, José Luis, Barbui, Corrado, Bryant, Richard A., Felez-Nobrega, Mireia, Figueiredo, Natasha, Kalisch, Raffael, Haro, Josep Maria, McDaid, David, Mediavilla, Roberto, Melchior, Maria, Nicaise, Pablo, Park, A-La, Petri-Romão, Papoula, Purgato, Marianna, van Straten, Annemieke, Tedeschi, Federico, Underhill, James, and Sijbrandij, Marit

Published
2023
Full Text
View/download PDF

32. Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures

Author

Figiel, Sandy, Yin, Wencheng, Doultsinos, Dimitrios, Erickson, Andrew, Poulose, Ninu, Singh, Reema, Magnussen, Anette, Anbarasan, Thineskrishna, Teague, Renuka, He, Mengxiao, Lundeberg, Joakim, Loda, Massimo, Verrill, Clare, Colling, Richard, Gill, Pelvender S., Bryant, Richard J., Hamdy, Freddie C., Woodcock, Dan J., Mills, Ian G., Cussenot, Olivier, and Lamb, Alastair D.

Published
2023
Full Text
View/download PDF

33. Views and experiences of migrants and stakeholders involved in social and health care for migrants in Italy during the COVID-19 pandemic: a qualitative study

Author

Lotito, Claudia, Turrini, Giulia, Purgato, Marianna, Bryant, Richard A., Felez-Nobrega, Mireia, Haro, Josep Maria, Lorant, Vincent, McDaid, David, Mediavilla, Roberto, Melchior, Maria, Nicaise, Pablo, Nosè, Michela, Park, A-La, McGreevy, Kerry R., Roos, Rinske, Tortelli, Andrea, Underhill, James, Martinez, Julian Vadell, Witteveen, Anke, Sijbrandij, Marit, and Barbui, Corrado

Published
2023
Full Text
View/download PDF

37. Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis

Author

Wang, Xin, Xie, Hong, Chen, Tian, Cotton, Andrew S, Salminen, Lauren E, Logue, Mark W, Clarke-Rubright, Emily K, Wall, John, Dennis, Emily L, O’Leary, Brian M, Abdallah, Chadi G, Andrew, Elpiniki, Baugh, Lee A, Bomyea, Jessica, Bruce, Steven E, Bryant, Richard, Choi, Kyle, Daniels, Judith K, Davenport, Nicholas D, Davidson, Richard J, DeBellis, Michael, deRoon-Cassini, Terri, Disner, Seth G, Fani, Negar, Fercho, Kelene A, Fitzgerald, Jacklynn, Forster, Gina L, Frijling, Jessie L, Geuze, Elbert, Gomaa, Hassaan, Gordon, Evan M, Grupe, Dan, Harpaz-Rotem, Ilan, Haswell, Courtney C, Herzog, Julia I, Hofmann, David, Hollifield, Michael, Hosseini, Bobak, Hudson, Anna R, Ipser, Jonathan, Jahanshad, Neda, Jovanovic, Tanja, Kaufman, Milissa L, King, Anthony P, Koch, Saskia BJ, Koerte, Inga K, Korgaonkar, Mayuresh S, Krystal, John H, Larson, Christine, Lebois, Lauren AM, Levy, Ifat, Li, Gen, Magnotta, Vincent A, Manthey, Antje, May, Geoffrey, McLaughlin, Katie A, Mueller, Sven C, Nawijn, Laura, Nelson, Steven M, Neria, Yuval, Nitschke, Jack B, Olff, Miranda, Olson, Elizabeth A, Peverill, Matthew, Phan, K Luan, Rashid, Faisal M, Ressler, Kerry, Rosso, Isabelle M, Sambrook, Kelly, Schmahl, Christian, Shenton, Martha E, Sierk, Anika, Simons, Jeffrey S, Simons, Raluca M, Sponheim, Scott R, Stein, Murray B, Stein, Dan J, Stevens, Jennifer S, Straube, Thomas, Suarez-Jimenez, Benjamin, Tamburrino, Marijo, 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, Zhu, Ye, Zhu, Xi, Thompson, Paul M, Morey, Rajendra A, and Liberzon, Israel

Subjects
Clinical Research, Behavioral and Social Science, Mental Health, Post-Traumatic Stress Disorder (PTSD), Neurosciences, Brain Disorders, Mental health, Cerebral Cortex, Genomics, Humans, Magnetic Resonance Imaging, Stress Disorders, Post-Traumatic, Temporal Lobe, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values

Published
2021

38. Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium

Author

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, and van der Wee, Nic JA

Subjects
Biological Psychology, Psychology, Brain Disorders, Anxiety Disorders, Physical Injury - Accidents and Adverse Effects, Biomedical Imaging, Clinical Research, Mental Health, Post-Traumatic Stress Disorder (PTSD), Mental Illness, Neurosciences, Behavioral and Social Science, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Anisotropy, Brain, Diffusion Tensor Imaging, Female, Humans, Male, Middle Aged, Stress Disorders, Post-Traumatic, White Matter, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

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.

Published
2021

42. Trauma and posttraumatic stress disorder modulate polygenic predictors of hippocampal and amygdala volume

Author

Zheng, Yuanchao, Garrett, Melanie E, Sun, Delin, Clarke-Rubright, Emily K, Haswell, Courtney C, Maihofer, Adam X, Elman, Jeremy A, Franz, Carol E, Lyons, Michael J, Kremen, William S, Peverill, Matthew, Sambrook, Kelly, McLaughlin, Katie A, Davenport, Nicholas D, Disner, Seth, Sponheim, Scott R, Andrew, Elpiniki, Korgaonkar, Mayuresh, Bryant, Richard, Varkevisser, Tim, Geuze, Elbert, Coleman, Jonathan, Beckham, Jean C, Kimbrel, Nathan A, Sullivan, Danielle, Miller, Mark, Hayes, Jasmeet, Verfaellie, Mieke, Wolf, Erika, Salat, David, Spielberg, Jeffrey M, Milberg, William, McGlinchey, Regina, Dennis, Emily L, Thompson, Paul M, Medland, Sarah, Jahanshad, Neda, Nievergelt, Caroline M, Ashley-Koch, Allison E, Logue, Mark W, and Morey, Rajendra A

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Neurosciences, Mental Health, Behavioral and Social Science, Brain Disorders, Post-Traumatic Stress Disorder (PTSD), Genetics, Anxiety Disorders, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Amygdala, Brain, Hippocampus, Humans, Magnetic Resonance Imaging, Stress Disorders, Post-Traumatic, Clinical Sciences, Public Health and Health Services, Clinical sciences, Biological psychology
Abstract

The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures. These were applied to a target sample enriched for childhood trauma and PTSD. Subcortical volume PGS from the discovery sample were strongly associated in our trauma/PTSD enriched sample (n = 7580) with respective subcortical volumes of the hippocampus (p = 1.10 × 10-20), thalamus (p = 7.46 × 10-10), caudate (p = 1.97 × 10-18), putamen (p = 1.7 × 10-12), and nucleus accumbens (p = 1.99 × 10-7). We found a significant association between the hippocampal volume PGS and hippocampal volume in control subjects from our sample, but was absent in individuals with PTSD (GxE; (beta = -0.10, p = 0.027)). This significant GxE (PGS × PTSD) relationship persisted (p

Published
2021

43. Genomic influences on self-reported childhood maltreatment.

Author

Dalvie, Shareefa, Maihofer, Adam X, Coleman, Jonathan RI, Bradley, Bekh, Breen, Gerome, Brick, Leslie A, Chen, Chia-Yen, Choi, Karmel W, Duncan, Laramie E, Guffanti, Guia, Haas, Magali, Harnal, Supriya, Liberzon, Israel, Nugent, Nicole R, Provost, Allison C, Ressler, Kerry J, Torres, Katy, Amstadter, Ananda B, Bryn Austin, S, Baker, Dewleen G, Bolger, Elizabeth A, Bryant, Richard A, Calabrese, Joseph R, Delahanty, Douglas L, Farrer, Lindsay A, Feeny, Norah C, Flory, Janine D, Forbes, David, Galea, Sandro, Gautam, Aarti, Gelernter, Joel, Hammamieh, Rasha, Jett, Marti, Junglen, Angela G, Kaufman, Milissa L, Kessler, Ronald C, Khan, Alaptagin, Kranzler, Henry R, Lebois, Lauren AM, Marmar, Charles, Mavissakalian, Matig R, McFarlane, Alexander, Donnell, Meaghan O', Orcutt, Holly K, Pietrzak, Robert H, Risbrough, Victoria B, Roberts, Andrea L, Rothbaum, Alex O, Roy-Byrne, Peter, Ruggiero, Ken, Seligowski, Antonia V, Sheerin, Christina M, Silove, Derrick, Smoller, Jordan W, Stein, Murray B, Teicher, Martin H, Ursano, Robert J, Van Hooff, Miranda, Winternitz, Sherry, Wolff, Jonathan D, Yehuda, Rachel, Zhao, Hongyu, Zoellner, Lori A, Stein, Dan J, Koenen, Karestan C, and Nievergelt, Caroline M

Subjects
Clinical Sciences, Public Health and Health Services, Psychology
Abstract

Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h2snp), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltreatment, and (4) quantify genetic overlap of childhood maltreatment with mental and physical health-related phenotypes, and condition the top hits from our analyses when such overlap is present. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n = 124,000) and a replication sample from the Psychiatric Genomics Consortium-posttraumatic stress disorder group (PGC-PTSD) (n = 26,290). h2snp for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression. PRS was calculated using PRSice and mtCOJO was used to perform conditional analysis. Two genome-wide significant loci associated with childhood maltreatment (rs142346759, p = 4.35 × 10-8, FOXP1; rs10262462, p = 3.24 × 10-8, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h2snp for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r2 = 0.0025; p = 1.8 × 10-15). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (rg = 0.70, p = 4.65 × 10-40), although we show evidence that our top hits may be specific to childhood maltreatment. This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. Speculatively, FOXP genes might influence externalizing traits and so be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with a range of phenotypes, may ultimately be useful in in developing targeted treatment and prevention strategies.

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results