المؤلفون: 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, Nievergelt, Caroline M

المصدر: Molecular Psychiatry. 27(12)

مصطلحات موضوعية: 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

الوصف: 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

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/98c4g3prTest

المؤلفون: 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, Peterson, Alan L

المصدر: Psychological Medicine. 52(16)

مصطلحات موضوعية: 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

الوصف: 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.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5gp3q7wgTest

المؤلفون: He, Qiang, Wang, Wenjing, Xu, Dingkang, Xiong, Yang, Tao, Chuanyuan, You, Chao, Ma, Lu, Ma, Junpeng, Nievergelt, Caroline M., Maihofer, Adam X., Klengel, Torsten, Atkinson, Elizabeth G., Chen, Chia Yen, Choi, Karmel W., Coleman, Jonathan R.I., Dalvie, Shareefa, Duncan, Laramie E., Logue, Mark W., 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, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles, Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Harnal, Supriya, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M.J., 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 A.M., 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 P.F., 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., Solovieff, Nadia, Sponheim, Scott R., Stein, Dan J., 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, Keith A., Young, Ross Mc D., Zhao, Hongyu, Zoellner, Lori A., Liberzon, Israel, Ressler, Kerry J., Haas, Magali, Koenen, Karestan C.

المساهمون: Cardiologie, Onderzoeksgroep 2, Brain, MGGZ, Hersenen-Medisch 1, Neurogenetica, Diagnostiek & Vroege Psychose Medisch

مصطلحات موضوعية: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Biological Psychiatry

الوصف: Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.

وصف الملف: application/pdf

العلاقة: https://dspace.library.uu.nl/handle/1874/451380Test

الإتاحة: https://dspace.library.uu.nl/handle/1874/451380Test

المؤلفون: Sheerin, Christina M., O’Hara-Payne, Rowan K., Lancaster, Eva E., Suarez-Rivas, Hailie, Chatzinakos, Chris, Prom-Wormley, Elizabeth C., Peterson, Roseann E.

المصدر: Frontiers in Genetics ; volume 14 ; ISSN 1664-8021

مصطلحات موضوعية: Genetics (clinical), Genetics, Molecular Medicine

الوصف: Introduction: Genetic factors impact alcohol consumption and use disorder (AUD), with large-scale genome-wide association studies (GWAS) identifying numerous associated variants. Aggregate genetic methods in combination with important environmental factors (e.g., interpersonal trauma [IPT]) can be applied to expand our understanding of the ways by which genetic and environmental variables work together to influence alcohol consumption and disordered use. The present study aimed to detail the relationships between genome-wide polygenic scores (PGS) for alcohol phenotypes (i.e., alcohol consumption and AUD status) and IPT exposure as well as the interaction between them across ancestry. Methods: Data were drawn from the Spit for Science (S4S) study, a US college student population, where participants reported on IPT exposure prior to college and alcohol consumption and problems during college (N = 9,006; ancestry: 21.3% African [AFR], 12.5% Admixed Americas [AMR], 9.6% East Asian [EAS], 48.1% European [EUR], 8.6% South Asian [SAS]). Two trans-ancestry PGS were constructed, one for alcohol consumption and another for AUD, using large-scale GWAS summary statistics from multiple ancestries weighted using PRS-CSx. Regression models were applied to test for the presence of associations between alcohol-PGS and IPT main and interaction effects. Results: In the meta-analysis across ancestry groups, IPT exposure and PGS were significantly associated with alcohol consumption (β IPT = 0.31, P IPT = 0.0002; β PGS = 0.09, P PGS = 0.004) and AUD (OR IPT = 1.12, P IPT = 3.5 × 10 −8 ; OR PGS = 1.02, P PGS = 0.002). No statistically significant interactions were detected between IPT and sex nor between IPT and PGS. When inspecting ancestry specific results, the alcohol consumption-PGS and AUD-PGS were only statistically significant in the EUR ancestry group (β PGS = 0.09, P PGS = 0.04; OR PGS = 1.02, P PGS = 0.022, respectively). Discussion: IPT exposure prior to college was strongly associated with alcohol outcomes in this ...

الإتاحة: https://doi.org/10.3389/fgene.2023.1274381Test

المؤلفون: 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, Nievergelt, Caroline M

المصدر: Translational psychiatry. 10(1)

مصطلحات موضوعية: Clinical Sciences, Public Health and Health Services, Psychology

الوصف: 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.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7v35b96pTest

المؤلفون: Nievergelt, Caroline M, Maihofer, Adam X, Atkinson, Elizabeth G, Chen, Chia-Yen, Choi, Karmel W, Coleman, Jonathan R I, Daskalakis, Nikolaos P, Duncan, Laramie E, Polimanti, Renato, Aaronson, Cindy, Amstadter, Ananda B, Andersen, Soren B, Andreassen, Ole A, Arbisi, Paul A, Ashley-Koch, Allison E, Austin, S Bryn, Avdibegoviç, Esmina, Babić, Dragan, Bacanu, Silviu-Alin, Baker, Dewleen G, Batzler, Anthony, Beckham, Jean C, Belangero, Sintia, Benjet, Corina, Bergner, Carisa, Bierer, Linda M, Biernacka, Joanna M, Bierut, Laura J, Bisson, Jonathan I, Boks, Marco P, Bolger, Elizabeth A, Brandolino, Amber, Breen, Gerome, Bressan, Rodrigo Affonseca, Bryant, Richard A, Bustamante, Angela C, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Børglum, Anders D, Børte, Sigrid, Cahn, Leah, Calabrese, Joseph R, Caldas-de-Almeida, Jose Miguel, Chatzinakos, Chris, Cheema, Sheraz, Clouston, Sean A P, Colodro-Conde, Lucía, Coombes, Brandon J, Cruz-Fuentes, Carlos S, Dale, Anders M, Dalvie, Shareefa, Davis, Lea K, Deckert, Jürgen, Delahanty, Douglas L, Dennis, Michelle F, Desarnaud, Frank, DiPietro, Christopher P, Disner, Seth G, Docherty, Anna R, Domschke, Katharina, Dyb, Grete, Kulenović, Alma Džubur, Edenberg, Howard J, Evans, Alexandra, Fabbri, Chiara, Fani, Negar, Farrer, Lindsay A, Feder, Adriana, Feeny, Norah C, Flory, Janine D, Forbes, David, Franz, Carol E, Galea, Sandro, Garrett, Melanie E, Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles F, Goleva, Slavina B, Gordon, Scott D, Goçi, Aferdita, Grasser, Lana Ruvolo, Guindalini, Camila, Haas, Magali, Hagenaars, Saskia, Hauser, Michael A, Heath, Andrew C, Hemmings, Sian M J, Hesselbrock, Victor, Hickie, Ian B, Hogan, Kelleigh, Hougaard, David Michael, Huang, Hailiang, Huckins, Laura M, Hveem, Kristian, Jakovljević, Miro, Javanbakht, Arash, Jenkins, Gregory D, Johnson, Jessica, Jones, Ian, Jovanovic, Tanja, Karstoft, Karen-Inge, Kaufman, Milissa L, Kennedy, James L, Kessler, Ronald C, Khan, Alaptagin, Kimbrel, Nathan A, King, Anthony P, Koen, Nastassja, Kotov, Roman, Kranzler, Henry R, Krebs, Kristi, Kremen, William S, Kuan, Pei-Fen, Lawford, Bruce R, Lebois, Lauren A M, Lehto, Kelli, Levey, Daniel F, Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D, Logue, Mark W, Lori, Adriana, Lu, Yi, Luft, Benjamin J, Lupton, Michelle K, Luykx, Jurjen J, Makotkine, Iouri, Maples-Keller, Jessica L, Marchese, Shelby, Marmar, Charles, Martin, Nicholas G, Martínez-Levy, Gabriela A, McAloney, Kerrie, McFarlane, Alexander, McLaughlin, Katie A, McLean, Samuel A, Medland, Sarah E, Mehta, Divya, Meyers, Jacquelyn, Michopoulos, Vasiliki, Mikita, Elizabeth A, Milani, Lili, Milberg, William, Miller, Mark W, Morey, Rajendra A, Morris, Charles Phillip, Mors, Ole, Mortensen, Preben Bo, Mufford, Mary S, Nelson, Elliot C, Nordentoft, Merete, Norman, Sonya B, Nugent, Nicole R, O'Donnell, Meaghan, Orcutt, Holly K, Pan, Pedro M, Panizzon, Matthew S, Pathak, Gita A, Peters, Edward S, Peterson, Alan L, Peverill, Matthew, Pietrzak, Robert H, Polusny, Melissa A, Porjesz, Bernice, Powers, Abigail, Qin, Xue-Jun, Ratanatharathorn, Andrew, Risbrough, Victoria B, Roberts, Andrea L, Rothbaum, Alex O, Rothbaum, Barbara O, Roy-Byrne, Peter, Ruggiero, Kenneth J, Rung, Ariane, Runz, Heiko, Rutten, Bart P F, de Viteri, Stacey Saenz, Salum, Giovanni Abrahão, Sampson, Laura, Sanchez, Sixto E, Santoro, Marcos, Seah, Carina, Seedat, Soraya, Seng, Julia S, Shabalin, Andrey, Sheerin, Christina M, Silove, Derrick, Smith, Alicia K, Smoller, Jordan W, Sponheim, Scott R, Stein, Dan J, Stensland, Synne, Stevens, Jennifer S, Sumner, Jennifer A, Teicher, Martin H, Thompson, Wesley K, Tiwari, Arun K, Trapido, Edward, Uddin, Monica, Ursano, Robert J, Valdimarsdóttir, Unnur, Van Hooff, Miranda, Vermetten, Eric, Vinkers, Christiaan H, Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Waszczuk, Monika, Weber, Heike, Wendt, Frank R, Werge, Thomas, Williams, Michelle A, Williamson, Douglas E, Winsvold, Bendik S, Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J, Xia, Yan, Xiong, Ying, Yehuda, Rachel, Young, Keith A, Young, Ross McD, Zai, Clement C, Zai, Gwyneth C, Zervas, Mark, Zhao, Hongyu, Zoellner, Lori A, Zwart, John-Anker, deRoon-Cassini, Terri, van Rooij, Sanne J H, van den Heuvel, Leigh L, Stein, Murray B, Ressler, Kerry J, Koenen, Karestan C

المصدر: Nat Genet ; ISSN:1546-1718 ; Volume:56 ; Issue:5

الوصف: 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.

العلاقة: https://doi.org/10.1038/s41588-024-01707-9Test; https://pubmed.ncbi.nlm.nih.gov/38637617Test

الإتاحة: https://doi.org/10.1038/s41588-024-01707-9Test
https://pubmed.ncbi.nlm.nih.gov/38637617Test

المؤلفون: Cusack, Shannon E. (ORCID 0000-0001-8103-0575), Hicks, Terrell A., Bourdon, Jessica, Sheerin, Christina M., Overstreet, Cassie M., Kendler, Kenneth S., Dick, Danielle M., Amstadter, Ananda B.

المصدر: Journal of American College Health. 2019 67(2):123-131.

تمت مراجعته من قبل الزملاء: Y

Page Count: 9

Sponsoring Agency: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)

الواصفات: Incidence, Posttraumatic Stress Disorder, Correlation, Depression (Psychology), Anxiety, Intervention, Prevention, Symptoms (Individual Disorders), Risk, Student Attitudes, Identification, College Freshmen, Personality Measures, Stress Variables, Drinking, Predictor Variables, Measures (Individuals), Peer Groups, Antisocial Behavior

مصطلحات جغرافية: Virginia

مستخلص: Objective:This study examined the prevalence and correlates of probable posttraumatic stress disorder (PTSD) in freshman entering college and prospective associations of probable PTSD with additional outcomes. Participants: 2,310 students with data collected from Fall 2014 through Spring 2015. Methods: Incoming freshman completed a survey assessing for relevant variables at the beginning of fall semester and during the spring semester. Results: Seventy percent of the sample endorsed experiencing at least one potentially traumatic event (PTE). 34.4% of PTE exposed individuals met criteria for probable PTSD. Female sex, higher depressive and anxiety symptoms, and interpersonal PTE count were positively associated with PTSD symptoms. Higher PTSD symptoms were associated with higher anxiety and depressive symptoms, and new-onset interpersonal PTE. Conclusions: Identification of factors contributing to risk for PTSD is essential to inform prevention and intervention efforts. Intervention efforts should be targeted to students experiencing PTSD symptoms as they enter college.

Abstractor: As Provided

المؤلفون: Grove, Allen B., Green, Brooke A., Kaye, Savannah M., Sheerin, Christina M.

المصدر: Brain Sciences (2076-3425); Feb2024, Vol. 14 Issue 2, p129, 12p

مصطلحات موضوعية: POST-traumatic stress disorder, BEHAVIOR therapy, STRESS tolerance (Psychology), VETERANS

مستخلص: Irrational beliefs of Demandingness, Catastrophizing, Low Frustration Tolerance, and Depreciation have demonstrated prevalence in disparate areas of life, including psychopathology, the military, politics, religion, and education. Individuals with mental health concerns, such as Post-Traumatic Stress Disorder (PTSD), endorse elevations in such thoughts compared to the general population. This commentary describes the rationale for focusing on irrational beliefs in efforts to address PTSD and presents the Rational Emotive Behavior Therapy (REBT)-Informed Group for PTSD as a potential novel application of a well-established intervention. In support of these suggestions, we present a narrative review of the published work on irrational beliefs and REBT tenets as relevant for PTSD. We then introduce and describe the REBT-Informed Group intervention, summarize the prior preliminary research conducted by our group, and present some novel data from a re-analysis of this prior work. We end with commentary related to future directions of REBT approaches for PTSD to address limitations and expand the impact of the treatment to military and other Veteran or civilian populations. [ABSTRACT FROM AUTHOR]

: Copyright of Brain Sciences (2076-3425) is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Maihofer, Adam X., Choi, Karmel W., Coleman, Jonathan R. I., 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, J. rgen, 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 M. J., 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 A. M., 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, Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., Mehta, Divya, Mellor, Rebecca, Michopoulos, Vasiliki, Milberg, William, Miller, Mark W., Morris, Charles Phillip, Mors, Ole, Mortensen, Preben B., 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., Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Kenneth J., Rung, Ariane, Rutten, Bart P. F., 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., 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, Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Yehuda, Rachel, Young, Keith A., Young, Ross McD., Zhao, Hongyu, Zoellner, Lori A., Haas, Magali, Lasseter, Heather, Provost, Allison C., Salem, Rany M., Sebat, Jonathan, Shaffer, Richard A., Wu, Tianying, Ripke, Stephan, Daly, Mark J., Ressler, Kerry J., Koenen, Karestan C., Stein, Murray B., Nievergelt, Caroline M.

المصدر: Maihofer , A X , Choi , K W , Coleman , J R I , Daskalakis , N P , Denckla , C A , Ketema , E , Morey , R A , Polimanti , R , Ratanatharathorn , A , Torres , K , Wingo , A P , Zai , C C , Aiello , A E , Almli , L M , Amstadter , A B , Andersen , S B , Andreassen , O A , Arbisi , P A , Ashley-Koch , A E , Austin , S B , Avdibegović , ....

الوصف: Background: Posttraumatic 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). Methods: A 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. Results: GWASs 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. Conclusions: Through 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.

العلاقة: https://research.vumc.nl/en/publications/9de5b8ae-bc8e-4ca9-b7e7-182d97abc6d9Test

الإتاحة: https://doi.org/10.1016/j.biopsych.2021.09.020Test
https://research.vumc.nl/en/publications/9de5b8ae-bc8e-4ca9-b7e7-182d97abc6d9Test
http://www.scopus.com/inward/record.url?scp=85120747015&partnerID=8YFLogxKTest

المؤلفون: Maihofer, Adam X., Engchuan, Worrawat, Huguet, Guillaume, Klein, Marieke, MacDonald, Jeffrey R., Shanta, Omar, Thiruvahindrapuram, Bhooma, Martineau, Jean-louis, Saci, Zohra, Jacquemont, Sebastien, Scherer, Stephen W., Ketema, Elizabeth, Aiello, Allison E., Amstadter, Ananda B., Avdibegovic, 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, Graca, Deckert, Jurgen, Delahanty, Douglas L., Domschke, Katharina, Dunlop, Boadie W., Dzubur-Kulenovic, Alma, Evans, Alexandra, Feeny, Norah C., Frantz, Carol E., Gautam, Aarti, Geuze, Elbert, Goci Uka, 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 A. M., Lewis, Catrin, Liberton, Isreal, Linnstaed, Sarah D., Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Mavissakalian, Matig R., McLauglin, Katie A., McLean, Samuel A., Mehta, Divya, Mellor, Rebecca, Morris, Charles Philip, Muhie, Seid, Orcutt, Holly K., Peverill, Matthew, Ratanatharathorn, Andrew, Risbrough, Victoria, Rizzo, Albert, Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Kenneth J., Rutten, Bart P. F., 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, Young, Ros McD., Zoellner, Lori A., Salem, Rany M., Shaffer, Richard, Wu, Tianying, Ressler, Kerry J., Stein, Murray B., Koenen, Karestan C., Sebat, Jonathan, Nievergelt, Caroline M.

الوصف: 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 < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

وصف الملف: application/pdf

العلاقة: https://orca.cardiff.ac.uk/id/eprint/151967/4/s41380-022-01776-4.pdfTest; Maihofer, Adam X., Engchuan, Worrawat, Huguet, Guillaume, Klein, Marieke, MacDonald, Jeffrey R., Shanta, Omar, Thiruvahindrapuram, Bhooma, Martineau, Jean-louis, Saci, Zohra, Jacquemont, Sebastien, Scherer, Stephen W., Ketema, Elizabeth, Aiello, Allison E., Amstadter, Ananda B., Avdibegovic, Esmina, Babic, Dragan, Baker, Dewleen G., Bisson, Jonathan I. https://orca.cardiff.ac.uk/view/cardiffauthors/A054456N.htmlTest orcid:0000-0001-5170-1243 orcid:0000-0001-5170-1243, Boks, Marco P., Bolger, Elizabeth A., Bryant, Richard A., Bustamante, Angela C., Caldas-de-Almeida, Jose Miguel, Cardoso, Graca, Deckert, Jurgen, Delahanty, Douglas L., Domschke, Katharina, Dunlop, Boadie W., Dzubur-Kulenovic, Alma, Evans, Alexandra https://orca.cardiff.ac.uk/view/cardiffauthors/A0078993.htmlTest orcid:0000-0002-7718-4413 orcid:0000-0002-7718-4413, Feeny, Norah C., Frantz, Carol E., Gautam, Aarti, Geuze, Elbert, Goci Uka, Aferdita, Hammamieh, Rasha, Jakovljevic, Miro, Jett, Marti, Jones, Ian https://orca.cardiff.ac.uk/view/cardiffauthors/A069946N.htmlTest orcid:0000-0001-5821-5889 orcid:0000-0001-5821-5889, Kaufman, Milissa L., Kessler, Ronald C., King, Anthony P., Kremen, William S., Lawford, Bruce R., Lebois, Lauren A. M., Lewis, Catrin https://orca.cardiff.ac.uk/view/cardiffauthors/A077322D.htmlTest orcid:0000-0002-3818-9377 orcid:0000-0002-3818-9377, Liberton, Isreal, Linnstaed, Sarah D., Lugonja, Bozo https://orca.cardiff.ac.uk/view/cardiffauthors/A2106311C.htmlTest orcid:0000-0003-4206-2835 orcid:0000-0003-4206-2835, Luykx, Jurjen J., Lyons, Michael J., Mavissakalian, Matig R., McLauglin, Katie A., McLean, Samuel A., Mehta, Divya, Mellor, Rebecca, Morris, Charles Philip, Muhie, Seid, Orcutt, Holly K., Peverill, Matthew, Ratanatharathorn, Andrew, Risbrough, Victoria, Rizzo, Albert, Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Kenneth J., Rutten, Bart P. F., 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, Young, Ros McD., Zoellner, Lori A., Salem, Rany M., Shaffer, Richard, Wu, Tianying, Ressler, Kerry J., Stein, Murray B., Koenen, Karestan C., Sebat, Jonathan and Nievergelt, Caroline M. 2022. Rare copy number variation in posttraumatic stress disorder. Molecular Psychiatry 27 , pp. 5062-5069. 10.1038/s41380-022-01776-4 https://doi.org/10.1038/s41380-022-01776-4Test file https://orca.cardiff.ac.uk/id/eprint/151967/4/s41380-022-01776-4.pdfTest

الإتاحة: https://doi.org/10.1038/s41380-022-01776-4Test
https://orca.cardiff.ac.uk/id/eprint/151967Test/
https://orca.cardiff.ac.uk/id/eprint/151967/4/s41380-022-01776-4.pdfTest