Browsing by Author "Dennis, Michelle F"

Now showing 1 - 5 of 5
  • Thumbnail Image
    ItemOpen Access
    Autobiographical memory for stressful events: the role of autobiographical memory in posttraumatic stress disorder.
    (Conscious Cogn, 2011-09) Rubin, David C; Dennis, Michelle F; Beckham, Jean C
    To provide the three-way comparisons needed to test existing theories, we compared (1) most-stressful memories to other memories and (2) involuntary to voluntary memories (3) in 75 community dwelling adults with and 42 without a current diagnosis of posttraumatic stress disorder (PTSD). Each rated their three most-stressful, three most-positive, seven most-important and 15 word-cued autobiographical memories, and completed tests of personality and mood. Involuntary memories were then recorded and rated as they occurred for 2 weeks. Standard mechanisms of cognition and affect applied to extreme events accounted for the properties of stressful memories. Involuntary memories had greater emotional intensity than voluntary memories, but were not more frequently related to traumatic events. The emotional intensity, rehearsal, and centrality to the life story of both voluntary and involuntary memories, rather than incoherence of voluntary traumatic memories and enhanced availability of involuntary traumatic memories, were the properties of autobiographical memories associated with PTSD.
  • Thumbnail Image
    ItemOpen Access
    Gene Expression Analysis in Three Posttraumatic Stress Disorder Cohorts Implicates Inflammation and Innate Immunity Pathways and Uncovers Shared Genetic Risk With Major Depressive Disorder.
    (Frontiers in neuroscience, 2021-01) Garrett, Melanie E; Qin, Xue Jun; Mehta, Divya; Dennis, Michelle F; Marx, Christine E; Grant, Gerald A; VA Mid-Atlantic MIRECC Workgroup; PTSD Initiative; Injury and Traumatic Stress (INTRuST) Clinical Consortium; Psychiatric Genomics Consortium PTSD Group; Stein, Murray B; Kimbrel, Nathan A; Beckham, Jean C; Hauser, Michael A; Ashley-Koch, Allison E
    Posttraumatic stress disorder (PTSD) is a complex psychiatric disorder that can develop following exposure to traumatic events. The Psychiatric Genomics Consortium PTSD group (PGC-PTSD) has collected over 20,000 multi-ethnic PTSD cases and controls and has identified both genetic and epigenetic factors associated with PTSD risk. To further investigate biological correlates of PTSD risk, we examined three PGC-PTSD cohorts comprising 977 subjects to identify differentially expressed genes among PTSD cases and controls. Whole blood gene expression was quantified with the HumanHT-12 v4 Expression BeadChip for 726 OEF/OIF veterans from the Veterans Affairs (VA) Mental Illness Research Education and Clinical Center (MIRECC), 155 samples from the Injury and Traumatic Stress (INTRuST) Clinical Consortium, and 96 Australian Vietnam War veterans. Differential gene expression analysis was performed in each cohort separately followed by meta-analysis. In the largest cohort, we performed co-expression analysis to identify modules of genes that are associated with PTSD and MDD. We then conducted expression quantitative trait loci (eQTL) analysis and assessed the presence of eQTL interactions involving PTSD and major depressive disorder (MDD). Finally, we utilized PTSD and MDD GWAS summary statistics to identify regions that colocalize with eQTLs. Although not surpassing correction for multiple testing, the most differentially expressed genes in meta-analysis were interleukin-1 beta (IL1B), a pro-inflammatory cytokine previously associated with PTSD, and integrin-linked kinase (ILK), which is highly expressed in brain and can rescue dysregulated hippocampal neurogenesis and memory deficits. Pathway analysis revealed enrichment of toll-like receptor (TLR) and interleukin-1 receptor genes, which are integral to cellular innate immune response. Co-expression analysis identified four modules of genes associated with PTSD, two of which are also associated with MDD, demonstrating common biological pathways underlying the two conditions. Lastly, we identified four genes (UBA7, HLA-F, HSPA1B, and RERE) with high probability of a shared causal eQTL variant with PTSD and/or MDD GWAS variants, thereby providing a potential mechanism by which the GWAS variant contributes to disease risk. In summary, we provide additional evidence for genes and pathways previously reported and identified plausible novel candidates for PTSD. These data provide further insight into genetic factors and pathways involved in PTSD, as well as potential regions of pleiotropy between PTSD and MDD.
  • Thumbnail Image
    ItemOpen Access
    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.
  • Thumbnail Image
    ItemOpen Access
    Large epigenome-wide association study identifies multiple novel differentially methylated CpG sites associated with suicidal thoughts and behaviors in veterans.
    (Frontiers in psychiatry, 2023-01) Kimbrel, Nathan A; Garrett, Melanie E; Evans, Mariah K; Mellows, Clara; Dennis, Michelle F; Hair, Lauren P; Hauser, Michael A; VA Mid-Atlantic MIRECC Workgroup; Ashley-Koch, Allison E; Beckham, Jean C

    Introduction

    The U.S. suicide mortality rate has steadily increased during the past two decades, particularly among military veterans; however, the epigenetic basis of suicidal thoughts and behaviors (STB) remains largely unknown.

    Methods

    To address this issue, we conducted an epigenome-wide association study of DNA methylation (DNAm) of peripheral blood samples obtained from 2,712 U.S. military veterans.

    Results

    Three DNAm probes were significantly associated with suicide attempts, surpassing the multiple testing threshold (FDR q-value <0.05), including cg13301722 on chromosome 7, which lies between the genes SLC4A2 and CDK5; cg04724646 in PDE3A; and cg04999352 in RARRES3. cg13301722 was also found to be differentially methylated in the cerebral cortex of suicide decedents in a publicly-available dataset (p = 0.03). Trait enrichment analysis revealed that the CpG sites most strongly associated with STB in the present sample were also associated with smoking, alcohol consumption, maternal smoking, and maternal alcohol consumption, whereas pathway enrichment analysis revealed significant associations with circadian rhythm, adherens junction, insulin secretion, and RAP-1 signaling, each of which was recently associated with suicide attempts in a large, independent genome-wide association study of suicide attempts of veterans.

    Discussion

    Taken together, the present findings suggest that SLC4A2, CDK5, PDE3A, and RARRES3 may play a role in STB. CDK5, a member of the cyclin-dependent kinase family that is highly expressed in the brain and essential for learning and memory, appears to be a particularly promising candidate worthy of future study; however, additional work is still needed to replicate these finding in independent samples.
  • Thumbnail Image
    ItemOpen Access
    The genetic architecture of the human cerebral cortex.
    (Science (New York, N.Y.), 2020-03) Grasby, Katrina L; Jahanshad, Neda; Painter, Jodie N; Colodro-Conde, Lucía; Bralten, Janita; Hibar, Derrek P; Lind, Penelope A; Pizzagalli, Fabrizio; Ching, Christopher RK; McMahon, Mary Agnes B; Shatokhina, Natalia; Zsembik, Leo CP; Thomopoulos, Sophia I; Zhu, Alyssa H; Strike, Lachlan T; Agartz, Ingrid; Alhusaini, Saud; Almeida, Marcio AA; Alnæs, Dag; Amlien, Inge K; Andersson, Micael; Ard, Tyler; Armstrong, Nicola J; Ashley-Koch, Allison; Atkins, Joshua R; Bernard, Manon; Brouwer, Rachel M; Buimer, Elizabeth EL; Bülow, Robin; Bürger, Christian; Cannon, Dara M; Chakravarty, Mallar; Chen, Qiang; Cheung, Joshua W; Couvy-Duchesne, Baptiste; Dale, Anders M; Dalvie, Shareefa; de Araujo, Tânia K; de Zubicaray, Greig I; de Zwarte, Sonja MC; den Braber, Anouk; Doan, Nhat Trung; Dohm, Katharina; Ehrlich, Stefan; Engelbrecht, Hannah-Ruth; Erk, Susanne; Fan, Chun Chieh; Fedko, Iryna O; Foley, Sonya F; Ford, Judith M; Fukunaga, Masaki; Garrett, Melanie E; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Green, Melissa J; Groenewold, Nynke A; Grotegerd, Dominik; Gurholt, Tiril P; Gutman, Boris A; Hansell, Narelle K; Harris, Mathew A; Harrison, Marc B; Haswell, Courtney C; Hauser, Michael; Herms, Stefan; Heslenfeld, Dirk J; Ho, New Fei; Hoehn, David; Hoffmann, Per; Holleran, Laurena; Hoogman, Martine; Hottenga, Jouke-Jan; Ikeda, Masashi; Janowitz, Deborah; Jansen, Iris E; Jia, Tianye; Jockwitz, Christiane; Kanai, Ryota; Karama, Sherif; Kasperaviciute, Dalia; Kaufmann, Tobias; Kelly, Sinead; Kikuchi, Masataka; Klein, Marieke; Knapp, Michael; Knodt, Annchen R; Krämer, Bernd; Lam, Max; Lancaster, Thomas M; Lee, Phil H; Lett, Tristram A; Lewis, Lindsay B; Lopes-Cendes, Iscia; Luciano, Michelle; Macciardi, Fabio; Marquand, Andre F; Mathias, Samuel R; Melzer, Tracy R; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Moreira, Jose CV; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Najt, Pablo; Nakahara, Soichiro; Nho, Kwangsik; Olde Loohuis, Loes M; Orfanos, Dimitri Papadopoulos; Pearson, John F; Pitcher, Toni L; Pütz, Benno; Quidé, Yann; Ragothaman, Anjanibhargavi; Rashid, Faisal M; Reay, William R; Redlich, Ronny; Reinbold, Céline S; Repple, Jonathan; Richard, Geneviève; Riedel, Brandalyn C; Risacher, Shannon L; Rocha, Cristiane S; Mota, Nina Roth; Salminen, Lauren; Saremi, Arvin; Saykin, Andrew J; Schlag, Fenja; Schmaal, Lianne; Schofield, Peter R; Secolin, Rodrigo; Shapland, Chin Yang; Shen, Li; Shin, Jean; Shumskaya, Elena; Sønderby, Ida E; Sprooten, Emma; Tansey, Katherine E; Teumer, Alexander; Thalamuthu, Anbupalam; Tordesillas-Gutiérrez, Diana; Turner, Jessica A; Uhlmann, Anne; Vallerga, Costanza Ludovica; van der Meer, Dennis; van Donkelaar, Marjolein MJ; van Eijk, Liza; van Erp, Theo GM; van Haren, Neeltje EM; van Rooij, Daan; van Tol, Marie-José; Veldink, Jan H; Verhoef, Ellen; Walton, Esther; Wang, Mingyuan; Wang, Yunpeng; Wardlaw, Joanna M; Wen, Wei; Westlye, Lars T; Whelan, Christopher D; Witt, Stephanie H; Wittfeld, Katharina; Wolf, Christiane; Wolfers, Thomas; Wu, Jing Qin; Yasuda, Clarissa L; Zaremba, Dario; Zhang, Zuo; Zwiers, Marcel P; Artiges, Eric; Assareh, Amelia A; Ayesa-Arriola, Rosa; Belger, Aysenil; Brandt, Christine L; Brown, Gregory G; Cichon, Sven; Curran, Joanne E; Davies, Gareth E; Degenhardt, Franziska; Dennis, Michelle F; Dietsche, Bruno; Djurovic, Srdjan; Doherty, Colin P; Espiritu, Ryan; Garijo, Daniel; Gil, Yolanda; Gowland, Penny A; Green, Robert C; Häusler, Alexander N; Heindel, Walter; Ho, Beng-Choon; Hoffmann, Wolfgang U; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Jack, Clifford R; Jang, MiHyun; Jansen, Andreas; Kimbrel, Nathan A; Kolskår, Knut; Koops, Sanne; Krug, Axel; Lim, Kelvin O; Luykx, Jurjen J; Mathalon, Daniel H; Mather, Karen A; Mattay, Venkata S; Matthews, Sarah; Mayoral Van Son, Jaqueline; McEwen, Sarah C; Melle, Ingrid; Morris, Derek W; Mueller, Bryon A; Nauck, Matthias; Nordvik, Jan E; Nöthen, Markus M; O'Leary, Daniel S; Opel, Nils; Martinot, Marie-Laure Paillère; Pike, G Bruce; Preda, Adrian; Quinlan, Erin B; Rasser, Paul E; Ratnakar, Varun; Reppermund, Simone; Steen, Vidar M; Tooney, Paul A; Torres, Fábio R; Veltman, Dick J; Voyvodic, James T; Whelan, Robert; White, Tonya; Yamamori, Hidenaga; Adams, Hieab HH; Bis, Joshua C; Debette, Stephanie; Decarli, Charles; Fornage, Myriam; Gudnason, Vilmundur; Hofer, Edith; Ikram, M Arfan; Launer, Lenore; Longstreth, WT; Lopez, Oscar L; Mazoyer, Bernard; Mosley, Thomas H; Roshchupkin, Gennady V; Satizabal, Claudia L; Schmidt, Reinhold; Seshadri, Sudha; Yang, Qiong; Alzheimer’s Disease Neuroimaging Initiative; CHARGE Consortium; EPIGEN Consortium; IMAGEN Consortium; SYS Consortium; Parkinson’s Progression Markers Initiative; Alvim, Marina KM; Ames, David; Anderson, Tim J; Andreassen, Ole A; Arias-Vasquez, Alejandro; Bastin, Mark E; Baune, Bernhard T; Beckham, Jean C; Blangero, John; Boomsma, Dorret I; Brodaty, Henry; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bustillo, Juan R; Cahn, Wiepke; Cairns, Murray J; Calhoun, Vince; Carr, Vaughan J; Caseras, Xavier; Caspers, Svenja; Cavalleri, Gianpiero L; Cendes, Fernando; Corvin, Aiden; Crespo-Facorro, Benedicto; Dalrymple-Alford, John C; Dannlowski, Udo; de Geus, Eco JC; Deary, Ian J; Delanty, Norman; Depondt, Chantal; Desrivières, Sylvane; Donohoe, Gary; Espeseth, Thomas; Fernández, Guillén; Fisher, Simon E; Flor, Herta; Forstner, Andreas J; Francks, Clyde; Franke, Barbara; Glahn, David C; Gollub, Randy L; Grabe, Hans J; Gruber, Oliver; Håberg, Asta K; Hariri, Ahmad R; Hartman, Catharina A; Hashimoto, Ryota; Heinz, Andreas; Henskens, Frans A; Hillegers, Manon HJ; Hoekstra, Pieter J; Holmes, Avram J; Hong, L Elliot; Hopkins, William D; Hulshoff Pol, Hilleke E; Jernigan, Terry L; Jönsson, Erik G; Kahn, René S; Kennedy, Martin A; Kircher, Tilo TJ; Kochunov, Peter; Kwok, John BJ; Le Hellard, Stephanie; Loughland, Carmel M; Martin, Nicholas G; Martinot, Jean-Luc; McDonald, Colm; McMahon, Katie L; Meyer-Lindenberg, Andreas; Michie, Patricia T; Morey, Rajendra A; Mowry, Bryan; Nyberg, Lars; Oosterlaan, Jaap; Ophoff, Roel A; Pantelis, Christos; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda WJH; Polderman, Tinca JC; Posthuma, Danielle; Rietschel, Marcella; Roffman, Joshua L; Rowland, Laura M; Sachdev, Perminder S; Sämann, Philipp G; Schall, Ulrich; Schumann, Gunter; Scott, Rodney J; Sim, Kang; Sisodiya, Sanjay M; Smoller, Jordan W; Sommer, Iris E; St Pourcain, Beate; Stein, Dan J; Toga, Arthur W; Trollor, Julian N; Van der Wee, Nic JA; van 't Ent, Dennis; Völzke, Henry; Walter, Henrik; Weber, Bernd; Weinberger, Daniel R; Wright, Margaret J; Zhou, Juan; Stein, Jason L; Thompson, Paul M; Medland, Sarah E; Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group
    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.