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2. The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder: A Two-Sample Mendelian Randomization and Population-Based Sibling Comparison Study

Author

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, Avdibegovic, Esmina, Borglum, Anders D., Babic, 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, Jose Miguel, Chen, Chia-Yen, Dale, Anders M., Dalvie, Shareefa, Deckert, Jürgen, Delahanty, Douglas L., Dennis, Michelle F., Disner, Seth G., Domschke, Katharina, Duncan, Laramie E., Kulenovic, Alma Dzubur, 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., Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, 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, 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, Bozo, 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 Bo, 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., Luella van den Heuvel, Leigh, 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, Wu, Tianying, Ripke, Stephan, Daly, Mark J., Ressler, Kerry J., Koenen, Karestan C., Stein, Murray B., Nievergelt, Caroline M., Wendt, Frank R., Garcia-Argibay, Miguel, Cabrera-Mendoza, Brenda, Valdimarsdóttir, Unnur A., Nivard, Michel G., Larsson, Henrik, Mattheisen, Manuel, and Meier, Sandra M.

Published
2023
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3. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

Author

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, and Martin, Alicia R

Subjects
Humans, Genetic Predisposition to Disease, Ubiquitin-Protein Ligases, Stress Disorders, Post-Traumatic, Sex Factors, African Continental Ancestry Group, European Continental Ancestry Group, Veterans, Female, Male, Genome-Wide Association Study, Genetic Loci, Datasets as Topic, Human Genome, Mental Health, Biotechnology, Clinical Research, Post-Traumatic Stress Disorder (PTSD), Anxiety Disorders, Prevention, Genetics
Abstract

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.

Published
2019

5. Potential causal association between gut microbiome and posttraumatic stress disorder

Author

Cardiologie, Onderzoeksgroep 2, Brain, MGGZ, Hersenen-Medisch 1, Neurogenetica, Diagnostiek & Vroege Psychose Medisch, 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., Cardiologie, Onderzoeksgroep 2, Brain, MGGZ, Hersenen-Medisch 1, Neurogenetica, Diagnostiek & Vroege Psychose Medisch, 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, and Koenen, Karestan C.

Published
2024

6. Potential causal association between gut microbiome and posttraumatic stress disorder

Author

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, 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., and Lori, Adriana

Abstract

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.

Published
2024

10. Feasibility of Virtual Reality Exposure Therapy in the Treatment of Danish Veterans with Post-Traumatic Stress Disorder:A Mixed Method Pilot Study

Author

Folke, Sofie, Roitmann, Nikolai, Poulsen, Stig Bernt, Andersen, Søren B., Folke, Sofie, Roitmann, Nikolai, Poulsen, Stig Bernt, and Andersen, Søren B.

Abstract

The BraveMind virtual reality exposure therapy (VRET) has been developed and has shown efficacy for U.S. service members and veterans. As the first study to date, the present study examined the feasibility of BraveMind VRET for non-U.S. military veterans. Moreover, the study sought to explore in-depth the participants' experiences with BraveMind VRET. Nine Danish veterans with post-traumatic stress disorder (PTSD) after deployment to Afghanistan participated in the study. PTSD, depression, and quality of life were assessed at pretreatment, post-treatment, and 3-month followup. The treatment consisted of 10 BraveMind VRET sessions. Semistructured interviews with treatment completers were conducted post-treatment to ascertain views about the treatment, in general, and the BraveMind VR system in particular. Thematic qualitative analysis was conducted at the semantic level using an inductive approach. There were significant reductions in pre- to post-treatment self-reported PTSD and significant improvements in quality of life. Treatment gains were maintained at 3-month followup. Pre- to post-treatment Cohen's d effect sizes were large for self-reported PTSD (PTSD Checklist-Civilian Version [PCL-C]: d = 1.55). Qualitative results indicated that the virtual environment of the BraveMind VR system does not entirely map the reality of Danish soldiers in Afghanistan. However, this was not experienced as a hindering factor in therapy. Findings indicate that BraveMind VRET is an acceptable, safe, and effective treatment for Danish veterans with PTSD. The qualitative results emphasize the importance of a strong therapeutic alliance, as VRET is experienced as more emotional straining than regular trauma-focused therapy.

Published
2023

11. Early prediction of mental health problems following military deployment:Integrating pre- and post-deployment factors in neural network models

Author

Karstoft, Karen Inge, Eskelund, Kasper, Gradus, Jaimie L., Andersen, Søren B., Nissen, Lars R., Karstoft, Karen Inge, Eskelund, Kasper, Gradus, Jaimie L., Andersen, Søren B., and Nissen, Lars R.

Abstract

Military personnel deployed to war zones are at increased risk of mental health problems such as posttraumatic stress disorder (PTSD) or depression. Early pre- or post-deployment identification of those at highest risk of such problems is crucial to target intervention to those in need. However, sufficiently accurate models predicting objectively assessed mental health outcomes have not been put forward. In a sample consisting of all Danish military personnel who deployed to war zones for the first (N = 27,594), second (N = 11,083) and third (N = 5,161) time between 1992 and 2013, we apply neural networks to predict psychiatric diagnoses or use of psychotropic medicine in the years following deployment. Models are based on pre-deployment registry data alone or on pre-deployment registry data in combination with post-deployment questionnaire data on deployment experiences or early post-deployment reactions. Further, we identified the most central predictors of importance for the first, second, and third deployment. Models based on pre-deployment registry data alone had lower accuracy (AUCs ranging from 0.61 (third deployment) to 0.67 (first deployment)) than models including pre- and post-deployment data (AUCs ranging from 0.70 (third deployment) to 0.74 (first deployment)). Age at deployment, deployment year and previous physical trauma were important across deployments. Post-deployment predictors varied across deployments but included deployment exposures as well as early post-deployment symptoms. The results suggest that neural network models combining pre- and early post-deployment data can be utilized for screening tools that identify individuals at risk of severe mental health problems in the years following military deployment.

Published
2023

18. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Author

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., 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 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., 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 Mc D., Young, Keith A., Zhao, Hongyu, Zoellner, Lori A., Liberzon, Israel, Ressler, Kerry J., Haas, Magali, Koenen, Karestan C., 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., 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 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., 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 Mc D., Young, Keith A., Zhao, Hongyu, Zoellner, Lori A., Liberzon, Israel, Ressler, Kerry J., Haas, Magali, and Koenen, Karestan C.

Abstract

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.

Published
2019

19. Post-traumatic stress following military deployment:Genetic associations and cross-disorder genetic correlations

Author

Wang, Yunpeng, Karstoft, Karen-Inge, Nievergelt, Caroline M, Maihofer, Adam X, Stein, Murray B, Ursano, Robert J, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Hougaard, David M, Andreassen, Ole A, Werge, Thomas, Thompson, Wesley K, Andersen, Søren B, Wang, Yunpeng, Karstoft, Karen-Inge, Nievergelt, Caroline M, Maihofer, Adam X, Stein, Murray B, Ursano, Robert J, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Hougaard, David M, Andreassen, Ole A, Werge, Thomas, Thompson, Wesley K, and Andersen, Søren B

Abstract

BACKGROUND: Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder that occurs with relatively high frequency after deployment to warzones (∼10%). While twin studies have estimated the heritability to be up to 40%, thus indicating a considerable genetic component in the etiology, the biological mechanisms underlying risk and development of PTSD remain unknown.METHODS: Here, we conduct a genome-wide association study (GWAS; N = 2,481) to identify genome regions that associate with PTSD in a highly homogenous, trauma-exposed sample of Danish soldiers deployed to war and conflict zones. We perform integrated analyses of our results with gene-expression and chromatin-contact datasets to prioritized genes. We also leverage on other large GWAS (N>300,000) to investigate genetic correlations between PTSD and other psychiatric disorders and traits.RESULTS: We discover, but do not replicate, one region, 4q31, close to the IL15 gene, which is genome-wide significantly associated with PTSD. We demonstrate that gene-set enrichment, polygenic risk score and genetic correlation analyses show consistent and significant genetic correlations between PTSD and depression, insomnia and schizophrenia.LIMITATIONS: The limited sample size, the lack of replication, and the PTSD case definition by questionnaire are limitations to the study.CONCLUSIONS: Our results suggest that genetic perturbations of inflammatory response may contribute to the risk of PTSD. In addition, shared genetic components contribute to observed correlations between PTSD and depression, insomnia and schizophrenia.

Published
2019

20. Mental Health Care for Service Members and Their Families Across the Globe

Author

McGraw, Kate, primary, Adler, Jamie, additional, Andersen, Søren B, additional, Bailey, Suzanne, additional, Bennett, Clare, additional, Blasko, Kelly, additional, Blatt, Andrew D, additional, Greenberg, Neil, additional, Hodson, Stephanie, additional, Pittman, Demietrice, additional, Ruscio, Aimee C, additional, Stoltenberg, Christian D G, additional, Tate, Karyn E, additional, and Kuruganti, Kanchana, additional

Published
2019
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21. Does size really matter? A multisite study assessing the latent structure of the proposed ICD-11 and DSM-5 diagnostic criteria for PTSD ¿El tamaño importa realmente? Un estudio multicentro que evalúa la estructura latente de la CIE-11 propuesta y los criterios diagnósticos del DSM-5 para el TEPT 标题：症状数量重要吗？ 一个评估ICD-11提案和DSM-5 PTSD诊断标准的潜在结构的多站点研究

Author

Hansen, Mai, Hyland, Philip, Karstof, Karen-Inge, Vaegter, Henrik B., Bramsen, Rikke H., Nielsen, Annie B.S., Armour, Cherie, Andersen, Søren B., Høybye, Mette Terp, Kongshøj Larsen, Simone, and Andersen, Tonny E.

Abstract

Background: Researchers and clinicians within the field of trauma have to choose between different diagnostic descriptions of posttraumatic stress disorder (PTSD) in the DSM-5 and the proposed ICD-11. Several studies support different competing models of the PTSD structure according to both diagnostic systems; however, findings show that the choice of diagnostic systems can affect the estimated prevalence rates. Objectives: The present study aimed to investigate the potential impact of using a large (i.e. the DSM-5) compared to a small (i.e. the ICD-11) diagnostic description of PTSD. In other words, does the size of PTSD really matter? Methods: The aim was investigated by examining differences in diagnostic rates between the two diagnostic systems and independently examining the model fit of the competing DSM-5 and ICD-11 models of PTSD across three trauma samples: university students (N = 4213), chronic pain patients (N = 573), and military personnel (N = 118). Results: Diagnostic rates of PTSD were significantly lower according to the proposed ICD-11 criteria in the university sample, but no significant differences were found for chronic pain patients and military personnel. The proposed ICD-11 three-factor model provided the best fit of the tested ICD-11 models across all samples, whereas the DSM-5 seven-factor Hybrid model provided the best fit in the university and pain samples, and the DSM-5 six-factor Anhedonia model provided the best fit in the military sample of the tested DSM-5 models. Conclusions: The advantages and disadvantages of using a broad or narrow set of symptoms for PTSD can be debated, however, this study demonstrated that choice of diagnostic system may influence the estimated PTSD rates both qualitatively and quantitatively. In the current described diagnostic criteria only the ICD-11 model can reflect the configuration of symptoms satisfactorily. Thus, size does matter when assessing PTSD. Planteamiento: Los investigadores y clínicos del campo del trauma pronto decidirán entre dos descripciones diagnósticas diferentes del trastorno de estrés postraumático (TEPT) en el DSM-5 y la propuesta CIE-11. Varios estudios apoyan diferentes modelos en competencia sobre la estructura del TEPT en función de ambos sistemas de diagnóstico; sin embargo, los resultados demuestran que la elección de los sistemas de diagnóstico puede afectar las tasas de prevalencia estimadas. Objetivos: y métodos. El presente estudio tenía como objetivo investigar el impacto potencial de usar una descripción del TEPT amplia (es decir, el DSM-5) en comparación con una pequeña (es decir, la CIE-11). En otras palabras, ¿el tamaño del TEPT importa realmente? El objetivo se investigó mediante el examen de las diferencias en las frecuencias de diagnóstico entre los dos sistemas de diagnóstico y examinando de forma independiente cómo se ajustaban los modelos en competencia para el TEPT del DSM-5 y la CIE-11 en tres muestras de trauma: estudiantes universitarios (N = 4213), pacientes con dolor crónico (N = 573) y personal militar (N = 118). Resultados: Las tasas diagnósticas del TEPT fueron significativamente más bajas según los criterios de la propuesta CIE-11 en la muestra universitaria, pero no se encontraron diferencias significativas para los pacientes con dolor crónico y el personal militar. El modelo de tres factores propuesto por la CIE-11 proporcionó el mejor ajuste de los modelos de la CIE-11 que fueron probados en todas las muestras. En cambio, el modelo híbrido de siete factores del DSM-5 proporcionó el mejor ajuste en las muestras universitaria y del dolor, y el modelo de Anhedonia de seis factores del DSM-5 en la muestra militar de los modelos probados del DSM-5. Conclusiones: Se pueden debatir las ventajas y desventajas de utilizar un conjunto amplio o reducido de síntomas para el TEPT; sin embargo, este estudio demostró que la elección del sistema de diagnóstico puede influir en las tasas estimadas del TEPT, tanto cualitativa como cuantitativamente. Al mismo tiempo, parece que, dados los criterios diagnósticos descritos actualmente, solo el modelo de la CIE-11 puede reflejar satisfactoriamente la configuración de los síntomas. Por lo tanto, el tamaño importa cuando se evalúa el TEPT. 背景：在创伤领域的研究者和临床工作者很快要在DSM-5和ICD-11提案种对两个不同的创伤后应激障碍(PTSD)诊断描述做出选择。一些研究根据不同的诊断系统支持不同的PTSD症状结构的竞争模型，但是研究发现显示不同的诊断系统的选择会影响对发生率的估计。 目标和方法：本研究旨在探究使用大量（如DSM-5）或者少量（如ICD-11）PTSD症状描述的潜在影响。换言之，PTSD的症状量是否真的重要？我们考察在两个不同诊断系统里的诊断率的差别，并分别在三个创伤样本里考察DSM-5和ICD-11 的PTSD竞争模型的拟合性：大学生样本（N=4213），长期疼痛病人（N=573）和军人样本（N=118）。 结果：在大学生样本里根据ICD-11提案的PTSD的诊断率显著更低，但是对长期疼痛病人和军人样本没有显著差别。ICD-11提案的三因子模型跨样本拟合最好，但DSM-5七因子混合模型在大学生和疼痛样本中拟合最好，DSM-5 六因子快感缺失模型在军人样本中拟合最好。 结论：使用一个广泛或者狭窄的PTSD症状集的优劣是可以争论的，但是本研究显示对诊断体系的选择可以从质性和量化角度影响对PTSD患病率的估计。同时，在目前的诊断标准中只有ICD-11模型可以令人满意地反映症状结果。因此在评估PTSD时，症状数量是重要的。

Published
2017

23. Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways

Author

Nievergelt, Caroline M., primary, Maihofer, Adam X., additional, Klengel, Torsten, additional, Atkinson, Elizabeth G., additional, Chen, Chia-Yen, additional, Choi, Karmel W., additional, Coleman, Jonathan R.I., additional, Dalvie, Shareefa, additional, Duncan, Laramie E., additional, Logue, Mark W., additional, Provost, Allison C., additional, Ratanatharathorn, Andrew, additional, Stein, Murray B., additional, Torres, Katy, additional, Aiello, Allison E., additional, Almli, Lynn M., additional, Amstadter, Ananda B., additional, Andersen, Søren B, additional, Andreassen, Ole A., additional, Arbisi, Paul A., additional, Ashley-Koch, Allison E., additional, Austin, S. Bryn, additional, Avdibegovic, Esmina, additional, Babić, Dragan, additional, Bækvad-Hansen, Marie, additional, Baker, Dewleen G., additional, Beckham, Jean C., additional, Bierut, Laura J., additional, Bisson, Jonathan I., additional, Boks, Marco P., additional, Bolger, Elizabeth A., additional, Børglum, Anders D., additional, Bradley, Bekh, additional, Brashear, Megan, additional, Breen, Gerome, additional, Bryant, Richard A., additional, Bustamante, Angela C., additional, Bybjerg-Grauholm, Jonas, additional, Calabrese, Joseph R., additional, Caldas-de-Almeida, José M., additional, Dale, Anders M., additional, Daly, Mark J., additional, Daskalakis, Nikolaos P., additional, Deckert, Jürgen, additional, Delahanty, Douglas L., additional, Dennis, Michelle F., additional, Disner, Seth G., additional, Domschke, Katharina, additional, Dzubur-Kulenovic, Alma, additional, Erbes, Christopher R., additional, Evans, Alexandra, additional, Farrer, Lindsay A., additional, Feeny, Norah C., additional, Flory, Janine D., additional, Forbes, David, additional, Franz, Carol E., additional, Galea, Sandro, additional, Garrett, Melanie E., additional, Gelaye, Bizu, additional, Gelernter, Joel, additional, Geuze, Elbert, additional, Gillespie, Charles, additional, Goci Uka, Aferdita, additional, Gordon, Scott D., additional, Guffanti, Guia, additional, Hammamieh, Rasha, additional, Harnal, Supriya, additional, Hauser, Michael A., additional, Heath, Andrew C., additional, Hemmings, Sian M.J., additional, Michael Hougaard, David, additional, Jakovljevic, Miro, additional, Jett, Marti, additional, Otto Johnson, Eric, additional, Jones, Ian, additional, Jovanovic, Tanja, additional, Qin, Xue-Jun, additional, Junglen, Angela G., additional, Karstoft, Karen-Inge, additional, Kaufman, Milissa L., additional, Kessler, Ronald C., additional, Khan, Alaptagin, additional, Kimbrel, Nathan A., additional, King, Anthony P., additional, Koen, Nastassja, additional, Kranzler, Henry R., additional, Kremen, William S., additional, Lawford, Bruce R., additional, Lebois, Lauren A.M., additional, Lewis, Catrin E., additional, Linnstaedt, Sarah D., additional, Lori, Adriana, additional, Lugonja, Bozo, additional, Luykx, Jurjen J., additional, Lyons, Michael J., additional, Maples-Keller, Jessica, additional, Marmar, Charles, additional, Martin, Alicia R., additional, Martin, Nicholas G., additional, Maurer, Douglas, additional, Mavissakalian, Matig R., additional, McFarlane, Alexander, additional, McGlinchey, Regina E., additional, McLaughlin, Katie A., additional, McLean, Samuel A., additional, McLeay, Sarah, additional, Mehta, Divya, additional, Milberg, William P., additional, Miller, Mark W., additional, Morey, Rajendra A., additional, Phillip Morris, Charles, additional, Mors, Ole, additional, Mortensen, Preben B., additional, Neale, Benjamin M., additional, Nelson, Elliot C., additional, Nordentoft, Merete, additional, Norman, Sonya B., additional, O’Donnell, Meaghan, additional, Orcutt, Holly K., additional, Panizzon, Matthew S., additional, Peters, Edward S., additional, Peterson, Alan L., additional, Peverill, Matthew, additional, Pietrzak, Robert H., additional, Polusny, Melissa A., additional, Rice, John P., additional, Ripke, Stephan, additional, Risbrough, Victoria B., additional, Roberts, Andrea L., additional, Rothbaum, Alex O., additional, Rothbaum, Barbara O., additional, Roy-Byrne, Peter, additional, Ruggiero, Ken, additional, Rung, Ariane, additional, Rutten, Bart P. F., additional, Saccone, Nancy L., additional, Sanchez, Sixto E., additional, Schijven, Dick, additional, Seedat, Soraya, additional, Seligowski, Antonia V., additional, Seng, Julia S., additional, Sheerin, Christina M., additional, Silove, Derrick, additional, Smith, Alicia K., additional, Smoller, Jordan W., additional, Solovieff, Nadia, additional, Sponheim, Scott R., additional, Stein, Dan J., additional, Sumner, Jennifer A., additional, Teicher, Martin H., additional, Thompson, Wesley K., additional, Trapido, Edward, additional, Uddin, Monica, additional, Ursano, Robert J., additional, van den Heuvel, Leigh Luella, additional, van Hooff, Miranda, additional, Vermetten, Eric, additional, Vinkers, Christiaan H., additional, Voisey, Joanne, additional, Wang, Yunpeng, additional, Wang, Zhewu, additional, Werge, Thomas, additional, Williams, Michelle A., additional, Williamson, Douglas E., additional, Winternitz, Sherry, additional, Wolf, Christiane, additional, Wolf, Erika J., additional, Wolff, Jonathan D., additional, Yehuda, Rachel, additional, Young, Keith A., additional, Young, Ross McD., additional, Zhao, Hongyu, additional, Zoellner, Lori A., additional, Liberzon, Israel, additional, Ressler, Kerry J., additional, Haas, Magali, additional, and Koenen, Karestan C., additional

Published
2018
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25. Cognitive ability and risk of post-traumatic stress disorder after military deployment:an observational cohort study

Author

Nissen, Lars R., Karstoft, Karen-Inge, Vedtofte, Mia S., Nielsen, Anni B. S., Osler, Merete, Mortensen, Erik L., Christensen, Gunhild T., Andersen, Søren B., Nissen, Lars R., Karstoft, Karen-Inge, Vedtofte, Mia S., Nielsen, Anni B. S., Osler, Merete, Mortensen, Erik L., Christensen, Gunhild T., and Andersen, Søren B.

Abstract

Background: Studies of the association between pre-deployment cognitive ability and post-deployment post-traumatic stress disorder (PTSD) have shown mixed results.Aims: To study the influence of pre-deployment cognitive ability on PTSD symptoms 6-8 months post-deployment in a large population while controlling for pre-deployment education and deployment-related variables.Method: Study linking prospective pre-deployment conscription board data with post-deployment self-reported data in 9695 Danish Army personnel deployed to different war zones in 1997-2013. The association between pre-deployment cognitive ability and post-deployment PTSD was investigated using repeated-measure logistic regression models. Two models with cognitive ability score as the main exposure variable were created (model 1 and model 2). Model 1 was only adjusted for pre-deployment variables, while model 2 was adjusted for both pre-deployment and deployment-related variables.Results: When including only variables recorded pre-deployment (cognitive ability score and educational level) and gender (model 1), all variables predicted post-deployment PTSD. When deployment-related variables were added (model 2), this was no longer the case for cognitive ability score. However, when educational level was removed from the model adjusted for deployment-related variables, the association between cognitive ability and post-deployment PTSD became significant.Conclusions: Pre-deployment lower cognitive ability did not predict post-deployment PTSD independently of educational level after adjustment for deployment-related variables.

Published
2017

26. Assessing PTSD in the military:Validation of a scale distributed to Danish soldiers after deployment since 1998

Author

Karstoft, Karen-Inge, Andersen, Søren B., Nielsen, Anni Brit Sternhagen, Karstoft, Karen-Inge, Andersen, Søren B., and Nielsen, Anni Brit Sternhagen

Abstract

Since 1998, soldiers deployed to war zones with the Danish Defense (≈31,000) have been invited to fill out a questionnaire on post-mission reactions. This provides a unique data source for studying the psychological toll of war. Here, we validate a measure of PTSD-symptoms from the questionnaire. Soldiers from two cohorts deployed to Afghanistan with the International Security Assistance Force (ISAF) in 2009 (ISAF7, N = 334) and 2013 (ISAF15, N = 278) filled out a standard questionnaire (Psychological Reactions following International Missions, PRIM) concerning a range of post-deployment reactions including symptoms of PTSD (PRIM-PTSD). They also filled out a validated measure of PTSD-symptoms in DSM-IV, the PTSD-checklist (PCL). We tested reliability of PRIM-PTSD by estimating Cronbach's alpha, and tested validity by correlating items, clusters, and overall scale with corresponding items in the PCL. Furthermore, we conducted two confirmatory factor analytic models to test the factor structure of PRIM-PTSD, and tested measurement invariance of the selected model. Finally, we established a screening and a clinical cutoff score by application of ROC analysis. We found high internal consistency of the PRIM-PTSD (Cronbach's alpha = 0.88; both cohorts), strong item-item (0.48–0.83), item-cluster (0.43–0.72), cluster-cluster (0.71–0.82) and full-scale (0.86–0.88) correlations between PRIM-PTSD and PCL. The factor analyses showed adequate fit of a one-factor model, which was also found to display strong measurement invariance across cohorts. ROC curve analysis established cutoff scores for screening (sensitivity = 1, specificity = 0.93) and clinical use (sensitivity = 0.71, specificity = 0.98). In conclusion, we find that PRIM-PTSD is a valid measure for assessing PTSD-symptoms in Danish soldiers following deployment.

Published
2017

27. Does size really matter? A multisite study assessing the latent structure of the proposed ICD-11 and DSM-5 diagnostic criteria for PTSD

Author

Hansen, Maj, primary, Hyland, Philip, additional, Karstoft, Karen-Inge, additional, Vaegter, Henrik B., additional, Bramsen, Rikke H., additional, Nielsen, Anni B. S., additional, Armour, Cherie, additional, Andersen, Søren B., additional, Høybye, Mette Terp, additional, Larsen, Simone Kongshøj, additional, and Andersen, Tonny E., additional

Published
2017
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30. The influence of pre-deployment cognitive ability on post-traumatic stress disorder symptoms and trajectories:The Danish USPER follow-up study of Afghanistan veterans

Author

Sørensen, Holger J, Andersen, Søren B, Karstoft, Karen-Inge, Madsen, Trine, Sørensen, Holger J, Andersen, Søren B, Karstoft, Karen-Inge, and Madsen, Trine

Abstract

Objective New trajectories of PTSD symptoms have recently been identified in war exposed army veterans. The aim of this army veterans study was to examine whether pre-deployment cognitive ability is associated with the risk of developing PTSD symptoms or non-resilient PTSD trajectories. Method Follow up study in 428 Danish soldiers, deployed to Afghanistan in 2009, who were assessed at six occasions from pre-deployment to three years post-deployment. Pre-deployment vulnerabilities, deployment and homecoming stressors were measured. Pre-deployment cognitive test scores on Børge Priens Prøve (based on logical, verbal, numerical and spatial reasoning) were converted to a mean of 100 and with a standard deviation of 15. Results Higher pre-deployment cognitive ability scores were associated with lower risk of PTSD symptoms as assessed by the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) 2.5 years post-deployment (OR=0.97; 95% CI 0.95-1.00) after adjustment for educational length, baseline PCL-C score and perceived war-zone stress. Compared to a resilient trajectory, a non-resilient relieved-worsening trajectory (high baseline mental symptoms, being symptom free during deployment and a drastic increase in PTSD symptoms at the final assessments of PTSD symptoms) had significantly lower cognitive scores by a mean difference of 14.5 (95% CI 4.7-24.3). This trajectory (n=9) comprised 26.5% of soldiers with moderate-severe PTSD symptoms 2.5 years post-deployment. Conclusion We confirmed an inverse association between pre-deployment cognitive ability and risk of PTSD symptoms, and observed significantly lower mean pre-deployment cognitive scores in one non-resilient PTSD trajectory. If replicated, this might inform relevant prevention efforts for soldiers at pre-deployment.

Published
2016

31. Early identification of posttraumatic stress following military deployment:Application of machine learning methods to a prospective study of Danish soldiers

Author

Karstoft, Karen Inge, Statnikov, Alexander, Andersen, Søren B., Madsen, Trine, Galatzer-Levy, Isaac R., Karstoft, Karen Inge, Statnikov, Alexander, Andersen, Søren B., Madsen, Trine, and Galatzer-Levy, Isaac R.

Abstract

Abstract Background Pre-deployment identification of soldiers at risk for long-term posttraumatic stress psychopathology after home coming is important to guide decisions about deployment. Early post-deployment identification can direct early interventions to those in need and thereby prevents the development of chronic psychopathology. Both hold significant public health benefits given large numbers of deployed soldiers, but has so far not been achieved. Here, we aim to assess the potential for pre- and early post-deployment prediction of resilience or posttraumatic stress development in soldiers by application of machine learning (ML) methods. Methods ML feature selection and prediction algorithms were applied to a prospective cohort of 561 Danish soldiers deployed to Afghanistan in 2009 to identify unique risk indicators and forecast long-term posttraumatic stress responses. Results Robust pre- and early postdeployment risk indicators were identified, and included individual PTSD symptoms as well as total level of PTSD symptoms, previous trauma and treatment, negative emotions, and thought suppression. The predictive performance of these risk indicators combined was assessed by cross-validation. Together, these indicators forecasted long term posttraumatic stress responses with high accuracy (pre-deployment: AUC=0.84 (95% CI=0.81-0.87), post-deployment: AUC=0.88 (95% CI=0.85-0.91)). Limitations This study utilized a previously collected data set and was therefore not designed to exhaust the potential of ML methods. Further, the study relied solely on self-reported measures. Conclusions Pre-deployment and early post-deployment identification of risk for long-term posttraumatic psychopathology are feasible and could greatly reduce the public health costs of war.

Published
2015

32. Community integration after deployment to Afghanistan:a longitudinal investigation of Danish soldiers

Author

Karstoft, Karen Inge, Armour, Cherie, Andersen, Søren B., Bertelsen, Mette, Madsen, Trine, Karstoft, Karen Inge, Armour, Cherie, Andersen, Søren B., Bertelsen, Mette, and Madsen, Trine

Abstract

Objective: In the years following military deployment, soldiers may experience problems integrating into the community. However, little is known about the nature and prevalence of these problems and if they relate to posttraumatic symptomatology.Methods: In a prospective, longitudinal study of Danish soldiers deployed to Afghanistan in 2009 (N = 743), we assessed community reintegration difficulties 2.5 years after home coming (study sample: N = 454). Furthermore, symptoms of posttraumatic stress disorder (PTSD) were assessed before, during, and after deployment. Trajectories of PTSD symptoms from a previously published latent growth mixture modeling analysis were used to address whether community reintegration difficulties differ as a result of course and level of PTSD symptoms.Results: Between 3.6 and 18.0 % reported to have some, a lot, or extreme difficulties in reintegration domains such as interpersonal functioning, productivity, community involvement, and self-care. Mean level of reintegration difficulties differed significantly across six PTSD symptom trajectories (range 6.35–36.00); with more symptomatic trajectories experiencing greater community reintegration difficulties.Conclusions: Reintegration difficulties after deployment are present in less than 20 % of Danish soldiers who return from Afghanistan. Difficulties are greater in individuals who follow symptomatic PTSD trajectories in the first years following deployment than in those who follow a low-stable trajectory with no or few symptoms.

Published
2015

35. Applicability of an Automated Model and Parameter Selection in the Prediction of Screening-Level PTSD in Danish Soldiers Following Deployment: Development Study of Transferable Predictive Models Using Automated Machine Learning

Author

Karstoft, Karen-Inge, Tsamardinos, Ioannis, Eskelund, Kasper, Andersen, Søren Bo, and Nissen, Lars Ravnborg

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundPosttraumatic stress disorder (PTSD) is a relatively common consequence of deployment to war zones. Early postdeployment screening with the aim of identifying those at risk for PTSD in the years following deployment will help deliver interventions to those in need but have so far proved unsuccessful. ObjectiveThis study aimed to test the applicability of automated model selection and the ability of automated machine learning prediction models to transfer across cohorts and predict screening-level PTSD 2.5 years and 6.5 years after deployment. MethodsAutomated machine learning was applied to data routinely collected 6-8 months after return from deployment from 3 different cohorts of Danish soldiers deployed to Afghanistan in 2009 (cohort 1, N=287 or N=261 depending on the timing of the outcome assessment), 2010 (cohort 2, N=352), and 2013 (cohort 3, N=232). ResultsModels transferred well between cohorts. For screening-level PTSD 2.5 and 6.5 years after deployment, random forest models provided the highest accuracy as measured by area under the receiver operating characteristic curve (AUC): 2.5 years, AUC=0.77, 95% CI 0.71-0.83; 6.5 years, AUC=0.78, 95% CI 0.73-0.83. Linear models performed equally well. Military rank, hyperarousal symptoms, and total level of PTSD symptoms were highly predictive. ConclusionsAutomated machine learning provided validated models that can be readily implemented in future deployment cohorts in the Danish Defense with the aim of targeting postdeployment support interventions to those at highest risk for developing PTSD, provided the cohorts are deployed on similar missions.

Published
2020
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