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Browsing Computational Biology - Publications by Author "Almli, Lynn M."
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ItemEffect of Combat Exposure and Posttraumatic Stress Disorder on Telomere Length and Amygdala Volume( 2020-07-01) Kang, Jee In ; Mueller, Susanne G. ; Wu, Gwyneth W.Y. ; Lin, Jue ; Ng, Peter ; Yehuda, Rachel ; Flory, Janine D. ; Abu-Amara, Duna ; Reus, Victor I. ; Gautam, Aarti ; Hood, Leroy ; Ressler, Kerry J. ; Lindqvist, Daniel ; Cho, Ji Hoon ; Coy, Michelle ; Desarnaud, Frank ; Bersani, Saverio ; Fossati, Silvia ; Hoke, Allison ; Kumar, Raina ; Li, Meng ; Makotkine, Iouri ; Miller, Stacy Ann ; Petzold, Linda ; Price, Laura ; Qian, Meng ; Scherler, Kelsey ; Srinivasan, Seshamalini ; Suessbrick, Anna ; Tang, Li ; Wu, Xiaogang ; Baxter, David ; Blessing, Esther ; Dean, Kelsey R. ; Daigle, Bernie J. ; Guffanti, Guia ; Wang, Kai ; Almli, Lynn M. ; Chakraborty, F. Nabarun ; Donohue, Duncan ; Kerley, Kimberly ; Kim, Taek Kyun ; Laska, Eugene ; Lee, Inyoul ; Lee, Min Young ; Lori, Adriana ; Lu, Liangqun ; Misganaw, Burook ; Muhie, Seid ; Newman, Jennifer ; Price, Nathan ; Qin, Shizhen ; Siegel, Carole ; Somvanshi, Pramod R. ; Thakur, Gunjan S. ; Zhou, Young ; Yang, Ruoting ; Hammamieh, Rasha ; Doyle, Francis J. ; Jett, Marti ; Marmar, Charles R. ; Mellon, Synthia H. ; Wolkowitz, Owen M.Background: Traumatic stress can adversely affect physical and mental health through neurobiological stress response systems. We examined the effects of trauma exposure and posttraumatic stress disorder (PTSD) on telomere length, a biomarker of cellular aging, and volume of the amygdala, a key structure of stress regulation, in combat-exposed veterans. In addition, the relationships of psychopathological symptoms and autonomic function with telomere length and amygdala volume were examined. Methods: Male combat veterans were categorized as having PTSD diagnosis (n = 102) or no lifetime PTSD diagnosis (n = 111) based on the Clinician-Administered PTSD Scale. Subjects were assessed for stress-related psychopathology, trauma severity, autonomic function, and amygdala volumes by magnetic resonance imaging. Results: A significant interaction was found between trauma severity and PTSD status for telomere length and amygdala volume after adjusting for multiple confounders. Subjects with PTSD showed shorter telomere length and larger amygdala volume than those without PTSD among veterans exposed to high trauma, while there was no significant group difference in these parameters among those exposed to low trauma. Among veterans exposed to high trauma, greater telomere shortening was significantly correlated with greater norepinephrine, and larger amygdala volume was correlated with more severe psychological symptoms and higher heart rates. Conclusions: These data suggest that the intensity of the index trauma event plays an important role in interacting with PTSD symptomatology and autonomic activity in predicting telomere length and amygdala volume. These results highlight the importance of trauma severity and PTSD status in predicting certain biological outcomes.
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ItemMulti-omic biomarker identification and validation for diagnosing warzone-related post-traumatic stress disorder( 2020-12-01) Dean, Kelsey R. ; Hammamieh, Rasha ; Mellon, Synthia H. ; Abu-Amara, Duna ; Flory, Janine D. ; Guffanti, Guia ; Wang, Kai ; Daigle, Bernie J. ; Gautam, Aarti ; Lee, Inyoul ; Yang, Ruoting ; Almli, Lynn M. ; Bersani, F. Saverio ; Chakraborty, Nabarun ; Donohue, Duncan ; Kerley, Kimberly ; Kim, Taek Kyun ; Laska, Eugene ; Young Lee, Min ; Lindqvist, Daniel ; Lori, Adriana ; Lu, Liangqun ; Misganaw, Burook ; Muhie, Seid ; Newman, Jennifer ; Price, Nathan D. ; Qin, Shizhen ; Reus, Victor I. ; Siegel, Carole ; Somvanshi, Pramod R. ; Thakur, Gunjan S. ; Zhou, Yong ; Baxter, David ; Bierer, Linda ; Blessing, Esther ; Cho, Ji Hoon ; Coy, Michelle ; Desarnaud, Frank ; Fossati, Silvia ; Hoke, Allison ; Kumar, Raina ; Li, Meng ; Makotkine, Iouri ; Miller, Stacy Ann ; Petzold, Linda ; Price, Laura ; Qian, Meng ; Scherler, Kelsey ; Srinivasan, Seshamalini ; Suessbrick, Anna ; Tang, Li ; Wu, Xiaogang ; Wu, Gwyneth ; Wu, Changxin ; Hood, Leroy ; Ressler, Kerry J. ; Wolkowitz, Owen M. ; Yehuda, Rachel ; Jett, Marti ; Doyle, Francis J. ; Marmar, CharlesPost-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using (1) data-driven methods, including Support Vector Machine with Recursive Feature Elimination and other standard or published methodologies, and (2) hypothesis-driven approaches, using previous genetic studies for polygenic risk, or other PTSD-related literature. After reassessment of ~30% of these participants, we refined this set of markers from 343 to 28, based on their performance and ability to track changes in phenotype over time. The final diagnostic panel of 28 features was validated in an independent cohort (26 cases, 26 controls) with good performance (AUC = 0.80, 81% accuracy, 85% sensitivity, and 77% specificity). The identification and validation of this diverse diagnostic panel represents a powerful and novel approach to improve accuracy and reduce bias in diagnosing combat-related PTSD.