Attachment Style Moderates Polygenic Risk for Incident Posttraumatic Stress in U.S. Military Veterans: A 7-Year, Nationally Representative, Prospective Cohort Study

Tamman, Amanda J. F.; Wendt, Frank R.; Pathak, Gita A.; Krystal, John H.; Southwick, Steven M.; Sippel, Lauren M.; Gelernter, Joel; Polimanti, Renato; Pietrzak, Robert H.

doi:10.1016/j.biopsych.2021.09.025

Cited by 7 publications

(10 citation statements)

References 83 publications

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“…We replicated previous findings [ 12 ], showing an association between the PTSD PRS on the number of intrusive memories independent of treatment condition. This is in line with studies showing an increased likelihood of developing PTSD in individuals with higher polygenic loadings for PTSD [ 13 , 14 , 70 , 71 ]. As intrusions are a hallmark symptom of PTSD, it is plausible that genetic vulnerability for PTSD affects the occurrence of intrusive memories.…”

Section: Discussionsupporting

confidence: 91%

Oxytocin vs. placebo effects on intrusive memory consolidation using a trauma film paradigm: a randomized, controlled experimental study in healthy women

et al. 2023

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Oxytocin administration during a trauma analogue has been shown to increase intrusive memories, which are a core symptom of post-traumatic stress disorder (PTSD). However, it is unknown whether oxytocin influences the acquisition or the consolidation of the trauma. The current study investigates the effect of the activation of the oxytocin system during the consolidation of an analogue trauma on the formation of intrusive memories over four consecutive days and whether this effect is influenced by individual neurobiological, genetic, or psychological factors. We conducted a randomized double-blind placebo-controlled study in 217 healthy women. They received either a single dose of intranasal oxytocin (24 IU) or placebo after exposure to a trauma film paradigm, which reliably induces intrusive memories. We used a general random forest to examine a potential heterogeneous treatment effect of oxytocin on the consolidation of intrusive memories. Furthermore, we used a poisson regression to examine whether salivary alpha amylase activity (sAA) as a marker of noradrenergic activity and cortisol response to the film, polygenic risk score (PRS) for psychiatric disorders, and psychological factors influence the number of intrusive memories. We found no significant effect of oxytocin on the formation of intrusive memories (F(2, 543.16) = 0.75, p = 0.51, ηp2 = 0.00) and identified no heterogeneous treatment effect. We replicated previous associations of the PRS for PTSD, sAA and the cortisol response on intrusive memories. We further found a positive association between high trait anxiety and intrusive memories, and a negative association between the emotion regulation strategy reappraisal and intrusive memories. Data of the present study suggest that the consolidation of intrusive memories in women is modulated by genetic, neurobiological and psychological factors, but is not influenced by oxytocin. Trial registration: NCT03875391.

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Section: Discussionsupporting

confidence: 91%

Oxytocin vs. placebo effects on intrusive memory consolidation using a trauma film paradigm: a randomized, controlled experimental study in healthy women

et al. 2023

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“…We replicated previous ndings [12], showing an association between the PTSD PRS on the number of intrusive memories independent of treatment condition. This is in line with studies showing an increased likelihood of developing PTSD in individuals with higher polygenic loadings for PTSD [13,14,72,73]. As intrusions are a hallmark symptom of PTSD, it is plausible that genetic vulnerability for PTSD affects the occurrence of intrusive memories.…”

Section: Neurobiological and Genetic Factors In Uencing The Number In...supporting

confidence: 86%

Oxytocin vs. placebo effects on intrusive memory consolidation using a trauma film paradigm: a randomized, controlled experimental study in healthy women

Maslahati

Wingenfeld

Hellmann-Regen

et al. 2022

Preprint

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Oxytocin administration during a trauma analogue has been shown to increase intrusive memories, which are a core symptom of Post-Traumatic Stress Disorder (PTSD). However, it is unknown whether oxytocin influences the acquisition or the consolidation of the trauma. The current study investigates the effect of the activation of the oxytocin system during the consolidation of an analogue trauma on the formation of intrusive memories over four consecutive days and whether this effect is influenced by individual neurobiological, genetic, or psychological factors. We conducted a randomized double-blind placebo-controlled study in 217 healthy women. They received either a single dose of intranasal oxytocin (24 IU) or placebo after exposure to a trauma film paradigm, which reliably induces intrusive memories. We used a general random forest to examine a potential heterogeneous treatment effect of oxytocin on the consolidation of intrusive memories. Furthermore, we used a poisson regression to examine whether salivary alpha amylase activity (sAA) as a marker of noradrenergic activity and cortisol response to the film, polygenic risk score (PRS) for psychiatric disorders, and psychological factors influence the number of intrusive memories. We found no significant effect of oxytocin on the formation of intrusive memories (t(-0.85) = 201.72, p = 0.40, Cohen’s d = 0.12, 95% CI -0.02–0.26) and identified no heterogeneous treatment effect. We replicated previous associations of the PRS for PTSD, sAA and the cortisol response on intrusive memories. We further found a positive association between high trait anxiety and intrusive memories, and a negative association between the emotion regulation strategy reappraisal and intrusive memories. Data of the present study suggest that the consolidation of intrusive memories is modulated by genetic, neurobiological and psychological factors, but is not influenced by oxytocin. Trial registration: NCT03875391.

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“…Consistent with other evidence of shared genetic underpinnings of mental disorders (Bulik-Sullivan et al, 2015;Gandal et al, 2018), PRS for PTSD diagnosis/symptom severity, as well as PRS for related disorders and traits (e.g. depression, neuroticism), have demonstrated associations with PTSD phenotypes (Misganaw et al, 2019;Tamman et al, 2022;Waszczuk et al, 2020).…”

Section: Introductionsupporting

confidence: 79%

Associations of polygenic risk scores with posttraumatic stress symptom trajectories following combat deployment

et al. 2023

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Background Identification of genetic risk factors may inform the prevention and treatment of posttraumatic stress disorder (PTSD). This study evaluates the associations of polygenic risk scores (PRS) with patterns of posttraumatic stress symptoms following combat deployment. Method US Army soldiers of European ancestry (n = 4900) provided genomic data and ratings of posttraumatic stress symptoms before and after deployment to Afghanistan in 2012. Latent growth mixture modeling was used to model posttraumatic stress symptom trajectories among participants who provided post-deployment data (n = 4353). Multinomial logistic regression models tested independent associations between trajectory membership and PRS for PTSD, major depressive disorder (MDD), schizophrenia, neuroticism, alcohol use disorder, and suicide attempt, controlling for age, sex, ancestry, and exposure to potentially traumatic events, and weighted to account for uncertainty in trajectory classification and missing data. Results Participants were classified into low-severity (77.2%), increasing-severity (10.5%), decreasing-severity (8.0%), and high-severity (4.3%) posttraumatic stress symptom trajectories. Standardized PTSD-PRS and MDD-PRS were associated with greater odds of membership in the high-severity v. low-severity trajectory [adjusted odds ratios and 95% confidence intervals, 1.23 (1.06–1.43) and 1.18 (1.02–1.37), respectively] and the increasing-severity v. low-severity trajectory [1.12 (1.01–1.25) and 1.16 (1.04–1.28), respectively]. Additionally, MDD-PRS was associated with greater odds of membership in the decreasing-severity v. low-severity trajectory [1.16 (1.03–1.31)]. No other associations were statistically significant. Conclusions Higher polygenic risk for PTSD or MDD is associated with more severe posttraumatic stress symptom trajectories following combat deployment. PRS may help stratify at-risk individuals, enabling more precise targeting of treatment and prevention programs.

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Attachment Style Moderates Polygenic Risk for Incident Posttraumatic Stress in U.S. Military Veterans: A 7-Year, Nationally Representative, Prospective Cohort Study

Cited by 7 publications

References 83 publications

Oxytocin vs. placebo effects on intrusive memory consolidation using a trauma film paradigm: a randomized, controlled experimental study in healthy women

Oxytocin vs. placebo effects on intrusive memory consolidation using a trauma film paradigm: a randomized, controlled experimental study in healthy women

Oxytocin vs. placebo effects on intrusive memory consolidation using a trauma film paradigm: a randomized, controlled experimental study in healthy women

Associations of polygenic risk scores with posttraumatic stress symptom trajectories following combat deployment

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