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  • 1
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    Online Resource
    Dissecting the heterogeneity of posttraumatic stress disorder: differences in polygenic risk, stress exposures, and course of PTSD subtypes
    Cambridge University Press (CUP) ; 2022
    In:  Psychological Medicine Vol. 52, No. 15 ( 2022-11), p. 3646-3654
    Details
    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 52, No. 15 ( 2022-11), p. 3646-3654
    Abstract: Definition of disorder subtypes may facilitate precision treatment for posttraumatic stress disorder (PTSD). We aimed to identify PTSD subtypes and evaluate their associations with genetic risk factors, types of stress exposures, comorbidity, and course of PTSD. Methods Data came from a prospective study of three U.S. Army Brigade Combat Teams that deployed to Afghanistan in 2012. Soldiers with probable PTSD (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition ≥31) at three months postdeployment comprised the sample ( N = 423) for latent profile analysis using Gaussian mixture modeling and PTSD symptom ratings as indicators. PTSD profiles were compared on polygenic risk scores (derived from external genomewide association study summary statistics), experiences during deployment, comorbidity at three months postdeployment, and persistence of PTSD at nine months postdeployment. Results Latent profile analysis revealed profiles characterized by prominent intrusions, avoidance, and hyperarousal (threat-reactivity profile; n = 129), anhedonia and negative affect (dysphoric profile; n = 195), and high levels of all PTSD symptoms (high-symptom profile; n = 99). The threat-reactivity profile had the most combat exposure and the least comorbidity. The dysphoric profile had the highest polygenic risk for major depression, and more personal life stress and co-occurring major depression than the threat-reactivity profile. The high-symptom profile had the highest rates of concurrent mental disorders and persistence of PTSD. Conclusions Genetic and trauma-related factors likely contribute to PTSD heterogeneity, which can be parsed into subtypes that differ in symptom expression, comorbidity, and course. Future studies should evaluate whether PTSD typology modifies treatment response and should clarify distinctions between the dysphoric profile and depressive disorders.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291721000428
    RVK:
    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1470300-2
    SSG: 5,2
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  • 2
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    Prospective study of polygenic risk, protective factors, and incident depression following combat deployment in US Army soldiers
    Cambridge University Press (CUP) ; 2020
    In:  Psychological Medicine Vol. 50, No. 5 ( 2020-04), p. 737-745
    Details
    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 50, No. 5 ( 2020-04), p. 737-745
    Abstract: Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk. Methods Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk. Results Polygenic risk showed a dose–response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk. Conclusions Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion – an index of perceived support and morale – was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291719000527
    RVK:
    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1470300-2
    SSG: 5,2
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  • 3
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    Online Resource
    Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk
    Elsevier BV ; 2024
    In:  Journal of Affective Disorders Vol. 351 ( 2024-04), p. 671-682
    Details
    In: Journal of Affective Disorders, Elsevier BV, Vol. 351 ( 2024-04), p. 671-682
    Type of Medium: Online Resource
    ISSN: 0165-0327
    URL: Article
    DOI: 10.1016/j.jad.2024.01.254
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 1500487-9
    SSG: 12
    SSG: 5,2
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  • 4
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    Genome‐wide analyses of psychological resilience in U.S. Army soldiers
    Wiley ; 2019
    In:  American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Vol. 180, No. 5 ( 2019-07), p. 310-319
    Details
    In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Wiley, Vol. 180, No. 5 ( 2019-07), p. 310-319
    Abstract: Though a growing body of preclinical and translational research is illuminating a biological basis for resilience to stress, little is known about the genetic basis of psychological resilience in humans. We conducted genome‐wide association studies (GWASs) of self‐assessed (by questionnaire) and outcome‐based (incident mental disorders from predeployment to postdeployment) resilience among European (EUR) ancestry soldiers in the Army study to assess risk and resilience in servicemembers. Self‐assessed resilience ( N  = 11,492) was found to have significant common‐variant heritability ( h 2 = 0.162, se = 0.050, p  = 5.37 × 10 −4 ), and to be significantly negatively genetically correlated with neuroticism ( r g  = −0.388, p  = .0092). GWAS results from the EUR soldiers revealed a genome‐wide significant locus on an intergenic region on Chr 4 upstream from doublecortin‐like kinase 2 (DCLK2) (four single nucleotide polymorphisms (SNPs) in LD; top SNP: rs4260523 [ p  = 5.65 × 10 −9 ] is an eQTL in frontal cortex), a member of the doublecortin family of kinases that promote survival and regeneration of injured neurons. A second gene, kelch‐like family member 36 (KLHL36) was detected at gene‐wise genome‐wide significance [ p  = 1.89 × 10 −6 ]. A polygenic risk score derived from the self‐assessed resilience GWAS was not significantly associated with outcome‐based resilience. In very preliminary results, genome‐wide significant association with outcome‐based resilience was found for one locus (top SNP: rs12580015 [ p  = 2.37 × 10 −8 ]) on Chr 12 downstream from solute carrier family 15 member 5 (SLC15A5) in subjects ( N = 581) exposed to the highest level of deployment stress. The further study of genetic determinants of resilience has the potential to illuminate the molecular bases of stress‐related psychopathology and point to new avenues for therapeutic intervention.
    Type of Medium: Online Resource
    ISSN: 1552-4841 , 1552-485X
    URL: Issue
    URL: Article
    DOI: 10.1002/ajmg.v180.5
    DOI: 10.1002/ajmg.b.32730
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2143866-3
    SSG: 12
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  • 5
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    Associations of polygenic risk scores with posttraumatic stress symptom trajectories following combat deployment
    Cambridge University Press (CUP) ; 2023
    In:  Psychological Medicine
    Details
    In: Psychological Medicine, Cambridge University Press (CUP)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291723000211
    RVK:
    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1470300-2
    SSG: 5,2
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  • 6
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    Genetic, environmental, and behavioral correlates of lifetime suicide attempt: Analysis of additive and interactive effects in two cohorts of US Army soldiers
    Springer Science and Business Media LLC ; 2023
    In:  Neuropsychopharmacology Vol. 48, No. 11 ( 2023-10), p. 1623-1629
    Details
    In: Neuropsychopharmacology, Springer Science and Business Media LLC, Vol. 48, No. 11 ( 2023-10), p. 1623-1629
    Abstract: Recently developed measures of genetic liability to suicide attempt may convey unique information regarding an individual’s risk of suicidal behavior. We calculated a polygenic risk score for suicide attempt (SA-PRS) for soldiers of European ancestry who participated in the Army STARRS New Soldier Study (NSS; n  = 6573) or Pre/Post Deployment Study (PPDS; n  = 4900). Multivariable logistic regression models were fit within each sample to estimate the association of SA-PRS with lifetime suicide attempt (LSA), and to examine whether SA-PRS displayed additive or interactive effects with environmental and behavioral risk/protective factors (lifetime trauma burden, childhood maltreatment, negative urgency impulsivity, social network size, perceived mattering, and dispositional optimism). Age, sex, and within-ancestry variation were included as covariates. Observed prevalence of LSA was 6.3% and 4.2% in the NSS and PPDS samples, respectively. In the NSS model, SA-PRS and environmental/behavioral factors displayed strictly additive effects on odds of LSA. Results indicated an estimated 21% increase in odds of LSA per 1 SD increase in SA-PRS [adjusted odds ratio (AOR; 95% CI) = 1.21 (1.09–1.35)] . In PPDS, the effect of SA-PRS varied by reports of optimism [AOR = 0.85 (0.74–0.98) for SA-PRS x optimism effect]. Individuals reporting low and average optimism had 37% and 16% increased odds of LSA per 1 SD increase in SA-PRS, respectively, whereas SA-PRS was not associated with LSA in those reporting high optimism. Overall, results suggested the SA-PRS had predictive value over and above several environmental and behavioral risk factors for LSA. Moreover, elevated SA-PRS may be more concerning in the presence of environmental and behavioral risk factors (e.g., high trauma burden; low optimism). Given the relatively small effect magnitudes, the cost and incremental benefits of utilizing SA-PRS for risk targeting must also be considered in future work.
    Type of Medium: Online Resource
    ISSN: 0893-133X , 1740-634X
    URL: Article
    DOI: 10.1038/s41386-023-01596-2
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2008300-2
    SSG: 15,3
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  • 7
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    Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury
    Springer Science and Business Media LLC ; 2023
    In:  Translational Psychiatry Vol. 13, No. 1 ( 2023-01-25)
    Details
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-01-25)
    Abstract: Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU] ) was associated with an increased likelihood of PTSD in the aftermath of mTBI. We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI ( n  = 714), a prospective longitudinal study of level 1 trauma center patients. One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury. We used summary statistics from recent GWAS studies of PTSD, MDD, and NEU to generate polygenic risk scores (PRS) for individuals in our sample. A multivariable model that included age, sex, pre-injury history of mental disorder, and cause of injury explained 7% of the variance in the PTSD outcome; the addition of the PTSD-PRS (and five ancestral principal components) significantly increased the variance explained to 11%. The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80–7.65) than in the lowest PTSD-PRS quintile. There was no evidence of a statistically significant interaction between PTSD-PRS and prior history of mental disorder, indicating that PTSD-PRS had similar predictive utility among those with and without pre-injury psychiatric illness. When added to the model, neither MDD-PRS nor NEU-PRS were significantly associated with the PTSD outcome. These findings show that the risk for PTSD in the context of mTBI is, in part, genetically influenced. They also raise the possibility that an individual’s PRS could be clinically actionable if used—possibly with other non-genetic predictors—to signal the need for enhanced follow-up and early intervention; this precision medicine approach needs to be prospectively studied.
    Type of Medium: Online Resource
    ISSN: 2158-3188
    URL: Article
    DOI: 10.1038/s41398-023-02313-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2609311-X
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  • 8
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    Effects of prior deployments and perceived resilience on anger trajectories of combat-deployed soldiers
    Cambridge University Press (CUP) ; 2023
    In:  Psychological Medicine Vol. 53, No. 5 ( 2023-04), p. 2031-2040
    Details
    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 53, No. 5 ( 2023-04), p. 2031-2040
    Abstract: Problematic anger is frequently reported by soldiers who have deployed to combat zones. However, evidence is lacking with respect to how anger changes over a deployment cycle, and which factors prospectively influence change in anger among combat-deployed soldiers. Methods Reports of problematic anger were obtained from 7298 US Army soldiers who deployed to Afghanistan in 2012. A series of mixed-effects growth models estimated linear trajectories of anger over a period of 1–2 months before deployment to 9 months post-deployment, and evaluated the effects of pre-deployment factors (prior deployments and perceived resilience) on average levels and growth of problematic anger. Results A model with random intercepts and slopes provided the best fit, indicating heterogeneity in soldiers' levels and trajectories of anger. First-time deployers reported the lowest anger overall, but the most growth in anger over time. Soldiers with multiple prior deployments displayed the highest anger overall, which remained relatively stable over time. Higher pre-deployment resilience was associated with lower reports of anger, but its protective effect diminished over time. First- and second-time deployers reporting low resilience displayed different anger trajectories (stable v . decreasing, respectively). Conclusions Change in anger from pre- to post-deployment varies based on pre-deployment factors. The observed differences in anger trajectories suggest that efforts to detect and reduce problematic anger should be tailored for first-time v . repeat deployers. Ongoing screening is needed even for soldiers reporting high resilience before deployment, as the protective effect of pre-deployment resilience on anger erodes over time.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291721003779
    RVK:
    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1470300-2
    SSG: 5,2
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