Utilization of machine learning for identifying symptom severity military-related PTSD subtypes and their biological correlates.
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ABSTRACT:
SUBMITTER: Siegel CE
PROVIDER: S-EPMC8058082 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Military personnel experience posttraumatic stress disorder (PTSD), which is associated with differential DNA methylation across the whole genome. However, the relationship between these DNA methylation patterns and clinically relevant increases in PTSD severity is not yet clearly understood. The purpose of this study was to identify differences in DNA methylation associated with PTSD symptoms and investigate DNA methylation changes related to increases in the severity of PTSD in military personnel. In this pilot study, a cross-sectional comparison was made between military personnel with PTSD (n = 8) and combat-matched controls without PTSD (n = 6). Symptom measures were obtained, and genome-wide DNA methylation was measured using methylated DNA immunoprecipitation (MeDIP-seq) from whole blood samples at baseline and 3 months later. A longitudinal comparison measured DNA methylation changes in military personnel with clinically relevant increases in PTSD symptoms between time points (PTSD onset) and compared methylation patterns to controls with no clinical changes in PTSD. In military personnel with elevated PTSD symptoms 3 months following baseline, 119 genes exhibited reduced methylation and 8 genes exhibited increased methylation. Genes with reduced methylation in the PTSD-onset group relate to the canonical pathways of netrin signaling, Wnt/Ca+ pathway, and axonal guidance signaling. These gene pathways relate to neurological disorders, and the current findings suggest that these epigenetic changes potentially relate to PTSD symptomology. This study provides some novel insights into the role of epigenetic changes in PTSD symptoms and the progression of PTSD symptoms in military personnel.
| S-EPMC5993080 | biostudies-literature
Project description:Using data from 570 male service members and their wives, the current study investigated over-time associations between male service members' self-report of posttraumatic stress disorder (PTSD) symptoms and marital functioning (marital satisfaction, positive bonding, conflict behavior) as perceived by both spouses. Analyses spanned 5 time points over a 2-year period and fully disentangled between- and within-subject effects. Higher levels of all four PTSD symptom clusters (numbing, hyperarousal, effortful avoidance, and reexperiencing) showed significant between-subject associations with lower levels of marital satisfaction and positive bonding, and higher levels of conflict for both men and women, whereas there were markedly fewer significant within-subject associations. When running models with all four PTSD symptom clusters entered at once, the primary between-subject finding was that men with higher numbing symptoms overall reported poorer marital functioning in all domains; there were no significant between-subject links between numbing and marital functioning for women. In contrast, within-subject effects for numbing were found for both men and women, linking increased numbing with decreased positive bonding and increased conflict behavior over time; women also had lower marital satisfaction when their husbands reported relatively higher numbing. Between-subject analyses also revealed that for men with higher average levels of effortful avoidance, wives reported lower levels of satisfaction and positive bonding, whereas men themselves reported less frequent conflict behavior. Finally, within-subject effects showed that at times when men reported increased hyperarousal, they also perceived increased marital conflict, whereas women surprisingly reported increased marital satisfaction. Implications of divergent between- and within-subject results are discussed. (PsycINFO Database Record
| S-EPMC5858587 | biostudies-literature
Project description:To test the validity and reliability of a new measure of clinical impairment in primary progressive aphasia (PPA), the Progressive Aphasia Severity Scale (PASS), and to investigate relationships with MRI-based cortical thickness biomarkers for localizing and quantifying the severity of anatomic abnormalities.Patients with PPA were rated using the PASS and underwent performance-based language testing and MRI scans that were processed for cortical thickness measures.The level of impairment in PASS fluency, syntax/grammar, and word comprehension showed strong specific correlations with performance-based measures of these domains of language, and demonstrated high interrater reliability. Left inferior frontal thinning correlated with impairment in fluency and grammar/syntax, while left temporopolar thinning correlated with impairment in word comprehension. Discriminant function analysis demonstrated that a combination of left inferior frontal, left temporopolar, and left superior temporal sulcal thickness separated the 3 PPA subtypes from each other with 100% accuracy (87% accuracy in a leave-one-out analysis).The PASS, a novel measure of the severity of clinical impairment within domains of language typically affected in PPA, demonstrates reliable and valid clinical-behavioral properties. Furthermore, the presence of impairment in individual PASS domains demonstrates specific relationships with focal abnormalities in particular brain regions and the severity of impairment is strongly related to the severity of anatomic abnormality within the relevant brain region. These anatomic imaging biomarkers perform well in classifying PPA subtypes. These data provide robust support for the value of this novel clinical measure and the new imaging measure as markers for potential use in clinical research and trials in PPA.
| S-EPMC2918888 | biostudies-other
Project description:Epigenetic factors modify the effects of environmental factors on biological outcomes. Identification of epigenetic changes that associate with PTSD is therefore a crucial step in deciphering mechanisms of risk and resilience. In this study, our goal is to identify epigenetic signatures associated with PTSD symptom severity (PTSS) and changes in PTSS over time, using whole blood DNA methylation (DNAm) data (MethylationEPIC BeadChip) of military personnel prior to and following combat deployment. A total of 429 subjects (858 samples across 2 time points) from three male military cohorts were included in the analyses. We conducted two different meta-analyses to answer two different scientific questions: one to identify a DNAm profile of PTSS using a random effects model including both time points for each subject, and the other to identify a DNAm profile of change in PTSS conditioned on pre-deployment DNAm. Four CpGs near four genes (F2R, CNPY2, BAIAP2L1, and TBXAS1) and 88 differentially methylated regions (DMRs) were associated with PTSS. Change in PTSS after deployment was associated with 15 DMRs, of those 2 DMRs near OTUD5 and ELF4 were also associated with PTSS. Notably, three PTSS-associated CpGs near F2R, BAIAP2L1 and TBXAS1 also showed nominal evidence of association with change in PTSS. This study, which identifies PTSD-associated changes in genes involved in oxidative stress and immune system, provides novel evidence that epigenetic differences are associated with PTSS.
| S-EPMC9106882 | biostudies-literature
Project description:Introduction: Psychiatric service dogs are increasingly being sought out by military veterans as a complementary intervention for posttraumatic stress disorder (PTSD). After receiving a service dog, many veterans continue training their service dog at home. Our objective was to explore the associations between training methods, PTSD severity, service dog behavior, and the veteran-service dog bond in a population of military veterans with PTSD. Methods: Post-9/11 military veterans with PTSD who had received a psychiatric service dog were recruited from a national service dog provider. A total of 111 veterans (M = 40.1 ± 8.3 years, 80% male) participated in an online survey regarding frequency of training methods, PTSD symptom severity, service dog behavior, and the human-animal bond. Service dogs were predominately Labrador Retriever purebreds or mixes of various breeds (66% male) and mostly obtained from shelters or rescues (58%). Training methods were divided into five categories: positive reinforcement (e.g., physical praise), negative punishment (e.g., ignoring the dog), positive punishment (e.g., verbal correction), dominance (e.g., alpha roll), and bond-based (e.g., co-sleeping). Data were analyzed using general linear models. Results: Veterans self-reported using all five categories of training methods at least once a month. More frequent use of positive punishment was associated with less closeness with their service dog (p = 0.02), more fear (p = 0.003), less eye contact (p < 0.0001), and less trainability (p = 0.04). More frequent use of positive reinforcement was associated with higher closeness to their service dog (p = 0.002) and perceived increased attachment behavior (p = 0.002) and playfulness (p = 0.002). More frequent use of bond-based methods was associated with higher closeness to their service dog (p = 0.02). PTSD severity was not significantly associated with reported dog behavior, temperament, or veteran-service dog closeness. Conclusion: Military veterans with PTSD service dogs reported using many training methods that were associated with different outcomes. In general, the reported use of positive reinforcement or bond-based training methods were associated with reporting more positive outcomes while the reported use of positive punishment was associated with reporting more negative outcomes. Educating service dog organizations and recipients about the impacts of training methods could be beneficial for service dog efficacy and welfare.
| S-EPMC6378910 | biostudies-literature
Project description:In a large sample of community-dwelling older adults with histories of exposure to a broad range of traumatic events, we examined the extent to which appraisals of traumatic events mediate the relations between insecure attachment styles and posttraumatic stress disorder (PTSD) symptom severity.Participants completed an assessment of adult attachment, in addition to measures of PTSD symptom severity, event centrality, event severity, and ratings of the A1 PTSD diagnostic criterion for the potentially traumatic life event that bothered them most at the time of the study.Consistent with theoretical proposals and empirical studies indicating that individual differences in adult attachment systematically influence how individuals evaluate distressing events, individuals with higher attachment anxiety perceived their traumatic life events to be more central to their identity and more severe. Greater event centrality and event severity were each in turn related to higher PTSD symptom severity. In contrast, the relation between attachment avoidance and PTSD symptoms was not mediated by appraisals of event centrality or event severity. Furthermore, neither attachment anxiety nor attachment avoidance was related to participants' ratings of the A1 PTSD diagnostic criterion.Our findings suggest that attachment anxiety contributes to greater PTSD symptom severity through heightened perceptions of traumatic events as central to identity and severe. (PsycINFO Database Record
| S-EPMC4844797 | biostudies-literature
Project description:BackgroundMemory-based alterations are among the hallmark symptoms of posttraumatic stress disorder (PTSD) and may be associated with the integrity of the hippocampus. However, neuroimaging studies of hippocampal volume in individuals with PTSD have yielded inconsistent results, raising the possibility that various moderators, such as genetic factors, may influence this association. We examined whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism, which has previously been shown to be associated with hippocampal volume in healthy individuals, moderates the association between PTSD and hippocampal volume.MethodsRecent war veterans underwent structural MRI on a 3 T scanner. We extracted volumes of the right and left hippocampus using FreeSurfer and adjusted them for individual differences in intracranial volume. We assessed PTSD severity using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to model the genotype (Val158Met polymorphism) × PTSD severity interaction and its association with hippocampal volume.ResultsWe included 146 white, non-Hispanic recent war veterans (90% male, 53% with diagnosed PTSD) in our analyses. A significant genotype × PTSD symptom severity interaction emerged such that individuals with greater current PTSD symptom severity who were homozygous for the Val allele showed significant reductions in left hippocampal volume.LimitationsThe direction of proposed effects is unknown, thus precluding definitive assessment of whether differences in hippocampal volume reflect a consequence of PTSD, a pre-existing characteristic, or both.ConclusionOur findings suggest that the COMT polymorphism moderates the association between PTSD and hippocampal volume. These results highlight the role that the dopaminergic system has in brain structure and suggest a possible mechanism for memory disturbance in individuals with PTSD.
| S-EPMC5373706 | biostudies-literature
Project description:The amygdala is a core component in neurobiological models of stress and stress-related pathologies, including post-traumatic stress disorder (PTSD). While numerous studies have reported increased amygdala activity following traumatic stress exposure and in PTSD, the findings regarding amygdala volume have been mixed. One reason for these mixed findings may be that the amygdala has been considered as a homogenous entity, while it in fact consists of several nuclei with unique cellular and connectivity profiles. Here, we investigated amygdala nuclei volumes of the basolateral and the centrocorticomedial complex in relation to PTSD symptom severity in 47 young survivors from the 2011 Norwegian terror attack 24-36 months post-trauma. PTSD symptoms were assessed 4-5, 14-15 and 24-36 months following the trauma. We found that increased PTSD symptom severity 24-36 months post-trauma was associated with volumetric reductions of all basolateral as well as the central and the medial nuclei. However, only the lateral nucleus was associated with longitudinal symptom development, and mediated the association between 4-5 months and 24-36 months post-trauma symptoms. The results suggest that the amygdala nuclei may be differentially associated with cross-sectional and longitudinal measures of PTSD symptom severity. As such, investigations of amygdala total volume may not provide an adequate index of the association between amygdala and stress-related mental illness.
| S-EPMC7431855 | biostudies-literature
Project description:Importance:Effective and efficient treatment is needed for posttraumatic stress disorder (PTSD) in active duty military personnel. Objective:To examine the effects of massed prolonged exposure therapy (massed therapy), spaced prolonged exposure therapy (spaced therapy), present-centered therapy (PCT), and a minimal-contact control (MCC) on PTSD severity. Design, Setting, and Participants:Randomized clinical trial conducted at Fort Hood, Texas, from January 2011 through July 2016 and enrolling 370 military personnel with PTSD who had returned from Iraq, Afghanistan, or both. Final follow-up was July 11, 2016. Interventions:Prolonged exposure therapy, cognitive behavioral therapy involving exposure to trauma memories/reminders, administered as massed therapy (n = 110; 10 sessions over 2 weeks) or spaced therapy (n = 109; 10 sessions over 8 weeks); PCT, a non-trauma-focused therapy involving identifying/discussing daily stressors (n = 107; 10 sessions over 8 weeks); or MCC, telephone calls from therapists (n = 40; once weekly for 4 weeks). Main Outcomes and Measures:Outcomes were assessed before and after treatment and at 2-week, 12-week, and 6-month follow-up. Primary outcome was interviewer-assessed PTSD symptom severity, measured by the PTSD Symptom Scale-Interview (PSS-I; range, 0-51; higher scores indicate greater PTSD severity; MCID, 3.18), used to assess efficacy of massed therapy at 2 weeks posttreatment vs MCC at week 4; noninferiority of massed therapy vs spaced therapy at 2 weeks and 12 weeks posttreatment (noninferiority margin, 50% [2.3 points on PSS-I, with 1-sided α = .05]); and efficacy of spaced therapy vs PCT at posttreatment. Results:Among 370 randomized participants, data were analyzed for 366 (mean age, 32.7 [SD, 7.3] years; 44 women [12.0%]; mean baseline PSS-I score, 25.49 [6.36]), and 216 (59.0%) completed the study. At 2 weeks posttreatment, mean PSS-I score was 17.62 (mean decrease from baseline, 7.13) for massed therapy and 21.41 (mean decrease, 3.43) for MCC (difference in decrease, 3.70 [95% CI,0.72 to 6.68]; P = .02). At 2 weeks posttreatment, mean PSS-I score was 18.03 for spaced therapy (decrease, 7.29; difference in means vs massed therapy, 0.79 [1-sided 95% CI, -∞ to 2.29; P = .049 for noninferiority]) and at 12 weeks posttreatment was 18.88 for massed therapy (decrease, 6.32) and 18.34 for spaced therapy (decrease, 6.97; difference, 0.55 [1-sided 95% CI, -∞ to 2.05; P = .03 for noninferiority]). At posttreatment, PSS-I scores for PCT were 18.65 (decrease, 7.31; difference in decrease vs spaced therapy, 0.10 [95% CI, -2.48 to 2.27]; P = .93). Conclusions and Relevance:Among active duty military personnel with PTSD, massed therapy (10 sessions over 2 weeks) reduced PTSD symptom severity more than MCC at 2-week follow-up and was noninferior to spaced therapy (10 sessions over 8 weeks), and there was no significant difference between spaced therapy and PCT. The reductions in PTSD symptom severity with all treatments were relatively modest, suggesting that further research is needed to determine the clinical importance of these findings. Trial Registration:clinicaltrials.gov Identifier: NCT01049516.
| S-EPMC5833566 | biostudies-literature
Project description:BackgroundCigarette smoking was consistently found to be more prevalent in individuals with schizophrenia than in other psychiatric groups and the general population. These findings have been interpreted as evidence of a specific association between schizophrenia and smoking. However, the supporting data come primarily from cross-sectional studies, which are susceptible to confounding. Our aim was to test specificity of this link longitudinally in an epidemiologic sample.MethodsA cohort of 542 inpatients with psychosis was followed for 10 years after first hospitalization, completing 5 face-to-face interviews. Assessments included ratings of specific symptoms (psychotic, negative, disorganized, and depressive), Global Assessment of Functioning, and a categorical measure of cigarette consumption. All participants were assigned longitudinal consensus diagnoses by study psychiatrists, and 229 were diagnosed with schizophrenia spectrum disorders (SZ).ResultsAt baseline, 52.4% of participants were current smokers and 69.3% were lifetime smokers. Smoking rates did not differ among the diagnostic groups (schizophrenia spectrum, major depressive, bipolar, or other psychotic disorder) at any assessment point. Smokers were more severely ill than nonsmokers but did not differ in specific symptoms either cross-sectionally or longitudinally. Among smokers, changes in cigarette consumption were linked only with changes in depression (beta = .16, P < .001).ConclusionsRates of smoking were elevated in subjects with schizophrenia but were just as high with other psychotic disorders. Smoking was not associated with psychotic symptoms, but cigarette consumption covaried with depression over time. Given the devastating health consequences of cigarette use, smoking cessation interventions are urgently needed in this population and should specifically address depression.
| S-EPMC2800136 | biostudies-literature