Suchergebnisse

Abstract Despite the sparseness of the currently available data, there is accumulating evidence of information processing impairment in post-traumatic stress disorder (PTSD). Studies of event-related potentials (ERPs) are the main tool in real time examination of information processing. In this paper, we sought to critically review the ERP evidence of information processing abnormalities in patients with PTSD. We also examined the evidence supporting the existence of a relationship between ERP abnormalities and symptom profiles or severity in PTSD patients. An extensive Medline search was performed. Keywords included PTSD or post-traumatic stress disorder, electrophysiology or EEG, electrophysiology, P50, P100, N100, P2, P200, P3, P300, sensory gating, CNV (contingent negative variation) and MMN (mismatch negativity). We limited the review to ERP adult human studies with control groups which were reported in the English language. After applying our inclusion-exclusion review criteria, 36 studies were included. Subjects exposed to wide ranges of military and civilian traumas were studied in these reports. Presented stimuli were both auditory and visual. The most widely studied components included P300, P50 gating, N100 and P200. Most of the studies reported increased P300 response to trauma-related stimuli in PTSD patients. A smaller group of studies reported dampening of responses or no change in responses to trauma-related and/or unrelated stimuli. P50 studies were strongly suggestive of impaired gating in patients with PTSD. In conclusion, the majority of reports support evidence of information processing abnormalities in patients with PTSD diagnosis. The predominance of evidence suggests presence of mid-latency and late ERP components differences in PTSD patients in comparison to healthy controls. Heterogeneity of assessment methods used contributes to difficulties in reaching firm conclusions regarding the nature of these differences. We suggest that future ERP-PTSD studies utilize standardized assessment scales that provide detailed information regarding the symptom clusters and the degree of symptom severity. This would allow assessment of electrophysiological indices-clinical symptoms relationships. Based on the available data, we suggest that ERP abnormalities in PTSD are possibly affected by the level of illness severity. If supported by future research, ERP studies may be used for both initial assessment and treatment follow-up.

Posttraumatic stress disorder (PTSD)—a chronic, debilitating condition, broadly characterized by emotion dysregulation—is prevalent among US military personnel who have returned from Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF). Selective serotonin reuptake inhibitors (SSRIs) are a first-line treatment for PTSD, but treatment mechanisms are unknown and patient response varies. SSRIs may exert their effects by remediating emotion regulatory brain activity and individual differences in patient response might be explained, in part, by pre-treatment differences in neural systems supporting the downregulation of negative affect. Thirty-four OEF/OIF veterans, 17 with PTSD and 17 without PTSD underwent 2 functional magnetic resonance imaging scans 12 weeks apart. At each scan, they performed an emotion regulation task; in the interim, veterans with PTSD were treated with the SSRI, paroxetine. SSRI treatment increased activation in both the left dorsolateral prefrontal cortex (PFC) and supplementary motor area (SMA) during emotion regulation, although only change in the SMA over time occurred in veterans with PTSD and not those without PTSD. Less activation of the right ventrolateral PFC/inferior frontal gyrus during pre-treatment emotion regulation was associated with greater reduction in PTSD symptoms with SSRI treatment, irrespective of pre-treatment severity. Patients with the least recruitment of prefrontal emotion regulatory brain regions may benefit most from treatment with SSRIs, which appear to augment activity in these regions.

To identify trajectories of posttraumatic stress (PTS) and depression symptom groups after deployment and determine the effect of alcohol use disorder on these trajectories, PTS symptoms were modeled using the PTSD Checklist in 472 Ohio National Guard members, and depression symptoms were modeled using the 9-item Patient Health Questionnaire in 727 Ohio National Guard members. There were 42% of participants who were resistant to PTS symptoms across the 4 years of study and 55.9% were resistant to depression symptoms. There were 19% and 42.2% of participants who showed resilience (experiencing slightly elevated symptoms followed by a decline, according to Bonanno et al., 2004) to depression and PTS symptoms, respectively. Mild and chronic dysfunction constituted the smallest trajectory groups across disorders. Marital status, deployment to an area of conflict, and number of lifetime stressors were associated with membership into different latent groups for depression (unstandardized beta estimates range: 0.69 to 1.37). Deployment to an area of conflict, number of lifetime potentially traumatic events and education predicted membership into different latent groups for PTS (unstandardized beta estimate range: 0.83 to 3.17). Alcohol use disorder was associated with an increase in both symptom outcomes (unstandardized beta estimate range: 0.20 to 9.45). These results suggest that alcohol use disorder may have contributed substantially to trajectories of psychopathology in this population.

BACKGROUND: Prevention of PTSD requires identification of subpopulations contributing most to the population burden of PTSD. This study examined the relative contribution of subthreshold PTSD and probable PTSD on future PTSD in a representative military cohort. METHODS: We analyzed data on 3,457 US National Guard members from the state of Ohio, assessed by telephone annually from 2008–2014. At each wave, participants were classified into one of three groups based on the PTSD Checklist: probable PTSD (DSM-IV-TR criteria), subthreshold PTSD (Criterion A1, at least one symptom in each cluster, symptom lasting longer than 30 days, and functional impairment), and no PTSD. We calculated the exposure rate, risk ratio (RR), and population attributable fraction (PAF) to determine the burden of future probable PTSD attributable to subthreshold PTSD compared to probable PTSD. RESULTS: The annualized prevalence of subthreshold PTSD and probable PTSD was respectively 11.9% and 5.0%. The RR for probable PTSD was twice as great among respondents with probable PTSD the prior interview than that of those with subthreshold PTSD (7.0 vs. 3.4); however, the PAF was considerably greater in participants with subthreshold PTSD the prior interview (PAF=35%; 95% CI=26.0–42.9%) than in those with probable PTSD (PAF=28.0%; 95% CI=21.8–33.8%). Results were robust to changes in subthreshold PTSD definition. CONCLUSIONS: Subthreshold PTSD accounted for a substantial proportion of this population's future PTSD burden. Population-based preventive interventions, compared to an approach focused exclusively on cases of diagnosable PTSD, is likely to affect the greatest reduction in this population's future PTSD burden.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with exaggerated threat processing and deficits in emotion modulation circuitry. It remains unknown how neural circuits are associated with response to evidence-based treatments for PTSD. METHOD: We examined associations between PTSD symptoms and indicators of neural response in key emotion processing and modulation regions. Fifty-six military Veterans with PTSD were randomly assigned to one of three evidence-based treatments (prolonged exposure, sertraline, and PE plus sertraline) in a randomized clinical trial ("PROGrESS"; 2018, Contemp Clin Trials, 64, 128–138). Twenty-seven combat-exposed controls (CCs) served as a comparison group at pretreatment. Before and after PTSD treatment, functional magnetic resonance imaging was used to assess brain activation and connectivity during the validated Shifted Attention Emotion Appraisal Task (2003, J Neurosci, 23, 5627–5633; 2013, Biol Psychiatry, 73, 1045–1053). RESULTS: Greater activation in emotion processing (anterior insula) and modulation (prefrontal cortex) regions and increased connectivity between attentional control (dorsolateral prefrontal cortex and superior parietal cortex) and emotion processing (amygdala) regions, at pretreatment, were associated with subsequent PTSD symptom improvement. CONCLUSIONS: This study is one of the first to examine task-based activation and functional connectivity in a PTSD treatment trial, and provides evidence to suggest that activation in and connectivity between emotion processing and modulation regions are important predictors of treatment response.

OBJECTIVE: Depression is one of the most common mental disorders in the United States in both civilian and military populations, but few prospective studies assess a wide range of predictors across multiple domains for new-onset (incident) depression in adulthood. Supervised machine learning methods can identify predictors of incident depression out of many different candidate variables, without some of the assumptions and constraints that underlie traditional regression analyses. The objectives of this study were to identify predictors of incident depression across 5 years of follow-up using machine learning, and to assess prediction accuracy of the algorithms. METHODS: Data were from a cohort of Army National Guard members free of history of depression at baseline (n = 1951 men and 298 women), interviewed once per year for probable depression. Classification trees and random forests were constructed and cross-validated, using 84 candidate predictors from the baseline interviews. RESULTS: Stressors and traumas such as emotional mistreatment and adverse childhood experiences, demographics such as being a parent or student, and military characteristics including paygrade and deployment location were predictive of probable depression. Cross-validated random forest algorithms were moderately accurate (68% for women and 73% for men). CONCLUSIONS: Events and characteristics throughout the life course, both in and outside of deployment, predict incident depression in adulthood among military personnel. Although replication studies are needed, these results may help inform potential intervention targets to reduce depression incidence among military personnel. Future research should further refine and explore interactions between identified variables.

To reveal post-traumatic stress disorder (PTSD) genetic risk influences on tissue-specific gene expression, we use brain and non-brain transcriptomic imputation. We impute genetically regulated gene expression (GReX) in 29,539 PTSD cases and 166,145 controls from 70 ancestry-specific cohorts and identify 18 significant GReX-PTSD associations corresponding to specific tissue-gene pairs. The results suggest substantial genetic heterogeneity based on ancestry, cohort type (military versus civilian), and sex. Two study-wide significant PTSD associations are identified in European and military European cohorts; ZNF140 is predicted to be upregulated in whole blood, and SNRNP35 is predicted to be downregulated in dorsolateral prefrontal cortex, respectively. In peripheral leukocytes from 175 marines, the observed PTSD differential gene expression correlates with the predicted differences for these individuals, and deployment stress produces glucocorticoid-regulated expression changes that include downregulation of both ZNF140 and SNRNP35. SNRNP35 knockdown in cells validates its functional role in U12-intron splicing. Finally, exogenous glucocorticoids in mice downregulate prefrontal Snrnp35 expression.

To reveal post-traumatic stress disorder (PTSD) genetic risk influences on tissue-specific gene expression, we use brain and non-brain transcriptomic imputation. We impute genetically regulated gene expression (GReX) in 29,539 PTSD cases and 166,145 controls from 70 ancestry-specific cohorts and identify 18 significant GReX-PTSD associations corresponding to specific tissue-gene pairs. The results suggest substantial genetic heterogeneity based on ancestry, cohort type (military versus civilian), and sex. Two study-wide significant PTSD associations are identified in European and military European cohorts; ZNF140 is predicted to be upregulated in whole blood, and SNRNP35 is predicted to be downregulated in dorsolateral prefrontal cortex, respectively. In peripheral leukocytes from 175 marines, the observed PTSD differential gene expression correlates with the predicted differences for these individuals, and deployment stress produces glucocorticoid-regulated expression changes that include downregulation of both ZNF140 and SNRNP35. SNRNP35 knockdown in cells validates its functional role in U12-intron splicing. Finally, exogenous glucocorticoids in mice downregulate prefrontal Snrnp35 expression.