Network analysis of PTSD and depressive symptoms in 158,139 treatment-seeking veterans with PTSD

Background In recent years, a new framework for analyzing and understanding posttraumatic stress disorder (PTSD) was introduced; the network approach. Up until now, network analysis studies of PTSD were largely conducted on small to medium sample sizes (N < 1,000), which might be a possible cause of variability in main findings. Moreover, only a limited number of network studies investigated comorbidity.Methods In this study, we utilized a large sample to conduct a network analysis of 17 symptoms of PTSD (DSM-IV), and compared it to the result of a second network consisting of symptoms of PTSD and depression (based on Patient Health Questionnaire-9 [PHQ-9]). Our sample consisted of 502,036 treatment-seeking veterans, out of which 158,139 had fully completed the assessment of symptoms of PTSD and a subsample of 32,841 with valid PCL and PHQ-9 that was administered within 14 days or less.Results Analyses found that in the PTSD network, the most central symptoms were feeling distant or cut off from others, followed by feeling very upset when reminded of the event, and repeated disturbing memories or thoughts of the event. In the combined network, we found that concentration difficulties and anhedonia are two of the five most central symptoms.Conclusion Our findings replicate the centrality of intrusion symptoms in PTSD symptoms' network. Taking into account the large sample and high stability of the network structure, we believe our study can answer some of the criticism regarding stability of cross-sectional network structures.Stress and Psychopatholog

Predictors of Treatment Attrition Among an Outpatient Clinic Sample of Youths With Clinically Significant Anxiety

Predictors of treatment attrition were examined in a sample of 197 youths (ages 5–18) with clinically-significant symptoms of anxiety seeking psychotherapy services at a community-based outpatient mental health clinic (OMHC). Two related definitions of attrition were considered: (a) clinician-rated dropout (CR), and (b) CR dropout qualified by phase of treatment (pre, early, or late phases) (PT). Across both definitions, rates of attrition in the OMHC sample were higher than those for anxious youths treated in randomized controlled trials, and comorbid depression symptoms predicted dropout, with a higher rate of depressed youths dropping out later in treatment (after 6 sessions). Using the PT definition, minority status also predicted attrition, with more African-American youths lost pre-treatment. Other demographic (age, gender, single parent status) and clinical (externalizing symptoms, anxiety severity) characteristics were not significantly associated with attrition using either definition. Implications for services for anxious youths in public service settings are discussed. Results highlight the important role of comorbid depression in the treatment of anxious youth and the potential value of targeted retention efforts for ethnic minority families early in the treatment process

Remodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder:Results from the ENIGMA-PGC PTSD Consortium

BACKGROUND: Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). METHODS: Neuroimaging and clinical data were aggregated from 29 research sites in >1,300 PTSD cases and >2,000 trauma-exposed controls (age 6.2-85.2 years) by the ENIGMA-PGC PTSD working group. Cortical regions in the network were rank-ordered by effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2 to 148) regions with the largest effect size for PTSD > non-PTSD formed hypertrophic networks, the largest effect size for PTSD < non-PTSD formed atrophic networks, and the smallest effect size of between-group differences formed stable networks. The mean structural covariance (SC) of a given n-region network was the average of all positive pairwise correlations and was compared to the mean SC of 5,000 randomly generated n-region networks. RESULTS: Patients with PTSD, relative to non-PTSD controls, exhibited lower mean SC in CT-based and SA-based atrophic networks. Comorbid depression, sex and age modulated covariance differences of PTSD-related structural networks. CONCLUSIONS: Covariance of structural networks based on CT and cortical SA are affected by PTSD and further modulated by comorbid depression, sex, and age. The structural covariance networks that are perturbed in PTSD comport with converging evidence from resting state functional connectivity networks and networks impacted by inflammatory processes, and stress hormones in PTSD

A Comparison of Methods to Harmonize Cortical Thickness Measurements Across Scanners and Sites

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME INT), (2) LME that models both site-specific random intercepts and age-related random slopes (LME INT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2–81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3–85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ 2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ 2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ 2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects

A comparison of methods to harmonize cortical thickness measurements across scanners and sites

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME INT), (2) LME that models both site-specific random intercepts and age-related random slopes (LME INT+ SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (X-2 (3) = 63.704, p < 0.001) as well as casecontrol differences in age-related cortical thinning (X-2 (3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (X-2 (3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.Stress-related psychiatric disorders across the life spa

Randomized Controlled Trial of Imagery Rehearsal for Posttraumatic Nightmares in Combat Veterans

STUDY OBJECTIVES: To examine the efficacy of imagery rehearsal (IR) combined with cognitive behavioral therapy for insomnia (CBT-I) compared to CBT-I alone for treating recurrent nightmares in military veterans with posttraumatic stress disorder (PTSD). METHODS: In this randomized controlled study, 108 male and female United States veterans of the Iraq and Afghanistan conflicts with current, severe PTSD and recurrent, deployment-related nightmares were randomized to six sessions of IR + CBT-I (n = 55) or CBT-I (n = 53). Primary outcomes were measured with the Nightmare Frequency Questionnaire (NFQ) and Nightmare Distress Questionnaire (NDQ). RESULTS: Improvement with treatment was significant (29% with reduction in nightmare frequency and 22% with remission). Overall, IR + CBT-I was not superior to CBT-I (NFQ: -0.12; 95% confidence interval = -0.87 to 0.63; likelihood ratio chi square = 4.7(3), P = .2); NDQ: 1.5, 95% confidence interval = -1.4 to 4.4; likelihood ratio chi square = 7.3, P = .06). CONCLUSIONS: Combining IR with CBT-I conferred no advantage overall. Further research is essential to examine the possibly greater benefit of adding IR to CBT-I for some subgroups of veterans with PTSD. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Cognitive Behavioral Therapy (CBT) for Nightmares in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans; Identifier: NCT00691626; URL: https://clinicaltrials.gov/ct2/show/NCT00691626

Treatment of Nightmares With Prazosin: A Systematic Review

Nightmares, frequently associated with posttraumatic stress disorder and clinically relevant in today's world of violence, are difficult to treat, with few pharmacologic options. We performed a systematic review to evaluate the evidence for the use of prazosin in the treatment of nightmares. A comprehensive search was performed using the databases EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews, from their inception to March 9, 2012, using keywords prazosin and nightmares/PTSD or associated terms (see text). Two authors independently reviewed titles and abstracts and selected relevant studies. Descriptive data and outcomes of interest from eligible studies were extracted by 1 author, and checked by 2 others. The risk of bias of randomized controlled trials (RCTs) was assessed independently by 2 reviewers. Articles met criteria for inclusion if prazosin was used to treat nightmares, and outcome measures included nightmares or related symptoms of sleep disorders. Our search yielded 21 studies, consisting of 4 RCTs, 4 open-label studies, 4 retrospective chart reviews, and 9 single case reports. The prazosin dose ranged from 1 to 16 mg/d. Results were mixed for the 4 RCTs: 3 reported significant improvement in the number of nightmares, and 1 found no reduction in the number of nightmares. Reduced nightmare severity with use of prazosin was consistently reported in the open-label trials, retrospective chart reviews, and single case reports