Thought control strategies and rumination in youth with acute stress disorder and posttraumatic stress disorder following single-event trauma

Objective: Certain thought control strategies for managing the intrusive symptoms of posttraumatic stress disorder (PTSD) are thought to play a key role in its onset and maintenance. Whereas measures exist for the empirical assessment of such thought control strategies in adults, relatively few studies have explored how children and adolescents manage posttraumatic intrusive phenomena. Methods: In a prospective longitudinal study of 10-16-year-olds with PTSD, who were survivors of road traffic collisions and assaults, a variety of thought control strategies were assessed in the acute phase. These included strategies thought to be protective (reappraisal, social support) as well as maladaptive (distraction, punishment, worry). Ruminative responses to the trauma were assessed at the follow-up assessment. Results: Posttraumatic stress symptoms (PTSS) at each assessment were associated with the use of punishment and reappraisal, whereas social support and rumination were associated with PTSS symptoms at follow-up. Distraction was unrelated to PTSS at any time point. Rumination accounted for variance in PTSS symptoms at follow-up, even when accounting for baseline PTSS, and was found to mediate the relationships between reappraisal and punishment at baseline and PTSS at the follow-up assessment. Conclusions: The present study found no evidence to support advocating any particular thought control strategy for managing the intrusive symptoms of PTSD in youth in the acute posttrauma phase, and raised concerns over the use of reappraisal coping strategies. The study underscores the importance of ruminative responses in the onset and maintenance of PTSD in trauma-exposed youth

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A systematic review and meta-analysis of PTSD symptoms at mid-treatment during trauma-focused treatment for PTSD

There is concern that trauma memory processing in psychological therapies leads to PTSD symptom exacerbation. We compared PTSD symptoms at mid-treatment in trauma-focused psychological therapy to control groups. We systematically searched multiple databases and searched grey literature. We included randomised controlled trials involving adults comparing trauma-focused psychological interventions with active non-trauma-focused interventions or waitlist conditions. Twenty-three studies met our inclusion criteria. We found no evidence of PTSD symptom exacerbation at mid-treatment in trauma-focused interventions compared to control groups (g=-.16, [95% confidence interval, CI, -.34,.03]). Sensitivity analyses with high quality studies (risk of bias assessment ≥ 7; g=-.25; [95% CI -.48, -.03], k=12) and studies with passive controls (g=-.32; [95% CI -.59, -.05], k=8) yielded small effect sizes favouring trauma-focused interventions. At post-treatment, trauma-focused interventions yielded a medium effect on PTSD symptoms compared to all controls (g=-.57; [CI -.79, -.35], k=23). Regarding depression, trauma-focused interventions yielded a small effect size compared to controls at mid-treatment (g=-.23; [95% CI -.39, -.08], k=12) and post-treatment (g=-.45; [CI -.66, -.25], k=12). This meta-analysis found no evidence that trauma-focused psychotherapies elicit symptom exacerbation at mid-treatment in terms of PTSD or depression symptoms. Instead, this meta-analysis suggests that the benefits of trauma-focused interventions can be experienced through improved depression and possibly PTSD before the conclusion of therapy. However, it is possible that symptom exacerbation occurred before mid-treatment and/or that people who experience symptom exacerbation drop out of studies and so are not included in the analysis

Rsu1 regulates ethanol consumption in Drosophila and humans

International audienceAlcohol abuse is highly prevalent, but little is understood about the molecular causes. Here, we report that Ras suppressor 1 (Rsu1) affects ethanol consumption in flies and humans. Drosophila lacking Rsu1 show reduced sensitivity to ethanol-induced sedation. We show that Rsu1 is required in the adult nervous system for normal sensitivity and that it acts downstream of the integrin cell adhesion molecule and upstream of the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase to regulate the actin cytoskeleton. In an ethanol preference assay, global loss of Rsu1 causes high naïve preference. In contrast, flies lacking Rsu1 only in the mushroom bodies of the brain show normal naïve preference but then fail to acquire ethanol preference like normal flies. Rsu1 is, thus, required in distinct neurons to modulate naïve and acquired ethanol preference. In humans, we find that polymorphisms in RSU1 are associated with brain activation in the ventral striatum during reward anticipation in adolescents and alcohol consumption in both adolescents and adults. Together, these data suggest a conserved role for integrin/Rsu1/Rac1/actin signaling in modulating reward-related phenotypes, including ethanol consumption, across phyla

Substance Use Initiation, Particularly Alcohol, in Drug-Naive Adolescents: Possible Predictors and Consequences From a Large Cohort Naturalistic Study

International audienceIt is unclear whether deviations in brain and behavioral development, which may underpin elevated substance use during adolescence, are predispositions for or consequences of substance use initiation. Here, we examine behavioral and neuroimaging indices at early and mid-adolescence in drug-naive youths to identify possible predisposing factors for substance use initiation and its possible consequences