Habituation of Distress and Craving During Treatment as Predictors of Change in PTSD Symptoms and Substance Use Severity

Objective—Increasing evidence supports the efficacy of trauma-focused exposure therapy in the treatment of posttraumatic stress disorder (PTSD) and co-occurring substance use disorders. Little is known, however, about the mechanisms of change in treatment for patients with PTSD and co-occurring substance use disorders. The aim of the present study was to examine whether within- and between-session habituation of distress and substance craving during imaginal exposure relates to treatment outcomes among U.S. military veterans with PTSD and a co-occurring substance use disorder (N = 54). Method—Veterans received Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure, a manualized integrated treatment combining prolonged exposure with cognitive-behavioral therapy for substance use disorders as part of a larger randomized clinical trial. Self-reported distress and craving ratings were collected during each imaginal exposure session. Results—Data were analyzed using a series of random intercept and slope multilevel linear and generalized linear models. Results revealed that between-session habituation of distress and craving was associated with greater improvement in PTSD symptoms during treatment. Between-session habituation of craving was also associated with a marginally greater reduction in frequency of substance use among participants still reporting use during treatment. Within-session habituation of distress was unrelated to treatment outcome. Conclusions—Together, these findings indicate that habituation in both distress and craving may be important in maximizing treatment outcome for patients with PTSD and comorbid substance use disorders

Global importance of large-diameter trees

Aim: To examine the contribution of large‐diameter trees to biomass, stand structure, and species richness across forest biomes. Location: Global. Time period: Early 21st century. Major taxa studied: Woody plants. Methods: We examined the contribution of large trees to forest density, richness and biomass using a global network of 48 large (from 2 to 60 ha) forest plots representing 5,601,473 stems across 9,298 species and 210 plant families. This contribution was assessed using three metrics: the largest 1% of trees ≥ 1 cm diameter at breast height (DBH), all trees ≥ 60 cm DBH, and those rank‐ordered largest trees that cumulatively comprise 50% of forest biomass. Results: Averaged across these 48 forest plots, the largest 1% of trees ≥ 1 cm DBH comprised 50% of aboveground live biomass, with hectare‐scale standard deviation of 26%. Trees ≥ 60 cm DBH comprised 41% of aboveground live tree biomass. The size of the largest trees correlated with total forest biomass (r2 = .62, p < .001). Large‐diameter trees in high biomass forests represented far fewer species relative to overall forest richness (r2 = .45, p < .001). Forests with more diverse large‐diameter tree communities were comprised of smaller trees (r2 = .33, p < .001). Lower large‐diameter richness was associated with large‐diameter trees being individuals of more common species (r2 = .17, p = .002). The concentration of biomass in the largest 1% of trees declined with increasing absolute latitude (r2 = .46, p < .001), as did forest density (r2 = .31, p < .001). Forest structural complexity increased with increasing absolute latitude (r2 = .26, p < .001). Main conclusions: Because large‐diameter trees constitute roughly half of the mature forest biomass worldwide, their dynamics and sensitivities to environmental change represent potentially large controls on global forest carbon cycling. We recommend managing forests for conservation of existing large‐diameter trees or those that can soon reach large diameters as a simple way to conserve and potentially enhance ecosystem services

Integrated Treatment of PTSD and Substance Use Disorders: The Mediating Role of PTSD Improvement in the Reduction of Depression

Posttraumatic stress disorder (PTSD) represents one of the most common mental health disorders, particularly among veterans, and is associated with significant distress and impairment. This highly debilitating disorder is further complicated by common comorbid psychiatric disorders, such as substance use disorders (SUD). Individuals with PTSD and co-occurring SUD also commonly present with secondary symptoms, such as elevated depression. Little is known, however, about how these secondary symptoms are related to treatment outcome. The aim of the present study, therefore, was to examine (1) the effects of treatment of comorbid PTSD/SUD on depressive symptoms; and (2) whether this effect was mediated by changes in PTSD severity or changes in SUD severity. Participants were 81 U.S. military veterans (90.1% male) with PTSD and SUD enrolled in a randomized controlled trial examining the efficacy of an integrated, exposure-based treatment (Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure; n = 54) versus relapse prevention (n = 27). Results revealed significantly lower depressive symptoms at post-treatment in the COPE group, as compared to the relapse prevention group. Examination of the mechanisms associated with change in depression revealed that reduction in PTSD severity, but not substance use severity, mediated the association between the treatment group and post-treatment depression. The findings underscore the importance of treating PTSD symptoms in order to help reduce co-occurring symptoms of depression in individuals with PTSD/SUD. Clinical implications and avenues for future research are discussed

Habituation of distress and craving during treatment as predictors of change in PTSD symptoms and substance use severity.

OBJECTIVE: Increasing evidence supports the efficacy of trauma-focused exposure therapy in the treatment of posttraumatic stress disorder (PTSD) and co-occurring substance use disorders. Little is known, however, about the mechanisms of change in treatment for patients with PTSD and co-occurring substance use disorders. The aim of the present study was to examine whether within- and between-session habituation of distress and substance craving during imaginal exposure relates to treatment outcomes among US military Veterans with PTSD and a co-occurring substance use disorder (N = 54). METHOD: Veterans received Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE), a manualized integrated treatment combining PE with cognitive behavioral therapy for substance use disorders as part of a larger randomized clinical trial. Self-reported distress and craving ratings were collected during each imaginal exposure session. RESULTS: Data were analyzed using a series of random intercept and slope multilevel linear and generalized linear models. Results revealed that between-session habituation of distress and craving was associated with greater improvement in PTSD symptoms during treatment. Between-session habituation of craving was also associated with a marginally greater reduction in frequency of substance use among participants still reporting use during treatment. Within-session habituation of distress was unrelated to treatment outcome. CONCLUSIONS: Together, these findings indicate that habituation in both distress and craving may be important in maximizing treatment outcome for patients with PTSD and comorbid substance use disorders

Factor structure and item response of psychosis symptoms among Kenyan adults

Background: The aim of this study was to evaluate the construct validity of the psychosis module of the Mini International Neuropsychiatric Interview version 7.0.2 (MINI-7). Method: We utilized data collected from 2738 participants with a primary psychotic or bipolar disorder. Par- ticipants were drawn from two Kenyan sites of a large multi-center neuropsychiatric genetic study. The factor structure of the MINI-7 psychosis items were explored using confirmatory factor analyses (CFA) and Item Response Theory approach, for the full sample and by gender. Results: The CFA revealed that a 1-factor model provided adequate fit for the MINI-7 psychosis items for the full sample (x2 = 397.92, df = 35, p \u3c .0001; RMSEA = 0.06; CFI = 0.92; TLI = 0.90) as well as for the female (x2 = 185.16.92, df = 35, p \u3c .0001; RMSEA = 0.06; CFI = 0.93; TLI = 0.91) and male groups (x2 = 242.09, df = 35, p \u3c .0001; RMSEA = 0.06; CFI = 0.92; TLI = 0.89). Item thresholds for the full sample, and female and male groups were highest for ‘odd beliefs’ ( 1.42, 1.33, and 1.51 respectively) and lowest for ‘visual hallucina- tions’ ( 0.03, 0.04, and 0.01 respectively). Limitations: Our study used a hospital-based population, which may have excluded patients with milder psychotic symptoms. Findings may therefore not be generalizable to the community setting. Conclusions: Our findings indicate good construct validity of the MINI-7 psychosis module, and provides support for use of the tool in diagnosing psychotic disorders in clinical settings in Keny

Distinct in vivo roles of secreted APP ectodomain variants APPsα and APPsβ in regulation of spine density, synaptic plasticity, and cognition

Increasing evidence suggests that synaptic functions of the amyloid precursor protein (APP), which is key to Alzheimer pathogenesis, may be carried out by its secreted ectodomain (APPs). The specific roles of APPsα and APPsβ fragments, generated by non-amyloidogenic or amyloidogenic APP processing, respectively, remain however unclear. Here, we expressed APPsα or APPsβ in the adult brain of conditional double knockout mice (cDKO) lacking APP and the related APLP2. APPsα efficiently rescued deficits in spine density, synaptic plasticity (LTP and PPF), and spatial reference memory of cDKO mice. In contrast, APPsβ failed to show any detectable effects on synaptic plasticity and spine density. The C-terminal 16 amino acids of APPsα (lacking in APPsβ) proved sufficient to facilitate LTP in a mechanism that depends on functional nicotinic α7-nAChRs. Further, APPsα showed high-affinity, allosteric potentiation of heterologously expressed α7-nAChRs in oocytes. Collectively, we identified α7-nAChRs as a crucial physiological receptor specific for APPsα and show distinct in vivo roles for APPsα versus APPsβ. This implies that reduced levels of APPsα that might occur during Alzheimer pathogenesis cannot be compensated by APPsβ

Systemic and T cell-associated responses to SARS-CoV-2 immunisation in gut inflammation (STAR SIGN study): effects of biologics on vaccination efficacy of the third dose of mRNA vaccines against SARS-CoV-2.

BACKGROUND Immunosuppressed patients with inflammatory bowel disease (IBD) experience increased risk of vaccine-preventable diseases such as COVID-19. AIMS To assess humoral and cellular immune responses following SARS-CoV-2 booster vaccination in immunosuppressed IBD patients and healthy controls. METHODS In this prospective, multicentre, case-control study, 139 IBD patients treated with biologics and 110 healthy controls were recruited. Serum anti-SARS-CoV-2 spike IgG concentrations were measured 2-16 weeks after receiving a third mRNA vaccine dose. The primary outcome was to determine if humoral immune responses towards booster vaccines differ in IBD patients under anti-TNF versus non-anti-TNF therapy and healthy controls. Secondary outcomes were antibody decline, impact of previous infection and SARS-CoV-2-targeted T cell responses. RESULTS Anti-TNF-treated IBD patients showed reduced anti-spike IgG concentrations (geometric mean 2357.4 BAU/ml [geometric SD 3.3]) when compared to non-anti-TNF-treated patients (5935.7 BAU/ml [3.9]; p < 0.0001) and healthy controls (5481.7 BAU/ml [2.4]; p < 0.0001), respectively. In multivariable modelling, prior infection (geometric mean ratio 2.00 [95% CI 1.34-2.90]) and vaccination with mRNA-1273 (1.53 [1.01-2.27]) increased antibody concentrations, while anti-TNF treatment (0.39 [0.28-0.54]) and prolonged time between vaccination and antibody measurement (0.72 [0.58-0.90]) decreased anti-SARS-CoV-2 spike antibodies. Antibody decline was comparable in IBD patients independent of anti-TNF treatment and antibody concentrations could not predict breakthrough infections. Cellular and humoral immune responses were uncoupled, and more anti-TNF-treated patients than healthy controls developed inadequate T cell responses (15/73 [20.5%] vs 2/100 [2.0%]; p = 0.00031). CONCLUSIONS Anti-TNF-treated IBD patients have impaired humoral and cellular immunogenicity following SARS-CoV-2 booster vaccination. Fourth dose administration may be beneficial for these patients