In randomized trials, prazosin, an α
-adrenoreceptor antagonist, has been effective in alleviating nightmares associated with post-traumatic stress disorder (PTSD) in military veterans.
We recruited ...veterans from 13 Department of Veterans Affairs medical centers who had chronic PTSD and reported frequent nightmares. Participants were randomly assigned to receive prazosin or placebo for 26 weeks; the drug or placebo was administered in escalating divided doses over the course of 5 weeks to a daily maximum of 20 mg in men and 12 mg in women. After week 10, participants continued to receive prazosin or placebo in a double-blind fashion for an additional 16 weeks. The three primary outcome measures were the change in score from baseline to 10 weeks on the Clinician-Administered PTSD Scale (CAPS) item B2 ("recurrent distressing dreams"; scores range from 0 to 8, with higher scores indicating more frequent and more distressing dreams); the change in score from baseline to 10 weeks on the Pittsburgh Sleep Quality Index (PSQI; scores range from 0 to 21, with higher scores indicating worse sleep quality); and the Clinical Global Impression of Change (CGIC) score at 10 weeks (scores range from 1 to 7, with lower scores indicating greater improvement and a score of 4 indicating no change).
A total of 304 participants underwent randomization; 152 were assigned to prazosin, and 152 to placebo. At 10 weeks, there were no significant differences between the prazosin group and the placebo group in the mean change from baseline in the CAPS item B2 score (between-group difference, 0.2; 95% confidence interval CI, -0.3 to 0.8; P=0.38), in the mean change in PSQI score (between-group difference, 0.1; 95% CI, -0.9 to 1.1; P=0.80), or in the CGIC score (between-group difference, 0; 95% CI, -0.3 to 0.3; P=0.96). There were no significant differences in these measures at 26 weeks (a secondary outcome) or in other secondary outcomes. At 10 weeks, the mean difference between the prazosin group and the placebo group in the change from baseline in supine systolic blood pressure was a decrease of 6.7 mm Hg. The adverse event of new or worsening suicidal ideation occurred in 8% of the participants assigned to prazosin versus 15% of those assigned to placebo.
In this trial involving military veterans who had chronic PTSD, prazosin did not alleviate distressing dreams or improve sleep quality. (Funded by the Department of Veterans Affairs Cooperative Studies Program; PACT ClinicalTrials.gov number, NCT00532493 .).
Alcohol-associated liver disease (ALD) pathologies include steatosis, inflammation, and injury, which may progress to fibrosis, cirrhosis, and cancer. The liver receives ~60% of fatty acids from ...adipose tissue triglyceride hydrolysis, but the role of this lipolytic pathway in ALD development has not been directly examined in any genetic animal models with selective inactivation of adipose lipolysis.
Using adipose-specific comparative gene identification-58 (CGI-58) knockout (FAT-KO) mice, a model of impaired adipose lipolysis, we show that mice deficient in adipose lipolysis are almost completely protected against ethanol-induced hepatic steatosis and lipid peroxidation when subjected to the National Institute on Alcohol Abuse and Alcoholism chronic and binge ethanol feeding model. This is unlikely due to reduced lipid synthesis because this regimen of ethanol feeding down-regulated hepatic expression of lipogenic genes similarly in both genotypes. In the pair-fed group, FAT-KO relative to control mice displayed increased hepatocyte injury, neutrophil infiltration, and activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) in the liver; and none of these were exacerbated by ethanol feeding. Activation of STAT3 is associated with a marked increase in hepatic leptin receptor mRNA expression and adipose inflammatory cell infiltration.
Our findings establish a critical role of adipose lipolysis in driving hepatic steatosis and oxidative stress during ALD development.
Objectives: We tested the preliminary efficacy of a transdiagnostic cognitive-behavioral treatment adapted to improve depression, anxiety, and co-occurring health risks (i.e., alcohol use, sexual ...compulsivity, condomless sex) among young adult gay and bisexual men. Treatment adaptations focused on reducing minority stress processes that underlie sexual orientation-related mental health disparities. Method: Young gay and bisexual men (n = 63; M age = 25.94) were randomized to immediate treatment or a 3-month waitlist. At baseline, 3-month, and 6-month assessments, participants completed self-reports of mental health and minority stress and an interview of past-90-day risk behavior. Results: Compared to waitlist, treatment significantly reduced depressive symptoms (b = −2.43, 95% CI: −4.90, 0.35, p < .001), alcohol use problems (b = −3.79, 95% CI: −5.94, −1.64, p < .001), sexual compulsivity (b = −5.09, 95% CI: −8.78, −1.40, p < .001), and past-90-day condomless sex with casual partners (b = −1.09, 95% CI: −1.80, −0.37, p < .001), and improved condom use self-efficacy (b = 10.08, 95% CI: 3.86, 16.30, p < .001). The treatment yielded moderate and marginally significant greater improvements than waitlist in anxiety symptoms (b = −2.14, 95% CI: −4.61, 0.34, p = .09) and past-90-day heavy drinking (b = −0.32, 95% CI: −0.71, 0.07, p = .09). Effects were generally maintained at follow-up. Minority stress processes showed small improvements in the expected direction. Conclusion: This study demonstrated preliminary support for the first intervention adapted to address gay and bisexual men's co-occurring health problems at their source in minority stress. If found to be efficacious compared to standard evidence-based treatments, the treatment will possess substantial potential for helping clinicians translate LGB-affirmative treatment guidelines into evidence-based practice.
What is the public health significance of this article?
Sexual orientation-related disparities in depression and anxiety co-occur with alcohol use, sexual compulsivity, and risky sexual behavior to form a syndemic health threat surrounding young gay and bisexual men. Clear and consistent evidence suggests that a major source of this syndemic is minority stress-the stress associated with stigma-related social disadvantage that compounds general life stress. This study represents the first test of an adapted cognitive-behavioral intervention designed to alleviate minority stress among young gay and bisexual men to improve the co-occurring health conditions facing this population.
Little is known about the prevalence of mental health outcomes in UK personnel at the end of the British involvement in the Iraq and Afghanistan conflicts.AimsWe examined the prevalence of mental ...disorders and alcohol misuse, whether this differed between serving and ex-serving regular personnel and by deployment status.
This is the third phase of a military cohort study (2014-2016; n = 8093). The sample was based on participants from previous phases (2004-2006 and 2007-2009) and a new randomly selected sample of those who had joined the UK armed forces since 2009.
The prevalence was 6.2% for probable post-traumatic stress disorder, 21.9% for common mental disorders and 10.0% for alcohol misuse. Deployment to Iraq or Afghanistan and a combat role during deployment were associated with significantly worse mental health outcomes and alcohol misuse in ex-serving regular personnel but not in currently serving regular personnel.
The findings highlight an increasing prevalence of post-traumatic stress disorder and a lowering prevalence of alcohol misuse compared with our previous findings and stresses the importance of continued surveillance during service and beyond.
All authors are based at King's College London which, for the purpose of this study and other military-related studies, receives funding from the UK Ministry of Defence (MoD). S.A.M.S., M.J., L.H., D.P., S.M. and R.J.R. salaries were totally or partially paid by the UK MoD. The UK MoD provides support to the Academic Department of Military Mental Health, and the salaries of N.J., N.G. and N.T.F. are covered totally or partly by this contribution. D.Mu. is employed by Combat Stress, a national UK charity that provides clinical mental health services to veterans. D.MacM. is the lead consultant for an NHS Veteran Mental Health Service. N.G. is the Royal College of Psychiatrists' Lead for Military and Veterans' Health, a trustee of Walking with the Wounded, and an independent director at the Forces in Mind Trust; however, he was not directed by these organisations in any way in relation to his contribution to this paper. N.J. is a full-time member of the armed forces seconded to King's College London. N.T.F. reports grants from the US Department of Defense and the UK MoD, is a trustee (unpaid) of The Warrior Programme and an independent advisor to the Independent Group Advising on the Release of Data (IGARD). S.W. is a trustee (unpaid) of Combat Stress and Honorary Civilian Consultant Advisor in Psychiatry for the British Army (unpaid). S.W. is affiliated to the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emergency Preparedness and Response at King's College London in partnership with Public Health England, in collaboration with the University of East Anglia and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, the Department of Health, Public Health England or the UK MoD.
Abstract Background This study examined the associations between measures of alcohol abuse/dependence (AAD) and violent offending and intimate partner violence (IPV) to age 30 in a New Zealand birth ...cohort. Methods Outcomes included: measures of violent offending, violence victimization, and physical IPV perpetration and victimization. The study also used measures of AAD symptoms; and time-dynamic covariate factors including life stress, other substance use, mental health status, peer and partner substance use and offending, and unemployment. Data were analysed using conditional fixed effects regression modelling augmented by time-dynamic covariate factors to control for confounding. Results Those with five or more AAD symptoms had unadjusted rates of violence outcomes that ranged from 4.10 to 11.85 times higher than those with no symptoms, but these associations did not differ by gender. Adjustment of the associations for both unobserved fixed effects and time-dynamic covariate factors reduced the magnitude of the associations for violent offending, violence victimization and IPV perpetration, with those with five or more AAD symptoms having rates of violence outcomes that were 1.91–3.58 times higher than those with no symptoms. However, control for both fixed effects and time-dynamic covariate factors reduced the associations between AAD symptoms and physical IPV victimization to statistical non-significance (IRR = 0.73, 95% CI: 0.51–1.06). Conclusions The results suggest a causal association between alcohol misuse and violent offending/victimization and IPV perpetration, with estimates suggesting that alcohol use disorder accounted for approximately 4.6–9.3% of the reported violent offending/victimization and IPV perpetration in the cohort.
Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder associated with disruption in social and occupational function. Transcranial magnetic stimulation (TMS) represents a ...novel approach to PTSD, and intermittent theta-burst stimulation (iTBS) is a new, more rapid administration protocol with data supporting efficacy in depression. The authors conducted a sham-controlled study of iTBS for PTSD.
Fifty veterans with PTSD received 10 days of sham-controlled iTBS (1,800 pulses/day), followed by 10 unblinded sessions. Primary outcome measures included acceptability (retention rates), changes in PTSD symptoms (clinician- and self-rated), quality of life, social and occupational function, and depression, obtained at the end of 2 weeks; analysis of variance was used to compare active with sham stimulation. Secondary outcomes were evaluated 1 month after treatment, using mixed-model analyses. Resting-state functional MRI was acquired at pretreatment baseline on an eligible subset of participants (N=26) to identify response predictors.
Retention was high, side effects were consistent with standard TMS, and blinding was successful. At 2 weeks, active iTBS was significantly associated with improved social and occupational function (Cohen's d=0.39); depression was improved with iTBS compared with the sham treatment (d=-0.45), but the difference fell short of significance, and moderate nonsignificant effect sizes were observed on self-reported PTSD symptoms (d=-0.34). One-month outcomes, which incorporated data from the unblinded phase of the study, indicated superiority of active iTBS on clinician- and self-rated PTSD symptoms (d=-0.74 and -0.63, respectively), depression (d=-0.47), and social and occupational function (d=0.93) (all significant). Neuroimaging indicated that clinical improvement was significantly predicted by stronger (greater positive) connectivity within the default mode network and by anticorrelated (greater negative) cross-network connectivity.
iTBS appears to be a promising new treatment for PTSD. Most clinical improvements from stimulation occurred early, which suggests a need for further investigation of optimal iTBS time course and duration. Consistent with previous neuroimaging studies of TMS, default mode network connectivity played an important role in response prediction.
Background and aims
Adolescent alcohol misuse is a growing global health concern. Substantial research suggests that parents have an important role in reducing young people's risk for early ...initiation of alcohol and alcohol‐related harms. To facilitate research translation, we conducted a systematic review and meta‐analyses of longitudinal studies examining the range of modifiable parenting factors that are associated with adolescent alcohol initiation and levels of later use/misuse.
Methods
A systematic literature search was conducted in PubMed, PsycINFO and Embase. Studies were included if they (i) used a longitudinal design; (ii) were published in English; (iii) measured any modifiable parenting factors in adolescence as predictors; (iv) assessed any alcohol‐related outcome variables in adolescence and/or alcohol‐related problems in adulthood; and (v) had a follow‐up interval of at least 1 year. Parental behaviours were categorized into 12 parenting factors. Stouffer's P analyses were used to determine whether the associations between variables were reliable; when there were sufficient studies available, meta‐analyses were also conducted to estimate mean effect sizes.
Results
Based on 131 studies, three risk factors (parental provision of alcohol, favourable parental attitudes towards alcohol use and parental drinking) and four protective factors (parental monitoring, parent–child relationship quality, parental support and parental involvement) were identified as longitudinal predictors of both alcohol initiation and levels of later alcohol use/misuse, based on their significant results in both Stouffer's P analyses and meta‐analyses. The mean effect sizes were mainly small (rs = −0.224 to 0.263).
Conclusions
Risk of adolescent alcohol misuse is positively associated with parental provision of alcohol, favourable parental attitudes towards alcohol use and parental drinking. It is negatively associated with parental monitoring, parent–child relationship quality, parental support and parental involvement.
Researchers recently have begun using Mechanical Turk (MTurk), an online crowdsourcing platform, to recruit addiction populations. However, whether the data obtained from substance users and gamblers ...on MTurk are reliable and valid is unknown. Herein, we assessed the internal and retest reliability of and concurrent and convergent validity of data obtained from addiction populations on MTurk. Current drinkers (N = 208), cannabis users (N = 200), and gamblers (N = 200) residing in the United States completed measures of alcohol, cannabis, and gambling severity, psychological constructs (e.g., impulsivity) related to addictions, overt and subtle measures of valid responding, and motivations for completing MTurk studies. Of the original sample, 88-92% of participants who provided informed consent for recontact completed a reassessment 1 week later. The internal consistency of the addiction severity measures ranged from α = .75 to .93. The stability over 1 week ranged from κ = .57 to .70 for categorical classification, and intraclass correlation coefficient (ICC) = .71 to .86 for continuous measures. The addiction measures were significantly correlated with each other and with other constructs related to addictive behaviors. Overall, 80-85% of participants provided valid responses. They reported attending and answering questions honestly, with financial motives being the most frequently endorsed motivation. After invalid responses were excluded, results remained the same for alcohol and gambling, but significant differences emerged for the cannabis sample. The results suggest that the self-report data obtained from alcohol and gambling populations are of high quality, however, caution is warranted with cannabis populations. MTurk shows promise as a recruitment tool for some addictive behaviors.
We conducted genome-wide association analyses of over 250,000 participants of European (EUR) and African (AFR) ancestry from the Million Veteran Program using electronic health record-validated ...post-traumatic stress disorder (PTSD) diagnosis and quantitative symptom phenotypes. Applying genome-wide multiple testing correction, we identified three significant loci in European case-control analyses and 15 loci in quantitative symptom analyses. Genomic structural equation modeling indicated tight coherence of a PTSD symptom factor that shares genetic variance with a distinct internalizing (mood-anxiety-neuroticism) factor. Partitioned heritability indicated enrichment in several cortical and subcortical regions, and imputed genetically regulated gene expression in these regions was used to identify potential drug repositioning candidates. These results validate the biological coherence of the PTSD syndrome, inform its relationship to comorbid anxiety and depressive disorders and provide new considerations for treatment.
The authors evaluated the effectiveness of brief cognitive-behavioral therapy (CBT) for the prevention of suicide attempts in military personnel.
In a randomized controlled trial, active-duty Army ...soldiers at Fort Carson, Colo., who either attempted suicide or experienced suicidal ideation with intent, were randomly assigned to treatment as usual (N=76) or treatment as usual plus brief CBT (N=76). Assessment of incidence of suicide attempts during the follow-up period was conducted with the Suicide Attempt Self-Injury Interview. Inclusion criteria were the presence of suicidal ideation with intent to die during the past week and/or a suicide attempt within the past month. Soldiers were excluded if they had a medical or psychiatric condition that would prevent informed consent or participation in outpatient treatment, such as active psychosis or mania. To determine treatment efficacy with regard to incidence and time to suicide attempt, survival curve analyses were conducted. Differences in psychiatric symptoms were evaluated using longitudinal random-effects models.
From baseline to the 24-month follow-up assessment, eight participants in brief CBT (13.8%) and 18 participants in treatment as usual (40.2%) made at least one suicide attempt (hazard ratio=0.38, 95% CI=0.16-0.87, number needed to treat=3.88), suggesting that soldiers in brief CBT were approximately 60% less likely to make a suicide attempt during follow-up than soldiers in treatment as usual. There were no between-group differences in severity of psychiatric symptoms.
Brief CBT was effective in preventing follow-up suicide attempts among active-duty military service members with current suicidal ideation and/or a recent suicide attempt.
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