Dataset Information

DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression.

ABSTRACT: DICER1 is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that blood DICER1 expression is significantly reduced in cases versus controls, and replicate this in two independent cohorts. Our follow-up studies find that lower blood DICER1 expression is significantly associated with increased amygdala activation to fearful stimuli, a neural correlate for PTSD. Additionally, a genetic variant in the 3' un-translated region of DICER1, rs10144436, is significantly associated with DICER1 expression and with PTSD&Dep, and the latter is replicated in an independent cohort. Furthermore, genome-wide differential expression survey of miRNAs in blood in PTSD&Dep reveals miRNAs to be significantly downregulated in cases versus controls. Together, our novel data suggest DICER1 plays a role in molecular mechanisms of PTSD&Dep through the DICER1 and the miRNA regulation pathway.

SUBMITTER: Wingo AP

PROVIDER: S-EPMC4686835 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression.

Wingo Aliza P AP Almli Lynn M LM Stevens Jennifer S JS Klengel Torsten T Uddin Monica M Li Yujing Y Bustamante Angela C AC Lori Adriana A Koen Nastassja N Stein Dan J DJ Smith Alicia K AK Aiello Allison E AE Koenen Karestan C KC Wildman Derek E DE Galea Sandro S Bradley Bekh B Binder Elisabeth B EB Jin Peng P Gibson Greg G Ressler Kerry J KJ

Nature communications 20151203

DICER1 is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that blood DICER1 expression is significantly reduced in cases versus controls, and replicate this in two independent cohorts. Our follow-up studies find ...[more]

PMID: 26632874

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Project description:Problem statementSeeking Safety (SS) is a widely implemented cognitive-behavioral therapy for comorbid post-traumatic stress disorder (PTSD) and substance use disorder (SUD). It is a present-focused coping skills model that is highly flexible, with varied methods of delivery, to maximize acceptability and client access. The purpose of this meta-analysis is to examine the effect of SS on comorbid PTSD and SUD across randomized control trials (RCTs). In addition, ours is the first meta-analysis to examine the dose-response of SS by comparing delivery of all 25 SS topics versus fewer.Methods and designArticles published before January 2, 2023 (CINAHL n = 16, PsycINFO n = 31, MEDLINE n = 27, Cochrane n = 38, and Scopus n = 618) were searched. Seven studies were included for meta-analysis and dose-response analysis.ResultsBased on effect sizes (ES), meta-analysis revealed that SS has a medium group, time (p = .04), and time by group effect on substance use per the Addiction Severity Index at 3 months and a small effect on Clinician-Administered PTSD Scale scores by group, a large effect by time, and a medium time by group (p = .002) effect at 6 months. Based on the pooled ES examining various measures across multiple timepoints, SS had small to medium effects on substance use by time, group, or time by group and medium to large effects on PTSD symptoms by time, group, or time by group (except for the group effect at 3-month follow-up). Significant effects were found for substance use by time at 3 and 6 months and for PTSD postintervention, at 6 months and 9 months by group, time, and time by group while only by time at 3 months. Meta-regression revealed that partial dose versions of SS generally function as well as the full dose version of SS when observing long-term effects (greater than 3 months).DiscussionFindings suggest SS has merit in treating PTSD symptoms and SUD. Based on the summarized effect sizes, SS appears more effective in reducing PTSD than substance use, which converges with the larger treatment outcome literature that consistently finds this. We explore reasons that treatment of SUD is more challenging than treating PTSD and offer suggestions for practitioners. We emphasize the need for future studies to utilize common measures and provide full details of treatment delivery for optimal comparison across studies.

Project description:BackgroundThe psychological treatment of comorbid post-traumatic stress disorder (PTSD) and substance use disorder (SUD) is clinically challenging, and outcomes are often poor.ObjectiveThis paper describes a systematic review and meta-analysis which sought to establish the current efficacy for a number of established psychological approaches for adults and adolescents, in comparison to interventions for SUD alone, or other active approaches, following a pre-registered protocol.MethodThis review followed PRISMA and Cochrane Collaboration guidelines. Data extraction and risk of bias judgements using Cochrane criteria were undertaken by all authors. Primary outcomes were PTSD severity and substance use post-treatment. The quality of findings was assessed using GRADE. Following a comprehensive search, conducted to 13 September 2021, 27 studies were included.ResultsWe found a relatively high level of dropout across studies. In our main comparisons, we found no benefits for present-focused treatment approaches aimed at improving coping skills beyond those for SUD-only interventions. We found modest benefits for trauma-focused intervention plus SUD intervention post-treatment for PTSD (standardized mean difference (SMD) = -0.36, 95% confidence interval (CI) -0.64, -0.08), and at 6-13 months for PTSD (SMD = -0.48, 95% CI -0.81, -0.15) and alcohol use (SMD = -0.23, 95% CI -0.44, -0.02). There were no benefits for cognitive restructuring interventions as a group, but we found a modest effect for integrated cognitive behavioural therapy (ICBT) for PTSD post-treatment (SMD = -0.33, 95% CI -0.62, -0.04). There was evidence of some benefit for trauma-focused intervention over present-focused intervention for PTSD from a single study and for reduction in dropout for incentivized attendance for trauma-focused intervention from another single study. Most findings were of very low quality.ConclusionThere is evidence that trauma-focused therapy and ICBT can improve PTSD for some individuals, but many patients do not fully engage with treatment and average treatment effects are modest.HighlightsFor PTSD, evidence was strongest for trauma-focused CBT-based approaches, but effects were modest.There was little evidence of any added benefit on substance use, beyond that of standard addiction treatments, for any included intervention.Dropout from treatment was high.

Dataset Information

DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression.

Publications

DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression.

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