Left hemisphere lateralization of the limbic system and frontoparietal network (FPN) correlates with positive and negative symptom improvement following cannabidiol (CBD) administration in psychosis and ultra-high risk (UHR) populations: A voxel-wise meta-analysis.

This voxel-wise meta-analysis assesses current findings about the neural correlates of cannabidiol on the positive and negative symptoms among individuals with psychosis or ultra-high risk (UHR) for psychosis. We used PubMed, EMBASE, and ScienceDirect as primary databases and initially retrieved 157 studies. After applying our eligibility criteria, 13 studies remained for inclusion. Ten studies focused on psychosis. Three studies focused on UHR. Quality assessment was performed for included articles using the RoB2 instrument. Statistical analysis implicated a voxel-wise meta-analysis of different task paradigms (emotion recognition, verbal memory recall, and inhibitory control) with a jackknife sensitivity measure, Egger's test of random effects, and a meta-regression with relevant covariates. Article quality was determined to be primarily low risk of bias, with some elements of unclear bias figuring across studies. Our results showed robust, convergent correlations between CBD administration and left hemisphere lateralization of limbic system and frontoparietal network (FPN) subregions across task paradigms in psychosis and UHR populations. Our meta-regression revealed that decreased limbic system activity correlated with positive symptom improvements, and decreased FPN activity correlated with negative symptom improvements. Lastly, sensitivity analyses determined that there was minimal risk bias or risk of confounding variables unduly influencing our meta-analyses (p > 0.05).

Therapeutic interventions impact brain function and promote post-traumatic growth in adults living with post-traumatic stress disorder: A systematic review and meta-analysis of functional magnetic resonance imaging studies.

Introduction: The present systematic review and meta-analysis explores the impacts of cognitive processing therapy (CPT), eye movement desensitization and reprocessing (EMDR), and prolonged exposure (PE) therapy on neural activity underlying the phenomenon of post-traumatic growth for adult trauma survivors. Methods: We utilized the following databases to conduct our systematic search: Boston College Libraries, PubMed, MEDLINE, and PsycINFO. Our initial search yielded 834 studies for initial screening. We implemented seven eligibility criteria to vet articles for full-text review. Twenty-nine studies remained for full-text review after our systematic review process was completed. Studies were subjected to several levels of analysis. First, pre-and post- test post-traumatic growth inventory (PTGI) scores were collected from all studies and analyzed through a forest plot using Hedges' g. Next, Montreal Neurological Institute (MNI) coordinates and t-scores were collected and analyzed using an Activation Likelihood Estimation (ALE) to measure brain function. T-scores and Hedges' g values were then analyzed using Pearson correlations to determine if there were any relationships between brain function and post-traumatic growth for each modality. Lastly, all studies were subjected to a bubble plot and Egger's test to assess risk of publication bias across the review sample. Results: Forest plot results indicated that all three interventions had a robust effect on PTGI scores. ALE meta-analysis results indicated that EMDR exhibited the largest effect on brain function, with the R thalamus (t = 4.23, p < 0.001) showing robust activation, followed closely by the R precuneus (t = 4.19, p < 0.001). Pearson correlation results showed that EMDR demonstrated the strongest correlation between increased brain function and PTGI scores (r = 0.910, p < 0.001). Qualitative review of the bubble plot indicated no obvious traces of publication bias, which was corroborated by the results of the Egger's test (p = 0.127). Discussion: Our systematic review and meta-analysis showed that CPT, EMDR, and PE each exhibited a robust effect on PTG impacts across the course of treatment. However, when looking closer at comparative analyses of neural activity (ALE) and PTGI scores (Pearson correlation), EMDR exhibited a more robust effect on PTG impacts and brain function than CPT and PE.

Stress and Susceptibility: A Systematic Review of Prenatal Epigenetic Risks for Developing Post-Traumatic Stress Disorder.

This review aims to systematically assess the current literature about prenatal epigenetic markers that lead to post-traumatic stress disorder susceptibility across the lifespan. Studies included in this review met several research criteria: Studies included (1) participants with a PTSD diagnosis according to the DSM-5, (2) prenatal epigenetic marker data that could be analyzed, and (3) explicit references to postnatal PTSD susceptibility. Our study sample fit within a timeframe of 2002 (the earliest recorded studies of prenatal susceptibility to post-traumatic stress disorder in the databases used) and February 2021 when the literature search for this review was terminated. Studies for this review were collated from PubMed, MEDLINE, Science Direct, and Boston College School of Social Work Library databases. A systematic search was conducted in these databases using basic keyword terms, such as "PSTD resilience" and "PTSD vulnerability," and then adding clarifying terms to refine specific searches, such as "epigenetics," "genetics," "epigenetic markers," "haplotypes," and "mRNA methylation." Based on these criteria and research methods, 33 studies remained for inclusion in the review sample. This review suggests that BDNF Val66-Met, a polymorphism of FKBP5, and an altered messenger ribonucleic acid methylation marker in NR3C1 present most often in cases of PTSD. These epigenetic markers might be implicated in central neurological processes related to post-traumatic stress disorder symptomatology.

The Neurophysiology Behind Trauma-Focused Therapy Modalities Used to Treat Post-Traumatic Stress Disorder Across the Life Course: A Systematic Review.

This review presents the current state of understanding of trauma-informed modalities in light of current research in neuroscience, analyzing which brain structures and processes are impacted by these modalities. Studies included in the present review met the inclusion criteria of 1) addressing post-traumatic stress disorder (PTSD) in a specific population, 2) treatment of PTSD using any of the evidence-based trauma-informed modalities considered in this review, and 3) presenting functional magnetic resonance imagery (fMRI) data, derived from BOLD signals and voxel-compression maps, of brain structures impacted by these trauma-informed modalities. Articles for this review were collated through PubMed and MEDLINE, using key terms in descending order, such as 'childhood trauma', 'adolescent trauma', and 'adulthood trauma', to 'PTSD', 'fMRI', and so on, depending on the modality in question. Based on these criteria and research methods, 37 studies remained for inclusion in the present review. Among a number of critical findings, this review demonstrates that eye movement desensitization and reprocessing (EMDR) and mindfulness therapy effectively deactivate hindbrain regions implicated in the downregulation of autonomic nervous system (ANS) hyperarousal. This review also shows that trauma-focused cognitive behavioral therapy (TF-CBT) and EMDR activate the hippocampus, anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC)-areas that are implicated in crucial cognitive, affective, and behavioral processes that aid trauma survivors in navigating their challenges.

Stable knockout of lanthionine synthase C-like protein-1 (LanCL1) from HeLa cells indicates a role for LanCL1 in redox regulation of deubiquitinating enzymes.

Lanthionine synthase C-like protein-1 (LanCL1) is a glutathione (GSH)-binding protein of uncertain function, widely expressed in mammalian cells. Recent data suggests that LanCL1 has glutathione S-transferase (GST)-like activity, while other reports claim that LanCL1 suppresses mitogen-activated kinase (MAPK) phosphorylation. In the present study, recombinant human LanCL1 had less than 10% the specific activity of GST. When CRISPR-Cas9 was used to stably ablate LanCL1 from HeLa cells, the resulting line was sensitized to H2O2 toxicity. [GSH], [GSSG], [GSH]/[GSSG] and GST activity were unaltered by LanCL1 knockout but glutathione reductase and glutathione peroxidase activities were significantly elevated. LanCL1-KO cells did not differ in basal or H2O2-induced p38-MAPK, ERK p42/p44 or JNK phosphorylation; however, MAPK-targeted transcription factor regulators c-Jun and IκBα were significantly decreased. Because c-Jun and IκBα levels are ubiquitin regulated, experiments addressed the hypothesis that LanCL1 affects ubiquitination dynamics. In the presence of the 26S proteasome inhibitor bortezomib, ubiquitinated proteins accumulated faster in LanCL1-KO cells, suggesting that LanCL1 positively regulates deubiquitination. The activity of ubiquitin C-terminal hydrolase (UCH), a major deubiquitinase (DUB) subclass, was significantly decreased in LanCL1-KO cells while protein levels of A20/TNFAIP3, USP9X and USP10 DUBs were significantly reduced. UCH activity in HeLa cell lysates was lost upon treatment with H2O2 and significantly recovered by addition of recombinant LanCL1 plus GSH. Taken together these data suggest that LanCL1 likely does not act as a GST-like enzyme in vivo, but rather modulates ubiquitin-dependent cell signaling pathways through positive regulation of redox-sensitive DUBs.