Chronic Stress最新文献

Background: Brain imaging and genetics are fields acquiring data at increasing speed, but more information does not always result in a better understanding of the underlying biology. We developed the ProcessGeneLists (PGL) approach to use genetics and mRNA gene expression data to generate regions of interest for imaging studies.

Methods: We applied PGL to past suicide attempt (ATT): We averaged the mRNA expression levels of genes (n = 130) possibly associated with ATT (p ≤ 10^-3 in a published genome-wide association study, GWAS) in each brain region studied in the Human Allen Brain Atlas (6 ex-vivo brains, 158 to 946 regions/brain have mRNA expression data) and compared that to the averaged mRNA expression levels of all other genes in each region in each brain in the atlas.

Results: PGL revealed 8 regions where "attempt-related genes" were differentially expressed (Wilcoxon test with Bonferroni correction 8.88^-11 = -6) and dorsolateral prefrontal cortex (dlPFC p_FWE < 0.05) in ATT. We genotyped one single nucleotide polymorphism (SNP) in each of the five genes (within 130 from GWAS) with most important subicular expression. AKAP7 (A-Kinase Anchoring Protein 7, important in hippocampal memory processes) showed an interaction between genotype, ATT, and subiculum/dlPFC RSFC.

Conclusion: PGL uncovered a brain function/genotype interaction in ATT by using published GWAS data to inform imaging studies. This could inform individualized therapies in the future.

Introduction: Disruption of maternal care using maternal separation (MS) models has provided significant evidence of the deleterious long-term effects of early life stress. Several preclinical studies investigating MS showed multiple behavioral and biomolecular alterations. However, there is still conflicting results from MS studies, which represents a challenge for reliability and replicability of those findings. Objective: To address that, this study was conducted to investigate whether MS would affect anxiety-like behaviors using a battery of classical tasks, as well as central and peripheral stress-related biomarkers. Methods: Male Balb/c mice were exposed to MS from postnatal day (PND) 2 to 14 for 180-min per day. Two independent cohorts were performed to evaluate both baseline and anxiety-like behavior responses to MS at PND60. We performed composite scores to evaluate MS effects on anxiety and risk assessment phenotypes. Also, we assessed mRNA gene expression in the medial pre-frontal cortex (mPFC) of glucocorticoid and mineralocorticoid receptors (GR and MR) using real-time PCR and peripheral corticosterone levels (CORT) to investigate possible neurobiological correlates to anxiety behaviors. Results: We found increased anxiety-like behavior and decreased risk assessment and exploratory behaviors in MS mice. The animals exposed to MS also presented a decrease in MR mRNA expression and higher levels of CORT compared to controls. Conclusions: Our findings reinforce the body of evidence suggesting that long-term MS induces effects on anxiety and risk assessment phenotypes following the exposure to a standardized MS protocol. Moreover, MS affected the expression of MR mRNA and induced significant changes on CORT response. This data highlights that the reprograming MS effects on HPA axis could be mediate by MR gene expression in mPFC and chronic overactivity of peripheral CORT levels.

Background: Our behavioral traits, and subsequent actions, could affect the risk of exposure to the coronavirus disease of 2019 (COVID-19). The current study aimed to determine whether unique brain networks are associated with the COVID-19 infection risk.

Methods: This research was conducted using the UK Biobank Resource. Functional magnetic resonance imaging scans in a cohort of general population (n = 3662) were used to compute the whole-brain functional connectomes. A network-informed machine learning approach was used to identify connectome and nodal fingerprints that are associated with positive COVID-19 status during the pandemic up to February fourth, 2021.

Results: The predictive models successfully identified 6 fingerprints that were associated with COVID-19 positive, compared to negative status (all p values < 0.005). Overall, lower integration across the brain modules and increased segregation, as reflected by internal within module connectivity, were associated with higher infection rates. More specifically, COVID-19 positive status was associated with 1) reduced connectivity between the central executive and ventral salience, as well as between the dorsal salience and default mode networks; 2) increased internal connectivity within the default mode, ventral salience, subcortical and sensorimotor networks; and 3) increased connectivity between the ventral salience, subcortical and sensorimotor networks.

Conclusion: Individuals are at increased risk of COVID-19 infections if their brain connectome is consistent with reduced connectivity in the top-down attention and executive networks, along with increased internal connectivity in the introspective and instinctive networks. These identified risk networks could be investigated as target for treatment of illnesses with impulse control deficits.

Stellate ganglion block (SGB) is a procedure involving the injection of a local anesthetic surrounding the stellate ganglion to inhibit sympathetic outflow. The objective of this review was to summarize existing evidence on the use of SGB in adults with psychiatric disorders. A systematic search identified 17 published studies and 4 registered clinical trials. Eighty-eight percent of published studies, including 2 randomized controlled trials (RCTs), used SGB for posttraumatic stress disorder (PTSD), although its use for schizophrenia spectrum disorders was also explored. Administration of 1 to 2 SGBs using right-sided laterality with 0.5% ropivacaine was most common. Preliminary evidence from clinical trials and case studies supports the feasibility of SGB for treating psychiatric disorders involving dysregulation of the sympathetic nervous system, although effectiveness evidence from RCTs is mixed. One RCT concluded that improvement in PTSD symptoms was significant, while the other concluded that it was nonsignificant. Improvements were noted within 5 minutes of SGB and lasted 1 month or longer. Registered clinical trials are exploring the use of SGB in new psychiatric disorders, including major depressive disorder and borderline personality disorder. More studies with larger sample sizes and alternate protocols are needed to further explore therapeutic potential of SGB for psychiatric disorders.