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Externalizing disorders are known to be partly heritable, but the biological pathways linking genetic risk to the manifestation of these costly behaviors remain under investigation. This study sought to identify neural phenotypes associated with genomic vulnerability for externalizing disorders.
One-hundred fifty-five White, non-Hispanic veterans were genotyped using a genome-wide array and underwent resting-state functional magnetic resonance imaging. Genetic susceptibility was assessed using an independently developed polygenic score (PS) for externalizing, and functional neural networks were identified using graph theory based network analysis. Tasks of inhibitory control and psychiatric diagnosis (alcohol/substance use disorders) were used to measure externalizing phenotypes.
A polygenic externalizing disorder score (PS) predicted connectivity in a brain circuit (10 nodes, nine links) centered on left amygdala that included several cortical [bilateral inferior frontal gyrus (IFG) pars triangularis, left rostral anterior cingulate cortex (rACC)] and subcortical (bilateral amygdala, hippocampus, and striatum) regions. Directional analyses revealed that bilateral amygdala influenced left prefrontal cortex (IFG) in participants scoring higher on the externalizing PS, whereas the opposite direction of influence was observed for those scoring lower on the PS. Polygenic variation was also associated with higher Participation Coefficient for bilateral amygdala and left rACC, suggesting that genes related to externalizing modulated the extent to which these nodes functioned as communication hubs.
Findings suggest that externalizing polygenic risk is associated with disrupted connectivity in a neural network implicated in emotion regulation, impulse control, and reinforcement learning. Results provide evidence that this network represents a genetically associated neurobiological vulnerability for externalizing disorders.
Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).
Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.
Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.
This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.
To test the hypothesis that long-term care facility (LTCF) residents with Clostridium difficile infection (CDI) or asymptomatic carriage of toxigenic strains are an important source of transmission in the LTCF and in the hospital during acute-care admissions.
A 6-month cohort study with identification of transmission events was conducted based on tracking of patient movement combined with restriction endonuclease analysis (REA) and whole-genome sequencing (WGS).
Veterans Affairs hospital and affiliated LTCF.
The study included 29 LTCF residents identified as asymptomatic carriers of toxigenic C. difficile based on every other week perirectal screening and 37 healthcare facility-associated CDI cases (ie, diagnosis >3 days after admission or within 4 weeks of discharge to the community), including 26 hospital-associated and 11 LTCF-associated cases.
Of the 37 CDI cases, 7 (18·9%) were linked to LTCF residents with LTCF-associated CDI or asymptomatic carriage, including 3 of 26 hospital-associated CDI cases (11·5%) and 4 of 11 LTCF-associated cases (36·4%). Of the 7 transmissions linked to LTCF residents, 5 (71·4%) were linked to asymptomatic carriers versus 2 (28·6%) to CDI cases, and all involved transmission of epidemic BI/NAP1/027 strains. No incident hospital-associated CDI cases were linked to other hospital-associated CDI cases.
Our findings suggest that LTCF residents with asymptomatic carriage of C. difficile or CDI contribute to transmission both in the LTCF and in the affiliated hospital during acute-care admissions. Greater emphasis on infection control measures and antimicrobial stewardship in LTCFs is needed, and these efforts should focus on LTCF residents during hospital admissions.