Background: Traditional and novel risk factors cannot sufficiently explain the differential susceptibility to cardiovascular disease (CVD). Epigenetics may serve to partially explain this residual disparity, with life course stressors shown to modify methylation of genes implicated in various diseases. Subclinical CVD is often comorbid with cognitive impairment (CI), which warrants research into the identification of common genes for both conditions.Methods: We conducted a systematic review of the existing literature to identify studies depicting the relationship between life course stressors, DNA methylation, subclinical CVD, and cognition.Results: A total of 16 articles (8 human and 8 animal) were identified, with the earliest published in 2008. Four genes (COMT,NOS3,Igfl1, andSod2) were analyzed by more than one study, but not in association with both CVD and CI. One gene (NR3C1) was associated with both outcomes, albeit not within the same study. There was some consistency among studies with markers used for subclinical CVD and cognition, but considerable variability in stress exposure (especially in human studies), cell type/tissue of interest, method for detection of DNA methylation, and risk factors. Racial and ethnic differences were not considered, but analysis of sex in one human study found statistically significant differentially methylated X-linked loci associated with attention and intelligence.Conclusions: This review suggests the need for additional studies to implement more comprehensive and methodologically rigorous study designs that can better identify epigenetic biomarkers to differentiate individuals vulnerable to both subclinical CVD and associated CI.

Adaptive behavior in response to adverse experiences facilitates faster recovery and less time spent engaging in maladaptive behaviors that contribute to psychopathology, including anxiety, depression, and posttraumatic stress disorder. Dysregulation of activity in the prefrontal cortex (PFC) has been implicated in these disorders, with stress further exacerbating these negative effects. Corticotropin-releasing factor is an important regulator of the stress-response system and may have a differential involvement in individuals who are especially susceptible to negative stress-related outcomes. A recent study by Chen et al. (Chen P, Lou S, Huang ZH, Wang Z, Shan QH, Wang Y, Yang Y, Li X, Gong H, Jin Y, Zhang Z, Zhou Z. Neuron 106: 301–315, 2020) has identified a novel subtype of GABAergic CRF interneurons in the dorsomedial PFC that, upon activation, can promote active responses and resilient behavior in response to stress.

Introduction: Attentional bias to reward-associated stimuli can occur even when it interferes with goal-driven behavior. One theory posits that dopaminergic signaling in the striatum during reward conditioning leads to changes in visual cortical and parietal representations of the stimulus used, and this, in turn, sustains attentional bias even when reward is discontinued. However, only a few studies have examined neural activity during both rewarded and unrewarded task phases.Methods: In the current study, participants first completed a reward-conditioning phase, during which responses to certain stimuli were associated with monetary reward. These stimuli were then included as non-predictive cues in a spatial cueing task. Participants underwent functional brain imaging during both task phases.Results: The results show that striatal activity during the learning phase predicted increased visual cortical and parietal activity and decreased ventro-medial prefrontal cortex activity in response to conditioned stimuli during the test. Striatal activity was also associated with anterior cingulate cortex activation when the reward-conditioned stimulus directed attention away from the target.Discussion: Our findings suggest that striatal activity during reward conditioning predicts the degree to which reward history biases attention through learning-induced changes in visual and parietal activities.

Background Habitual behavior and attentional bias are distinct cognitive processes that both contribute to inflexible behavior and are commonly observed in addiction. While animal studies provide strong evidence for an association between adolescent alcohol use and impairments in behavioral flexibility in adulthood, such a link in human research has not yet been explored. Moreover, since reduced flexible behavior serves as a risk factor for escalating alcohol intake, continued alcohol consumption use in adulthood may further exacerbate any deficits associated with adolescent drinking. Methods We used principal component analysis to create composite scores for adolescent and past year alcohol use, based on self-report measures from a healthy adult sample. Group differences in alcohol use were examined in relation to habitual responding (n=71) and attentional bias (n=44) toward non-drug reward cues, using two behavioral flexibility tasks. We used linear regression analyses to explore associations between past year alcohol use and behavioral flexibility outcomes in adults with histories of light versus heavy adolescent alcohol use. Results Heavy adolescent alcohol use was characterized by earlier drinking onset and higher binge-drinking frequency before age 18. Adults with a history of heavy adolescent alcohol use demonstrated significantly greater habitual responding compared to those with lighter use. Among this group, greater past year alcohol use was also associated with increased difficulty disengaging attention from non-drug reward cues. Conclusions These results indicate that adolescent and current alcohol use may differentially impact habitual responding and attentional bias towards non-drug reward cues. Notably, this is the first human study to explore both aspects of behavioral inflexibility in relation to different periods of alcohol use within the same adult sample.

Opioid use disorder is a public health problem with disastrous effects for young people and their families. Opioid use shares risk factors with other substances; there may be additional unique motives and experiences associated with opioid use with potential implications for improving prevention. The present study used surveys and interviews to elicit retrospective accounts of 30 young adults (19 female) in recovery from opioid use disorder to examine (1) self-reported motives for opioid use, and (2) experiences and factors that participants associate with opioid use as compared to other substances. Motives reported for past opioid use on surveys were enhancement (i.e., fun or excitement) and coping (i.e., to forget worries or cheer up when in a bad mood), followed by conformity and social motives. Through analysis of interview data, we found that: experiences of opioid use differed from experiences associated with other substances, with effects described in terms of escape and numbing (theme 1); and the ability (early in use) to remain/appear functional (theme 2). Participants reported perceptions of lower risk of harm compared to other substances (theme 3). For some, access was the main factor reported to contribute to opioid use (theme 4). Evidence-based prevention approaches focused on environmental strategies (such as prescription regulation policies) and individual strategies (such as coping skills and prevention education) are relevant for opioid use prevention. Additional supplemental approaches are needed to focus on misperceptions among young people that prescription medications confer lower risk than other substances.

Background: Habitual behavior and attentional bias are distinct cognitive processes that contribute to inflexible behavior. While animal studies provide strong evidence for an association between adolescent alcohol use and impairments in behavioral flexibility in adulthood, such a link in human research has not yet been explored. Moreover, since reduced flexible behavior serves as a risk factor for escalating alcohol intake, continued alcohol use in adulthood may further exacerbate any deficits associated with adolescent drinking. Methods: We used principal component analysis to create composite scores for adolescent and past-year alcohol use, based on self-report measures from a healthy adult sample. Group differences in alcohol use were examined in relation to habitual responding (n=71) and attentional bias (n=44) toward non-drug reward cues, using two behavioral flexibility tasks. We used linear regression analyses to explore associations between alcohol use and behavioral flexibility outcomes in adults with histories of light versus heavy adolescent alcohol use. Results: Heavy adolescent alcohol use was largely characterized by binge drinking before age 18. Adults with a history of heavy adolescent alcohol use demonstrated greater habitual responding compared to those with lighter use. Among this group, greater past-year alcohol use was also associated with increased difficulty disengaging attention from non-drug reward cues. Conclusions: These results suggest that adolescent and past-year alcohol use may differentially impact habitual responding and attentional bias towards non-drug reward cues. Notably, this is the first human study to explore both aspects of behavioral inflexibility in relation to different periods of alcohol use.