Introduction: The current study assessed the impact of self-reported stress measures on microRNA (miRNA) profiles in saliva exosomes. Saliva is one of the most accessible and non-invasive bodily fluids and exosomal miRNAs in saliva could be useful in (1) measuring stress states and (2) distinguishing between individuals suffering from high levels of chronic stress vs. adverse childhood experiences (ACEs). miRNAs are small, noncoding RNAs that act as gene regulators. Several studies have shown differential expressions of certain miRNA in neurological diseases and in stress, post-traumatic stress syndrome (PTSD) and anxiety. Detailed analyses of miRNA expressions and profiling of miRNAs among populations with various exposures to traumatic and life stressors have not been carried out. The goal of our study was to discover miRNAs associated with high chronic stress or childhood trauma.Method: This study sought to explore miRNA expression in African American young women from a small, southern Historically Black College and University (HBCU). Twelve participants completed the social readjustment rating scale (SRRS), ACEs scale, and saliva collection and were divided into three groups based on ACE and chronic stress score: Low Chronic Stress (LCS; n = 4); High Chronic Stress (HCS; n = 4); High Chronic Stress + High ACEs (HCS+HA; n=4). A custom-made miRNA Taqman-Array tested for fold change in four miRNAs (i.e., miR-19b, miR-187, miR-34a and miR-135-3p).Results: There was a significant downregulation of miR-19b (χ²(2, N=12) = 7.42, p < 0.01, η²= 0.915), miR-187 (χ² (2, N = 12) = 7.36, p < 0.05, η²= 0.598), and miR-34a (χ²(2, N = 12) = 7.42, p < 0.05, η²= 0.60). in both the HCS and the HCS+HA groups vs. LCS. Interestingly, miR-135-3p (χ²(2, N = 12) = 8.00, p < 0.05, η²= 0.67. was upregulated in the HCS group vs. LCS and HCS+LA. Expression for miR-135-3p was not significantly different between LCS + HCS+HA.Conclusion: Our analyses shows that miRNA extracted from salivary exosomes can be a reliable biomarker for stress and miR-135a-3p appears to be the most upregulated between LCS and HCS individuals and a potential candidate to corroborate self-reports on self-assessments and predict negative health outcomes. Given that HCS+HA did not show an upregulation of miR-135-3p but had similar expression in the other three miRs compared to HCS group may indicate an adaptive stress response following early life adversity. Further, downregulation in miR-135-3p in individuals with high levels of chronic stress could point to unknown childhood trauma exposure (e.g. closed adoptions, dissociative amnesia, abuse). A major limitation in this study is the small sample size and future directions include determining the predictive validity of these miRNAs in predicting onset of physical and mental health outcomes for early interventions in larger studies.

This review synthesizes preclinical evidence on the behavioral and neurobiological effects of cannabis exposure during prenatal and adolescent developmental periods, with a focus on anxiety, social behavior, learning and memory, and associated brain changes. Understanding the differential impact of cannabis exposure across these windows is critical, given the increasing prevalence of cannabis use and the rising potency of its primary psychoactive component, delta-9-tetrahydrocannabinol (THC). Both prenatal and adolescent periods represent vulnerable windows for disruption of the endocannabinoid system, which plays a central role in typical neurodevelopment. Exogenous activation of this system via THC can lead to atypical brain maturation and subsequent behavioral impairments. These impairments are associated with region-specific alterations in cortical and subcortical structures and are highly dependent on the timing of exposure. For instance, prenatal exposure may disrupt medial prefrontal cortex development, leading to long-term social deficits while sparing memory function. In contrast, adolescent exposure tends to impair hippocampal function, resulting in learning and memory deficits. The manuscript is organized developmentally, beginning with the effects of prenatal exposure and then discussing consequences of adolescent exposure. By delineating the distinct behavioral and neurobiological outcomes associated with the timing of cannabis exposure, this review highlights the importance of developmental stage in assessing the risks of exogenous cannabinoid use and identifies critical periods for targeted research and intervention.

This commentary addresses some of the contemporary challenges to recovery research from the neuroscience perspective. The authors examine advances in the neuroscience of substance use disorder while highlighting the fact that equal advances have not been made in advancing understanding of recovery from substance use disorder.

Background: Alcohol use is common during emerging adulthood and has been associated with impairments in executive functioning, including cognitive flexibility. Individual differences in affective distress, early life adversity, and genetic variation in dopaminergic signaling pathways may contribute to variability in cognitive flexibility among young adults. The present study examined the relationships among proximal affective distress, distal early life stress, alcohol use, and the functional COMT Val158Met polymorphism. Methods: Seventy-two college-aged adults completed measures of adverse childhood experiences (ACEs), affective distress, alcohol use, and cognitive flexibility. Cognitive flexibility was assessed using both behavioral measures from a Number-Letter task and self-reported cognitive flexibility using the Cognitive Flexibility Inventory (CFI). An exploratory factor analysis was conducted on measures of depression, anxiety, stress, affect, and state–trait anxiety to derive a latent affective distress factor. General linear models examined the effects of affective distress, drinking status, and COMT Val158Met genotype, on cognitive flexibility outcomes. Results: Higher affective distress was associated with lower scores on the CFI Control subscale, indicating reduced perceived behavioral control. This relationship was significantly stronger among individuals reporting alcohol use. Affective distress also interacted with drinking status to predict behavioral cognitive flexibility, such that greater distress was associated with poorer task-switching performance only with prior alcohol use. This interaction was further moderated by COMT genotype. Specifically, Val/Val individuals showed greater reductions in cognitive flexibility conditions of elevated affective distress and alcohol use, whereas Met-carriers showed relatively stable performance across conditions. ACEs were positively associated with affective distress but did not predict cognitive flexibility outcomes. Conclusion: Proximal affective distress, but not early life adversity, emerged as a key correlate of both perceived and behavioral cognitive flexibility in emerging adults, particularly among individuals reporting alcohol use. COMT genotype moderated these relationships, suggesting that dopaminergic variation may influence sensitivity to current affective and alcohol-related cognitive demands with limited impacts from early life stress. These findings highlight the importance of considering affective, behavioral, and biological factors jointly when examining cognitive flexibility and alcohol-related risk during emerging adulthood.