The maternal separation (MS) paradigm is an animal model of early life stress. Animals subjected to MS during the first 2 weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA) of various drugs of abuse including cocaine, ethanol, and amphetamine. However, no studies have yet examined the effects of MS on methamphetamine (METH) SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, we also investigated group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) core. Long–Evans pups and dams were separated on postnatal days (PND) 2–14 for either 180 (MS180) or 15 min (MS15). Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion) in 15 2-h daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.

Throughout the 20th century a body of literature concerning the long-lasting effects of the early environment was produced. Adverse experiences in early life, or early-life stress (ELS), is associated with a higher risk of developing various psychiatric illnesses. The mechanisms driving the complex interplay between ELS and adult phenotype has baffled many investigators for decades. Over the last decade, the new field of neuroepigenetics has emerged as one possible mechanism by which ELS can have far-reaching effects on adult phenotype, behavior, and risk for psychiatric illness. Here we review two commonly investigated epigenetic mechanisms, histone modifications and DNA methylation, and the emerging field of neuroepigenetics as they relate to ELS. We discuss the current animal literature demonstrating ELS-induced epigenetic modulation of gene expression that results in altered adult phenotypes. We also briefly discuss other areas in which neuroepigenetics has emerged as a potential mechanism underlying environmental and genetic interactions.

Background: While early life exposures such as mode of birth, breastfeeding, and antibiotic use are established regulators of microbiome composition in early childhood, recent research suggests that the social environment may also exert influence. Two recent studies in adults demonstrated associations between socioeconomic factors and microbiome composition. This study expands on this prior work by examining the association between family socioeconomic status (SES) and host genetics with microbiome composition in infants and children. Methods: Family SES was used to predict a latent variable representing six genera abundances generated from whole-genome shotgun sequencing. A polygenic score derived from a microbiome genome-wide association study was included to control for potential genetic associations. Associations between family SES and microbiome diversity were assessed. Results: Anaerostipes, Bacteroides, Eubacterium, Faecalibacterium, and Lachnospiraceae spp. significantly loaded onto a latent factor, which was significantly predicted by SES (p < 0.05) but not the polygenic score (p > 0.05). Our results indicate that SES did not predict alpha diversity but did predict beta diversity (p < 0.001). Conclusions: Our results demonstrate that modifiable environmental factors influence gut microbiome composition at an early age. These results are important as our understanding of gut microbiome influences on health continue to expand.

Vascular contributions to cognitive impairment and dementia (VCID) include structural and functional blood vessel injuries linked to poor neurocognitive outcomes. Smoking might indirectly increase the likelihood of cognitive impairment by exacerbating vascular disease risks. Sex disparities in VCID have been reported, however, few studies have assessed the sex-specific relationships between smoking and memory performance and with contradictory results. We investigated the associations between sex, smoking, and cardiovascular disease with verbal learning and memory function. Using MindCrowd, an observational web-based cohort of ~ 70,000 people aged 18–85, we investigated whether sex modifies the relationship between smoking and cardiovascular disease with verbal memory performance. We found significant interactions in that smoking is associated with verbal learning performance more in women and cardiovascular disease more in men across a wide age range. These results suggest that smoking and cardiovascular disease may impact verbal learning and memory throughout adulthood differently for men and women.