Environmental Effects on Brain Estrogen Receptor Expression and Aggression

Best undergraduate poster award at the Society for Behavioral Neuroendocrinology conference, 2007It is broadly accepted that the environment influences the effects of genes on behavior, but the mechanisms mediating these environmental effects on phenotype are poorly defined. The present study examined whether photoperiod (day length) and reproductive experience, two important environmental variables, affect gene expression to influence aggressive behavior. Individuals respond to photoperiod because it predicts important variability in the environment; male rodents use photoperiod to time adaptive behaviors such as mating and aggression. For example, mating is more likely in rodents housed in long, summer-like days when testosterone concentrations are high, whereas aggression in some rodent species is paradoxically elevated when housed in short, winter-like days when testosterone concentrations are low. Previous work in Peromyscus polionotus indicated that brain estrogen receptor alpha expression is increased in short days (8L:16D), whereas brain estrogen receptor beta expression is increased in long days (16L:8D). Hormone manipulation studies suggested that the photoperiodic effect on aggression occurs independently of changes in estrogen receptor expression. This hypothesis was tested directly by examining the effects of photoperiod on aggression and estrogen receptor expression in monogamous P. californicus, which do not reduce testes size in short days. I also examined how aggression changes in relation to parental behavior. Nulliparous male P. californicus were significantly more aggressive when housed in short versus long days, and parental males were also significantly more aggressive than nulliparous mice kept in long days. Neither photoperiod nor reproductive experience affected the expression of either estrogen receptor subtype in brain nuclei that are components of the brain “social behavior network.” These results suggest that the effects of photoperiod and reproduction on aggression are independent of changes in estrogen receptor expression. Additionally, these data emphasize the importance of studying the biological mechanisms mediating aggression under different environmental conditions in order to better understand the neurobiological bases of this complex social behavior. Advisor: Randy J. NelsonSBS Undergraduate Research Award to M.S.F.NIH MH57535 to R.J.N.NSF grant IOS-16897 to R.J.N.No embarg

Behavioral disinhibition and cortisol reactivity as a function of psychosocial stress and personality in adolescents

Although the developmental period of adolescence is characterized by impulsive and risk-taking behaviors, explanations for the range of behavioral disinhibition across adolescents that include biological, personality, and environmental factors have not been fully elucidated. Additionally, these factors may affect changes in stress responses that occur during this period. To inform this area of research, we examined the interaction between psychosocial stress exposure and the personality traits of Negative Emotionality (NEM) and Constraint (CON) on behavioral disinhibition (as indexed by impulsivity and riskiness tasks) and salivary cortisol reactivity in a sample of 88 adolescents. Results demonstrated that NEM and CON were protective of impulsivity and riskiness, respectively, for adolescents in the no-stress condition. Importantly, low CON adolescents in the no-stress condition were more risky than low CON adolescents in the stress condition, while there was no effect of Stress Group for high CON adolescents. Further, low CON adolescents exposed to psychosocial stress exhibited greater cortisol reactivity compared to high CON adolescents, suggesting that individuals low in CON may mobilize greater resources (e.g., cortisol reactivity, cognitive control) in stressful relative to non-stressful situations. Results suggest that distinct facets of behavioral disinhibition are differentially affected by stress and personality traits in adolescents

Genome-wide polygenic scores, executive function, and attention-deficit/hyperactivity disorder in youth

Although attention-deficit/hyperactivity disorder (ADHD) is highly heritable, the processes by which genetic risk affects its development are poorly understood. Potential mechanisms that may contribute to the development of ADHD, possibly by sharing common genetic risk, include impairments in executive functions. The goal of the present study was to clarify associations among genome-wide polygenic scores, executive functions, and ADHD in a subsample of 4,226 youth to determine whether executive dysfunctions mediate the relationship between cumulative genetic risk and a dimensional trait measure of ADHD. Polygenic scores derived from genome-wide association studies of ADHD and (low) educational attainment, but not tobacco smoking, were associated with increased ADHD in a non-clinical, independent sample of youth. A common executive function factor mediated the relationship between genetic risk associated with low educational attainment and ADHD. These results demonstrate that polygenic risk for clinically-diagnosed ADHD is also associated with a dimensional trait measure of ADHD in a non-clinical sample of youth and that there is common genetic influence on risk for low educational attainment and ADHD. In addition, results demonstrate that executive dysfunction is one mechanism through which genetic variants influence ADHD and suggest that executive functions may be targets of intervention development

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It is broadly accepted that the environment influences the effects of genes on behavior, but the mechanisms mediating these environmental effects on phenotype are poorly defined. The present study examined whether photoperiod (day length) and reproductive experience, two important environmental variables, affect gene expression to influence aggressive behavior. Individuals respond to photoperiod because it predicts important variability in the environment; male rodents use photoperiod to time adaptive behaviors such as mating and aggression. For example, mating is more likely in rodents housed in long, summer-like days when testosterone concentrations are high, whereas aggression in some rodent species is paradoxically elevated when housed in short, winter-like days when testosterone concentrations are low. Previous work in Peromyscus polionotus indicated that brain estrogen receptor alpha (ERα) expression is increased in short days (8L:16D), whereas brain estrogen receptor beta (ERβ) expression is increased in long days (16L:8D). Hormone manipulation studies suggested that the photoperiodic effect on aggression occurs independently of changes in ER expression. This hypothesi