Self-reported ratings of sleep quality and symptoms of poor sleep have been linked to increased risk of coronary heart disease (CHD), Type 2 diabetes, and hypertension with recent evidence suggesting stronger associations in women. At this time, the mechanisms of action that underlie these gender-specific associations are incompletely defined. The current study examined whether gender moderates the relation of subjective sleep and sleep-related symptoms to indices of inflammation, coagulation, insulin resistance (IR), and psychosocial distress, factors associated with increased risk of cardiovascular and metabolic disorders. Subjects were 210 healthy men and women without a history of sleep disorders. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality and frequency of sleep symptoms. In multivariate-adjusted models, overall poor sleep quality, more frequent problems falling asleep (≥ 2 night/week), and longer periods to fall asleep (≥ 30 min) were associated with greater psychosocial distress, higher fasting insulin, fibrinogen and inflammatory biomarkers, but only for women. The data suggest that subjective ratings of poor sleep, greater frequency of sleep-related symptoms, and longer period of time to fall asleep are associated with a mosaic of biobehavioral mechanisms in women and that these gender-specific associations have direct implications to recent observations suggesting gender differences in the association between symptoms of poor sleep and cardiovascular disease.

Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnoverFindexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)Fin a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity  genotype interaction (P ¼ 0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender  genotype interaction (P ¼ 0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P ¼ 0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function.