Genetic influences on hormonal markers of chronic hypothalamic-pituitary-adrenal function in human hair.

BACKGROUND: Cortisol is the primary output of the hypothalamic-pituitary-adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary and serum measures are strongly influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function. METHOD: In a socio-economically diverse sample of 1070 twins/multiples (ages 7.80-19.47 years) from the Texas Twin Project, we estimated effects of sex, age and socio-economic status (SES) on hair concentrations of cortisol and its inactive metabolite, cortisone, along with their interactions with genetic and environmental factors. This is the first genetic study of hair neuroendocrine concentrations and the largest twin study of neuroendocrine concentrations in any tissue type. RESULTS: Glucocorticoid concentrations increased with age for females, but not males. Genetic factors accounted for approximately half of the variation in cortisol and cortisone. Shared environmental effects dissipated over adolescence. Higher SES was related to shallower increases in cortisol with age. SES was unrelated to cortisone, and did not significantly moderate genetic effects on either cortisol or cortisone. CONCLUSIONS: Genetic factors account for sizable proportions of glucocorticoid variation across the entire age range examined, whereas shared environmental influences are modest, and only apparent at earlier ages. Chronic glucocorticoid output appears to be more consistently related to biological sex, age and genotype than to experiential factors that cluster within nuclear families.

The cortisol awakening response predicts major depression: predictive stability over a 4-year follow-up and effect of depression history.

BACKGROUND: The cortisol awakening response (CAR) has been shown to predict major depressive episodes (MDEs) over a 1-year period. It is unknown whether this effect: (a) is stable over longer periods of time; (b) is independent of prospective stressful life events; and (c) differentially predicts first onsets or recurrences of MDEs. METHOD: A total of 270 older adolescents (mean age 17.06 years at cortisol measurement) from the larger prospective Northwestern-UCLA Youth Emotion Project completed baseline diagnostic and life stress interviews, questionnaires, and a 3-day cortisol sampling protocol measuring the CAR and diurnal rhythm, as well as up to four annual follow-up interviews of diagnoses and life stress. RESULTS: Non-proportional person-month survival analyses revealed that higher levels of the baseline CAR significantly predict MDEs for 2.5 years following cortisol measurement. However, the strength of prediction of depressive episodes significantly decays over time, with the CAR no longer significantly predicting MDEs after 2.5 years. Elevations in the CAR did not significantly increase vulnerability to prospective major stressful life events. They did, however, predict MDE recurrences more strongly than first onsets. CONCLUSIONS: These results suggest that a high CAR represents a time-limited risk factor for onsets of MDEs, which increases risk for depression independently of future major stressful life events. Possible explanations for the stronger effect of the CAR for predicting MDE recurrences than first onsets are discussed.

Relationship functioning and home and work demands predict individual differences in diurnal cortisol patterns in women.

In 70 middle-class mothers of 2-year-old children, individual differences in mothers' morning cortisol levels, cortisol decreases across the day and average cortisol levels were predicted from demographic and medical control variables, maternal relationship functioning and home and work demands. For two days, salivary cortisol levels were measured in the morning immediately after wakeup, four times in the afternoon, and in the evening immediately prior to bedtime. Hierarchical linear modeling (HLM) growth curve analyses were used to estimate the intercept (early morning level), slope (steepness of decline in cortisol values across the day), and the average height of each mother's cortisol curve across the waking hours. HLM and multiple regression techniques were then used to predict individual differences in these parameters from the variables of interest. Time of day accounted for 72% of the variation in mothers' observed cortisol values across the day. After controlling for demographic and medical variables, positive relationship functioning was associated with higher morning cortisol levels and a steeper decline in cortisol across the day, while greater hours of maternal employment and a greater number of children in the household were associated with lower morning cortisol values and a less steep decline in cortisol levels across the day. Variables predicting higher morning values also predicted higher average cortisol levels, while variables predicting lower morning cortisol predicted lower average cortisol levels. The full model including selected control, relationship functioning and home and work demand variables accounted for 40% of the variance in mothers' morning cortisol values, 43% of the variance in cortisol slopes and 35% of the variability in mothers' average cortisol levels. This study presents the first evidence of associations between psychological variables and individual differences in the organization of cortisol levels across the waking day in normal adult women.

Adult attachment classification and self-reported psychiatric symptomatology as assessed by the Minnesota Multiphasic Personality Inventory--2.

This study examined differences in self-reported psychiatric symptomatology on the Minnesota Multiphasic Personality Inventory-2 according to adult attachment status on the Adult Attachment Interview in first-time mothers from a high-risk poverty sample. Participants reported fairly high levels of symptomatology regardless of attachment status. The dismissing adult attachment group reported comparatively little psychiatric distress, emphasized independence, and scored the lowest on self-reported anxiety. The preoccupied group was highest on a range of indices of psychiatric symptoms indicative of self-perceived distress and relationship problems. The autonomous group's scores ranged between the scores of the other 2 groups on most scales. These different symptom patterns are consistent with adult attachment status as an index of self-representation and as a set of strategies for processing emotions and thoughts related to distress and to attachment relationships.