Leah D. Doane

Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence

Levels of the stress-sensitive hormone cortisol increase dramatically in the first 30-40min after waking, an effect known as the cortisol awakening response (CAR). There is considerable cross-sectional evidence that psychosocial stress is associated with an increased CAR, and the CAR has been found to be altered in the presence of stress-related diseases, including major depressive disorder (MDD). To date, no prospective longitudinal studies have examined whether individual differences in the CAR serve as a premorbid risk factor for MDD. In a sample of 230 late adolescents, clinical diagnoses of MDD were predicted from the CAR as well as other indicators of basal cortisol functioning gathered 1 year earlier, including: waking cortisol levels, bedtime cortisol levels, the size of the CAR, average cortisol, and the slope of the diurnal cortisol rhythm across the waking day. Age and gender, health and health behaviors, baseline neuroticism, exposure to stressful life events and past episodes of mood and anxiety disorders were included as covariates, to help ensure effects are attributable to the CAR rather than related variables. A higher baseline CAR was associated with a significantly increased risk of developing MDD by follow-up, even when excluding individuals with baseline MDD. No other baseline cortisol measures were significant prospective predictors of MDD. In summary, the CAR is a significant prospective risk factor for the development of MDD in young adults, providing some support for the possibility that a heightened CAR may play a role in the etiology of major depressive disorder.

Loneliness and Cortisol: Momentary, Day-to-day, and Trait Associations

In attempts to understand the social determinants of health, strong associations have been found between measures of loneliness, physiological stress processes, and physical and mental health outcomes. Feelings of loneliness are hypothesized to have implications for physiological stress processes, including activity of the hypothalamic-pituitary-adrenal (HPA) axis. In a community sample of young adults, multilevel modeling was used to examine whether trait and state feelings of loneliness were related to changes in levels of the stress-sensitive hormone cortisol, and whether the associations between loneliness and cortisol were mediated or moderated by the presence of concurrent depression or high levels of chronic life stress. Results indicated that trait loneliness was associated with a flattening of the diurnal cortisol rhythm. In addition, both daily and momentary state variations in loneliness were related to cortisol. Prior day feelings of loneliness were associated with an increased cortisol awakening response the next morning and momentary experiences of loneliness during the day were associated with momentary increases in cortisol among youth who also had high chronic interpersonal stress. Results were significant after covarying current depression, both chronic and momentary reports of stress, and medical and lifestyle covariates. This study expanded on prior work by investigating and revealing three different time courses of association between loneliness and HPA axis activity in young adults: trait, daily and momentary.

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.

Adolescents’ expectations for the future predict health behaviors in early adulthood

Health-related behaviors in adolescence establish trajectories of risk for obesity and chronic degenerative diseases, and they represent an important pathway through which socio-economic environments shape patterns of morbidity and mortality. Most behaviors that promote health involve making choices that may not pay off until the future, but the factors that predict an individuals investment in future health are not known. In this paper we consider whether expectations for the future in two domains relevant to adolescents in the U.S.-perceived chances of living to middle age and perceived chances of attending college-are associated with an individuals engagement in behaviors that protect health in the long run. We focus on adolescence as an important life stage during which habits formed may shape trajectories of disease risk later in life. We use data from a large, nationally representative sample of American youth (the US National Longitudinal Study of Adolescent Health) to predict levels of physical activity, fast food consumption, and cigarette smoking in young adulthood in relation to perceived life chances in adolescence, controlling for baseline health behaviors and a wide range of potentially confounding factors. We found that adolescents who rated their chances of attending college more highly exercised more frequently and smoked fewer cigarettes in young adulthood. Adolescents with higher expectations of living to age 35 smoked fewer cigarettes as young adults. Parental education was a significant predictor of perceived life chances, as well as health behaviors, but for each outcome the effects of perceived life chances were independent of, and often stronger than, parental education. Perceived life chances in adolescence may therefore play an important role in establishing individual trajectories of health, and in contributing to social gradients in population health.

Neuroticism and Introversion are Associated with Salivary Cortisol Patterns in Adolescents

Previous studies have yielded equivocal findings on the relationship between personality and cortisol activity. The present study examined associations between personality and cortisol activity in a large, diverse adolescent sample, while partialling the effects of relevant demographic and health-related covariates. A subsample of 230 participants (57% of whom reported elevated neuroticism) was selected from a larger sample of 16-18-year olds involved in a study on risk factors for emotional disorders. Subsample participants completed a battery of personality questionnaires, and saliva collection was requested several months later on three consecutive days at six time points per day, from wakeup to bedtime. Associations between personality and cortisol rhythms were examined using multilevel growth curve modeling. Neuroticism (N) and introversion (I) were significantly and differentially associated with features of diurnal cortisol patterns. Specifically, a significant N x gender interaction was observed, demonstrating flatter cortisol rhythms across the waking day among male participants with higher N. Elevated I, however, was associated with lower cortisol awakening responses for both male and female participants, and higher cortisol at the time of waking for male participants only. The present study supports personality as a significant predictor of diurnal cortisol patterns in late adolescence, after accounting for the effects of demographic and health covariates, and suggests that gender plays a role in moderating associations between personality and cortisol.

Incorporating hypothalamic-pituitary-adrenal axis measures into preventive interventions for adolescent depression: are we there yet?

Altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis is a robust correlate of major depression in adults, and to a lesser extent, in adolescents. Premorbid differences in HPA axis function have been found to prospectively predict the onset of adolescent depression. To what extent might our knowledge of HPA axis function in adolescents with, or at risk for, depression, help guide efforts to prevent depression in this age group? We review evidence regarding the role of the HPA axis in the development of adolescent depression, and examine whether and which HPA axis measures might be useful in guiding prevention efforts as (a) as a criterion by which to select youth at risk for depression, (b) as a predictor of which youth will be most responsive to prevention efforts, and (c) as an indicator of whether prevention/intervention efforts are working. We conclude that our current understanding of the HPA axis, and its measurement, in adolescent depression are not sufficiently precise to be of immediate practical use in improving prevention efforts. Incorporating HPA axis measures into prevention studies, however, would be immensely useful in clarifying the role of the HPA axis in adolescent depression, such that future prevention efforts might more confidently rely on HPA axis information.

Reciprocal Relations Between Objectively Measured Sleep Patterns and Diurnal Cortisol Rhythms in Late Adolescence

PURPOSE To examine how hours of sleep and wake times relate to between-person differences and day-to-day changes in diurnal cortisol rhythms in late adolescence. METHODS Older adolescents (N = 119) provided six cortisol samples (wakeup, +30 minutes, +2 hours, +8 hours, +12 hours, and bedtime) on each of three consecutive days while wearing an actigraph. We examined how average (across 3 days) and day-to-day changes in hours of sleep and wake times related to diurnal cortisol patterns. RESULTS On average, more hours of sleep related to steeper decline in cortisol across the days. Day-to-day analyses revealed that the hours of sleep of the previous night predicted steeper diurnal slopes the next day, whereas greater waking cortisol levels and steeper slopes predicted more hours of sleep and a later wake time the next day. CONCLUSION Our results suggest a bidirectional relationship between sleep and hypothalamic-pituitary-adrenal axis activity.

Latent trait cortisol (LTC) levels: Reliability, validity, and stability

The regulation of the hypothalamic pituitary adrenal (HPA) axis has received empirical attention as a mechanism contributing to individual differences in health and human development. A variety of sampling tactics and strategies index daily HPA axis functioning including the cortisol awakening response (CAR), the diurnal slope, and the area under the curve (AUGg). In an ethnically diverse sample (54% European-American, 23% Latino) of 82 adolescents (24% male, M age=18.05 years), we assessed salivary cortisol 45 times over the transition to college: 5 times per day, over 3 sequential days, across 3 waves (initially, 5, and 9 months later). Samples were collected at waking; 30 min, 3, and 8h post waking; and bedtime. Latent state-trait modeling indicated that the waking and 30 min post waking samples contributed to indices of within and across wave latent trait cortisol (LTC) levels. As such, a latent trait factor of cortisol was derived to reflect both within- and across-wave trait components of the variance in cortisol. LTC was distinct from the CAR, differentially predicted components of the diurnal profile across the day, and was highly stable across assessment waves (months). As preliminary evidence for convergent validity of LTC levels, childhood trauma was positively associated with LTC. Findings document the reliability, divergent and convergent validity, and stability of a latent trait factor of individual differences in HPA axis activity that may provide a cost efficient alternative to existing strategies and minimize participant burden.

Within-person variations in self-focused attention and negative affect in depression and anxiety: A diary study

This study examined within-person co-occurrence of self-focus, negative affect, and stress in a community sample of adolescents with or without emotional disorders. As part of a larger study, 278 adolescents were interviewed about emotional disorders. Later, they completed diary measures over three days, six times a day, reporting their current thoughts, affect, and levels of stress. Negative affect was independently related to both concurrent stress and self-focus. Importantly, the association between negative affect and self-focus was stronger among participants with a recent unipolar mood disorder, compared to those with an anxiety disorder, comorbid anxiety and depression, or those without an emotional disorder. The implications of these findings to theories of self-focus and its role in emotional disorders are discussed.

Adverse Adolescent Relationship Histories and Young Adult Health: Cumulative Effects of Loneliness, Low Parental Support, Relationship Instability, Intimate Partner Violence, and Loss

PURPOSE To examine the associations between adverse interpersonal relationship histories experienced during adolescence and health in young adulthood in a large, nationally representative sample. METHODS Using data from Waves I, II, and III of the National Longitudinal Study of Adolescent Health, multiple adverse relationship experiences were examined, including high loneliness, low perceived parental support, frequent transitions in romantic relationships (relationship instability), exposure to intimate partner violence, and loss by death of important relationship figures. These histories are assessed, both individually and in a relationship risk index, as predictors of self-reported general health and depressive symptoms at Wave III (ages, 18-27), controlling for baseline (Wave I) health and for demographic and health behavior covariates. RESULTS Net of baseline health and covariates, each type of relationship risk (experienced between Wave I and Wave III) was related to either depression or general health at Wave III, with the strongest effects seen for exposure to intimate partner violence. In addition, a cumulative relationship risk index examining the extent to which youth experienced high levels of multiple relationship risk factors revealed that each additional adverse relationship experience increased the odds of reporting worse mental and general health at Wave III, with increases occurring in an additive manner. CONCLUSION Multiple types of adverse relationship experiences predicted increases in poorer general health and depressive symptoms from adolescence to early adulthood. Consistent with a cumulative risk hypothesis, the more types of adverse relationship a youth experienced, the worse were their young adult health outcomes.