Depression Research

Current Projects: Unipolar Depression

Depression Surge in Adolescence & Gender Differences: Biocognitive Mechanisms

Why does depression surge so dramatically in adolescence, especially for females?  Despite the great scientific and public health significance of this question, the mechanisms underlying the surge in depression and emergence of gender differences in depression during adolescence remain elusive.

This project is relevant to NIMH’s mission to understand the causes of depression in youth, role of minority and gender status in depression, and targets for early intervention.  The aims of this project are to examine the generality to African-Americans of this surge in depression and emergence of gender differences as well as to examine the mechanisms underlying these developmental phenomena from the perspective of an innovative cognitive vulnerability X transactional stress model, embedded within a normative adolescent brain and cognitive development context.

To this end, a large-scale prospective, longitudinal study of 12-13 year old community youth (evenly divided between males and females and Caucasians and African-Americans) and their parents is being conducted.  Assessments of the adolescents’ cognitive vulnerabilities (negative cognitive styles, rumination, self-referent information processing, autobiographical memories), normative cognitive development (executive functions – attention, working memory, decision-making, future orientation), early childhood stressors, racial identity, and psychiatric diagnoses are conducted at Time 1 and yearly thereafter.  Assessments of depressive and anxiety symptoms, stressful life events, hopelessness, emotional abuse and peer victimization, emotional clarity, body image, perceived discrimination, and pubertal status occur every 6 months.  In addition, assessments of parental psychopathology, maternal cognitive vulnerabilities, and parenting styles are also obtained at Time 1 and yearly.

Results will have very significant implications for prevention of depression.   Knowledge of mechanisms underlying the adolescent surge in depression would suggest interventions for short-circuiting it and the great impairment it portends for young adulthood.  Specifically, results will suggest optimal features of preventive interventions for depression in youth regarding: identification of youth to target, timing, psychological or biological processes to target, and interventions for girls vs. boys and African-Americans vs. Caucasians.

Risk for Adolescent Depression:  Stress, Cognitive Vulnerability, and Inflammation

Rates of depressive symptoms and diagnoses rise markedly between ages 15-18. Despite the scientific and public health significance, the mechanisms responsible for the adolescent surge in depression are not fully understood.

Cognitive vulnerability – stress models have contributed importantly to our understanding of the increased incidence of depression in adolescence; however, these models do not adequately explain some of the somatic symptoms or incorporate biological stress mechanisms through which cognitive vulnerability evokes depression. A separate exciting body of research on immune correlates of depression has highlighted the role of proinflammatory pathways; yet, only some depressed individuals exhibit inflammation. This project provides a novel and compelling integration of the cognitive vulnerability – stress framework and the proinflammatory model of depression as applied to adolescence. The research has the potential to solve puzzles and limitations faced by both models when considered separately. The findings may help to account for the full spectrum of depressive symptoms and identify cognitively vulnerable individuals as especially likely to evince signs of cytokine dysregulation and increased reactivity to stressful events. Moreover, it is known that early childhood adversity contributes to both the development of cognitive vulnerability and a proinflammatory bias. The primary goal is to determine the role of inflammatory states in combination with cognitive vulnerabilities, stress, and childhood adversity as contributors that underlie the rise in adolescent depression.

A multiwave, 4-year prospective study will be conducted with an existing, well-characterized community sample of 300 adolescents, including similar numbers of males and females and Caucasians and African-Americans, just reaching the critical age when the dramatic rise in depression begins. We will conduct yearly blood draws to assess proinflammatory and regulatory cytokines (a multicytokine array of 7 cytokines) and C-reactive protein (CRP), in parallel with ongoing assessments of life stress and depression and anxiety symptoms every 6 months. Cognitive vulnerabilities and depression and anxiety diagnoses will be obtained yearly, along with a history of childhood adversity in this unique cohort of urban adolescents. We also will examine interleukin-6 (IL- 6) reactivity to an acute stressor (Trier Social Stress Test) to determine how individual variation in cognitive reactivity translates into increased IL-6 release.

This project fills a crucial knowledge gap about normal development of immunity in adolescence and its role in the dramatic rise in adolescent depression. It may lead to novel interventions for depression that target cognitive influences on cytokine responses to stress, as well as pharmacological manipulations of cytokines to address symptoms such as fatigue, anhedonia, and withdrawal.