The developmental timing of the increase in the rate and the emergence of sex differences in depression points to adolescence as a critical period for understanding the causal mechanisms underlying the development of depressive disorders in females. Adolescent neural development is likely to play a key role in the etiology of depression, but little is known about the interface between the development of neural circuitry and depression across adolescence. In response to PA-09-108 Women's Mental Health and Sex/Gender Differences Research, we will determine if developmental changes in the neural circuitry engaged by emotionally evocative stimuli are related to adolescent depression in girls. Mapping developmental trajectories of depression symptoms onto relevant neural systems will further our understanding of the maturational changes in brain function that contribute to age-related vulnerability. Investigators: Drs. Keenan, Guyer and Forbes are the PIs;they began collaborating on the neuroscience of depression two years ago. Dr. Kevin Grimm, a statistician specializing in longitudinal modeling, and Dr. Alison Hipwell an expert in female mental health, are Co- Investigators. Consultants are Drs. Gang Chen, Ronald Dahl, Constance Hammen, and Daniel Pine. Innovation: Brain-behavior perturbations in information processing are a major focus of clinical neuroscience research. Developmental shifts in neural circuits during adolescence are critical to understanding the emergence of psychopathology during this period. No study to date, however, has been designed to test the hypothesis that development of the functional connections between affective and cognitive circuits during the adolescent period is related to depression-onset, or to characterize the patterns of neural development that in fact confer risk for depression onset. Approach: This proposal builds on a recently completed NIMH-funded study of precursors to depression in girls, in which depression symptoms and negative life events were documented from ages 9-14. Half of the sample was selected on measures indicative of high risk for developing depressive disorders. For this PA, we propose to study this sample from ages 15-19 years and to conduct annual assessments of depression and environmental stressors and annual assessments of emotional memory and reward processing using neuroimaging. Developmental patterns in functional connectivity between amygdala-ventral-lateral prefrontal cortex (vlPFC) circuitry and striatum-medial prefrontal cortex (mPFC) circuitry during memory for emotional faces and reward processing, respectively, will be captured across four time points, as will environmental stress exposure. Environment: This proposal involves a multi-institutional investigation at the Universities of Chicago, Pittsburgh, and California-Davis. Assessments of depression, stress exposure, and brain function will be conducted in the University of Pittsburgh's Department of Psychiatry and the Neuroimaging of Emotional Disorders Lab at Western Psychiatric Institute and Clinic, which is internationally recognized for research on brain functioning and child psychopathology.

Public Health Relevance

We propose to determine if developmental changes in how the brain responds to emotional stimuli during adolescence can inform us regarding which girls are at risk for developing depressive disorders. Adolescence appears to be a time of vulnerability in terms of developing circuits in the brain that help regulate emotional responses. By conducting a longitudinal study from ages 15-19 we will be able to examine individual differences in brain functioning from mid to late adolescence and test whether different pathways to developing mature brain circuits explains individual differences in risk for depression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH093605-02
Application #
8289421
Study Section
Psychosocial Development, Risk and Prevention Study Section (PDRP)
Program Officer
Garriock, Holly A
Project Start
2011-07-01
Project End
2016-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
2
Fiscal Year
2012
Total Cost
$605,057
Indirect Cost
$19,923
Name
University of Chicago
Department
Psychiatry
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Nelson, Eric E; Jarcho, Johanna M; Guyer, Amanda E (2016) Social re-orientation and brain development: An expanded and updated view. Dev Cogn Neurosci 17:118-27
Guyer, Amanda E; Silk, Jennifer S; Nelson, Eric E (2016) The neurobiology of the emotional adolescent: From the inside out. Neurosci Biobehav Rev 70:74-85
Moses-Kolko, Eydie L; Forbes, Erika E; Stepp, Stephanie et al. (2016) The influence of motherhood on neural systems for reward processing in low income, minority, young women. Psychoneuroendocrinology 66:130-7
Casement, Melynda D; Keenan, Kate E; Hipwell, Alison E et al. (2016) Neural Reward Processing Mediates the Relationship between Insomnia Symptoms and Depression in Adolescence. Sleep 39:439-47
Lichenstein, Sarah D; Verstynen, Timothy; Forbes, Erika E (2016) Adolescent brain development and depression: A case for the importance of connectivity of the anterior cingulate cortex. Neurosci Biobehav Rev 70:271-287
Romens, Sarah E; Casement, Melynda D; McAloon, Rose et al. (2015) Adolescent girls' neural response to reward mediates the relation between childhood financial disadvantage and depression. J Child Psychol Psychiatry 56:1177-84
Hall, Martica H; Casement, Melynda D; Troxel, Wendy M et al. (2015) Chronic Stress is Prospectively Associated with Sleep in Midlife Women: The SWAN Sleep Study. Sleep 38:1645-54
Jacobs, Rachel H; Orr, Jonathan L; Gowins, Jennifer R et al. (2015) Biomarkers of intergenerational risk for depression: a review of mechanisms in longitudinal high-risk (LHR) studies. J Affect Disord 175:494-506
Casement, Melynda D; Shaw, Daniel S; Sitnick, Stephanie L et al. (2015) Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence. Soc Cogn Affect Neurosci 10:416-23
Keenan, Kate; Culbert, Kristen M; Grimm, Kevin J et al. (2014) Timing and tempo: Exploring the complex association between pubertal development and depression in African American and European American girls. J Abnorm Psychol 123:725-36

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