Brain-Behavioral Predictors of Interpersonal Stress Generation and Depression Risk in Adolescent Girls

Risk for major depressive disorder (MDD) onset dramatically increases during adolescence, particularly for girls. There is a vital need to elucidate the underlying mechanisms of MDD risk to improve early risk detection and targeted preventions. The stress generation model posits interpersonal stress generation (I-StressGen) as a

mechanism of risk and proposes that youth with preexisting MDD vulnerabilities actively contribute to the occurrence of interpersonal stressful life events in their lives (i.e., I-StressGen), which in turn exacerbates their risk for MDD. Although the impact of I-StressGen on prospective MDD risk in adolescents is well-established,

the precise mechanisms contributing to I-StressGen remain unclear. Self-report research indicates increased affective reactivity during negative social interactions as a promising mechanism contributing to I-StressGen, though this has not been directly tested. The underlying neural mechanisms of I-StressGen also remain

unexamined, despite work suggesting that greater social stress is associated with aberrant activation in corticolimbic regions during tasks probing response to negative social interactions. Therefore, the overarching goal of the proposed study is to obtain a fine-grained, mechanistic understanding of the role of brain and

behavioral affective reactivity during negative social interactions as it relates to I-StressGen and subsequent MDD risk in female adolescents. The proposed study will enroll a risk-enhanced sample of 90 female adolescents (ages 13-15) and will utilize neuroimaging (fMRI) and ecological momentary assessment (EMA) to examine brain

and behavior indices of socio-affective reactivity as predictors of I-StressGen and depression symptoms across a multi-wave one year follow-up. In doing so, the current study will test whether affective reactivity during negative social interactions at the neural (Aim 1) and real-world behavioral (Aim 2) level prospectively predicts I-

StressGen, and whether I-StressGen mediates the relation between this socio-affective reactivity and prospective increases in female adolescents’ depression symptoms (Aim 3). The proposed study and parallel training plan will allow the Candidate to build upon her current expertise in adolescent stress and MDD risk and

develop new skills in four key areas: (1) fMRI, (2) EMA, (3) advanced statistical multilevel modeling, and (4) professional development. The rich academic environment at the University of Illinois at Chicago coupled with the collective expertise of the Candidate’s mentorship team in fMRI methodology, developmental affective

neuroscience, EMA, and advanced statistical techniques will facilitate successful implementation of the proposed study and training plan. The acquisition of these skills will be integral to launching the Candidate’s independent career as a translational scientist focused on delineating brain-behavioral mechanisms of adolescent MDD risk

within the context of real-world interpersonal stress. Results from this study will inform the development of future grants focused on characterizing socio-affective brain and behavior mechanisms and aberrant developmental trajectories contributing to the emergence of maladaptive stress processes and MDD onset in adolescence.