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Multilevel assessment of the neurobiological threat system in depressed adolescents: Interplay between the limbic system and hypothalamic–pituitary–adrenal axis

Published online by Cambridge University Press:  25 November 2014

Bonnie Klimes-Dougan ,
Lynn E. Eberly ,
Melinda Westlund Schreiner ,
Patrick Kurkiewicz ,
Alaa Houri ,
Amanda Schlesinger ,
Kathleen M. Thomas ,
Bryon A. Mueller ,
Kelvin O. Lim  and
Kathryn R. Cullen
Bonnie Klimes-Dougan*
Affiliation:
University of Minnesota
Lynn E. Eberly
Affiliation:
University of Minnesota
Melinda Westlund Schreiner
Affiliation:
University of Minnesota
Patrick Kurkiewicz
Affiliation:
University of Minnesota
Alaa Houri
Affiliation:
University of Minnesota
Amanda Schlesinger
Affiliation:
University of Iowa
Kathleen M. Thomas
Affiliation:
University of Minnesota
Bryon A. Mueller
Affiliation:
University of Minnesota
Kelvin O. Lim
Affiliation:
University of Minnesota
Kathryn R. Cullen
Affiliation:
University of Minnesota
*
Address correspondence and reprint requests to: Bonnie Klimes-Dougan, Department of Psychology, University of Minnesota, N412 Elliot Hall, 75 East River Road, Minneapolis, MN 55455; E-mail: klimes@umn.edu.
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Abstract

Integrative, multilevel approaches investigating neurobiological systems relevant to threat detection promise to advance understanding of the pathophysiology of major depressive disorder (MDD). In this study we considered key neuronal and hormonal systems in adolescents with MDD and healthy controls (HC). The goals of this study were to identify group differences and to examine the association of neuronal and hormonal systems. MDD and HC adolescents (N = 79) aged 12–19 years were enrolled. Key brain measures included amygdala volume and amygdala activation to an emotion face-viewing task. Key hormone measures included cortisol levels during a social stress task and during the brain scan. MDD and HC adolescents showed group differences on amygdala functioning and patterns of cortisol levels. Amygdala activation in response to emotional stimuli was positively associated with cortisol responses. In addition, amygdala volume was correlated with cortisol responses, but the pattern differed in depressed versus healthy adolescents, most notably for unmedicated MDD adolescents. The findings highlight the value of using multilevel assessment strategies to enhance understanding of pathophysiology of adolescent MDD, particularly regarding how closely related biological threat systems function together while undergoing significant developmental shifts.

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