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Orbitofrontal cortex activity and connectivity predict future depression symptoms in adolescence.

ABSTRACT: Background:Major depressive disorder is a leading cause of disability worldwide; however, little is known about pathological mechanisms involved in its development. Research in adolescent depression has focused on reward sensitivity and striatal mechanisms implementing it. The contribution of loss sensitivity to future depression, as well as the orbitofrontal cortex (OFC) mechanisms critical for processing losses and rewards, remain unexplored. Furthermore, it is unclear whether OFC functioning interacts with familial history in predicting future depression. Methods:In this longitudinal study we recorded functional magnetic resonance imaging (fMRI) data while 229 adolescent females with or without parental history of depression completed a monetary gambling task. We examined if OFC blood-oxygen-level-dependent (BOLD) response and functional connectivity during loss and win feedback was associated with depression symptoms concurrently and prospectively (9 months later), and whether this relationship was moderated by parental history of depression. Results:Reduced OFC response during loss was associated with higher depression symptoms concurrently and prospectively, even after controlling for concurrent depression, specifically in adolescents with parental history of depression. Similarly, increased OFC-posterior insula connectivity during loss was associated with future depression symptoms but this relationship was not moderated by parental history of depression. Conclusions:This study provides the first evidence for loss-related alterations in OFC functioning and its interaction with familial history of depression as possible mechanisms in the development of depression. While the current fMRI literature has mainly focused on reward, the present findings underscore the need to include prefrontal loss processing in existing developmental models of depression.

SUBMITTER: Jin J

PROVIDER: S-EPMC5720380 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Orbitofrontal cortex activity and connectivity predict future depression symptoms in adolescence.

Jin Jingwen J Narayanan Ananth A Perlman Greg G Luking Katherine K DeLorenzo Christine C Hajcak Greg G Klein Daniel N DN Kotov Roman R Mohanty Aprajita A

Biological psychiatry. Cognitive neuroscience and neuroimaging 20170227 7

<h4>Background</h4>Major depressive disorder is a leading cause of disability worldwide; however, little is known about pathological mechanisms involved in its development. Research in adolescent depression has focused on reward sensitivity and striatal mechanisms implementing it. The contribution of loss sensitivity to future depression, as well as the orbitofrontal cortex (OFC) mechanisms critical for processing losses and rewards, remain unexplored. Furthermore, it is unclear whether OFC func ...[more]

PMID: 29226267

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Project description:BackgroundGirls' depressive symptoms typically increase in adolescence, with individual differences in course and severity being key risk factors for impaired emotional functioning in young adulthood. Given the continued brain white matter (WM) maturation that occurs in adolescence, the present study tested whether structural connectivity patterns in late adolescence are associated with variation in the course of depression symptom severity throughout adolescence.MethodParticipants were girls (N = 115) enrolled in a multiyear prospective cohort study of risk for depression. Initial depression severity (intercept) at age 10 and change in severity (linear slope) across ages 10-19 were examined in relation to WM tractography collected at age 19. Network-based statistic analyses were used to identify clusters showing variation in structural connectivity in association with depressive symptom intercept, slope, and their interaction.ResultsHigher initial depressive severity and steeper positive slope (separately) were associated with greater structural connectivity between temporal, subcortical socioaffective, and occipital regions. Intercept showed more connectivity associations than slope. The interaction effect indicated that higher initial symptom severity and a steeper negative slope (i.e., alleviating symptoms) were related to greater connectivity between cognitive control regions. Moderately severe symptoms that worsened over time were followed by greater connectivity between self-referential and cognitive regions (e.g., posterior cingulate and frontal gyrus).ConclusionsHigher depressive symptom severity in early adolescence and increasing symptom severity over time may forecast structural connectivity differences in late adolescence, particularly in pathways involving cognitive and emotion-processing regions. Understanding how clinical course relates to neurobiological correlates may inform new treatment approaches to adolescent depression.

Dataset Information

Orbitofrontal cortex activity and connectivity predict future depression symptoms in adolescence.

Publications

Orbitofrontal cortex activity and connectivity predict future depression symptoms in adolescence.

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