Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression

Colm G Connolly; Tiffany C Ho; Eva Henje Blom; Kaja Z LeWinn; Matthew D Sacchet; Olga Tymofiyeva; Alan N Simmons; Tony T Yang

doi:10.1016/j.jad.2016.09.026

Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression

J Affect Disord. 2017 Jan 1:207:86-94. doi: 10.1016/j.jad.2016.09.026. Epub 2016 Sep 23.

Authors

Colm G Connolly¹, Tiffany C Ho², Eva Henje Blom³, Kaja Z LeWinn⁴, Matthew D Sacchet⁵, Olga Tymofiyeva⁶, Alan N Simmons⁷, Tony T Yang⁴

Affiliations

¹ Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA. Electronic address: colm.connolly@ucsf.edu.
² Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA; Department of Psychology, Stanford University, Stanford, CA, USA.
³ Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁴ Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA.
⁵ Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA; Department of Psychology, Stanford University, Stanford, CA, USA; Neurosciences Program, Stanford University, Stanford, CA, USA.
⁶ Department of Radiology & Biomedical Imaging, University of California, San Francisco, 1700 4th St., San Francisco, CA, USA.
⁷ Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, USA; Veterans Affairs San Diego Health Care System, La Jolla, CA, USA.

Abstract

Background: The incidence of major depressive disorder (MDD) rises during adolescence, yet the neural mechanisms of MDD during this key developmental period are unclear. Altered amygdala resting-state functional connectivity (RSFC) has been associated with both adolescent and adult MDD, as well as symptom improvement in response to treatment in adults. However, no study to date has examined whether amygdala RSFC is associated with changes in depressive symptom severity in adolescents.

Method: We examined group differences in amygdala RSFC between medication-naïve depressed adolescents (N=48) and well-matched healthy controls (N=53) cross-sectionally. We then longitudinally examined whether baseline amygdala RSFC was associated with change in depression symptoms three months later in a subset of the MDD group (N=24).

Results: Compared to healthy controls, depressed adolescents showed reduced amygdala-based RSFC with the dorsolateral prefrontal cortex (DLPFC)and the ventromedial prefrontal cortex (VMPFC). Within the depressed group, more positive baseline RSFC between the amygdala and insulae was associated with greater reduction in depression symptoms three months later.

Limitations: Only a subset of depressed participants was assessed at follow-up and treatment type and delivery were not standardized.

Conclusions: Adolescent depression may be characterized by dysfunction of frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional regulation, whereas those circuits (amygdala-insula) subserving affective integration may index changes in depression symptom severity and may therefore potentially serve as a candidate biomarker for treatment response. Furthermore, these results suggest that the biomarkers of MDD presence are distinct from those associated with change in depression symptoms over time.

Keywords: Adolescent major depression; Amygdala; Dorsolateral prefrontal cortex; Resting-state; Ventromedial prefrontal cortex.

MeSH terms

Adolescent
Amygdala / diagnostic imaging
Amygdala / physiopathology*
Brain / diagnostic imaging
Brain / physiopathology
Case-Control Studies
Cerebral Cortex / diagnostic imaging
Cerebral Cortex / physiopathology
Depression / diagnostic imaging
Depression / physiopathology*
Depression / psychology
Depressive Disorder, Major / diagnostic imaging
Depressive Disorder, Major / physiopathology*
Depressive Disorder, Major / psychology
Disease Progression
Emotions
Female
Functional Neuroimaging
Humans
Longitudinal Studies
Magnetic Resonance Imaging
Male
Neural Pathways / diagnostic imaging
Neural Pathways / physiopathology
Prefrontal Cortex / diagnostic imaging
Prefrontal Cortex / physiopathology*
Rest
Self-Control
Severity of Illness Index

Abstract

MeSH terms

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