New research
Intrinsic Amygdala Functional Connectivity in Youth With Bipolar I Disorder

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Objective

Bipolar disorder (BD) commonly begins during adolescence and may continue into adulthood. Studies in adults with BD suggest that disruptions in amygdalar neural circuitry explain the pathophysiology underlying the disorder. Importantly, however, amygdala subregion networks have not yet been examined in youth close to mania onset. The goal of this study was to compare resting state functional connectivity patterns in amygdala subregions in youth with bipolar I disorder with patterns in healthy controls.

Method

Centromedial, laterobasal, and superficial amygdala subdivisions were assessed during rest and examined in relation to clinical measures of mania in youth (14–20 years old) with bipolar I disorder who experienced only a single episode of mania (BD; n = 20) and age-matched healthy comparison youth without any personal or family history of DSM-IV Axis I disorders (HC; n = 23).

Results

Relative to HC youth, youth with BD exhibited decreased connectivity between the laterobasal subdivision of the amygdala and the hippocampus and precentral gyrus, and increased connectivity between the laterobasal subdivision and the precuneus. Connectivity between the right laterobasal amygdala and right hippocampus was positively correlated with levels of anxiety in BD but not in HC youth, and connectivity between the right laterobasal amygdala and right precuneus was negatively correlated with insight about bipolar illness.

Conclusion

Youth with BD have abnormal amygdala resting state network connections to regions that are critical for emotional processing and self-awareness. Longitudinal studies are needed to determine whether these aberrant patterns in youth with BD can be altered with intervention and can influence the course of disorder.

Section snippets

Participants

The university’s panel of medical research in human participants approved this research protocol. After hearing a complete description of the study, parents and youth less than 18 years of age gave written informed consent and assent, respectively; youth aged 18 years or more gave written informed consent. Youth (aged 13–21 years) with bipolar I disorder (n = 20) were recruited either by referral to a pediatric bipolar disorders clinic or from the surrounding community. HC youth (n = 23)

Participants

Demographic and clinical variables are presented in Table 1. BD and HC groups were balanced for gender (χ2 = 0.151, p = .79) and handedness (χ2 = 0.022, p = .88). There were no significant group differences in age (t41 = −0.69, p = .49), WASI scores (t41 = 1.28, p = .21), or pubertal status (t41 = −0.445, p = .659). As expected, the group with BD had higher YMRS (t41 = −6.95, p < .001) and CDRS scores (t41 = −7.36, p < .001) and lower CGAS global functioning ratings (t = 12.98, p < .001) than

Discussion

This study was designed to examine differences in amygdala subregion resting state functional connectivity between youth with bipolar I disorder and typically developing controls. Although youth with bipolar I disorder did not demonstrate predicted aberrant connectivity between the amygdala and the VLPFC, ACC, or insula, they did exhibit anomalous patterns of resting state functional connectivity between the laterobasal amygdala subregion and other regions critical for the processing and

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    Clinical guidance is available at the end of this article.

    This article was reviewed under and accepted by ad hoc editor Guido K.W. Frank, MD.

    This research was supported by the Klingenstein Third Generation Foundation (Fellowship in Depression to Dr. Manpreet Singh), the American Psychiatric Association’s Young Minds in Psychiatry Award, the National Institute of Mental Health (NIMH) grants K23-MH085919 (to Dr. Manpreet Singh) and R01-MH74849 (to Dr. Ian Gotlib), and Stanford’s Child Health Research Institute to Dr. Manpreet Singh.

    The authors thank Manish Saggar, PhD, of Stanford University, for his assistance with data analysis and interpretation. They also wish to thank Meghan Howe, LCSW, of Stanford University, for her assistance in diagnostic assessments, and Tenah Acquaye, BA, and Erica Marie Sanders, BA, of Stanford University, for their assistance in scheduling and running the participants.

    Disclosure: Dr. Chang has received research support from GlaxoSmithKline, Merck, and NIMH, and has served as an unpaid consultant for Bristol-Myers Squibb and as a paid consultant for Sunovion, Actavis, and Janssen. Drs. Singh and Gotlib and Mr. Kelley report no biomedical financial interests or potential conflicts of interest.

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    Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.