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Heterogeneity of amygdala response in major depressive disorder: the impact of lifetime subthreshold mania

Published online by Cambridge University Press:  09 May 2012

J. C. Fournier ,
M. T. Keener ,
B. C. Mullin ,
D. M. Hafeman ,
E. J. LaBarbara ,
R. S. Stiffler ,
J. Almeida ,
D. M. Kronhaus ,
E. Frank  and
M. L. Phillips
J. C. Fournier*
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA
M. T. Keener
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA
B. C. Mullin
Affiliation:
Department of Psychiatry and Behavioral Sciences, Children's Hospital Colorado, Aurora, CO, USA
D. M. Hafeman
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA
E. J. LaBarbara
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA
R. S. Stiffler
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA
J. Almeida
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA
D. M. Kronhaus
Affiliation:
St Catharine's College and Computer Laboratory, University of Cambridge, Cambridge, UK
E. Frank
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA
M. L. Phillips
Affiliation:
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA
*
*Address for correspondence: J. C. Fournier, Ph.D., University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. (Email: [email protected])
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Abstract

Background

Patients with major depressive disorder (MDD) present with highly heterogeneous symptom profiles. We aimed to examine whether individual differences in amygdala activity to emotionally salient stimuli were related to heterogeneity in lifetime levels of depressive and subthreshold manic symptoms among adults with MDD.

Method

We compared age- and gender-matched adults with MDD (n = 26) with healthy controls (HC, n = 28). While undergoing functional magnetic resonance imaging, participants performed an implicit emotional faces task: they labeled a color flash superimposed upon initially neutral faces that dynamically morphed into one of four emotions (angry, fearful, sad, happy). Region of interest analyses examined group differences in amygdala activity. For conditions in which adults with MDD displayed abnormal amygdala activity versus HC, within-group analyses examined amygdala activity as a function of scores on a continuous measure of lifetime depression-related and mania-related pathology.

Results

Adults with MDD showed significantly greater right-sided amygdala activity to angry and happy conditions than HC (p < 0.05, corrected). Multiple regression analyses revealed that greater right-amygdala activity to the happy condition in adults with MDD was associated with higher levels of subthreshold manic symptoms experienced across the lifespan (p = 0.002).

Conclusions

Among depressed adults with MDD, lifetime features of subthreshold mania were associated with abnormally elevated amygdala activity to emerging happy faces. These findings are a first step toward identifying biomarkers that reflect individual differences in neural mechanisms in MDD, and challenge conventional mood disorder diagnostic boundaries by suggesting that some adults with MDD are characterized by pathophysiological processes that overlap with bipolar disorder.

Keywords

Bipolar disorderbrain imagingemotion processingindividual differencesmajor depressive disorder
Type
Original Articles
Information
Psychological Medicine , Volume 43 , Issue 2 , February 2013 , pp. 293 - 302
Copyright
Copyright © Cambridge University Press 2012

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