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Articles, Behavioral/Systems/Cognitive

Individual Differences in Amygdala-Medial Prefrontal Anatomy Link Negative Affect, Impaired Social Functioning, and Polygenic Depression Risk

Avram J. Holmes, Phil H. Lee, Marisa O. Hollinshead, Leah Bakst, Joshua L. Roffman, Jordan W. Smoller and Randy L. Buckner
Journal of Neuroscience 12 December 2012, 32 (50) 18087-18100; DOI: https://doi.org/10.1523/JNEUROSCI.2531-12.2012
Avram J. Holmes
1Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138,
2Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129,
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Phil H. Lee
3Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114,
4Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, and
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Marisa O. Hollinshead
1Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138,
2Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129,
5Howard Hughes Medical Institute at Harvard University, Cambridge, Massachusetts 02138
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Leah Bakst
1Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138,
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Joshua L. Roffman
4Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, and
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Jordan W. Smoller
3Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114,
4Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, and
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Randy L. Buckner
1Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138,
2Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129,
4Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, and
5Howard Hughes Medical Institute at Harvard University, Cambridge, Massachusetts 02138
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Abstract

Individual differences in affective and social processes may arise from variability in amygdala-medial prefrontal (mPFC) circuitry and related genetic heterogeneity. To explore this possibility in humans, we examined the structural correlates of trait negative affect in a sample of 1050 healthy young adults with no history of psychiatric illness. Analyses revealed that heightened negative affect was associated with increased amygdala volume and reduced thickness in a left mPFC region encompassing the subgenual and rostral anterior cingulate cortex. The most extreme individuals displayed an inverse correlation between amygdala volume and mPFC thickness, suggesting that imbalance between these structures is linked to negative affect in the general population. Subgroups of participants were further evaluated on social (n = 206) and emotional (n = 533) functions. Individuals with decreased mPFC thickness exhibited the poorest social cognition and were least able to correctly identify facial emotion. Given prior links between disrupted amygdala–mPFC circuitry and the presence of major depressive disorder (MDD), we explored whether the individual differences in anatomy observed here in healthy young adults were associated with polygenic risk for MDD (n = 438) using risk scores derived from a large genome-wide association analysis (n = 18,759). Analyses revealed associations between increasing polygenic burden for MDD and reduced cortical thickness in the left mPFC. These collective findings suggest that, within the healthy population, there is significant variability in amygdala–mPFC circuitry that is associated with poor functioning across affective and social domains. Individual differences in this circuitry may arise, in part, from common genetic variability that contributes to risk for MDD.

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The Journal of Neuroscience: 32 (50)
Journal of Neuroscience
Vol. 32, Issue 50
12 Dec 2012
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Individual Differences in Amygdala-Medial Prefrontal Anatomy Link Negative Affect, Impaired Social Functioning, and Polygenic Depression Risk
Avram J. Holmes, Phil H. Lee, Marisa O. Hollinshead, Leah Bakst, Joshua L. Roffman, Jordan W. Smoller, Randy L. Buckner
Journal of Neuroscience 12 December 2012, 32 (50) 18087-18100; DOI: 10.1523/JNEUROSCI.2531-12.2012

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Individual Differences in Amygdala-Medial Prefrontal Anatomy Link Negative Affect, Impaired Social Functioning, and Polygenic Depression Risk
Avram J. Holmes, Phil H. Lee, Marisa O. Hollinshead, Leah Bakst, Joshua L. Roffman, Jordan W. Smoller, Randy L. Buckner
Journal of Neuroscience 12 December 2012, 32 (50) 18087-18100; DOI: 10.1523/JNEUROSCI.2531-12.2012
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