| Increased medial orbitofrontal and amygdala activation: evidence for a systems-level endophenotype of bipolar I disorder. | |
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MedLine Citation:
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PMID: 22267184 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Bipolar I disorder is highly heritable, but endophenotypes of the disorder mediating genetic risk are only beginning to be defined. The authors investigate state- and trait-related neural mechanisms related to motivation in euthymic bipolar patients and unaffected first-degree relatives of bipolar patients to define the status of motivational processing as a neural systems-level endophenotype. METHOD: Our study comprised two samples; the first consisted of 19 euthymic bipolar patients and 19 matched comparison subjects, and the second included 22 relatives and 22 matched comparison subjects. Motivational processing was assessed with a probabilistic reversal learning task during event-related functional MRI. Data were analyzed using a region-of-interest approach restricting analysis to the medial and lateral orbitofrontal cortex, the amygdala, the anterior cingulate cortex, and the striatum. RESULTS: The authors observed increased activation in response to reward and reward reversal contingencies in the left medial orbitofrontal cortex in patients with bipolar disorder and in the right medial orbitofrontal cortex in their relatives. Activation of the amygdala in response to reward reversal was increased in patients and relatives. In response to reward, activation of the amygdala was greater only in relatives, but there was a significant negative correlation between medication and amygdala activation in patients. CONCLUSIONS: These results identify increased activity of the orbitofrontal cortex and the amygdala, related to heightened sensitivity to reward and deficient prediction error signal, as a candidate endophenotype of bipolar disorder. The results support a role of motivational processing in the risk architecture of bipolar disorder and identify a new systems-level therapeutic target for the illness. |
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Authors:
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Julia Linke; Andrea Victoria King; Marcella Rietschel; Jana Strohmaier; Michael Hennerici; Achim Gass; Andreas Meyer-Lindenberg; Michèle Wessa |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The American journal of psychiatry Volume: 169 ISSN: 1535-7228 ISO Abbreviation: Am J Psychiatry Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-03-12 Completed Date: 2012-04-25 Revised Date: 2012-05-02 |
Medline Journal Info:
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Nlm Unique ID: 0370512 Medline TA: Am J Psychiatry Country: United States |
Other Details:
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Languages: eng Pagination: 316-25 Citation Subset: AIM; IM |
Affiliation:
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Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health in Mannheim, Germany. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Amygdala / physiopathology* Bipolar Disorder / etiology, physiopathology* Case-Control Studies Corpus Striatum / physiopathology Family Female Frontal Lobe / physiopathology* Functional Neuroimaging Gyrus Cinguli / physiopathology Humans Magnetic Resonance Imaging Male Middle Aged Motivation Phenotype Reversal Learning / physiology Reward |
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