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Schizophrenia Bulletin Advance Access first published online on March 30, 2009
This version published online on April 16, 2009
Schizophrenia Bulletin, doi:10.1093/schbul/sbp012
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© The Author 2009. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Amygdalofrontal Functional Disconnectivity and Aggression in Schizophrenia

Matthew J. Hoptman1,2,3, Debra D'Angelo2, Dean Catalano2,4, Cristina J. Mauro2, Zarrar E. Shehzad5, A. M. Clare Kelly5,6, Francisco X. Castellanos5,6,7, Daniel C. Javitt3,4 and Michael P. Milham5
2 Division of Clinical Research, Nathan Kline Institute, Orangeburg, NY
3 Department of Psychiatry, New York University School of Medicine, New York, NY
4 Program in Cognitive Neuroscience and Schizophrenia, Nathan Kline Institute, Orangeburg, NY
5 The Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, New York University Child Study Center, New York, NY
6 Department of Child and Adolescent Psychiatry, New York University School of Medicine, New York, NY
7 Office of the Director, Nathan Kline Institute, Orangeburg, NY

1 To whom correspondence should be addressed; Division of Clinical Research, Nathan Kline Institute, 140 Old Orangeburg Road, Building 35, Orangeburg, NY 10962; tel: 845-398-6569, fax: 845-398-6566, e-mail: Hoptman{at}nki.rfmh.org.

A significant proportion of patients with schizophrenia demonstrate abnormalities in dorsal prefrontal regions including the dorsolateral prefrontal and dorsal anterior cingulate cortices. However, it is less clear to what extent abnormalities are exhibited in ventral prefrontal and limbic regions, despite their involvement in social cognitive dysfunction and aggression, which represent problem domains for patients with schizophrenia. Previously, we found that reduced white matter integrity in right inferior frontal regions was associated with higher levels of aggression. Here, we used resting-state functional magnetic resonance imaging to examine amygdala/ventral prefrontal cortex (vPFC) functional connectivity (FC) and its relation to aggression in schizophrenia. Twenty-one healthy controls and 25 patients with schizophrenia or schizoaffective disorder participated. Aggression was measured using the Buss Perry Aggression Questionnaire. Regions of interest were placed in the amygdala based on previously published work. A voxelwise FC analysis was performed in which the mean time series across voxels for this bilateral amygdala seed was entered as a predictor in a multiple regression model with motion parameters and global, cerebrospinal fluid, and white matter signals as covariates. Patients showed significant reductions in FC between amygdala and vPFC regions. Moreover, in patients, the strength of this connection showed a significant inverse relationship with aggression, such that lower FC was associated with higher levels of self-rated aggression. Similar results were obtained for 2 other measures—Life History of Aggression and total arrests. These results suggest that amygdala/vPFC FC is compromised in schizophrenia and that this compromise is associated with aggression.

Keywords: amygdala / functional connectivity / aggression / schizophrenia

Updated to correct affiliations for 2, 4, and 7.


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