Article

Amygdalofrontal functional disconnectivity and aggression in schizophrenia

Division of Clinical Research, Nathan Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.
Schizophrenia Bulletin (Impact Factor: 8.61). 04/2009; 36(5):1020-8. DOI: 10.1093/schbul/sbp012
Source: PubMed

ABSTRACT 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.

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    • "Schizophrenia is a severe neuropsychiatric disorder that represents the 18th leading cause of years lived with disability globally (Whiteford et al., 2013) and has an estimated point prevalence of 0.5% to 1.0% (Tandon et al., 2008). Functional and structural disconnectivity are among the most reproducible neurophysiological abnormalities associated with schizophrenia (Burns et al., 2003; Whalley et al., 2005; Liang et al., 2006; Begre and Koenig, 2008; Konrad and Winterer, 2008; Hoptman et al., 2010; Qiu et al., 2010; Whitford et al., 2011; Shi et al., 2012a,b; Curčić-Blake et al., 2013; Rane et al., 2013; Straube et al., 2013; Tepest et al., 2013) (recently reviewed by Schmitt et al. (2011)). "
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    • "As well as reflecting underlying anatomical connectivity (Park and Friston, 2013), RSFC has also been shown to correspond to the brain's functional architecture in response to external stimuli (Raichle and Mintun, 2006; Smith et al., 2009), as evidenced by findings that intrinsic resting-state brain activity can predict task-evoked brain activation during different cognitive tasks (Fox et al., 2006, 2007; Mennes et al., 2010; Liu et al., 2011; Mennes et al., 2011; Zou et al., 2013). RSFC has also been used to characterize functional brain networks correlated with individual differences in behavioral traits, such as personality, autistic trait and aggression (Di Martino et al., 2009; Hoptman et al., 2010; Adelstein et al., 2011). To our knowledge, only two studies have explored the neural correlates of risk propensity using RSFC (Cox et al., 2010; Han et al., 2012). "
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    • "). Abnormalities in functional connectivity during resting state have also showed correlations with general psychotic symptomatology (Bluhm et al., 2007) and aggression (Hoptman et al., 2010). "
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