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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    ABSTRACT: Neuroinflammation and white matter pathology have each been independently associated with schizophrenia, and experimental studies have revealed mechanisms by which the two can interact in vitro, but whether these abnormalities simultaneously co-occur in people with schizophrenia remains unclear.
    Schizophrenia Research 06/2014; 161(1). DOI:10.1016/j.schres.2014.04.041 · 4.43 Impact Factor
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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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    ABSTRACT: Men are more risk prone than women, but the underlying basis remains unclear. To investigate this question, we developed a trait-like measure of risk propensity which we correlated with resting-state functional connectivity to identify sex differences. Specifically, we used short- and long-range functional connectivity densities to identify associated brain regions and examined their functional connectivities in resting-state functional magnetic resonance imaging (fMRI) data collected from a large sample of healthy young volunteers. We found that men had a higher level of general risk propensity (GRP) than women. At the neural level, although they shared a common neural correlate of GRP in a network centered at the right inferior frontal gyrus, men and women differed in a network centered at the right secondary somatosensory cortex, which included the bilateral dorsal anterior/middle insular cortices and the dorsal anterior cingulate cortex. In addition, men and women differed in a local network centered at the left inferior orbitofrontal cortex. Most of the regions identified by this resting-state fMRI study have been previously implicated in risk processing when people make risky decisions. This study provides a new perspective on the brain-behavioral relationships in risky decision making and contributes to our understanding of sex differences in risk propensity.
    Frontiers in Behavioral Neuroscience 01/2014; 8:2. DOI:10.3389/fnbeh.2014.00002 · 4.16 Impact Factor
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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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    ABSTRACT: CONSIDERING THAT SINGLE LOCATIONS OF STRUCTURAL AND FUNCTIONAL ABNORMALITIES ARE INSUFFICIENT TO EXPLAIN THE DIVERSE PSYCHOPATHOLOGY OF SCHIZOPHRENIA, NEW MODELS HAVE POSTULATED THAT THE IMPAIRMENTS ASSOCIATED WITH THE DISEASE ARISE FROM A FAILURE TO INTEGRATE THE ACTIVITY OF LOCAL AND DISTRIBUTED NEURAL CIRCUITS: the "abnormal neural connectivity hypothesis." In the last years, new evidence coming from neuroimaging have supported and expanded this theory. However, despite the increasing evidence that schizophrenia is a disorder of neural connectivity, so far there are no treatments that have shown to produce a significant change in brain connectivity, or that have been specifically designed to alleviate this problem. Brain-Computer Interfaces based on real-time functional Magnetic Resonance Imaging (fMRI-BCI) are novel techniques that have allowed subjects to achieve self-regulation of circumscribed brain regions. In recent studies, experiments with this technology have resulted in new findings suggesting that this methodology could be used to train subjects to enhance brain connectivity, and therefore could potentially be used as a therapeutic tool in mental disorders including schizophrenia. The present article summarizes the findings coming from hemodynamics-based neuroimaging that support the abnormal connectivity hypothesis in schizophrenia, and discusses a new approach that could address this problem.
    Frontiers in Psychiatry 03/2013; 4:17. DOI:10.3389/fpsyt.2013.00017
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