Dysregulation of Arousal and Amygdala-Prefrontal Systems in Paranoid Schizophrenia

Abstract

This is the first study to reveal a functional disconnection in autonomic and central systems for processing threat-related signals in patients with paranoid schizophrenia. Paranoid cognition may reflect an internally generated cycle of misattribution regarding incoming fear signals due to a breakdown in the regulation of these systems.

Neural bases for impaired social cognition in schizophrenia and autism spectrum disorders

“…More normative activation of social cognitive regions for nonparanoid relative to paranoid individuals is consistent with previous work showing normal levels of amygdala activation in non-paranoid schizophrenia during passive viewing of emotional facial expressions (Williams et al, 2004) and may help explain why individuals with non-paranoid schizophrenia rated faces similarly to healthy individuals. The finding that this differentiation between subgroups is also present during complex social information processing and in other regions implicated in social cognition underscores the vital importance of symptoms and sub-typing for fully understanding social cognitive deficits in schizophrenia.…”

“…Further, only minimal differences in social cognition have been observed between individuals with autism and those with schizophrenia when the latter group was higher in paranoid symptoms (Craig et al, 2004;Pilowsky et al, 2000). Thus, based on this evidence and in conjunction with work suggesting greater amygdala activation in NP-SCZ relative to P-SCZ (Phillips et al, 1999;Williams et al, 2004), we tentatively hypothesized that the ASD and P-SCZ groups would show less amygdala activation than the NP-SCZ group.…”

“…Significant clusters of activation within each ROI were identified based on a statistical threshold of p<.05 (uncorrected) and a spatial extent of 3 contiguous voxels (Holt et al, 2006;Williams et al, 2004). Clusters showing a main effect across all four groups were explored with post-hoc paired comparisons.…”

“…complex social judgments; Craig et al, 2004;Pilowsky et al, 2000); however, our understanding of these deficits, and the potential similarities between disorders, remains incomplete. Specifically, behavioral findings are complicated by heterogeneity within disorders, particularly in schizophrenia, as individuals with persecutory delusions perform differently both at behavioral and neural levels on social cognitive tasks relative to individuals without persecutory delusions (Bentall et al, 2001;Davis and Gibson, 2000;Phillips et al, 1999;Ueno et al, 2004;Williams et al, 2004). Additionally, despite evidence of abnormal activation in the neural systems of social cognition in schizophrenia and autism (Pinkham et al, 2003;Pelphrey et al, 2004), no studies have used fMRI to directly compare the neural substrates underlying social cognitive performance in both disorders.…”

“…trustworthiness) of faces in four groups: highfunctioning individuals with autism spectrum disorders (ASD), paranoid individuals with schizophrenia (P-SCZ), non-paranoid individuals with schizophrenia (NP-SCZ), and nonclinical healthy controls. As previous research has demonstrated significantly greater amygdala activation in non-paranoid, relative to paranoid individuals with schizophrenia (Phillips et al, 1999;Williams et al, 2004), two separate groups of patients with schizophrenia were recruited in order to provide the most comprehensive comparison with ASD and to account for known differences between schizophrenia subgroups. Further, decisions of trustworthiness were employed due to previous work demonstrating that these judgments fully engage the neural regions implicated in social cognition in healthy individuals (Winston et al, 2002) and to the likelihood that these judgments would be particularly salient in assessing differences between paranoid and non-paranoid individuals.…”