BNST and amygdala connectivity are altered during threat anticipation in schizophrenia

Abstract

In schizophrenia, impairments in affect are prominent and anxiety disorders are prevalent. Neuroimaging studies of fear and anxiety in schizophrenia have focused on the amygdala and show alterations in connectivity. Emerging evidence suggests that the bed nucleus of the stria terminalis (BNST) also plays a critical role in anxiety, especially during anticipation of an unpredictable threat; however, previous studies have not examined the BNST in schizophrenia. In the present study, we examined BNST function and connectivity in people with schizophrenia (n = 31; n = 15 with comorbid anxiety) and controls (n = 15) during anticipation of unpredictable and predictable threat. A secondary analysis tested for differences in activation and connectivity of the central nucleus of the amygdala (CeA), which has also been implicated in threat anticipation. Analyses tested for group differences in both activation and connectivity during anticipation of unpredictable threat and predictable threat (p < .05). Relative to controls, individuals with schizophrenia showed stronger BNST-middle temporal gyrus (MTG) connectivity during unpredictable threat anticipation and stronger BNST-MTG and BNST-dorsolateral prefrontal connectivity during predictable threat anticipation. Comparing subgroups of individuals with schizophrenia and a comorbid anxiety disorder (SZ+ANX) to those without an anxiety disorder (SZ-ANX) revealed broader patterns of altered connectivity. During unpredictable threat anticipation, the SZ+ANX group had stronger BNST connectivity with regions of the salience network (insula, dorsal anterior cingulate cortex). During predictable threat anticipation, the SZ+ANX group had stronger BNST connectivity with regions associated with fear processing (insula, extended amygdala, prefrontal cortex). A secondary CeA analysis revealed a different pattern; the SZ+ANX group had weaker CeA connectivity across multiple brain regions during threat anticipation compared to the SZ-ANX group. These findings provide novel evidence for altered functional connectivity during threat anticipation in schizophrenia, especially in individuals with comorbid anxiety.

Keywords: Anxiety; Extended amygdala; Fear; Unpredictable threat.