Cingulum and abnormal psychological stress response in schizophrenia

Stress is implicated in many aspects of schizophrenia, including heightened distress intolerance. We examined how affect and microstructure of major brain tracts involved in regulating affect may contribute to distress intolerance in schizophrenia. Patients with schizophrenia spectrum disorders (n = 78) and community controls (n = 95) completed diffusion weighted imaging and performed psychological stress tasks. Subjective affect was collected pre and post stressors. Individuals who did not persist during one or both stress tasks were considered distress intolerant (DI), and otherwise distress tolerant (DT). Fractional anisotropy (FA) of the dorsal cingulum showed a significant diagnosis x DT/DI phenotype interaction (p = 0.003). Post-hoc tests showed dorsal cingulum FA was significantly lower in DI patients compared with DI controls (p < 0.001), but not different between DT groups (p = 0.27). Regarding affect responses to stress, irritability showed the largest stress-related change (p < 0.001), but irritability changes were significantly reduced in DI patients compared to DI controls (p = 0.006). The relationship between irritability change and performance errors also differed among patients (ρ = -0.29, p = 0.011) and controls (ρ = 0.21, p = 0.042). Further modeling highlighted the explanatory power of dorsal cingulum for predicting DI even after performance and irritability were taken into account. Distress intolerance during psychological stress exposure is related to microstructural properties of the dorsal cingulum, a key structure for cognitive control and emotion regulation. In schizophrenia, the affective response to psychological stressors is abnormal, and distress intolerant patients had significantly reduced dorsal cingulum FA compared to distress intolerant controls. The findings provide new insight regarding distress intolerance in schizophrenia.