Neural correlates of positive and negative symptoms through the illness course: an fMRI study in early psychosis and chronic schizophrenia

Psychotic illness is associated with cognitive control deficits and abnormal recruitment of neural circuits subserving cognitive control. It is unclear to what extent this dysfunction underlies the development and/or maintenance of positive and negative symptoms typically observed in schizophrenia. In this study we compared fMRI activation on a standard Stroop task and its relationship with positive and negative symptoms in early psychosis (EP, N = 88) and chronic schizophrenia (CHR-SZ, N = 38) patients. CHR-SZ patients showed reduced frontal, striatal, and parietal activation across incongruent and congruent trials compared to EP patients. Higher positive symptom severity was associated with reduced activation across both trial types in supplementary motor area (SMA), middle temporal gyrus and cerebellum in EP, but not CHR-SZ patients. Higher negative symptom severity was associated with reduced cerebellar activation in EP, but not in CHR-SZ patients. A negative correlation between negative symptoms and activation in SMA and precentral gyrus was observed in EP patients and in CHR-SZ patients. The results suggest that the neural substrate of positive symptoms changes with illness chronicity, and that cognitive control related neural circuits may be most relevant in the initial development phase of positive symptoms. These findings also highlight a changing role for the cerebellum in the development and later maintenance of both positive and negative symptoms

Cognitive correlates of abnormal myelination in psychosis

Psychotic illness has consistently been associated with deficits in cognitive function and reduced white matter integrity in the brain. However, the link between white matter disruptions and deficits in cognitive domains remains poorly understood. We assessed cognitive performance and white matter myelin water fraction (MWF) using multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) in recent-onset psychosis patients and age-matched healthy controls (HC). Psychosis patients showed deficits in working memory, phonological and semantic fluency, general intelligence quotient and reduced MWF in the left temporal white matter compared to HC. MWF in the left inferior fronto-occipital fasciculus and inferior longitudinal fasciculus was positively associated with intelligence quotient and verbal fluency in patients, and fully mediated group differences in performance in both phonological and semantic verbal fluency. There was no association between working memory and MWF in the left temporal white matter. Negative symptoms demonstrated a negative association with MWF within the left inferior and superior longitudinal fasciculi. These findings indicate that psychosis-related deficits in distinct cognitive domains, such as verbal fluency and working memory, are not underpinned by a single common dysfunction in white matter connectivity