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

Lucy D Vanes,Katie Wong,Krisna Patel,Erica Barry,Elias Mouchlianitis,Sukhwinder Shergill,Timea Szentgyorgyi,Megan Thomas,Dan Joyce

doi:10.1038/s41598-019-51023-0

Abstract

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.

Highlights

Deficits in executive functions are a core characteristic of psychotic disorders
Both patient groups showed a similar range of Positive and Negative Syndrome Scale (PANSS) positive (EP: min = 7, max = 35; chronic patients with a diagnosis of schizophrenia (CHR-SZ): min = 7, max = 26) and negative (EP: min = 7, max = 30; CHR-SZ: min = 7, max = 29) scores, indicating that correlative analyses within each group would cover a similar range of symptom severity
We assessed whole-brain activation on a Stroop task and correlations with symptom severity in a large sample of early psychosis (EP) patients compared to a sample of chronic schizophrenia (CHR-SZ) patients

Summary

Introduction

Deficits in executive functions are a core characteristic of psychotic disorders. Patients with psychosis typically display impaired performance on tasks involving executive functions such as cognitive control, working memory, planning, and cognitive flexibility[1,2,3]. It is possible that the mechanisms underlying the initial development of symptoms during the early phases of the illness differ from those in the later more chronic maintenance phase[23], and regions associated with psychotic symptoms are likely to vary through the course of the illness Such a process may mirror habituation in the processing of perceptual stimuli or motor and cognitive learning, whereby a shift can be observed in the neural regions associated with early developmental and later more settled processing during the same task[24,25]. A classic approach to identifying symptom-related brain activation is to clarify the regions showing abnormal activation in patients compared to healthy controls, and to test for correlations with symptoms within these regions[29] This method has the advantage of establishing a direct link between dysfunctional cognitive processing and clinical psychopathology. Throughout the last two decades, the focus has shifted increasingly toward the use of task-related fMRI, only few studies report the relationship between brain activation and symptom severity irrespective of activation differences relative to healthy control groups[37,38,39,40]

Methods

Results

Conclusion