The Structural Neural Substrates of Persistent Negative Symptoms in First-Episode of Non-Affective Psychosis: A Voxel-Based Morphometry Study

OBJECTIVES An important subset of patients with schizophrenia present clinically significant persistent negative symptoms (PNS). Identifying the neural substrates of PNS could help improve our understanding and treatment of these symptoms. METHODS This study included 64 non-affective first-episode of psychosis (FEP) patients and 60 healthy controls; 16 patients displayed PNS (i.e., at least one primary negative symptom at moderate or worse severity sustained for at least six consecutive months). Using voxel-based morphometry (VBM), we explored for gray matter differences between PNS and non-PNS patients; patient groups were also compared to controls. All comparisons were performed at p < 0.05, corrected for multiple comparisons. RESULTS PNS patients had smaller gray matter in the right frontal medial-orbital gyrus (extending into the inferior frontal gyrus) and right parahippocampal gyrus (extending into the fusiform gyrus) compared to non-PNS patients. Compared to controls, PNS patients had smaller gray matter in the right parahippocampal gyrus (extending into the fusiform gyrus and superior temporal gyrus); non-PNS patients showed no significant differences to controls. CONCLUSION Neural substrates of PNS are evident in FEP patients. A better understanding of the neural etiology of PNS may encourage the search for new medications and/or alternative treatments to better help those affected.