Abstract
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.
Highlights
In schizophrenia, negative symptoms are defined as the absence or diminution of normal behavior in the areas of affect, speech, and goal-directed behavior
A supplementary voxel-based morphometry (VBM) analysis was performed using a more lenient significance threshold (p < 0.001, uncorrected) and we found reduced gray matter (GM) in persistent negative symptoms (PNS) patients compared to controls in several frontal regions [anterior cingulate; middle cingulate; medial–orbital frontal gyrus; and inferior orbital frontal gyrus]
NEURAL SUBSTRATES OF PRIMARY NEGATIVE SYMPTOMS Compared to non-PNS patients, PNS patients displayed significantly smaller gray matter (GM) volumes in the right medial– orbital frontal gyrus extending into the inferior frontal gyrus
Summary
Negative symptoms are defined as the absence or diminution of normal behavior in the areas of affect (blunted affect, anhedonia–asociality), speech (alogia), and goal-directed behavior (avolition–apathy; Carpenter et al, 1988). Primary negative symptoms are considered intrinsic to schizophrenia while secondary negative symptoms may occur in association with or be caused by positive, depressive, or extrapyramidal symptoms (from possible side effects of neuroleptic medications; Buchanan, 2007). Patients with enduring primary negative symptoms can be classified as having deficit syndrome (DS) or persistent negative symptoms (PNS). The SDS rules out secondary negative symptoms by assessing anxiety, medication effects, psychotic symptoms, mental retardation, and depression. Only those diagnosed with a schizophrenia spectrum disorder can be classified with DS (Kirkpatrick et al, 1989)
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