Neuroimaging evidence for the deficit subtype of schizophrenia
Voineskos AN., Foussias G., Lerch J., Felsky D., Remington G., Rajji TK., Lobaugh N., Pollock BG., Mulsant BH.
Importance: A major obstacle to the identification of the neurobiological correlates of schizophrenia is the substantial clinical heterogeneity present in this disorder. Dividing schizophrenia into "deficit" and "nondeficit" subtypes may reduce heterogeneity and facilitate identification of neurobiological markers of disease. Objective: To determine whether patients with deficit schizophrenia differ from patients with nondeficit schizophrenia and healthy controls in neuroimaging-based measures of white matter tracts and gray matter morphology. Design: A cross-sectional neuroimaging study of patients with the deficit or nondeficit subtype of schizophrenia and healthy controls. Setting: University hospital. Participants: Seventy-seven patients with schizophrenia and 79 healthy controls. Interventions: All participants were administered the Structured Clinical Interview for DSM-IV-TR Axis I Disorders and the Positive and Negative Syndrome Scale; IQ was measured using the Wechsler Test for Adult Reading; global cognitive impairment was grossly assessed using the Mini-Mental State Examination; comorbid physical illness burden was measured by administration of the Clinical Information Rating Scale-Geriatrics; high-resolution magnetic resonance imaging was performed as part of a multimodal imaging protocol; and deficit status was determined using the proxy scale for the deficit syndrome. Main Outcome Measures : Diffusion-based measures of white matter tracts, cortical thickness, cortical surface area, and volumes of subcortical structures. Results: In both an individually matched approach (18 patients with deficit schizophrenia, 18 patients with non-deficit schizophrenia, and 18 healthy controls) and an unmatched population-based approach (18 patients with deficit schizophrenia, 59 patients with nondeficit schizophrenia, and 79 health controls), the patients with deficit schizophrenia demonstrated disruption of white matter tracts compared with patients with nondeficit schizophrenia and healthy controls at the right inferior longitudinal fasciculus, the right arcuate fasciculus, and the left uncinate fasciculus. These findings were supported in patients with first-episode schizophrenia (n=20) who had a deficit score that was strongly correlated with disruption at these same tracts. In contrast, patients with schizophrenia of either subtype exhibited cortical thickness reductions compared with healthy controls, in nearidentical neuroanatomic patterns. Surface areas and subcortical volumes did not differ significantly among the 3 groups. Conclusions and Relevance: The convergence of findings in our individually matched sample, our unmatched overall sample, and our first-episode schizophrenia sample demonstrate (1) white matter tract disruption as a neurobiological feature of the deficit syndrome and (2) reductions in cortical thickness as a common feature of patients with a diagnosis of schizophrenia. When taken with previous results in gray matter, our findings in white matter tracts point to neural circuitry important for socioemotional function as a core neurobiological feature of the deficit subtype of schizophrenia. ©2013 American Medical Association. All rights reserved.