Distress and Negative Subtypes of Schizophrenia: Identification, Characterization, and Neurostructural Profiles

Background Heterogeneity in schizophrenia spectrum disorders is a major challenge to implementing personalized medicine and uncovering etiological pathways. Recent work identified subtypes of schizophrenia that exhibit unique patterns of clinical symptoms and features using a common clinical scale. The current study sought to: 1) Replicate prior identification of subtypes using the Positive and Negative Syndrome Scale (PANSS) in a new cohort of people with schizophrenia; 2) Further characterize differences between subtypes in symptoms, affect, cognition, functioning, and personality; 3) Determine if brain structure abnormalities vary across subtypes. Study Design Phenotypic data were obtained on 356 individuals with schizophrenia spectrum disorders. Structural brain MRI data were acquired on a subset of 203 individuals with schizophrenia and 186 healthy people. A 2-step cluster analysis of PANSS data was used to identify subtypes of schizophrenia. Subtypes were compared on characteristics and brain volume. Study Results Clustering revealed three clusters aligning with previous subtypes: distress, negative, and low symptom. The distress subtype demonstrated higher levels of negative emotions, neuroticism, and schizotypal personality traits. The negative subtype exhibited more severe cognitive impairment, higher levels of disorganized and anhedonia symptoms, and worse functioning. Abnormalities in cortical volumes followed a gradient, the negative subtype demonstrated the largest number of cortical regions with smaller volume relative to healthy people, followed by the distress subtype, then the low symptom subtype. In contrast, smaller subcortical volumes were consistent across subtypes. Conclusions Our findings support the presence of subtypes of schizophrenia spectrum disorders that differ in affect, cognition, functioning, personality, and brain structure.