Deconstructing Negative Symptoms in Individuals at Clinical High-Risk for Psychosis: Evidence for Volitional and Diminished Emotionality Subgroups That Predict Clinical Presentation and Functional Outcome.

Abstract

Negative symptoms are characteristic of schizophrenia and closely linked to numerous outcomes. A body of work has sought to identify homogenous negative symptom subgroups-a strategy that can promote mechanistic understanding and precision medicine. However, our knowledge of negative symptom subgroups among individuals at clinical high-risk (CHR) for psychosis is limited. Here, we investigated distinct negative symptom profiles in a large CHR sample (N = 244) using a cluster analysis approach. Subgroups were compared on external validators that are (1) commonly observed in the schizophrenia literature and/or (2) may be particularly relevant for CHR individuals, informing early prevention and prediction. We observed 4 distinct negative symptom subgroups, including individuals with (1) lower symptom severity, (2) deficits in emotion, (3) impairments in volition, and (4) global elevations. Analyses of external validators suggested a pattern in which individuals with global impairments and volitional deficits exhibited more clinical pathology. Furthermore, the Volition group endorsed more disorganized, anxious, and depressive symptoms and impairments in functioning compared to the Emotion group. These data suggest there are unique negative symptom profiles in CHR individuals, converging with studies in schizophrenia indicating motivational deficits may be central to this symptom dimension. Furthermore, observed differences in CHR relevant external validators may help to inform early identification and treatment efforts.