Deconstructing negative symptoms of schizophrenia: avolition-apathy and diminished expression clusters predict clinical presentation and functional outcome

Abstract

Background: Previous studies indicate that negative symptoms reflect a separable domain of pathology from other symptoms of schizophrenia. However, it is currently unclear whether negative symptoms themselves are multi-faceted, and whether sub-groups of patients who display unique negative symptom profiles can be identified.

Methods: A data-driven approach was used to examine the heterogeneity of negative symptom presentations in two samples: Study 1 included 199 individuals with schizophrenia assessed with a standard measure of negative symptoms and Study 2 included 169 individuals meeting criteria for deficit schizophrenia (i.e., primary and enduring negative symptoms) assessed with a specialized measure of deficit symptoms. Cluster analysis was used to determine whether different groups of patients with distinct negative symptoms profiles could be identified.

Results: Across both studies, we found evidence for two distinctive negative symptom sub-groups: one group with predominantly Avolition-Apathy (AA) symptoms and another with a predominantly Diminished Expression (DE) profile. Follow-up discriminant function analyses confirmed the validity of these groups. AA and DE negative symptom sub-groups significantly differed on clinically relevant external validators, including measures of functional outcome, premorbid adjustment, clinical course, disorganized symptoms, social cognition, sex, and ethnicity.

Conclusions: These results suggest that distinct subgroups of patients with elevated AA or DE can be identified within the broader diagnosis of schizophrenia and that these subgroups show clinically meaningful differences in presentation. Additionally, AA tends to be associated with poorer outcomes than DE, suggesting that it may be a more severe aspect of psychopathology.

Figure 1. Means and SEs for SANS Factor Scores in AA, DE, and LOW-NEG Clusters (Panel A) and Three-Cluster Solution Plotted in Discriminant Function Space (Panel B) for Study 1

Note. Panel A: Values represent Means and SEs for Z-scores of standardized factor scores calculated for each subject. Higher values represent greater symptom severity. Panel B: Cluster 1 = Diminished Expression; Cluster 2 = Avolition-Apathy; Cluster 3 = Low Negative Symptoms.

Figure 2. Means and SEs for SDS Factor Scores in AA and DE Clusters (Panel A) and Two-Cluster Solution Plotted in Discriminant Function Space (Panel B) for Study 2

Note. Panel A: Values represent Means and SEs for Z-scores of standardized factor scores calculated for each subject. Higher values represent greater symptom severity. Panel B: Cluster 1 = Diminished Expression; Cluster 2 = Avolition-Apathy.