Secondary Sources of Negative Symptoms in Those Meeting Criteria for a Clinical High-Risk Syndrome

Background: Negative symptoms are diagnostic characteristics of schizophrenia. They can result from primary (i.e., idiopathic) or secondary (i.e., due to other factors such as depression, anxiety, psychosis, disorganization, medication effects) features of the illness. Although secondary sources of negative symptoms are prevalent among individuals meeting criteria for clinical high-risk syndromes that are due to high rates of comorbidity, the extent to which secondary sources account for variance in negative symptom domains is unknown. Addressing this gap is an important step in informing vulnerability models and treatments for negative symptoms. This study aimed to investigate secondary sources of negative symptoms in those meeting criteria for a clinical high-risk syndrome (N = 192). Methods: Simultaneous regression and hierarchical partitioning methods were used to determine the proportion of variance explained by selective serotonin reuptake inhibitor use, anxiety, depression, unusual thought content, and disorganized communication in predicting severity of five negative symptom domains (avolition, anhedonia, asociality, blunted affect, and alogia). Results: Findings revealed that depression explained the largest proportion of variance in avolition, asociality, and anhedonia. Anxiety was the most predictive of blunted affect, and selective serotonin reuptake inhibitor use explained the most variance in alogia. Analyses within male and female samples revealed that in males, depression explained a large proportion of variance in several negative symptom domains, while in females, selective serotonin reuptake inhibitor use explained variance in alogia. Conclusions: Results highlight heterogeneity in variance explained by secondary sources of negative symptoms. These findings guide treatment development for secondary sources of negative symptoms. Furthermore, results inform etiologic models of psychosis and negative symptom conceptualizations.