Abstract
BackgroundSchizophrenia is a highly heterogeneous disorder with positive and negative symptoms being characteristic manifestations of the disease. While these two symptom domains are usually construed as distinct and orthogonal, little is known about the longitudinal pattern of negative symptoms and their linkage with the positive symptoms. This study assessed the temporal interplay between these two symptom domains and evaluated whether the improvements in these symptoms were inversely correlated or independent with each other.MethodsThis post hoc analysis used data from a multicenter, randomized, open-label, 1-year pragmatic trial of patients with schizophrenia spectrum disorder who were treated with first- and second-generation antipsychotics in the usual clinical settings. Data from all treatment groups were pooled resulting in 399 patients with complete data on both the negative and positive subscale scores from the Positive and Negative Syndrome Scale (PANSS). Individual-based growth mixture modeling combined with interplay matrix was used to identify the latent trajectory patterns in terms of both the negative and positive symptoms. Pearson correlation coefficients were calculated to examine the relationship between the changes of these two symptom domains within each combined trajectory pattern.ResultsWe identified four distinct negative symptom trajectories and three positive symptom trajectories. The trajectory matrix formed 11 combined trajectory patterns, which evidenced that negative and positive symptom trajectories moved generally in parallel. Correlation coefficients for changes in negative and positive symptom subscale scores were positive and statistically significant (P < 0.05). Overall, the combined trajectories indicated three major distinct patterns: 1) dramatic and sustained early improvement in both negative and positive symptoms (n = 70, 18%), 2) mild and sustained improvement in negative and positive symptoms (n = 237, 59%), and 3) no improvement in either negative or positive symptoms (n = 82, 21%).ConclusionsThis study of symptom trajectories over 1 year shows that changes in negative and positive symptoms were neither inversely nor independently related with each other. The positive association between these two symptom domains supports the notion that different symptom domains in schizophrenia may depend on each other through a unified upstream pathological disease process.
Highlights
Schizophrenia is a highly heterogeneous disorder with positive and negative symptoms being characteristic manifestations of the disease
We seek to provide insight into the dynamic, individual-level interaction between negative and positive symptoms. Insight gained from these analyses could aid in management of patients with schizophrenia by raising awareness of the dynamic interplay between these two characteristic symptom domains and may help shed light on the pathological disease process of schizophrenia. Study population This analysis was based on data from a multicenter, randomized, open-label, 1-year pragmatic trial studying the cost-effectiveness of olanzapine as the first-line treatment of schizophrenia in the United States
Negative symptom trajectories To identify the different trajectory subtypes in terms of negative symptoms, data from 400 patients with complete 1-year Positive and Negative Syndrome Scale (PANSS) negative subscale scores were fit to a sequential series of quadratic growth models that reflected one to five different trajectory latent classes
Summary
Schizophrenia is a highly heterogeneous disorder with positive and negative symptoms being characteristic manifestations of the disease. While these two symptom domains are usually construed as distinct and orthogonal, little is known about the longitudinal pattern of negative symptoms and their linkage with the positive symptoms. It has been long recognized that schizophrenia is a highly heterogeneous disease in terms of etiology, symptom manifestation, and treatment response [1,2,3] Data from both randomized controlled trials [4,5,6,7] and a 30-year long observational study [8] has shown that treatment response is heterogeneous and is typically captured by four or five trajectory groups with symptom severity defined by the aggregated symptom scores. Hypotheses on the glutamatergic system suggest that glutamate is involved in the mediation of both positive and negative symptoms of schizophrenia in the same direction, the data are inferential regarding drugs are currently in late stage clinical development [23]
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