Abstract
Background
There is considerable evidence supporting the association between extrapyramidal symptoms (EPS) and psychotic symptoms in patients with schizophrenia (SCZ). However, it is not well understood whether such an association exists in individuals without SCZ and how the association differs from those with SCZ. Our aim was to examine the associations of EPS with psychotic symptoms and compare them between SCZ and non-SCZ individuals.
Methods
We used data from a 10-year community-based study of homeless or precariously housed persons from Vancouver, Canada. Diagnosis of SCZ was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Severity of psychotic symptoms was rated using the Positive and Negative Syndrome Scale (PANSS). Severity of parkinsonism, dyskinesia, and dystonia was rated using the Extrapyramidal Symptom Rating Scale (ESRS), and akathisia using the Barnes Akathisia Rating Scale (BARS). Presence of EPS was defined as having at least moderate severity on the ESRS (i.e., ≥4 out of 8) or BARS (i.e., ≥3 out of 5) Clinical Global Impression-Severity (CGI-S) scale. Absence of EPS was defined as scoring ≤2 on the ESRS or ≤1 on the BARS CGI-S scale. Two-way analysis of covariance was performed using SCZ and EPS as independent variables and PANSS five factors (i.e., positive symptoms, negative symptoms, disorganization, excitement, and depression) as dependent variables, controlling for age, antipsychotic users, and cocaine- or methamphetamine-dependent individuals. Multiple linear regression analysis was performed for both SCZ and non-SCZ groups, controlling for the same confounding variables, to examine 1) associations of the severity of EPS subtypes with PANSS factors and 2) whether the presence of multiple EPS subtypes would be associated with increased SCZ symptoms relative to the presence of a single subtype.
Results
A total of 223 participants were included in this study (mean age: 44.1 ± 12.0 years; 76.1% male). Eighty-four participants met the diagnosis of SCZ, of whom 39 met our criteria for having EPS and 32 for not having EPS. The remaining 139 participants were not diagnosed with SCZ, of whom 50 had EPS and 72 did not. None of the participants had clinically significant dystonia. Overall, significant main effects of EPS were found for total symptoms (F1,182 = 24.4, p < 0.001), negative symptoms (F1,182 = 16.3, p < 0.001), disorganization (F1,181 = 16.6, p < 0.001), and excitement (F1,182 = 15.8, p < 0.001), but not positive symptoms or depression. The presence of EPS was associated with greater total symptoms and disorganization in both SCZ and non-SCZ groups. Significant interaction effects between SCZ and EPS were found for negative symptoms (F1,182 = 6.0, p = 0.015) and excitement (F1,182 = 3.9, p = 0.050), where the presence of EPS was associated with greater negative symptoms and excitement in SCZ participants, but not in non-SCZ participants. Consistent in both SCZ and non-SCZ groups, there were significant positive associations of the severity of 1) parkinsonism with negative symptoms, 2) dyskinesia with disorganization and total symptoms, and 3) akathisia with excitement. The presence of multiple EPS subtypes, relative to a single subtype, was not associated with significant increases in any SCZ symptoms, except a significant increase in excitement in non-SCZ participants.
Discussion
The presence of EPS is clearly associated with greater symptoms of SCZ, even in individuals without SCZ. People with SCZ may experience greater negative symptoms and excitement as a result of EPS than those without SCZ. Subtypes of EPS are distinctively associated with factors of SCZ symptoms. Future studies should elucidate the mechanisms underlying these associations.
HIGH MOBILITY GROUP BOX-1 LEVELS IN SCHIZOPHRENIA: POTENTIAL BIOMARKER OF REMISSION PHASE
