F12. CHANGES IN BRAIN INFLAMMATION ARE RELATED TO SYMPTOMS AND AEROBIC EXERCISE IN FIRST EPISODE SCHIZOPHRENIA

Abstract

Research continues to show that persistent brain inflammation may be one mechanism through which genetic, biological, or environmental risk factors might impact the etiology and psychopathology of schizophrenia. Elevated levels of pro-inflammatory and lower levels of anti-inflammatory cytokines have been reported in meta-analyses of multi-episode schizophrenia patients when compared to controls. Similar findings have been described in meta-analysis in first episode schizophrenia patients for cytokines such as IL1β, sIL2r, IL-6, and TNF-α. Certain cytokines might be key participants in the regulation of neuro-inflammation in schizophrenia. Specifically, IL-6, a pro-inflammatory cytokine, may act as a primary regulator. In fact, IL-6 in multi-episode patients has been associated inversely with symptoms. Yet, little is known about the role these cytokines play in first episode schizophrenia patients and how best to reduce their impact. Outpatients in the early course of schizophrenia who were being treated in the UCLA Aftercare Program were assessed at baseline and at a 6-month follow-up point. Patients were within 2 years of their first psychotic episode, were an average of 22.6 years old and had an average of 13.1 years of education. Patients were participants in a RCT of Cognitive Training alone vs Cognitive Training & Exercise. For 25 patients, we assayed blood collected at baseline and 6 months for IL-6. To assess symptoms, we administered the BPRS at baseline and every two weeks up to the 6-month study end point. We examined the relationship between changes in the pro-inflammatory cytokine IL-6 and the change in depression from baseline to the 6-month follow-up point. We found increases in levels of IL-6 were significantly related to increases in BPRS depressive symptoms (n=25, r=.40, p=.04). In examining the RCT effects, the group by time effect was not statistically significant. However, within the Cognitive Training & Exercise group, the number of aerobic exercise sessions completed was significantly correlated with the amount of reduction in brain inflammation as measured by IL-6 (n=13, r=-.63, p=.02). This is the first study to examine in first episode schizophrenia patients the longitudinal relationship between cytokines and symptoms over time and the effects of aerobic exercise on cytokines. The study findings indicate that an increase in a pro-inflammatory cytokine is associated with an increase in depressive symptoms during six months of treatment. Associations between cytokine level and depression suggest that inflammation might have deleterious effects on the early course of these symptoms. The reductions observed in IL-6 with aerobic exercise suggests that exercise may be a promising intervention to reduce the deleterious effects of brain inflammation.