SU63. Association Between Inflammatory Markers and Negative Symptoms in Individuals With Persistent Symptoms of Schizophrenia Treated With Clozapine
Year: 2017
Type: conference-abstract
Abstract: Background: Negative symptoms of schizophrenia have consistently been identified as those features of the disorder that are most predictive of functional impairment and poor outcome. One pathophysiologic pathway that may contribute to negative symptoms in schizophrenia is inflammation. There is a growing literature that inflammatory cytokines may be linked to negative symptoms in individuals with schizophrenia, and no one has explored this specific connection in patients on clozapine. Methods: Ten participants (9 M, 1 F) with diagnoses of schizophrenia or schizoaffective disorder, treated with clozapine at Grady Memorial Hospital in Atlanta GA, were included in this analysis. Persistent symptoms were defined by PANSS cutoff scores, treatment with clozapine for at least 3 months, a documented clozapine level >350 ng/ml, and no change in clozapine dose greater than 100 mg in the past month. High-sensitivity c-reactive protein (hsCRP), interleukin (IL) 1beta, IL-6, IL-10, and tumor necrosis factor (TNF) were measured. Clinical rating scales included the PANSS, SANS, and WHODAS 2.0. Pearson correlation coefficients were calculated for the relationship among inflammatory markers and negative symptoms. Results: Mean clozapine dose was 557.5 mg (SD 128.05). Mean clozapine level was 759.8 mcg/l (SD 601.68). IL-1beta was significantly correlated with the passive/apathetic social withdrawal (r = 0.657, P = .039) and the disturbance of volition (r = 0.686, P = .029) items of the PANSS, as well as the avolition—impersistence at work or school (r = 0.644, P = .045), global rating of avolition-apathy (r = 0.751, P = .012), and the attention—social inattentiveness (r = 0.665, P = .036) items of the SANS. IL-10 was negatively correlated with the emotional withdrawal (r = −0.638, P = .047) and the passive/apathetic social withdrawal (r = −0.655, P = .04) items of the PANSS as well as the negative symptom total score of the PANSS (r = −0.792, P = .006). IL-10 was also negatively correlated with the total score of the WHODAS 2.0 (r = −0.792, P = .006). Conclusion: IL-1beta, a proinflammatory cytokine, was significantly correlated with avolition and social deficits. Moreover, IL-10, an anti-inflammatory cytokine, was negatively correlated with similar negative symptom items and a measure of real-world function. Though the sample size is small, these data suggest that inflammation may be relevant for these negative symptom domains. Indeed, administration of inflammatory stimuli has been reliably linked to deficits in reward processing and motivation via effects of inflammatory cytokines on regions of the basal ganglia, including the ventral striatum. Individuals with depression and increased inflammation also exhibit decreased functional connectivity in reward circuits in association with anhedonia. Future work should further explore the relationship between negative symptoms and inflammation in individuals with schizophrenia.
Source: Schizophrenia Bulletin
Institutions: Emory University, University of Washington
Language: English
Subfield: Biological Psychiatry
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2602022029