Association of C-reactive protein and metabolic risk with cognitive effects of Lurasidone in patients with schizophrenia

Abstract Background: Accumulating evidence has implicated inflammation in insulin resistance as well as the pathophysiology of cognitive impairments in neuropsychiatric disorders. This post-hoc analysis based on placebo-controlled trial of lurasidone investigated the effect of inflammation (indexed by CRP) and metabolic risk factors on cognitive performance in patients with schizophrenia. Methods: Acutely exacerbated patients with schizophrenia were randomized to lurasidone (80 or 160 mg/day), quetiapine XR 600 mg/day, or placebo. A wide-range CRP test and a cognitive assessment using the CogState computerized battery were performed at baseline and 6 weeks. Associations of log-transformed CRP, high density lipoprotein (HDL), and the homeostatic measurement assessment of insulin resistance (HOMA-IR) with treatment response were evaluated. Results: CRP combined with HDL, triglyceride-to-HDL (TG/HDL) ratio, or HOMA-IR at study baseline were significant moderators of the cognitive improvement associated with lurasidone 160 mg/day (vs. placebo) treatment (p  Conclusions: Findings from this post-hoc analysis suggest that low CRP and HOMA-IR, as well as a healthy lipid profile (high HDL or low TG/HDL), were associated with an enhanced cognitive improvement with lurasidone 160 mg/d in patients with schizophrenia. These findings underscore the importance of maintaining a low profile of metabolic risk in patients with schizophrenia.