The effect of minocycline on amelioration of cognitive deficits and pro-inflammatory cytokines levels in patients with schizophrenia

Abstract

BackgroundCognitive deficits of schizophrenia are predictors of poor function, but antipsychotic medication has limited efficacy for cognitive deficits. These deficits in learning and memory may result from activity of pro-inflammatory cytokines, which microglia produce. The microglia inhibitor minocycline might arrest this cytokine damage to the hippocampus and reverse the cognitive deficits of schizophrenia. MethodsA double-blind, placebo-controlled study involved 75 patients with schizophrenia who randomly received low dose (100 mg/day) or high dose minocycline (200 mg/day) or placebo added to risperidone. MATRICS Consensus Cognitive Battery (MCCB) was used to assess the cognitive functioning, and serum levels of Interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor–α (TNF-α) were assessed. ResultsMinocyclinehigh dose group was significantly superior to minocyclinelow dose or placebo group not only for the improvements in cognitive tests' scores as well (P < 0.05), but for IL-1β and IL-6 serum levels reduction (P < 0.01). The amelioration of cognitive deficits with minocycline correlated not only with the remission of negative symptoms, but also with the reduction in serum levels of IL-1β and IL-6. ConclusionsMinocycline adjunctive treatment was effective in improving cognitive deficits of patients with schizophrenia. The beneficial effect of minocycline may be related to reducing pro-inflammatory cytokines through microglia inhibition.