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

Schizophr Res. 2019 Oct:212:92-98. doi: 10.1016/j.schres.2019.08.005. Epub 2019 Aug 12.

Abstract

Background: Cognitive 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.

Methods: A 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.

Results: Minocyclinehigh 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.

Conclusions: Minocycline 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.

Keywords: Cognition; Interleukin-1β; Interleukin-6; Minocycline; Schizophrenia; Tumor necrosis factor–α.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Antipsychotic Agents / administration & dosage*
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / physiopathology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / drug therapy*
  • Interleukin-1beta / blood
  • Interleukin-1beta / drug effects*
  • Interleukin-6 / blood*
  • Male
  • Microglia / drug effects*
  • Middle Aged
  • Minocycline / administration & dosage
  • Minocycline / pharmacology*
  • Risperidone / administration & dosage
  • Schizophrenia / blood
  • Schizophrenia / complications
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / drug effects*
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Antipsychotic Agents
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Minocycline
  • Risperidone