Minocycline as a potential treatment in the early stages of schizophrenia: a translational approach

Abstract

Despite the wide variety of currently available antipsychotics, their efficacy is limited only to the improvement in positive symptoms. In addition, longitudinal cohort studies of patients with first episode psychosis show worsening in different psychopathological domains and progressive loss of brain gray matter volumes. Beyond changes in neurotransmitter systems, most notably in the dopaminergic and glutamatergic systems, there is growing evidence of an immune and inflammatory component in the pathophysiology of schizophrenia, indicating an increase of cytokines (e.g., interleukin 1β, interleukin 6 and TNF-α) and microglial activation in patients with this disorder. Growing evidence indicates that minocycline may enhance the antipsychotic treatment and may prevent some brain changes observed in the early stages of schizophrenia. Minocycline is a tetracycline with broad anti-inflammatory activity and with evidence of neuroprotective action. However, the precise effects of minocycline in the CNS are still elusive. In the other hand, several points can be addressed, providing rational hypotheses for understanding how minocycline can improve symptoms and modulate brain structure and function in schizophrenia. In this article, relevant data about minocycline action are reviewed, linking bench to bedside. The potent inhibition of brain microglia activation and the broad anti-inflammatory effects of minocycline, in addition to indirect modulation of dopaminergic and glutamatergic systems, may mediate the effects of minocycline in schizophrenia. Further longitudinal studies with larger samples and measurement of inflammatory markers are needed to evaluate the potential of minocycline as adjunctive treatment in schizophrenia.