First Episode Psychosis: The Commensal Gut Microbiota Perspective

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Sylvie Bowden
Kenya A. Costa-Dookhan
Sri Mahavir Agarwal
Margaret Hahn



The rates of type 2 diabetes (T2D) in patients with schizophrenia (SCZ) are 3-5-fold higher than in the general population, contributing to a two-fold higher mortality due to cardiovascular disease (CVD). Antipsychotics, namely second-generation antipsychotics (SGAs), the cornerstone of treatment for this illness, induce weight gain and increase risk for diabetes. Accumulating research has demonstrated that the gut microbiome (GMB) plays a primary function in energy metabolism and could be a central factor in the pathophysiology of obesity and metabolic dysfunction. Antipsychotics are well known to contribute to metabolic dysregulation in patients with SCZ possibly through their impact on the GMB. This effect may be mediated by changes in dietary pattern induced by antipsychotics. Alterations in the GMB therefore may be contributing to both the etiology and concurrent metabolic dysregulation observed in schizophrenia spectrum disorders.


In this review, we aim explore how GMB affect the pathophysiology and treatment in this difficult to treat condition. We will review the GMB in relation to patients with first episode psychosis and the changes that occur within the microbiota when antipsychotic medication is introduced. The focus will be on SGAs, given their high propensity to cause weight gain and other metabolic side effects (namely glucose dysfunction, insulin resistance). The interplay between the GMB and SGAs will be explored further by examining neurotransmitter modulations, endocrine system function, and dietary changes.  This commentary highlights the need for more large scale, clinical studies investigating antipsychotic induced changes to the gut microbiome and the importance of making changes to a patient’s care pathway with the GMB in mind.