The microbiome-gut-brain axis: implications for schizophrenia and antipsychotic induced weight gain.

With the emergence of knowledge implicating the human gut microbiome in the development and regulation of several physiological systems, evidence has accumulated to suggest a role for the gut microbiome in psychiatric conditions and drug response. A complex relationship between the enteric nervous system, the gut microbiota and the central nervous system has been described which allows for the microbiota to influence and respond to a variety of behaviors and psychiatric conditions. Additionally, the use of pharmaceuticals may interact with and alter the microbiota to potentially contribute to adverse effects of the drug. The gut microbiota has been described in several psychiatric disorders including depression and anxiety, but only a few reports have discussed the role of the microbiome in schizophrenia. The following review examines the evidence surrounding the gut microbiota in behavior and psychiatric illness, the role of the microbiota in schizophrenia and the potential for antipsychotics to alter the gut microbiota and promote adverse metabolic events.

Genome-wide association studies of placebo and duloxetine response in major depressive disorder.

We investigated variants associated with treatment response in depressed patients treated with either the antidepressant duloxetine or placebo using a genome-wide approach. Our sample (N=391) included individuals aged 18-75 years, diagnosed with major depressive disorder and treated with either duloxetine or placebo for up to 8 weeks. We conducted genome-wide associations for treatment response as operationalized by percentage change in Montgomery-Åsberg Depression Rating Scale score from baseline, as well as mixed models analyses across five time points. In the placebo-treated subsample (N=205), we observed a genome-wide association with rs76767803 (ß=0.69, P=1.25 × 10-8) upstream of STAC1. STAC1 rs76767803 was also associated with response using mixed model analysis (χ2=3.95; P=0.001). In the duloxetine-treated subsample (N=186), we observed suggestive associations with ZNF385D (rs4261893; ß=-0.46, P=1.55 × 10-5), NCAM1 (rs2303377; ß=0.45, P=1.76 × 10-5) and MLL5 (rs117986340; ß=0.91, P=3.04 × 10-5). Our findings suggest that a variant upstream of STAC1 is associated with placebo response, which might have implications for treatment optimization, clinical trial design and drug development.