The effects of antipsychotic medications on microbiome and weight gain in children and adolescents

Abstract

Background Atypical antipsychotics, also known as second-generation antipsychotics, are commonly prescribed as treatment for psychotic disorders in adults, as well as in children and adolescents with behavioral problems. However, in many cases, second-generation antipsychotics have unwanted side effects, such as weight gain, potentially further increasing risk for morbidities including obesity, diabetes, and cardiovascular disease. While various mechanisms for this weight gain have been proposed, including effects on metabolic hormone signaling, recent evidence points to the importance of the gut microbiome in this process. The microbial communities residing within the gut are affected by second-generation antipsychotics and can confer weight gain. Main text This review summarizes recent findings and presents data linking second-generation antipsychotics, gut microbiota alterations and weight gain. The review focuses on children and adolescent populations, which have not previously received much attention, but are of great interest because they may be most vulnerable to gut microbiome changes and may carry long-term metabolic effects into adulthood. Conclusions We present correlations between second-generation antipsychotics, gut microbiota alterations and weight gain, and suggest some mechanisms that may link them. A better understanding of the underlying mechanisms may lead to the design of improved treatments for psychotic disorders with fewer harmful side effects.

Metabolomics approach revealed robust changes in amino acid and biogenic amine signatures in patients with schizophrenia in the early course of the disease

“…Many factors, additionally to treatment, contribute to the elevation of BMI in patients with FEP, including effects of metabolic hormone signalling, genetic susceptibility, lifestyle change, and unhealthy food habits 36,37 . Furthermore, recent evidence points also to the importance of gut microbial composition in this process 38 .…”

Risk Factors Associated with Recurrent Clostridioides difficile Infection

“…Increased gut permeability leads to the augmentation of the synthesis of the pro-inflammatory cytokine and secondary to inflammation [57]. Moreover, the medication used in the treatment of mental illness can bring changes to the gut microbiome [57,58]. In the study, dementia increases the risk of relapse of CDI by 3.26 times (OR = 3.26, 95% CI = 1.26-8.41, p = 0.014).…”

“…Depression is based on chronic inflammation of the brain, and, via cytokines, responsible for changing gut permeability and microbiome composition. Increased gut permeability leads to the augmentation of the synthesis of the pro-inflammatory cytokine and secondary to inflammation [57]. Moreover, the medication used in the treatment of mental illness can bring changes to the gut microbiome [57,58].…”

The Other Obesity Epidemic—Of Drugs and Bugs

“…Bacteroidetes phylum activates AhR by generating propionate which forms AhR ligands with indole. Depletion of these microbes by psychotropic drugs may alter the bioavailability and metabolism of these agents ( 10 ). For example, OLZ-induced Bacteroidetes phylum depletion and lower propionate, may under-activate AhR, suppressing the expression of CYP1A2 gene.…”

“…Historically, psychotropic drugs have been known to possess antimicrobial properties but their role in causing dysbiosis was only appreciated after the microbiome discovery. For example, most studies in humans show that AAP-treated patients develop an obesogenic microbial pattern, marked by increased Firmicutes and Actinobacteria phyla and decreased Bacteroidetes ( 10 , 11 ). Interestingly, AAP-upregulated phyla have the capability to synthesize heme, likely enabling them not only to survive but also thrive in iron-scarce conditions due to nutrients left behind by the non-surviving competitors.…”