Why antipsychotics cause weight gain

A new study showed that weight gain induced by second-generation antipsychotics (SGAs) is associated with a proinflammatory phenotype, which drives metabolic disease in adults with obesity [1]. The study allows for a unique insight into the effect of weight gain on the immune system over time.

SGAs are associated with significant weight gain, cardiometabolic side effects, and an increased risk of chronic diseases such as diabetes and heart disease. Children on antipsychotics seem to be at higher risk of early weight gain, irrespective of the applied SGA. Obesity is associated with a state of low-grade chronic inflammation, resulting in dysregulation of immune system responses.

Prof. Louise Gallagher (University of Dublin, Ireland) explained that the aim of the study was to investigate the effect of SGAs on immunophenotype, immune cell responses, and cardiometabolic function in children (5–18 years) longitudinally over 12 months.

The results showed rapid weight gain within 3 months of commencing SGA treatment, especially in children with a lower BMI at baseline. The proinflammatory cytokines TNF-alpha and IL-17 increased within 3 months after commencing SGAs. IL-17 is released from mucosal-associated invariant T cells (MAIT cells) and is associated with insulin resistance. The frequency of MAIT cells also increased on SGAs. The study results confirmed that MAIT cells produce inflammatory cytokines, which are differentially regulated by dopamine. Prof. Gallagher noted that inflammatory MAIT cells are implicated in the development of metabolic disease: a recent study showed that an increase in MAIT cells promoted metabolic dysfunction in a mouse model [2]. The inflammatory changes found in this cohort of SGAs are similar to those found in previous studies on childhood obesity [1].

Prof. Gallagher summarised the importance of this research: “We showed novel mechanisms behind weight gain that occurs with antipsychotic medication. We identified targets in the inflammatory response to antipsychotics, allowing implementation of prevention strategies, such as identifying those most at risk of having a proinflammatory profile, as well as novel targets to potentially reduce these side effects. Our study offers a unique insight into the effect of weight gain on the immune system over time.”

1. 
   
   1. Gallagher L. Antipsychotics cause the development of an inflammatory phenotype: a 12-month longitudinal study. S.10.02, ECNP 2021 Congress, 2–5 October.
   2. Toubal A. Nat Commun. 2020;11(1):1–22.

 

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Posted on 26 November, 202116 February, 2024