Appetite effects of prefrontal stimulation depend on COMT Val158Met polymorphism: a randomized clinical trial

Authors: FASSINI, PRISCILA - Harvard University; DAS, SAI KRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SUEN, VIVIAN - Universidad De Sao Paulo; MAGEROWSKI, GRETA - Harvard University; MARCHINI, JULIO SERGIO - Universidad De Sao Paulo; ARAUJO DA SILVA JR, WILSON - Universidad De Sao Paulo; CHANGYU, SHEN - Harvard University; ALONSO-ALONSO, MIGUEL - Harvard University

Submitted to: Appetite
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/12/2019
Publication Date: 5/13/2019
Citation: Fassini, P.G., Das, S., Suen, V.M., Magerowski, G., Marchini, J., Araujo da Silva Jr, W., Changyu, S., Alonso-Alonso, M. 2019. Appetite effects of prefrontal stimulation depend on COMT Val158Met polymorphism: a randomized clinical trial. Appetite. https://doi.org/10.1016/j.appet.2019.05.015.
DOI: https://doi.org/10.1016/j.appet.2019.05.015

Interpretive Summary: Dopamine is released by nerve cells in response to rewarding stimuli, including food. It also plays an important role in the control of appetite. An approved treatment approach which targets brain area(s) by sending a constant, low-intensity current may help reduce appetite if aimed at the reward centers of the brain. However, responses to this treatment vary widely. We examined whether a specific variation of a gene that controls dopamine activity may explain differences in appetite and responses to this treatment. Adult women with obesity were enrolled in a weight loss program and randomly assigned to receive either the approved treatment or a placebo treatment. Participants with the gene variant who received the approved treatment experienced a significant reduction in appetite. Meanwhile, those who did not have the gene variant maintained high levels of appetite despite receiving treatment. These results suggest that differences in genetic makeup that influence dopamine activity also impact the effects of treatments targeted to reduce appetite.

Technical Abstract: The regulation of appetite is supported by dopamine-modulated brain circuits. Recent studies have shown that transcranial direct current stimulation (tDCS) aimed at increasing the excitability of the dorsolateral prefrontal cortex can reduce appetite, but the underlying mechanisms remain unknown, and response variability is large. The aim of this study was to determine whether individual differences in Catechol-O-methyl transferase (COMT) Val158Met polymorphism can influence tDCS effects on appetite. Thirty-eight adult women with obesity, classified as carriers or non-carriers of the Met allele, underwent a randomized, double-blind, sham-controlled tDCS intervention involving three phases: Phase I, target engagement (immediate effects of tDCS on working memory performance), Phase II, tDCS only (10 sessions, two weeks), and Phase III, tDCS + hypocaloric diet: (6 sessions, two weeks, 30% energy intake reduction, inpatient). Data were analyzed using linear mixed-effects models and mixed ANCOVA. Appetite was evaluated using visual analogue scales. We found that Met-carriers receiving active tDCS were the only participants who experienced a significant reduction of appetite over time. Conversely, Met non-carriers maintained high levels of appetite during the intervention; this effect was driven by a delayed paradoxical rise in appetite after stimulation. Working memory task performance at phase I correlated with subsequent appetite change in a COMT-dependent manner: speed improvements during the task predicted appetite increase in Met carriers and appetite reduction in Met non-carriers. Our findings suggest that genotype differences impacting dopamine levels influence prefrontal tDCS effects on appetite. This source of variability should be considered in the design of future studies.