The serotonin gene 5-HTTLPR and brain food-reward responses during sadness: a mood-induction neuroimaging study

• Published in: Journal of affective disorders Vol. 384; pp. 1 - 11
• Main Authors: Markus, C. Rob, Keulers, Esther H.H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2025
• Subjects: 5-HTTLPR; Adult; Affect - physiology; Affective-mood; Alleles; Brain - physiology; Female; fMRI; Food; Food-reward; Genotype; Humans; Magnetic Resonance Imaging; Male; Motivation - physiology; Psychiatric/Mental Health; Reward; Serotonin Plasma Membrane Transport Proteins - genetics; Stress; Young Adult; Affective-mood; fMRI; Food-reward; 5-HTTLPR; Stress
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2025.05.010

High-calorie foods become particularly rewarding and difficult to resist under affective stressful circumstances. Individuals carrying the short allele variant of the serotonin transporter gene (s-allele 5-HTTLPR) often exhibit enhanced emotional and neuroendocrine stress responsiveness, which increases their risk to gain weight or to develop obesity. To explore whether homozygous S-allele 5-HTTLPR carriers are more sensitive to the rewarding effects of high- compared to low-calorie foods during sad mood. Methods: From a large (n = 827) DNA 5-HTTLPR database, a selected subgroup of homozygous S-allele and L-allele carriers were monitored for affective-motivational (mood, wanting-liking) and neural (fMRI) food-reward responsiveness during a food exposure task, before and after sad mood induction. Brain responsiveness was measured for high versus low calorie food pictures in a set of appetitive- and cognitive control ROIs, respectively. Mood induction significantly increased sad mood in the majority of participants. Analyses revealed a genotype x mood induction interaction in cognitive control but not in affective ROIs. LL- compared to SS-carriers exhibited greater contrast value in the inferior frontal sulcus, dorsolateral PFC and superior parietal lob when viewing high- compared to low-calorie food pictures, which only in LL-genotypes significantly declined after sad mood induction. LL- compared to SS-genotypes may have stronger high-calorie food responses in cognitive control brain areas in the absence of stress indicating better capacity to resist the rewarding effects of palatable foods. •Brain reward responses to palatable foods under stress are moderated by 5HT genotypes•A gene x Stress interaction on brain food reward is evidenced in cognitive-control ROI•LL- compared to SS-genotypes may have better cognitive control to resist food reward