Ketone 3-hydroxybutyrate: a biomarker of aggression?

Abstract

Aggression is a complex behavior broadly involving many body systems, commonly investigated at the biological level within specific pathways. Studying metabolites in relation to aggression can shed light on the biology of aggression in a broader context of various biological pathways affecting behavior. Associations between metabolites and aggression are not well known. Here, using a selected set of 11 low molecular weight metabolites including amino acids and ketones, we aimed to identify metabolites that associate with adolescent aggression. Our dataset is a sub-sample of a population-based, longitudinal study of Finnish twins born in 1983-1987 with available plasma samples at age 22 and aggression levels rated in adolescence (N=725) by parents of the twins (at age 12), their teachers (at ages 12 & 14), or the twins and their co-twins (at ages 14 & 17). Linear regression models, adjusted for age, sex, body mass index and the clustered twin data, were used with the metabolite as the outcome and aggression levels as predictors. Five metabolites showed unadjusted correlations greater than 0.1 with aggression. However, we found that aggression showed consistent negative associations only with 3-hydroxybutyrate, a ketone body produced in the fasting state. Effect sizes for different single raters were generally similar in magnitude, while age 12 teacher-rated aggression and age 14 self-rated aggression were both significant predictors of 3-hydroxybutyrate in multi-rater modeling. These exploratory results indicate ketone metabolism as a possible new pathway to investigate further to better understand the biology of aggression.