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Ketone body 3-hydroxybutyrate: a biomarker of aggression?

By alyce m whipp, eero vuoksimaa, Tellervo Korhonen, rene pool, lannie ligthart, fiona hagenbeek, M. Bartels, leonie-helen bogl, lea pulkkinen, richard j rose, Dorret I Boomsma, Jaakko Kaprio

Posted 16 May 2020
medRxiv DOI: 10.1101/2020.05.13.20100347

Human aggression is a complex behavior, the biological underpinnings of which remain poorly known. To gain insights into aggression biology, we studied relationships with aggression of 11 low-molecular-weight metabolites (amino acids, ketone bodies), processed using 1H nuclear magnetic resonance spectroscopy. We used a discovery sample of young adults and an independent adult replication sample. We studied 725 young adults from a population-based Finnish twin cohort born 1983-87, with aggression levels rated in adolescence (ages 12, 14, 17) by multiple raters and blood plasma samples at age 22. Linear regression models specified metabolites as the dependent and aggression ratings as independent variables, and included several fixed effects. All metabolites showed low correlations with aggression, with only one - 3-hydroxybutyrate, a ketone body produced during fasting - showing significant (negative) associations with aggression. Effect sizes for different raters were generally similar in magnitude, while teacher-rated (age 12) and self-rated aggression (age 14) were both significant predictors of 3-hydroxybutyrate in multi-rater models. In an independent replication sample of 960 adults from the Netherlands Twin Register, higher self-rated aggression was also related to lower levels of 3-hydroxybutyrate. These exploratory epidemiologic results warrant further studies on the role of ketone metabolism in aggression.

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