Ketone body 3-hydroxybutyrate as a biomarker of aggression

Abstract

Human aggression is a complex behaviour, 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 1983–1987, 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 response variable and aggression ratings as predictor variables, and included several potential confounders. 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 (age 14) aggression 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 aggression (self-rated) was also related to lower levels of 3-hydroxybutyrate. These exploratory epidemiologic results warrant further studies on the role of ketone metabolism in aggression.

Roux-En-Y Gastric Bypass (RYGB) Surgery during High Liquid Sucrose Diet Leads to Gut Microbiota-Related Systematic Alterations

“…Increased hepatic even/odd chain fatty acid ratio and reduced leptin levels in RYGB support the hypothesis that RYGB leads to upregulated lipolysis as reflected by increased levels of the ketone body 3-hydroxybutyrate in RYGB animal plasma. 3-Hydroxybutyrate is produced by the liver in lipolysis and serves as the primary energy substrate via beta-oxidation and acetyl-CoA for the TCA cycle when glucose is depleted [70]. During lipolysis, long-chain fatty acids can be transported only within chylomicrons, which are therefore highly upregulated [71].…”

The genetic background of the associations between sense of coherence and mental health, self-esteem and personality

“…This evidence of overlap in genetic liability to individual variation in SOC with psychological well-being, dimensions of mental health and personality creates opportunities for further research. The search for endophenotypes that mediate effects of dispositional genes on observed phenotypes of psychopathology [ 44 ] can be extended to endophenotypic pathways for risk-relevant behavioral precursors as illustrated by a study suggesting a novel metabolic biomarker, ketone body 3-hydroxybutyrate, of aggression [ 45 ]. Such research is responsive to the call to create a holistic framework for enhanced understanding of mental health traits, proposed by the National Institute of Mental Health’s Research Domain Criteria (RDoC) Initiative [ 46 ].…”

Editorial: Molecular links between metabolism and neural dysfunction

“…Using high-throughput 1 H nuclear magnetic resonance spectroscopy (NMR) to profile the metabolites, the study identified a significant negative association of plasma valine and leucine with depression. The same group previously identified ketone body 3-hydroxybutyrate as a biomarker of aggression (Whipp et al, 2021 ), highlighting the potential of metabolomic biomarkers in different types of mental health problems.…”