Ketone body 3-hydroxybutyrate as a biomarker of aggression

A. M. Whipp*, E. Vuoksimaa, T. Korhonen, R. Pool, A. But, L. Ligthart, F. A. Hagenbeek, M. Bartels, L. H. Bogl, L. Pulkkinen, R. J. Rose, D. I. Boomsma, J. Kaprio

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Article number5813
Pages (from-to)1-10
Number of pages10
JournalScientific Reports
Volume11
Issue number1
Early online date12 Mar 2021
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
FinnTwin12 wishes to thank all participating twins, their parents and teachers. Data collection in FinnTwin12 was supported by NIAAA12502, AA-00145, AA-08315 (to RJR) and the Academy of Finland (Grants 100499, 205585, 118555, 141054 and 264146 to JK). JK has been supported by the Academy of Finland (Grants 308248 and 312073). EV has been supported by the Academy Research Fellow funding from the Academy of Finland (Grant 314639). TK was supported by the Academy of Finland (Grant 1309119). This project has also received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 874724. NTR warmly thanks all twins and family members for their participation. NTR data collection and analyses were supported by the Netherlands Organization for Scientific Research: Netherlands Twin Registry Repository: researching the interplay between genome and environment (480-15-001/674); the European Union Seventh Framework Program (FP7/2007-2013): ACTION Consortium (Aggression in Children: Unravelling gene-environment interplay to inform Treatment and InterventiON strategies; grant number 602768) and Biobanking and Biomolecular Resources Research Infrastructure Netherlands (BBMRI-NL: 184.021.007 and 184.033.111). Additionally, we wish to thank Teemu Palviainen M.Sc. for his statistical help, and Dr. Mariëlle Zondervan-Zwijnenburg for her advice regarding Bayesian modelling.

Publisher Copyright:
© 2021, The Author(s).

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Funding

FinnTwin12 wishes to thank all participating twins, their parents and teachers. Data collection in FinnTwin12 was supported by NIAAA12502, AA-00145, AA-08315 (to RJR) and the Academy of Finland (Grants 100499, 205585, 118555, 141054 and 264146 to JK). JK has been supported by the Academy of Finland (Grants 308248 and 312073). EV has been supported by the Academy Research Fellow funding from the Academy of Finland (Grant 314639). TK was supported by the Academy of Finland (Grant 1309119). This project has also received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 874724. NTR warmly thanks all twins and family members for their participation. NTR data collection and analyses were supported by the Netherlands Organization for Scientific Research: Netherlands Twin Registry Repository: researching the interplay between genome and environment (480-15-001/674); the European Union Seventh Framework Program (FP7/2007-2013): ACTION Consortium (Aggression in Children: Unravelling gene-environment interplay to inform Treatment and InterventiON strategies; grant number 602768) and Biobanking and Biomolecular Resources Research Infrastructure Netherlands (BBMRI-NL: 184.021.007 and 184.033.111). Additionally, we wish to thank Teemu Palviainen M.Sc. for his statistical help, and Dr. Mariëlle Zondervan-Zwijnenburg for her advice regarding Bayesian modelling.

FundersFunder number
National Institute on Alcohol Abuse and AlcoholismK05AA000145

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