Effects of childhood trauma on aggressive behaviors and hippocampal function: the modulation of COMT haplotypes

Chao Wang; Linfei Zhu; Wenyu Zheng; Hanyuzhu Peng; Jiaojian Wang; Yue Cui; Bing Liu; Tianzi Jiang

doi:10.1093/psyrad/kkad013

Effects of childhood trauma on aggressive behaviors and hippocampal function: the modulation of COMT haplotypes

Psychoradiology. 2023 Sep 6:3:kkad013. doi: 10.1093/psyrad/kkad013. eCollection 2023.

Authors

Chao Wang¹, Linfei Zhu¹, Wenyu Zheng¹, Hanyuzhu Peng¹, Jiaojian Wang², Yue Cui^{3

4}, Bing Liu⁵, Tianzi Jiang^{3

4}

Affiliations

¹ School of Psychology, Shenzhen University, Shenzhen 518060, China.
² State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China.
³ Brainnetome Center, Chinese Academy of Sciences, Beijing 100190, China.
⁴ National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
⁵ State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China.

Abstract

Background: Aggression is a commonly hostile behavior linked to the hippocampal activity. Childhood trauma (CT) exposure has been associated with altered sensitization of the hypothalamic-pituitary-adrenal (HPA) axis and hippocampal volume，which could increase violent aggressive behaviors. Additionally, Catechol-O-methyltransferase (COMT), the major dopamine metabolism enzyme, is implicated in stress responsivity, including aggression. Hence, CT exposure may affect aggression through the effect on the hippocampal function, which might also be modulated by the COMT variations.

Objectives: This study examined whether both CT and haplotypes of COMT moderate hippocampal function and thus affect human aggressive behavior.

Methods: We obtained bilateral hippocampal functional connectivity maps using resting state functional magnetic resonance imaging (MRI) data. COMT haplotype estimation was performed using Haploview 4.2 and PHASE 2.1. Then we constructed a moderated mediation model to study the effect of the CTQ × COMT on aggressive behavior.

Results: Three major haplotypes were generated from thirteen single nucleotide polymorphisms (SNPs) within the COMT gene and formed three haplotypes corresponding to high, medium, and low enzymatic activity of COMT. The results showed interactive relationships between the Childhood Trauma Questionnaire (CTQ) and COMT with respect to the functional connectivity (FC) of the bilateral hippocampus (HIP)-orbital frontal cortex (OFC). Specifically, CT experience predicted lower negative HIP-OFC coupling in the APS and HPS haplotypes corresponding to the medium and high enzymatic activity of COMT, but greater FC in the LPS haplotypes corresponding to the low enzymatic activity. We also observed a conditional mediation effect of the right HIP-OFC coupling in the link between COMT and aggressive behavior that was moderated by CT experience.

Conclusions: These results suggest that CT and COMT have a combined effect on aggressive behavior through hippocampal function. This mediation analysis sheds light on the influence of childhood experience on aggressive behavior in different genetic backgrounds.

Keywords: COMT; aggression; childhood trauma; hippocampus.