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Neurochemical Alterations in Aggression: A Meta-Analysis

Psychiatry Res. 2025 Jun 16;351:116595. doi: 10.1016/j.psychres.2025.116595. Online ahead of print.

ABSTRACT

Aggressive behaviours pose a significant threat to both individual and societal security. Increasing evidence suggests that individuals exhibiting such behaviours demonstrate altered neurochemical levels including metabolites, neurotransmitters and receptors. However, findings from previous studies have shown inconsistencies. This study aimed to elucidate these neurochemical alterations through a case-control meta-analysis. A comprehensive literature search was conducted using Web of Science, Medline, and PubMed databases, identifying forty eligible studies (registration number: CRD420251014162). The neurochemicals examined included indictors of serotonin (5-HT), dopamine, N-acetyl aspartate (NAA), glutamate, glutamine, choline, creatine, phosphocreatine, myo-inositol, gamma-aminobutyric acid, homovanillic acid, norepinephrine, 3-methoxy-4-hydroxy-phenylglycol, neuropeptide Y-like immunoreactivity, and substance P-like immunoreactivity. These studies investigated neurochemical changes in the cerebrospinal fluid (CSF) and various brain regions, including the prefrontal cortex, orbital frontal cortex, anterior cingulate cortex, middle temporal gyrus, medial temporal lobe, parietal cortex, striatum, thalamus, amygdala, hippocampus, midbrain, and brainstem. Our meta-analysis revealed a significant reduction in NAA levels in the prefrontal cortex of individuals exhibiting aggressive behaviours compared to controls. Furthermore, NAA levels demonstrated a negative correlation with the severity of aggressive behaviours. The findings for the other neurochemicals all did not reach statistical significance. These findings suggest that reduced prefrontal NAA levels may serve as a neurobiological correlate of aggressive behaviours, with implications for developing assessment tools and targeted interventions.

PMID:40543113 | DOI:10.1016/j.psychres.2025.116595

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