Citation

Manchia M, Carpiniello B, Valtorta F, Comai S. ACS Chem. Neurosci. 2017; 8(5): 961-972.

Copyright

(Copyright © 2017, American Chemical Society)

DOI

10.1021/acschemneuro.6b00427

PMID

28378993

Abstract

Aggressive individuals have higher rates of mental illness compared to non-aggressive individuals. Multiple factors, including psychosocial, genetic, and neurobiological determinants modulate the liability to both aggressive behavior and mental illness. Concerning the latter factors, multiple lines of evidence have shown a dysfunction in the serotonin (5-HT) system occurring in aggressive and in mentally ill individuals. In particular, a reduced 5-HT activity has been associated with depression as well as with aggressive behavior, especially with impulsive aggression. Consistently, psychopharmacological interventions aimed at boosting the 5-HT system (e.g. with selective serotonin reuptake inhibitors) have demonstrated therapeutic efficacy in a high percentage of patients with either or both pathological conditions. Current knowledge does not yet allow to clearly disentangle whether 5-HT dysfunction, most often a 5-HT deficiency, is the consequence of the aggressive/violent behavior, of the underlying mental disease/s, or the expression of the comorbidity. Future studies are thus needed to clarify the association between changes in 5-HT levels, altered activity of 5-HT receptors and their intracellular signaling cascades, and modifications of 5-HT genes, and in particular the neurobiological link between the altered 5-HT machinery and aggressive behavior in the context or in the absence of mental illness. In this review, we employ a dimensional approach to discuss the trivariate relationship among the 5-HT system, aggressive behaviour, and mental illness, focusing our attention on 5-HT levels, 5-HT receptors, metabolic enzymes and their genes. Emphasis is given to controversial findings, still unanswered questions, and future perspectives.

Language: en