title: Serotonin Dysfunction, Aggressive Behavior, and Mental Illness: Exploring the Link Using a Dimensional Approach.
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, 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 cause or 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 behavior, 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.
authors.affiliation: Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari , 09121 Cagliari, Italy.|Department of Pharmacology, Dalhousie University , Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Mirko
authors.identifier: 0000-0003-4175-6413
authors.initials: M
authors.lastname: Manchia
authors.affiliation: Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari , 09121 Cagliari, Italy.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Carpiniello
authors.affiliation: San Raffaele Scientific Institute and Vita Salute University , Via Olgettina 58, 20132 Milano, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Valtorta
authors.affiliation: San Raffaele Scientific Institute and Vita Salute University , Via Olgettina 58, 20132 Milano, Italy.
authors.forename: Stefano
authors.identifier: 0000-0002-5686-7194
authors.initials: S
authors.lastname: Comai
mesh_terms: D000374:Aggression / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Serotonin; aggressive behavior; bipolar disorder; depression; schizophrenia