The role of the serotonergic system at the interface of aggression and suicide

Abstract

Alterations in serotonin (5-HT) neurochemistry have been implicated in the aetiology of all major neuropsychiatric disorders, ranging from schizophrenia to mood and anxiety-spectrum disorders. This review will focus on the mulifaceted implications of 5-HT-ergic dysfunctions in the pathophysiology of aggressive and suicidal behaviours. After a brief overview of the anatomical distribution of the 5-HT-ergic system in the key brain areas that govern aggression and suicidal behaviours, the implication of 5-HT markers (5-HT receptors, transporter as well as synthetic and metabolic enzymes) in these conditions is discussed. In this regard, particular emphasis is placed on the integration of pharmacological and genetic evidence from animal studies with the findings of human experimental and genetic association studies. Traditional views postulated an inverse relationship between 5-HT and aggression and suicidal behaviours; however, ample evidence has shown that this perspective may be overly simplistic, and that such pathological manifestations may reflect alterations in 5-HT homeostasis due to the interaction of genetic, environmental and gender-related factors, particularly during early critical developmental stages. The development of animal models that may capture the complexity of such interactions promises to afford a powerful tool to elucidate the pathophysiology of impulsive aggression and suicidability, and find new effective therapies for these conditions.

High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

“…Alterations in serotonin (5-Ht) neurochemistry have been implicated in the aetiology of all major cerebral disorders, ranging from schizophrenia to mood and anxiety-spectrum disorders including epilepsy (Di Giovanni et al 2008;Bombardi and Di Giovanni 2013;Bortolato et al 2013). Moreover, a dysfunctional serotonergic system might be responsible for the occurrence of concomitant diseases such as temporal lobe epilepsy (tLE) and comorbid depression and cognitive impairments and depression (Kanner and Balabanov 2002;Garcia 2012;theodore et al 2012).…”

Serotonergic modulation of suicidal behaviour: integrating preclinical data with clinical practice and psychotherapy

“…With regard to 5-Ht receptor dysfunction in suicide and aggression, the most studied have been the 5-Ht 1 , 5-Ht 2 subtypes (Bortolato et al 2013;Panariello et al 2011). We will focus on 5-Ht 2 receptors that have been implicated in a wide variety of conditions including obesity, anxiety, depression, obsessive compulsive disorder, schizophrenia, migraine and erectile dysfunction (Di Giovanni et al 2008.…”

“…this is a process in which specific adenosine residues are converted to inosine resulting in functional recoding of the mRnA that can generate up to 24 different protein isoforms with distinct functional properties. Post-mortem, animal and pharmacological studies have suggested that 5-Ht2C receptor and their altered RnA editing is involved in the pathophysiology of mental disorders including aggression and suicide, although results remain inconsistent (Panariello et al 2011;Bortolato et al 2013;Di Giovanni et al 2006. For instance, an increased density of prefrontal cortex 5-Ht 2C R mRnA (Pandey et al 2006) and differences in pre-mRnA editing of these receptors between control subjects and suicidal victims have been found (Gurevich et al 2002;Dracheva et al 2008).…”

“…On a neurobiological level, dysfunction of the serotonergic system has been shown to be implicated in a number of psychiatric afflictions including MDD, BPD and suicide (Oquendo and Mann 2000;Bortolato et al 2013;Di Giovanni et al 2008). Many studies have provided important information regarding the anatomy, development and functional organization of the 5-Ht system and the alterations in this system that are present within the brain of the suicidal patient (Pandey 2013).…”

Clinical and genetic factors associated with suicide in mood disorder patients

“…Strong neurobiological evidence points toward serotonergic and noradrenergic dysfunction [35][36][37]. Dysregulation in serotonin (5-HT) neurotransmission also appears to be related to impulsiveaggressive behavior [38], which influences suicidal behavior as an intermediate phenotype [39].…”