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.

Systematic review with meta‐analysis: the prevalence of anxiety and depression in patients with irritable bowel syndrome

“…In the meta‐analysis by Lee et al, IBS‐C patients indicated the highest SMD for anxiety and depression, and it was explained that this is probably due to an imbalance of 5‐hydroxytryptamine (5‐HT) secretion, leading to constipation in these patients. 5‐HT belongs to the intestinal serotonin system helping better gastrointestinal motility, which is also present in the central nervous system as a neurotransmitter contributing in mental health . So, it is probable that the low responsiveness of 5‐HT in both of the central and peripheral regions lead to the psychiatric problems in IBS‐C patients.…”

Octopamine neuron dependent aggression requires dVGLUT from dual-transmitting neurons

“…Finally, monoamine-expressing neurons play key roles in human behavior including aggression and illnesses that have an aggressive component such as depression, addiction, anxiety, and Alzheimer's [86,87]. While progress is being made in addressing the functional complexities of dual transmission, the possible pathological implications of glutamate co-release by monoamine neurons remains virtually unknown.…”

Gut-Brain Axis: Probiotic,Bacillus subtilis, Prevents Aggression via the Modification of the Central Serotonergic System

“…In GF mice, gut microbiota also modulates the 5-HT synthesis and release at both the brain and peripheral levels directly and indirectly via the microbiota-host interactions [148]. Reduced 5-HT activity (a 5-HT deficiency) has been associated with personality traits (interspecific social behavior), such as impulsivity and aggression, and deteriorated stress coping capability (increased stress response) in humans and various animals [149,150] including chickens [24,[151][152][153][154].…”