Serotonin, genetic variability, behaviour, and psychiatric disorders - a review

Abstract

Brain monoamines, and serotonin in particular, have repeatedly been shown to be linked to different psychiatric conditions such as depression, anxiety, antisocial behaviour, and dependence. Many studies have implicated genetic variability in the genes encoding monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) in modulating susceptibility to these conditions. Paradoxically, the risk variants of these genes have been shown, in vitro, to increase levels of serotonin, although many of the conditions are associated with decreased levels of serotonin. Furthermore, in adult humans, and monkeys with orthologous genetic polymorphisms, there is no observable correlation between these functional genetic variants and the amount or activity of the corresponding proteins in the brain. These seemingly contradictory data might be explained if the association between serotonin and these behavioural and psychiatric conditions were mainly a consequence of events taking place during foetal and neonatal brain development. In this review we explore, based on recent research, the hypothesis that the dual role of serotonin as a neurotransmitter and a neurotrophic factor has a significant impact on behaviour and risk for neuropsychiatric disorders through altered development of limbic neurocircuitry involved in emotional processing, and development of the serotonergic neurons, during early brain development.

Variants of the Monoamine Oxidase A gene (MAOA) predict free-riding behavior in women in a strategic public goods experiment.

“…Fergusson and colleagues demonstrate that the combination of a range of adverse environmental and personal factors together with the MAOA-L variant, but not genotype alone, triggers antisocial behavior (Fergusson et al, 2012). Brain imaging studies clearly show that functional genetic variants of MAOA a) have an effect on the brain development; b) are modulators of environmental factors in terms of gene-environment interactions, which often display sex differences; and c) result in developmental alterations to specific neuronal circuits, causing different responses to external stimuli (Nordquist & Oreland, 2010). However, the fact that one single variant in a given gene is (moderately) associated with variability in a given trait should not be over-interpreted.…”

Acute responsivity of the serotonergic system to S-citalopram and positive emotionality – The moderating role of the 5-HTTLPR

“…Nordquist and Oreland (2010) as well as Whitaker-Azmitia (2005) have summarized findings regarding the neurotrophic effects of serotonin. They argue that an excess of serotonin during early neuronal development-which might be caused by the short variant of the 5-HTTLPR-could lead to morphological and functional changes, including circuits involved in emotional processing as well as in serotonergic neurons themselves, thereby likely leading to behavioral and emotional alterations in later life.…”

Candidate Genes and Political Behavior

“…Studies that have attempted to demonstrate the effects of MAOA-uVNTR genotypes on in vivo (as opposed to in vitro) brain levels of MAO-A have had mixed, largely negative results (Alia- Klein et al 2008;Cirulli and Goldstein 2007;Fowler et al 2007;Nordquist and Oreland 2010). According to a recent review (Nordquist and Oreland 2010, 2), "in adult humans, and monkeys with orthologous genetic polymorphisms [polymorphisms having the same function in two different species], there is no observable correlation between these functional genetic variants [of MAOA] and the amount or activity of the corresponding proteins in the brain.…”