Well-studied components of this system are the serotonin (5-HT) apply for it receptors 2A (5-HT2A), 1B (5-HT1B), and 2C (5-HT2C), and the key regulators of 5-HT metabolism: tryptophan hydroxylase 1 and 2 (TPH1 and TPH2) and monoamine oxidase A (MAO-A) (Figure 1). The receptors 5-HT2A, 5-HT2C, and 5-HT1B are members of a family of receptors linked to guanine-nucleotide-binding proteins (G-protein-coupled receptor; GPCR) expressed on the cell body and dendrites of serotoninergic neurons in the brain [3]. The receptors 5-HT2A and 5-HT2C are the main excitatory receptor subtypes among the GPCRs for 5-HT, whereas the 5-HT1B receptor is thought to act as a nerve terminal autoreceptor, inhibiting the release of 5-HT.

After acting at its receptor, 5-HT is metabolized by MAO-A (Figure 1), and therefore MAO activity may play a critical role in the regulation of the serotoninergic system and in the pathogenesis of depressive disorders [4].Figure 1Contribution of tryptophan hydroxylase and MAO in serotonin metabolism. Tryptophan hydroxylase catalyzes the monooxygenation of tryptophan to 5-hydroxytryptophan, which is subsequently decarboxylated to form serotonin (5-hydroxytryptamine; 5-HT). Monoamine …The gene encoding 5-HT2A (HTR2A) is considered to be a candidate gene for depression. Genetic association has been reported between the c.102C>T polymorphism in the HTR2A gene and depression, as well as suicidal behavior in patients with mood disorders and schizophrenia [5�C7], although several studies have failed to replicate these findings [8].

It is likely that other serotoninergic genes are involved in gene-environment interactions related to depression. Among them, the gene encoding the 5-HT1B receptor (HTR1B) has been correlated to attempted suicide in patients with major depression, because altered postmortem 5-HT1B receptor binding was found to be associated with suicide in some of the studies [9]. A common c.861G>C polymorphism of the HTR1B gene was identified in the coding region of the gene, and major depression appears to be associated with this locus [10]. A strong association between suicide and receptor genes of the serotoninergic system has presented evidence for yet another 5-HT receptor gene located on human chromosome Xq24, the 5-HT2C receptor gene (HTR2C) [11]. This receptor Carfilzomib mediates the release of dopamine (DA) in the brain and can cause anxiety, depression, and compulsive behaviors in human subjects due to the mechanism of rapid downregulation by serotonin. The structural variant c.