Serotonin transporter gene polymorphisms and affective disorder-related phenotypes

Serotonin (5-hydroxytryptamine) is implicated in several psychiatric disorders such as anxiety, mood disorders, obsessive compulsive disorders and autism. The serotonin transporter, which ends the activity of serotonin in the brain after its release from serotonergic neurons, is a key protein in the serotonergic pathway as it regulates the concentration of serotonin in the synaptic cleft. Tricyclic antidepressants and serotonin reuptake inhibitors bind to sites that overlap with the serotonin binding site, thus reducing 5-hydroxytryptamine reuptake. Genetic factors have long been implicated in the etiology of bipolar disorder and unipolar depression, therefore the serotonin transporter gene is a strong candidate gene for affective disorders and in mood disorder-related phenotypes. Two polymorphisms of the transporter gene have been extensively studied in association with affective disorders (unipolar, bipolar, depressive symptoms, seasonal affective disorder) and more recently in response to antidepressants. Associations have also been reported between the serotonin transporter gene polymorphisms and transnosographical entities such as anxiety-related traits and suicidal behaviors. Both approaches obtained conflicting results. This review attempts to clarify the phenotypic uncertainties and the conflicting association results obtained with the serotonin transporter gene polymorphisms in psychiatry.