Serotonin System of the Brain in the Mechanism of Seasonal Affective Disorder

Seasonal affective disorder (SAD) is a complex of depressive-like disorders observed in the autumn/ winter period. SAD is a significant economic, social and medical problem. There are numerous but contradictory clinical data on the involvement of the serotonin (5-HT) system of the brain in the mechanism of SAD and on the association of mutations in the genes encoding enzymes of metabolism, transporter and receptors of 5-HT with the risk of this pathology. The review examines in detail both clinical observations and all available experimental data on the effect of short daylight exposure on the 5-HT system of the brain and 5-HT-dependent behavior in two laboratory objects, mice and zebrafish (Danio rerio). The following general patterns were revealed in the two species: (1) a decrease in motor activity and an increase in anxiety under mild stress and (2) an increase in the level of the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the brain of mice and fish kept for a long time under short-day conditions. In mice, keeping under short-day conditions sharply increases the severity of depressive-like behavior in the forced swimming test. At the same time, in these two species, no association between the reduced activity of the key enzyme of 5-HT synthesis, tryptophan hydroxylase, and the severity of behavioral disorders caused by short-day exposure was observed. Despite the fact that the 5-HT system of the brain is undoubtedly involved in the mechanism of SAD, it apparently is not a key one in the mechanism of the severity of this pathology.