What are the genetic implications of serotonin utilization and production in the etiology of major depressive disorder (clinical depression)?

Updated: Aug 06, 2020
  • Author: Jerry L Halverson, MD; Chief Editor: David Bienenfeld, MD  more...
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Other studies also suggest that genes controlling either the production or utilization of serotonin play an important role in the pathogenesis of depression. The TPH2 gene encodes tryptophan hydroxylase, which is the rate-limiting enzyme in the synthesis of serotonin. An in vitro study of a TPH2 polymorphism, R441H, found an approximately 80% loss in serotonin production.

The clinical significance of this polymorphism remains uncertain, however. Zhang et al found that the allele was more common in a cohort of patients with major depression than in a control population, [20] but a later study by Garriock et al did not find any patients with the R441H mutation in a cohort with major depression, a control group, or a group with bipolar disorder. [21]

The HTR3A and HTR3B regions, which encode serotonin receptors and are located at chromosome 11q23.2, are also known to be associated with major depression in both European and Japanese populations. Yamada et al surveyed 29 polymorphisms located within the HTR3A and HTR3B genes and found a single-nucleotide polymorphism that was associated with depression in females. [22]

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