Role of tryptophan hydroxylase in the etiology of depression
Tryptophan hydroxylase has two isoforms , which are encoded by the TPH1 and TPH2 genes. This enzyme is involved in the synthesis of melatonin and serotonin. Tryptophan hydroxylase accelerates the attachment of the OH group to 5-hydroxytryptophan. Isoform 1 encoded by TPH1 is associated with the development of drug addiction and schizophrenia. Gene expression is noted in the nervous system and peripheral organs. Isoform 2 of tryptophan hydroxylase affects the synthesis of serotonin (5-HT) in the brain. The TPH2 gene is located on chromosome 12q. It has been associated with the development of major depression. In 2005 P. Zill with co-authors discovered a functional polymorphism Arg441His, which led to a decrease in serotonin secretion by 80%. Several variants of the gene have been associated with suicidal behavior. The lack of serotonin synthesis was due to genetic variations in the TPH2 gene. They led to the development of unipolar depression.
A meta-analysis of 183 articles devoted to genetic polymorphisms of 102 genes showed that variations in the genes APOE ( apolipoprotein ), MTHFR (methylene tetrahydrofolate reductase ), GNB3 (guanine nucleotide binding protein beta-3), SLC6A4 (serotonin transporter) increase the risk of disease unipolar depression.
The presence of genetic markers of depression suggests a change in the concept of diagnosis and treatment of this disease.