Association of TPH1 and TPH2 Gene Polymorphisms with the Risk of Developing Psychoneurological Disorders

• Published in: Neuroscience and behavioral physiology Vol. 52; no. 3; pp. 462 - 469
• Main Authors: Moskaleva, P. V., Shnayder, N. A., Dmitrenko, D. V., Shilkina, O. S., Neznanov, N. G., Nasyrova, R. F.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2022; Springer Nature B.V
• Subjects: Attention deficit hyperactivity disorder; Behavioral Sciences; Biomedical and Life Sciences; Biomedicine; Epilepsy; Gene polymorphism; Melatonin; Mental disorders; Metabolism; Neurobiology; Neurosciences; Neurotransmitters; Obsessive compulsive disorder; Precision medicine; Schizophrenia; Serotonin; Single-nucleotide polymorphism; Tryptophan; Tryptophan hydroxylase; synthesis; epilepsy; attention deficit hyperactivity disorder; gene; schizophrenia; obsessive compulsive disorder; central nervous system; anxiety; serotonin; tryptophan hydroxylase; depression; melatonin; single-nucleotide polymorphism; tryptophan; bipolar affective disorder
• ISSN: 0097-0549; 1573-899X
• DOI: 10.1007/s11055-022-01260-0

The question of the involvement of impairments to the metabolism of melatonin and its precursors (tryptophan and serotonin) in the development of psychoneurological disorders has recently been under active discussion. The melatoninergic and serotoninergic systems play an important role in the pathogenesis of these disorders, the genetic predisposition to impairments at different stages in the metabolism of these neurotransmitters (from synthesis to release) having particular importance. The present review addresses the first stage in melatonin metabolism – its synthesis, i.e., the first of a cascade of reactions which is key and limiting in the formation of its precursor serotonin. Two types of tryptophan hydroxylase, the enzyme catalyzing this process, have been identified in humans. These enzymes are encoded by the genes TPH1 and TPH2 , respectively. Results from associative molecular-genetic studies in recent years have demonstrated a link between carriership of a series of single-nucleotide polymorphisms (SNP) in the TPH1 and TPH2 genes with the risk of developing schizophrenia, bipolar affective disorder, anxious-depressive disorders, obsessive compulsive disorders, attention deficit hyperactivity disorder, and epilepsy. However, results obtained from some studies are contradictory, which can be explained by differences in study design, small cohorts in most studies, and different social-geographic characteristics (race, ethnicity, nationality). Consideration of genetically determined impairments in the first stage of melatonin synthesis in real clinical practice may help find novel approaches to pathogenetic and disease-modifying therapies, which is consistent with the current state of personalized medicine.