Tryptophan hydroxylase gene polymorphism in bipolar disorder: A pilot study

Bipolar disorder (BD), mostly beginning in the late adolescence and early adulthood and with recurrent episodes during chronic illness course, genetic susceptibility is thought to play a major role in the etiology. During the episodes, the main functions of the central nervous system as cognition, thinking, perception, affect, judgment, adjustment, and behavior coordination may be derailed. BD may manifest in various clinical forms. It is seen in similar frequencies in both gender and lifetime prevalence is between %0.5-1.5. For a long time, many illnesses including depression, mood disorders, migraine, obsessive-compulsive disorder, obesity are thought to be caused by psychological stress. However, the results of the recent studies increasingly detected the role of the neurotransmitters, mainly serotonin (5-hydroxytryptamine, 5- HT). Although a relatively simple chemical structure, serotonin plays a complex role in biologic systems. Balance problems in serotonin levels may lead to many illnesses. Advances within the molecular genetics acquired important data came out about the genetic etiology of BD and gave promises for researchers. Many chromosomal disorders, gene loci and anomalies associated with BD are reported. But, most of the studies lacking replication of the results. Tryptophan hydroxylase (TPH), is the main enzyme catalyzing the first step in the formation and amount of serotonin. For this reason, brain and CSF activity and level of serotonin directly influenced by the polymorphisms in the TPH gene. Asserting the association of TPH gene polymorphism with some psychiatric disorders, considering the studies about serotonin's effect on TPH gene brain and the neurotransmitter monoamines and studies concerning the level of CSF serotonin in BD patients, for the first time in Turkish population we aimed to investigate distribution of TPH gene A/C polymorphism; A and C alleles; AA, AC ve CC genotypes in BD patients and healthy control subjects. For this purpose, in our study, we have investigated the distribution of TPH A218C polymorphism in 116 BD and 150 healthy control subjects. In female patients, AA genotype is found to be higher than the female controls. Among subjects and controls, there was not any difference neither for genotype nor for allelic distribution. Also, no difference was detected allele and genotype distribution for gender among patient groups. As a result, the TPH gene A218C polymorphism distribution is found different among female patients and female controls. Depending on this finding, we report one of the possible reasons for different course and clinical presentation of the disease in male and female Bipolar patients. In conclusion, the association of BD and TPH gene A218C polymorphism, in different views, need to be detected in the new research. In advancing years studies with independent sample groups containing more patients are needed. Focusing on phenotypic subtypes of the disorder will give the possibility of studying in genetically homogenous groups and the genes in a complex disorder will be strongly detected. Possible important subtypes include BD with and without suicidal behavior, BD with an early/late beginning, rapid cycling, responding/nonresponding to lithium. Moreover, clinical presentation and signs, data concerning course (number of episodes and type etc.) of the disorder and researchs including the relation of the gene may give rise to new horizons.