Tryptophan hydroxylase gene 218A/C polymorphism is associated with somaticanxiety in major depressive disorder

Background: Abnormalities in functioning of the central serotonergic system have been implicated in the pathogenesis of depressive illness and suicida l behavior. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin, therefore, it may play an important role in reg ulation or control of serotonin functions. The aim of the present investiga tion was to determine whether there is an association between TPH gene poly morphism and major depression, particularly in patients with suicidal ideat ion. Methods. A total of 135 unrelated patients suffering from major depres sive disorder and 196 normal unrelated controls were included in the study. All controls and patients were Caucasian. A biallelic polymorphism at the tryptophan hydroxylase locus was genotyped. Results: No significant differe nce between controls and depressed subjects in TPH gene polymorphism was de tected. There was no association between TPH gene polymorphism and suicidal ideation. Total HAMD scores were not different between the genotypes or al leles in patients. However, among the HAMD clusters, somatic anxiety was si gnificantly associated with TPH genotypes and alleles in that patients with 218A/A genotype had a significantly higher somatic anxiety scores compared to other genotypes. Limitation: Potential confounding effect of population stratification can not be excluded. The functional relevance of the TPH ge ne 218A/C polymorphism is. at present, uncertain. Conclusion: The polymorph ism in serotonergic system related genes may be associated with depressive symptoms in major depressive disorder. The results suggest that analysis of clusters that narrow down the phenotype may be more suitable in genetic st udies of major depressive illness. (C) 2001 Elsevier Science B.V. All right s reserved.