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

Background: Abnormalities in functioning of the central serotonergic system have been implicated in the pathogenesis of depressive illness and suicidal behavior. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin, therefore, it may play an important role in regulation or control of serotonin functions. The aim of the present investigation was to determine whether there is an association between TPH gene polymorphism and major depression, particularly in patients with suicidal ideation. Methods. A total of 135 unrelated patients suffering from major depressive 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 difference between controls and depressed subjects in TPH gene polymorphism was detected. There was no association between TPH gene polymorphism and suicidal ideation. Total HAMD scores were not different between the genotypes or alleles in patients. However, among the HAMD clusters, somatic anxiety was significantly 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 gene 218A/C polymorphism is. at present, uncertain. Conclusion: The polymorphism 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 studies of major depressive illness. (C) 2001 Elsevier Science B.V. All rights reserved.