Tyrosine hydroxylase gene associated with depressive symptomatology in mood disorder

Abstract

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of dopamine and norepinephrine. It may be involved in the pathophysiology of psychiatric disorders and positive associations have been reported for TH gene markers in mood disorders. While most replications failed to confirm the initial findings, other papers suggested a potential role of this gene in the etiology of mood disorders. Among the many different reasons for a lack of consistent replications, a critical role is played by the "correct" phenotype identification. Actually, up to now the only classification criteria has been the psychiatric diagnosis, but within the same psychiatric diagnoses the symptomatologic presentation may vary dramatically depending upon severity, presence of psychotic features or other psychopathologic traits. Thus, the aim of our study is to evaluate a possible association for TH gene with symptomatology in a sample of subjects affected by mood disorders. We have developed a phenotype definition based on the observed symptomatology divided into the four factors "Excitement," "Depression," "Delusion," and "Disorganization." Our sample includes 46 mood disorder subjects, investigated by the OPCRIT (operational criteria checklist for psychotic illness) checklist for their symptomatological pattern and typed for TH variants by polymerase chain reaction (PCR) amplification. Depressive factor was associated with TH variants (F = 4.79, df = 4, 87, P = 0.006), with TH*2 subjects presenting lower depressive scores. Subjects with genotype TH*2/2 were the only ones in the sample to report mild depressive episodes. TH variants may be related with depressive symptomatology in subjects affected by mood disorders.

Molecular epidemiology of major depressive disorder

“…Among polymorphisms in the TH gene identified so far, a pentaallelic polymorphism consisting of several numbers of tetranucleotide repeats [or microsatellite polymorphism (TCAT) n ] in intron 1 and three SNPs, namely Val81Met, Leu205Pro and Val468Met, may alter the functional activity of TH protein. A tetranucleotide repeat in intron 1 has been reported to play a role in psychiatric illnesses [122][123][124][125].…”

Tyrosine hydroxylase gene in linkage disequilibrium with mood disorders

“…31 Our TH association with depressive symptomatology among affective patients supports the hypothesis that the clinical heterogeneity of psychiatric diagnoses may bias most association studies based on the diagnosis. 20,32 As an example, an affective sample with a low rate of severely ill patients may obscure a true association. Polarity also may represent a stratification bias, in fact there is growing evidence from family studies supporting the differentiation between unipolar and bipolar I disorder.…”

Canine Tyrosine Hydroxylase (TH) Gene and Dopamine .BETA.-Hydroxylase (DBH) Gene: Their Sequences, Genetic Polymorphisms, and Diversities among Five Different Dog Breeds

“…The TH is the rate-limiting enzyme in the synthesis of catecholamines, and is responsible for the conversion of tyrosine to dopa. Polymorphisms on this gene are reported to be related to human personality [29], mood disorders [16,18,35], schizophrenia [22,38] and essential hypertension [36]. The DBH converts dopamine to noradrenalin.…”