Tyrosine hydroxylase gene associated with
depressive symptomatology in mood disorder

by
Serretti A, Macciardi F, Verga M, Cusin C, Pedrini S, Smeraldi E
Istituto Scientifico H. San Raffaele,
Department of Neuroscience,
University of Milano School of Medicine, Milan, Italy.
Connecticut Mental Health Center, Department of Psychiatry,
Yale University School of Medicine, New Haven 06519, USA.
robert.berman@yale.edu
Am J Med Genet 1998 Mar 28; 81(2):127-30


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.

NADH
Tyrosine
Rolipram
Dopamine
Noradrenaline
Biogenic amines
New antidepresants
Noradrenaline depletion
Noradrenaline and mood
Catecholamine depletion
New ways to treat depression
The catecholamine hypothesis of depression


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