Noradrenergic dysfunction due to abnormalities in the tyrosine hydroxylase (TH) gene has been implicated in the pathogenesis of suicidal behavior in mood disorders.
The study could not support the involvement of tyrosine hydroxylase, catechol-O-methyl transferase and Wolfram syndrome 1 polymorphisms in mood disorders.
The D2 and D3 dopamine receptors were, therefore, not a major liability factor for mood disorders in our sample, whereas TH may play a role in a subgroup of patients.
To find variants in the tyrosine hydroxylase (TH) gene that are associated with schizophrenia, mood disorders, or alcohol dependence, all of the exons, the exon-intron boundaries, and the 5' promoter region of the TH gene were systematically screened for variants by single-strand conformation polymorphism analysis followed by direct nucleotide sequencing.
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.
No significant differences in allele and genotype frequencies were observed between the two groups, providing further evidence against a major role for the tyrosine hydroxylase gene in the etiology of major affective disorders.
These results provide some support for linking affective disorder to this genetic region and suggest that additional linkage and association studies should be conducted to determine whether tyrosine hydroxylase or a nearby locus contributes to susceptibility to bipolar affective disorder in some families.
We present the results of a linkage analysis using polymorphic DNA segments within the TH gene and the nearby dopamine D4 receptor (DRD4) gene in 6 families multiply affected with affective disorder.
Therefore, we tested 88 patients with affective disorders and 99 healthy control persons for association of restriction fragment length polymorphism (RFLP) alleles at the tyrosine hydroxylase locus.