Tyrosine hydroxylase gene not linked to manic-depression in seven of eight pedigrees

We ascertained 8 multigenerational pedigrees afflicted with multiple cases of bipolar and recurrent major depressive disorder. Alterations in dopaminergic and noradrenergic neurotransmission have been implicated in the pathogenesis of this disease, and tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of these two catecholamines. As TH mutations could underlie susceptibility to manic-depression, we carried out a linkage analysis between this disease in 8 families and two RFLP probes that map to the TH gene region on the short arm of chromosome 11. Evidence of linkage was not found in 7 of 8 kindreds.