Excess tyrosine hydroxylase restriction fragment length polymorphism homozygosity in unipolar but not bipolar patients: A preliminary report

Searching for genetic risk factors of major affective disorders, segregation and association methodologies are being applied to these complex diseases which will hopefully lead to a better understanding of their genetic etiology. Tyrosine hydroxylase (TH), the rate-limiting enzyme in the metabolism of catecholamines, has been considered a candidate gene in bipolar affective disorder (BPAD) and unipolar affective disorder (UPAD). Indeed, a dysfunction of the catecholaminergic system is likely to be implicated in the pathogenesis of affective disorders (Schatzberg and Schildkraut 1995 for review). The TH gene is located on the short arm of chromosome 11 (1 lp15) and has been the subject of numerous linkage and association studies in BPAD. Linkage with TH was tested in different set of BPAD families. Most reports significantly excluded linkage between the TH gene and BPAD (Pauls et al 1991; Mendlewicz et al 1991; Mitchell et al 1991; Coon et al 1993; De bruyn et al 1994; Detera-Wadleigh et al 1994; Ewald et al 1994), however, in some families linkage