A polymorphism in the dopamine beta-hydroxylase gene is associated with "paranoid ideation" in patients with major depression.

BACKGROUND Increased dopaminergic activity may play a primary role in psychotic depression. Dopamine beta-hydroxylase (DbetaH) catalyses the key step in biosynthesis of the neurotransmitter noradrenaline from dopamine, and low DbetaH activity is a possible risk factor for developing psychotic depression. An exon 2 polymorphism (DBH*444 g/a) of the DbetaH gene (DBH) is significantly associated with both serum and cerebrospinal fluid levels of DbetaH. METHODS We determined the genotype of the DBH*444g/a polymorphism in a cohort of 164 patients with major depression and examined the association of this polymorphism with paranoid ideation, interpersonal sensitivity, and psychoticism on the Hopkins Symptom Checklist. RESULTS Patients who possessed the A allele were significantly more likely to have higher scores for interpersonal sensitivity and paranoia than patients without the A allele (p =.004 and p =.048, respectively), suggesting that this allele may predispose patients to paranoia in major depression. In addition, we found an association between prolactin levels in men and DBH*444 g/a genotype such that homozygous G individuals displayed significantly higher levels than homozygous A or heterozygote individuals. CONCLUSIONS Depressed patients with the GG genotype of DbetaH have lower scores for interpersonal sensitivity and paranoid ideation. The GG genotype may be protective against the development of psychosis in the presence of a major depressive episode.