Dopa decarboxylase genotypes may influence age at onset of schizophrenia

Several lines of evidence implicate dopa decarboxylase (DDC) with schizophr enia. By analysis of two putative functional DDC variants in 173 schizophre nic patients, and 204 controls we tested the hypotheses that DDC is involve d in: (1) predisposition, to schizophrenia; and (2) modulation of age at di sease onset.. No association was observed with schizophrenia as a whole, wh ereas an association between DDC genotypes and age at dis ease onset was su ggested in males (P = 0.03). This association was most pronounced in relati on to genotypes of haplotypes comprising. both variants, suggesting an addi tive model where one variant mediates, early and the other late onset. Acco rdingly, the haplotype- based genotypes could be assigned into three groups by their possible relative effect on age at onset: an 'early', 'neutral' a nd 'late' group. Dividing, the male schizophrenics into four groups with in creasing age at onset, the 'early' genotypes were seen to decrease, in freq uency from 51.5% to: 16.7% while the late genotypes increased from 12.1%, t o 33.3% (P = 0.02). The difference in mean age. at. onset between male pati ents with 'early' genotypes vs patients with, 'late' genotypes was, close t o 5 years (95% Cl: 0.7-8.8). Thus, DDC may possibly act as a modulator of a ge at onset in male schizophrenics.