This investigation of fluvoxamine and fluoxetinenorfluoxetine distributions in vivo; n ϭ 13) and brain-to-plasma concentration ratios (10 Ϯ 2; n ϭ 12) were similar to those of combined fluoxetine-norfluoxetine (CFnorfluoxetine) (13 Ϯ 6 M; n ϭ 4 and 10 Ϯ 6; n ϭ 4). Fluvoxamine brain elimination half-life (79 Ϯ 24 hours; n ϭ 4) was significantly shorter than that of CF-norfluoxetine (382 Ϯ 48 hours; n ϭ 2). Fluvoxamine brain-to-plasmahalf-life-ratio was

Disturbances in dopamine neurotransmission have been postulated to underlie schizophrenia. We report data from two independent studies of a Ball polymorphism in the dopamine D3 receptor gene in patients with schizophrenia. In both studies, more patients than controls were homozygous (p= 0005, p = 0008). When pooled data were analysed, this difference was highly significant (p = 00001) with a relative risk of schizophrenia in homozygotes of 2-61 (95% confidence intervals 1P60-426 in the first exon that gives rise to a glycine to serine substitution in the N-terminal extracellular domain. This results in the creation of a BalI restriction enzyme site.8 The failure of ourselves and others to show genetic linkage between schizophrenia and this polymorphism in multiply affected families (unpublished data) makes it unlikely that a mutation in D3 is a major factor predisposing to illness in the majority of such families. However, we have also tested the hypothesis that variation at this locus might be associated with more subtle differences in liability to develop schizophrenia by comparing allele and genotype frequencies in patients and controls. We present data from two independent studies carried out in the UK and France. Materials and methodsIn the UK study, 68 unrelated patients with schizophrenia (25 female and 43 male) were recruited. All patients satisfied the DSMIII-R criteria for schizophrenia. Sixty-eight controls (29 female and 39 male) were recruited from among the married in members of families seeking DNA diagnosis in the

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