Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.
There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.
MRC Unit on Anxiety and Stress Disorders, University of Stellenbosch, Medical School, PO Box 19063, Tygerberg 7505, South Africa. smjh@sun.ac.za
Sîan M J
SM
Hemmings
Craig J
CJ
Kinnear
Christine
C
Lochner
Dana J H
DJ
Niehaus
James A
JA
Knowles
Johanna C
JC
Moolman-Smook
Valerie A
VA
Corfield
Dan J
DJ
Stein
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D015331:Cohort Studies; D015897:Comorbidity; D005787:Gene Frequency / Q000235:genetics; D040741:Genetic Load; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D011985:Receptors, Serotonin / Q000235:genetics*; D013019:South Africa; D020323:Tics / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005879:Tourette Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D014256:Trichotillomania / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics
C493599:DRD4 protein, human; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D050638:Receptors, Dopamine D4