Platelet serotonergic markers as endophenotypes for obsessive-compulsive disorder.
Although compelling evidence has shown that obsessive-compulsive disorder (OCD) has a strong genetic component, its genetic basis remains to be elucidated. Identifying biological abnormalities in nonaffected relatives is one of the strategies advocated to isolate genetic vulnerability factors in complex disorders. Since peripheral serotonergic disturbances are frequently observed in OCD patients, the aim of this study was to investigate if they could represent endophenotypes, by searching for similar abnormalities in the unaffected parents of OCD patients. We assessed whole blood serotonin (5-HT) concentration, platelet 5-HT transporter (5-HTT) and 5-HT2A receptor-binding characteristics, and platelet inositol trisphosphate (IP3) content in a sample of OCD probands (n = 48) and their unaffected parents (n = 65), and compared them with sex- and age-matched controls (n = 113). Lower whole blood 5-HT concentration, fewer platelet 5-HTT-binding sites, and higher platelet IP3 content were found in OCD probands and their unaffected parents compared to controls. Whole blood 5-HT concentration showed a strong correlation within families (p < 0.001). The only parameter that appeared to discriminate affected and unaffected subjects was 5-HT2A receptor-binding characteristics, with increased receptor number and affinity in parents and no change in OCD probands. The presence of peripheral serotonergic abnormalities in OCD patients and their unaffected parents supports a familial origin of these disturbances. These alterations may serve as endophenotypic markers in OCD, and could contribute to the study of the biological mechanisms and genetic underpinnings of the disorder.
Delorme
Richard
R
INSERM U 513, Faculté de Médecine, Créteil, France. delorme@im3.inserm.fr
Betancur
Catalina
C
Callebert
Jacques
J
Chabane
Nadia
N
Laplanche
Jean-Louis
JL
Mouren-Simeoni
Marie-Christine
MC
Launay
Jean-Marie
JM
Leboyer
Marion
M
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000493:pharmacokinetics; D000328:Adult; D015415:Biomarkers; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D007099:Imipramine / Q000493:pharmacokinetics; D015544:Inositol 1,4,5-Trisphosphate / Q000097:blood; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D008238:Lysergic Acid Diethylamide / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D009771:Obsessive-Compulsive Disorder / Q000097:blood* / Q000235:genetics; D017374:Paroxetine / Q000493:pharmacokinetics; D011863:Radioimmunoassay / Q000379:methods; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D012701:Serotonin / Q000097:blood*; D018490:Serotonin Agents / Q000493:pharmacokinetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D014316:Tritium / Q000493:pharmacokinetics
D018759:Adrenergic Uptake Inhibitors; D015415:Biomarkers; D007099:Imipramine; D015544:Inositol 1,4,5-Trisphosphate; D007456:Iodine Isotopes; D008238:Lysergic Acid Diethylamide; D017374:Paroxetine; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors; D014316:Tritium