1. ¹INSERM U 513, Faculté de Médecine, Créteil, France
2. ²Service de Psychopathologie de l'Enfant et de l'Adolescent, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris, France
3. ³Service de Biochimie, Hôpital Lariboisière, Paris, France
4. ⁴Service de Psychiatrie, Hôpital Henri Mondor et Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Créteil, France

Correspondence: Dr R Delorme, INSERM U513, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil cedex, France. Tel: +33 1 49 81 35 14; Fax: +33 1 49 81 36 85; E-mail: delorme@im3.inserm.fr

Received 30 July 2004; Revised 17 February 2005; Accepted 3 March 2005; Published online 11 May 2005.

Abstract

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-HT_2A 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-HT_2A 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.