Platelet serotonergic markers as endophenotypes for obsessive-compulsive disorder

被引:25
作者
Delorme, R
Betancur, C
Callebert, J
Chabane, N
Laplanche, JL
Mouren-Simeoni, MC
Launay, JM
Leboyer, M
机构
[1] Fac Med, INSERM, U513, F-94010 Creteil, France
[2] Hop Robert Debre, Assistance Publ Hop Paris, Serv Psychopathol Enfant & Adolescent, F-75019 Paris, France
[3] Hop Lariboisiere, Serv Biochim, F-75475 Paris, France
[4] Hop Henri Mondor & Albert Chenevier, Assistance Publ Hop Paris, Psychiat Serv, Creteil, France
关键词
serotonin; serotonin transporter; 5-HT2A receptor; binding; inositol triphosphate; intrafamilial correlation;
D O I
10.1038/sj.npp.1300752
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:1539 / 1547
页数:9
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