Platelet Serotonergic Markers as Endophenotypes for Obsessive-Compulsive Disorder

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 receptorbinding characteristics, and platelet inositol trisphosphate (IP 3 ) content in a sample of OCD probands (n ¼ 48) and their unaffected parents (n ¼ 65), and compared them with sex-and age-matched controls (n ¼ 113). Lower whole blood 5-HT concentration, fewer platelet 5-HTT-binding sites, and higher platelet IP 3 content were found in OCD probands and their unaffected parents compared to controls. Whole blood 5-HT concentration showed a strong correlation within families (po0.001). 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.

Intrafamilial Correspondences on Platelet [3H-]Paroxetine-Binding Indices in Bulimic Probands and their Unaffected First-Degree Relatives

“…Such a 'trait', insofar as it is associated with risk of developing bulimic symptoms, but occurs 'invisibly' (ie in the absense of active clinical symptoms) in bulimics' unaffected relatives, meets criteria for what is often called an 'endophenotype'Fan intrinsic trait that may convey susceptibility to a particular phenotypic expression (Gottesman, 2003). Paroxetine-binding results we obtain in bulimic women and their relatives are, furthermore, highly compatible with those obtained by other investigators in relatives of individuals suffering disorders as diverse as obsessive-compulsive disorder (Delorme et al, 2005) or manic-depressive illness (Leboyer et al, 1999). An obvious implication is that, if we are observing an 'endophenotype', it is not one that defines specific vulnerability to a bulimic syndrome, but rather a generalized risk (perhaps of syndromes characterized by breakdown of behavioral, affective, and/or appetitive controls).…”

“…No study has as yet examined whether or not familial tendencies (compatible with a hereditary 'trait') exist on 5-HT indices among relatives of eating-disorder sufferers. However, suggesting that this may be true of other psychopathological syndromes, unaffected relatives of obsessive-compulsive disorder (Delorme et al, 2005) and manic-depressive (Leboyer et al, 1999) patients are reported to have reduced platelet 5-HT reuptake. The present study explored the possibility that mothers and sisters of bulimic probands (even when free of eating or psychiatric symptoms) might evince reduced platelet 5-HT reuptake activity, compared to relatives of normal-eater controls.…”

Genetic Polymorphism of the Serotonin Transporter Gene, SLC6A4 rs16965628, Is Associated with Obsessive Compulsive Disorder

“…Lower serotonin content was found on the platelets of patients with OCD relative to normal controls (Delorme et al, , 2005. The SLC6A4 gene taking place on chromosome 17q11.1-17q12 can modulate mood, sleep, and cognitive functions.…”

Endophenotypes of obsessive–compulsive disorder: Current status and future directions

“…In the following sections the evidence for CEPs from both theoretical perspectives is reviewed. Delorme et al (2005) investigated platelet serotonergic markers as proxy measures of central serotonergic functioning. OCD probands and their unaffected parents, compared to healthy controls, had lower whole blood 5-HT concentration, fewer platelet 5-HTT-binding sites, and higher platelet inositol trisphosphate content.…”