a~ot. PS~GnA~Y 121 1991~121-t30 Platclct 5-HT2 Scrotonin Receptor Binding Sites in Autistic Children and Their First-Degree Relatives Bruce D. Perry, Edwin H. Cook, Jr., Bennett L. Leven~fl, Mark S. Wainwright, and Daniel X. Freedman We examined platelet serotonin2 [5-hydroxytryptaminez (5-HTz)] receptor binding sites, whole blood serotonin (5-HT), and plasma norepinephrine (NE) in male autistic children and their first-degree relatives. Saturation studies utilizing 1251-spiroperidol labeled the 5-HTz sites with an affinity of 224.6 +_. 84.4 pmollL (Ke). No group differences, Le., autistic (n = 12), siblings (n = 6), parents (n = 22), control (adult; n = 7: child; n = 10), were seen for either the Kd or the total number of sites (Bm,~: 14.3 +. 10.9 fmollmg protein). No correlations were found in any group between binding parameters (Kd or B,,~) and whole blood 5-HT. For the parental group, inverse correlations were found between NE and B~.~ (standing NE, rs = -0.67, n = 21, p = 0.~1; supine NE, rs = -0.49, n = 22, p = 0.021). In the autistic group, no correlation was seen between plasma NE and B,,~. A correlation between the autistic boys" B~ and their fathers' B,~ was observed (r~ = 0.79, n = 11, p = 0.004). These findings suggest (1) circulating NE may be involved in heterologous regulation of 5-HTz receptors in the platelet and (2) genetic (paternal-filial)factors may play a role in the expression of 5- HT2 binding sites in the platelet These preliminary findings are discussed in relation to heterologous receptor regulation. The relationship: between these findings and either the pathophysiology of autism or hyperserotonemia in autism are unknown. Introduction Increased whole blood serotonin [5-hydroxytroptamine (5-HT)] (Schain and Friedman 1961) has been the most widely replicated neurobiological finding in autism (for review, see Yuwiler and Freedman 1987: Anderson et al 1987b). More recent studies have examined serotonin receptors and measures of serotonin receptor functioning in autism (Todd and Ciaranello 1985; McBride et al 1989). In a preliminary report, McBride et al (1989) observed a decreased number of platelet 5-HT2 receptor sites and altered serotonin- induced platelet aggregation in autistic adult males. In the present study we examined platelet 5-HT2 receptor binding sites in 12 autistic children and their first-degree relatives. The object of the present study was to clarify and extend previous reports of platelet 5- From the Section of Child and Adolescent Psychiatry, Depmm~nts of Psychiatry and Pediatrics, The University of Chicago, Chicago, IL 60637 (BDP, EHC, BLL, MSW). and the Neumpsychiatric Institute, University of California, Los Angeles, CA(DXF). Address reprint requests to Bruce D. Perry, M.D., Ph.D., Laboratory of Developmental N ~ , ~ t of Psychiau'y Box 411, The University of Chicago, Chicago, IL 60637. Received August 12, 1989; revised November 20, 1990. @ 1991 Society of Biological Psychiatry 0006-3223/91/$03.50