Platelet serotonin studies in hyperserotonemic relatives of children with autistic disorder.
Platelet serotonin (5-HT) studies were conducted with 12 hyperserotonemic and 12 normoserotonemic age-, sex-, and relationship-matched relatives of autistic probands. Each group consisted of 7 mothers, 4 fathers, and 1 sister of autistic children and adolescents. The density (Bmax) of platelet 5-HT2 receptor binding sites, labelled with [3H]-lysergic acid diethylamide (LSD), was significantly lower in 11 hyperserotonemic subjects compared to 12 normoserotonemic subjects (40.9 +/- 13.5 fmol/mg protein, 59.6 +/- 13.2; p < 0.004). The affinity (Kd) for [3H]-LSD binding did not differ. Although the density (Bmax) of [3H]-paroxetine binding did not differ between groups, there was a small difference in the affinity (Kd) for [3H]-paroxetine binding (hyperserotonemic 47.6 +/- 9.0 pM, normoserotonemic 54.8 +/- 12.1; p < 0.05). There were no significant differences in platelet 5-HT uptake, or in thrombin-stimulated 5-HT release. Basal, 5-HT-stimulated, and arginine-vasopressin (AVP)-stimulated inositol phosphate production, as well as basal, prostaglandin E1 (PGE1)-, and forskolin-stimulated cAMP production did not differ. There were significant correlations between whole blood 5-HT levels and LSD Bmax (rs = -0.63, N = 23, p < 0.002) and whole blood 5-HT levels and 5-HT uptake Vmax (rs = 0.56, N = 18, p < 0.02). However, [3H]-LSD labelled 5-HT2 binding and 5-HT uptake were not correlated with each other. Hyperserotonemia of autism may be heterogeneous with one subgroup of subjects with increased 5-HT uptake and another subgroup with decreased 5-HT2 binding.
Cook
E H
EH
Department of Psychiatry, University of Chicago, IL 60637.
Arora
R C
RC
Anderson
G M
GM
Berry-Kravis
E M
EM
Yan
S Y
SY
Yeoh
H C
HC
Sklena
P J
PJ
Charak
D A
DA
Leventhal
B L
BL
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D001321:Autistic Disorder / Q000097:blood* / Q000235:genetics*; D001692:Biological Transport; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002648:Child; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008237:Lysergic Acid / Q000097:blood; D008297:Male; D017374:Paroxetine / Q000097:blood; D010976:Platelet Count; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000097:blood*
D011985:Receptors, Serotonin; D005576:Colforsin; D012701:Serotonin; D017374:Paroxetine; D000242:Cyclic AMP; D000527:Alprostadil; D008237:Lysergic Acid; D015056:1-Methyl-3-isobutylxanthine