Effects of serotonin transporter promoter genotype on platelet serotonin transporter functionality in depressed children and adolescents.
OBJECTIVE
To investigate possible associations between serotonin transporter (5-HTT) promoter genotypic variants (l/l, l/s, and s/s) and differential regulation of platelet 5-HTT functionality parameters in a group of drug-naive depressed children and adolescents and healthy controls.


METHODS
Children and adolescents with major depression (n = 18) defined by DSM-III-R criteria and normal controls (n = 21) were assessed both for platelet serotonin functionality and for genotypic variants on 5-HTT promoter region. Four parameters were considered: (1) serotonin uptake rate (Vmax); (2) serotonin dissociation constant (K(m)); (3) paroxetine binding and density of site (Bmax); and (4) paroxetine dissociation constant (Kd).


RESULTS
Depressed children had lower Vmax and K(m). Control subjects with l/l genotype had significantly higher Vmax than control subjects with l/s and s/s genotype. Control subjects with l/l genotype also had significantly higher Vmax than their depressed homologs. In contrast, Vmax was not significantly different between depressed and nondepressed subjects who carried the other 2 genotypes. The 5-HTT promoter genotype, diagnoses, or their interaction had no effect on the other serotonin parameters.


CONCLUSIONS
While showing a significant decrease of Vmax and K(m) in a group of drug-naive depressed children and adolescents, these data suggest that l/l genotype has a substantial effect on the decrease of Vmax during a depressive episode.
Nobile
M
M
Child Psychiatry Unit, Istituto Scientifico Eugenio Medea, Bosisio Parini, Italy. mnobile@bp.lnf.it
Begni
B
B
Giorda
R
R
Frigerio
A
A
Marino
C
C
Molteni
M
M
Ferrarese
C
C
Battaglia
M
M
D000293:Adolescent; D001792:Blood Platelets / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D003866:Depressive Disorder / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005809:Genes, Regulator / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D012701:Serotonin / Q000493:pharmacokinetics*
D002352:Carrier Proteins; D012701:Serotonin