A pharmacogenetic study of escitalopram in autism spectrum disorders.
OBJECTIVE
To determine the effect of serotonin transporter polymorphism promoter region (5-HTTPLR) genotypic variation (low, intermediate, and high expression groups) on response to escitalopram treatment of children and adolescents with autism spectrum disorders (ASDs).


METHODS
The study used a forced titration, open label design, with genotype blind until study completion. Participants were children and adolescents aged 4-17 years of age with a confirmed ASD (autistic disorder, Asperger's disorder, or pervasive developmental disorder, not otherwise specified).


RESULTS
There was an interaction between genotype group and time on the Aberrant Behavior Checklist (ABC) Irritability Subscale (primary outcome variable) (linear maximum marginal likelihood estimation=-4.84, Z=-2.89, SE=1.67, P=0.004). Examination of baseline to last visit revealed that a genotype grouping based on a previous study of platelet 5-HT uptake revealed less response in the genotype group that had S/S genotype for 5-HTTLPR and did not have a diplotype in intron 1 previously shown to be associated with increased platelet 5-HT uptake.


CONCLUSIONS
This genotype-blind, prospective pharmacogenetic study found the group of subjects with associated with the lowest platelet 5-HT uptake from previous study had the smallest reduction in ABC-Irritability scores after open label treatment with escitalopram. Replication is necessary to confirm these findings.
Owley
Thomas
T
Department of Psychiatry, Institute for Juvenile Research, University of Illinois at Chicago, 1747 West Roosevelt Road, Chicago, IL 60608, USA.
Brune
Camille W
CW
Salt
Jeff
J
Walton
Laura
L
Guter
Steve
S
Ayuyao
Nelson
N
Gibbons
Robert D
RD
Leventhal
Bennett L
BL
Cook
Edwin H
EH
D000293:Adolescent; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001792:Blood Platelets / Q000378:metabolism; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D002675:Child, Preschool; D015283:Citalopram / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D007508:Irritable Mood / Q000187:drug effects; D008297:Male; D010552:Personality Assessment; D010597:Pharmacogenetics; D012701:Serotonin / Q000097:blood; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human