Pharmacogenetic Study of Serotonin Transporter and 5HT2A Genotypes in Autism.
OBJECTIVE
The purpose of this study was to determine whether polymorphisms in the serotonin transporter (SLC6A4) and serotonin-2A receptor (HTR2A) genes are associated with response to escitalopram in patients with autism spectrum disorder (ASD).


METHODS
Forty-four participants with ASD were enrolled in a 6 week, forced titration, open label examination of the selective serotonin reuptake inhibitor (SSRI) escitalopram. Doses increased at weekly intervals starting at 2.5mg daily with a maximum possible dose of 20 mg daily achieved by the end of the study. If adverse events were experienced, participants subsequently received the previously tolerated dose for the duration of study. SLC6A4 (5-HTTLPR) and HTR2A (rs7997012) genotype groups were assessed in relation to treatment outcomes and drug doses.


RESULTS
Insistence on sameness and irritability symptoms significantly improved over the course of the 6 week treatment period (p<0.0001) in this open-label trial. There were no significant differences observed in the rate of symptom improvement over time across genotype groups. Similarly, dosing trajectory was not significantly associated with genotype groups.


CONCLUSIONS
Previous studies have identified SLC6A4 and HTR2A associations with SSRI response in patients with depression and 5-HTTLPR (SLC6A4) associations with escitalopram response in ASD. We did not observe evidence for similar relationships in this ASD study.
1 Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago , Chicago, Illinois.
Fedra
F
Najjar
2 Department of Psychiatry, Rush University , Chicago, Illinois.
Thomas
T
Owley
3 Department of Psychiatry, University of Texas Southwestern Medical Center , Dallas Texas.
Matthew W
MW
Mosconi
4 Department of Psychiatry, University of Minnesota , Minneapolis, Minnesota.
Suma
S
Jacob
5 Department of Public Health Sciences, University of Chicago , Chicago, Illinois.
Kwan
K
Hur
1 Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago , Chicago, Illinois.
Stephen J
SJ
Guter
3 Department of Psychiatry, University of Texas Southwestern Medical Center , Dallas Texas.
John A
JA
Sweeney
5 Department of Public Health Sciences, University of Chicago , Chicago, Illinois.
Robert D
RD
Gibbons
1 Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago , Chicago, Illinois.
Edwin H
EH
Cook
6 Department of Experimental and Clinical Pharmacology, University of Minnesota , Minneapolis, Minnesota.
Jeffrey R
JR
Bishop
D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000188:drug therapy* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015283:Citalopram / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
D015283:Citalopram; D044402:Receptor, Serotonin, 5-HT2A; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human