Fluoxetine response in impulsive-aggressive behavior and serotonin transporter polymorphism in personality disorder.
BACKGROUND
Disturbances in central serotonin function have been implicated in impulsive and aggressive behavior. A deletion/insertion polymorphism within the 5-HT transporter promoter gene (5-HTTLPR) is thought to be associated with disturbed impulse control, anxiety, and depression. The serotonin transporter (5-HTT) is the primary action site for selective serotonin reuptake inhibitors (SSRIs). Several studies of major depression have shown that the l allele of 5-HTTLPR is associated with better SSRI antidepressant effects than the s allele.


METHODS
This study investigates the association between response of impulsivity to treatment with fluoxetine and 5-HTTLPR polymorphism in 49 personality disordered patients. Additionally, we studied TPH1, 5HT1B and 5HT2C receptor polymorphisms as predictors of response in this population.


RESULTS
Results reveal that patients with the l/l genotype of 5-HTTLPR had a significantly better response to fluoxetine when compared to s allele carriers, as evaluated on the basis of total (P<0.05) and Aggression subscale (P<0.01) Overt Aggression Scale Modified-score percentage change. There were no significant associations between fluoxetine response and TPH1 (A218C) (-6525 A>G) (-5806 G>T), HTR1B (G861C) and HTR2C (G68C) genotype groups.


CONCLUSIONS
This is the first study assessing the association between these polymorphisms and anti-impulsive response to fluoxetine in personality disorder. As the s genotype is associated with a poorer selective serotonin reuptake inhibitors response in major depression, bulimia nervosa and borderline personality disorder, it could represent a common biological background for SSRI response.
Silva
Hernán
H
Psychiatric Clinic of University of Chile, Santiago de Chile, Chile. hsilva@med.uchile.cl
Iturra
Patricia
P
Solari
Aldo
A
Villarroel
Juana
J
Jerez
Sonia
S
Jiménez
Marco
M
Galleguillos
Felipe
F
Bustamante
Maria Leonor
ML
D000293:Adolescent; D000328:Adult; D000368:Aged; D000374:Aggression / Q000187:drug effects / Q000502:physiology; D000483:Alleles; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010554:Personality Disorders / Q000188:drug therapy / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D055815:Young Adult
D005473:Fluoxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors