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 I allele of 5-HTTLPR is associated wit 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 I/I 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. Conclusion 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. Psychiatr Genet 20:25-30 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.