Fluoxetine response in impulsive-aggressive behavior and serotonin transporter polymorphism in personality disorder.

Abstract

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.

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.

• Authors: Hernán Silva, Patricia Iturra, Aldo Solari, Juana Villarroel, Sonia Jerez, Marco Jiménez, Felipe Galleguillos, Maria Leonor Bustamante
• Journal: Psychiatric genetics (Psychiatr Genet) Vol. 20 Issue 1 Pg. 25-30 (Feb 2010) ISSN: 1473-5873 [Electronic] England
• PMID: 20010449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Serotonin Plasma Membrane Transport Proteins
• Serotonin Uptake Inhibitors
• Fluoxetine

Topics

• Adolescent
• Adult
• Aged
• Aggression (drug effects, physiology)
• Alleles
• Female
• Fluoxetine (therapeutic use)
• Genotype
• Humans
• Impulsive Behavior (drug therapy, genetics)
• Male
• Middle Aged
• Personality Disorders (drug therapy, genetics)
• Polymorphism, Genetic (genetics)
• Psychiatric Status Rating Scales
• Serotonin Plasma Membrane Transport Proteins (genetics)
• Selective Serotonin Reuptake Inhibitors (therapeutic use)
• Young Adult