Polymorphism in the serotonin transporter gene and moderators of prolactin response to meta-chlorophenylpiperazine in African-American cocaine abusers and controls.
Serotonin (5-HT) function is altered in several psychiatric disorders, including cocaine dependence (CD), and its role in impulsive-aggressive behaviors has been widely studied. However, the relationship between psychopathological and behavioral dimensions and mechanisms of 5-HT alterations remains unclear. We investigated the relationship of a polymorphism in the 5' promoter region of the serotonin transporter gene (5-HTTLPR) with prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP) in a sample of 68 African-American individuals, 35 CD subjects and 33 controls. We also examined whether measures of impulsivity, hostility and sensation seeking influenced the relationship between the 5-HTTLPR polymorphism and PRL response to m-CPP in this sample. Individuals with the SS genotype showed significantly heightened PRL response to the challenge compared with the LL and LS genotypes. No influence of gender or substance abuse condition was observed. Hostility was associated with blunted PRL response in the total sample. Cocaine abuse was the most significant moderator of DeltaPRL (peak PRL-baseline PRL), and the interaction of genetic, behavioral and psychopathological measures helped predict most of the observed DeltaPRL (62.5%). Although these results need replication, variation in the 5-HTTLPR gene appears to influence measures of 5-HT function and interact with disease state and personality dimensions to account for 5-HT disturbances in African-American populations.
Mannelli
Paolo
P
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Patkar
Ashwin A
AA
Peindl
Kathleen
K
Tharwani
Haresh
H
Gopalakrishnan
Raman
R
Hill
Kevin P
KP
Berrettini
Wade H
WH
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000374:Aggression / Q000523:psychology; D019970:Cocaine-Related Disorders / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D017931:DNA Primers / Q000235:genetics; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000208:ethnology / Q000235:genetics / Q000523:psychology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D011795:Surveys and Questionnaires
D017931:DNA Primers; D010879:Piperazines; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D011388:Prolactin; C015068:1-(3-chlorophenyl)piperazine