Preliminary effects of bupropion and the promoter region (HTTLPR) serotonin transporter (SLC6A4) polymorphism on smoking behavior in schizophrenia.
In the current study, we investigated how individual variants in the serotonin promoter gene, previously associated with smoking cessation and linked to anxiety-related personality traits, were associated with individual differences in responsiveness to bupropion and cognitive behavioral therapy (CBT) in a clinical population. We hypothesize that subjects with the long allele may be less responsive to treatment. Altogether 61 schizophrenic patients (46 M, 15 F) on stable neuroleptic medication were initially enrolled in a smoking reduction program (prospective, double-blind, placebo-controlled) including cognitive behavioral therapy plus placebo or CBT plus bupropion. Additionally, subjects were genotyped for a polymorphism in the serotonin transporter (SLC6A4). Thirty-two subjects (23 M, 9 F) completed a 14-week course of treatment. While both groups of subjects demonstrated significant reductions in smoking behavior due to CBT, subjects receiving bupropion did not show significant differences in smoking behavior when compared to placebo. In addition, analysis by SPSS repeated measures multivariate showed a significant sex by SLC6A4 genotype interaction on the number of cigarettes smoked. Only male subjects with at least one short promoter region allele (short/short and short/long combined) showed a reduction in cigarette consumption as a result of treatment. This study provides preliminary evidence of how polymorphisms in the serotonin transporter can be informative in predicting individual responses to smoking reduction therapy.
Bloch
Boaz
B
Psychiatry Department, HaEmek Hospital, Afula, Israel.
Reshef
Alon
A
Cohen
Tamara
T
Tafla
Amos
A
Gathas
Samich
S
Israel
Salomon
S
Gritsenko
Inga
I
Kremer
Ilana
I
Ebstein
Richard P
RP
D000328:Adult; D016642:Bupropion / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy / Q000379:methods; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications / Q000235:genetics; D012565:Schizophrenic Psychology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012907:Smoking / Q000235:genetics* / Q000628:therapy
D018765:Dopamine Uptake Inhibitors; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D016642:Bupropion