BACKGROUND: Genetic variation of the promoter for the serotonin transporter (5-HTT) gene has been associated with its functional capacity. In vitro, carriers of a short allele (s-carriers) of the 5-HTT promoter display significant reduction in 5-HTT capacity. Dysfunction of 5-HTT has been observed in alcoholic individuals. We assessed whether the allelic constitution of the 5-HTT gene is associated with reduced serotonin transporter availability among alcoholic individuals. METHODS: We genotyped the 5-HTT promoter region and measured the availability of serotonin transporter protein with [I-123]beta-CIT SPECT in the raphe area in 14 abstinent male alcoholic subjects and 8 age-matched control subjects of European American descent. RESULTS: Among control subjects, the ratio of in vivo 5-HTT availability for ll-homozygous individuals relative to s-carriers was comparable to serotonin uptake ratios measured in vitro. There was a significant interaction of diagnosis and 5-HTT promoter genotype on 5-HTT availability (p <.01). Among controls, ll-homozygous individuals displayed a significant increase as compared with s-carriers. The availability of raphe 5-HTT was significantly reduced in ll-homozygous alcoholic individuals and was negatively correlated with their amount of alcohol consumption. Among s-carriers, 5-HTT availability did not differ significantly between control and alcoholic subjects. CONCLUSIONS: Our preliminary findings suggest an association between 5-HTT allelic constitution and in vivo measurements of human serotonin transporter availability, and a potentially selective susceptibility of ll-homozygous individuals to the neurotoxic effects of chronic excessive alcohol consumption.
BACKGROUND: Genetic variation of the promoter for the serotonin transporter (5-HTT) gene has been associated with its functional capacity. In vitro, carriers of a short allele (s-carriers) of the 5-HTT promoter display significant reduction in 5-HTT capacity. Dysfunction of 5-HTT has been observed in alcoholic individuals. We assessed whether the allelic constitution of the 5-HTT gene is associated with reduced serotonin transporter availability among alcoholic individuals. METHODS: We genotyped the 5-HTT promoter region and measured the availability of serotonin transporter protein with [I-123]beta-CIT SPECT in the raphe area in 14 abstinent male alcoholic subjects and 8 age-matched control subjects of European American descent. RESULTS: Among control subjects, the ratio of in vivo 5-HTT availability for ll-homozygous individuals relative to s-carriers was comparable to serotonin uptake ratios measured in vitro. There was a significant interaction of diagnosis and 5-HTT promoter genotype on 5-HTT availability (p <.01). Among controls, ll-homozygous individuals displayed a significant increase as compared with s-carriers. The availability of raphe 5-HTT was significantly reduced in ll-homozygous alcoholic individuals and was negatively correlated with their amount of alcohol consumption. Among s-carriers, 5-HTT availability did not differ significantly between control and alcoholic subjects. CONCLUSIONS: Our preliminary findings suggest an association between 5-HTT allelic constitution and in vivo measurements of humanserotonin transporter availability, and a potentially selective susceptibility of ll-homozygous individuals to the neurotoxic effects of chronic excessive alcohol consumption.
Authors: Samanta Yubero-Lahoz; Mario A Ayestas; Bruce E Blough; John S Partilla; Richard B Rothman; Rafael de la Torre; Michael H Baumann Journal: Eur J Pharmacol Date: 2011-11-03 Impact factor: 4.432
Authors: Matthias Reimold; Astrid Knobel; Michael A Rapp; Anil Batra; Klaus Wiedemann; Andreas Ströhle; Anke Zimmer; Peter Schönknecht; Michael N Smolka; Daniel R Weinberger; David Goldman; Hans-Jürgen Machulla; Roland Bares; Andreas Heinz Journal: Psychopharmacology (Berl) Date: 2010-06-29 Impact factor: 4.530
Authors: M Reimold; M N Smolka; A Zimmer; A Batra; A Knobel; C Solbach; A Mundt; H U Smoltczyk; D Goldman; K Mann; G Reischl; H-J Machulla; R Bares; A Heinz Journal: J Neural Transm (Vienna) Date: 2007-08-22 Impact factor: 3.575
Authors: S J Bull; P Huezo-Diaz; E B Binder; J F Cubells; G Ranjith; C Maddock; C Miyazaki; N Alexander; M Hotopf; A J Cleare; S Norris; E Cassidy; K J Aitchison; A H Miller; C M Pariante Journal: Mol Psychiatry Date: 2008-05-06 Impact factor: 15.992