title: The influence of 5-HTT and COMT genotypes on verbal fluency in ecstasy users.
abstract: Deficits in verbal fluency associated with ecstasy use have been well established; however, the mechanisms underlying this impairment have yet to be elucidated. In this study we investigated for the first time whether there was a disproportionate impairment in two cognitive subcomponents of verbal fluency: clustering (ability to generate words within the same subcategory) and switching (ability to change the subcategory). We also investigated a possible association between ecstasy use and verbal fluency in subjects genotyped for 5-HTT (5-HTTLPR and 5-HTTVNTR) and COMT (val(108/158)met, rs165599 and rs2097603) polymorphisms, in order to find a potential implication of genetic factors. Ecstasy polydrug users (n = 30) and non-ecstasy users (n = 41) were evaluated in both semantic and phonemic fluency. Results showed that ecstasy users had poorer semantic (but not phonemic) fluency performance than controls. Detailed analysis of clustering and switching performance revealed that this impairment was associated with poorer clustering mechanisms. Clustering was also modulated by the COMT rs165599 polymorphism independently of the group. A specific effect of the 5-HTTLPR polymorphism on switching performance was also found, with ss carriers performing significantly worse than ls and ll carriers, suggesting a serotonin modulation of frontal-executive flexibility. Based on the impaired clustering and switching strategies observed in ecstasy users, it might be proposed that both semantic knowledge and retrieval are impaired in this population. The verbal fluency deficit in ecstasy users may be attributable to a disruption of frontal-striatal circuits directly related with the serotonin function as well as a depletion of lexical-semantic stores mediated by temporal structures.
authors.affiliation: Human Pharmacology and Clinical Neurosciences Research Group-Neuropsychopharmacology Program, Institut Municipal d'Investigació Mèdica (IMIM), Barcelona, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Fagundo
authors.forename: Elisabet
authors.initials: E
authors.lastname: Cuyàs
authors.forename: Antonio
authors.initials: A
authors.lastname: Verdejo-Garcia
authors.forename: Olha
authors.initials: O
authors.lastname: Khymenets
authors.forename: Klaus
authors.initials: K
authors.lastname: Langohr
authors.forename: Rocio
authors.initials: R
authors.lastname: Martín-Santos
authors.forename: Magí
authors.initials: M
authors.lastname: Farré
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005838:Genotype; D006213:Hallucinogens; D006579:Heterozygote; D006801:Humans; D013287:Illicit Drugs; D008037:Linguistics; D008297:Male; D008385:Marijuana Smoking / Q000009:adverse effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013060:Speech; D013064:Speech Disorders / Q000139:chemically induced; D019966:Substance-Related Disorders / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D013287:Illicit Drugs; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase; D018817:N-Methyl-3,4-methylenedioxyamphetamine