title: Serotonin transporter genotype is associated with cognitive performance but not regional 5-HT1A receptor binding in humans.
abstract: The human serotonin transporter (5-HTT) gene is one of the most extensively studied in psychiatry. A functional polymorphism in the promoter region of the 5-HTT gene (5-HTTLPR) has been associated with several psychiatric disorders as well as anxiety-related personality traits. In search of a mechanistic understanding of the functional implications of 5-HTTLPR, the influence of this polymorphism on regional 5-HT1A receptor density has previously been examined in two positron emission tomography (PET) studies in humans, yielding, however, contradictory results. In the present study, 54 control subjects were examined with [11C]WAY 100635 PET and a battery of cognitive tests. Regional binding potential (BP) of [11C]WAY 100635 to 5-HT1A receptor was calculated for the dorsal raphe nuclei, the hippocampus, the anterior cingulate, the insula, the temporal cortex and the frontal cortex. The influence of 5-HTTLPR genotype on regional 5-HT1A BP and cognitive performance was investigated. No differences in 5-HT1A receptor density between carriers and non-carriers of the S allele were found. Thus, we could not replicate any of the previously reported associations between 5-HTTLPR and 5-HT1A density. There was, however, a highly significant association between 5-HTTLPR genotype and performance in Wisconsin Card Sorting Test; carriers of the S allele had a superior performance compared to the LL carriers. These observations suggest that functional implications of the 5-HTTLPR polymorphism are not likely to be mediated by differences in 5-HT1A expression levels and that other biomarkers must be considered for future investigations at phenotype level.
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry and Stockholm Brain Institute, Stockholm, Sweden.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Borg
authors.forename: Susanne
authors.initials: S
authors.lastname: Henningsson
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Saijo
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Jessica
authors.initials: J
authors.lastname: Bah
authors.forename: Lars
authors.initials: L
authors.lastname: Westberg
authors.forename: Johan
authors.initials: J
authors.lastname: Lundberg
authors.forename: Hristina
authors.initials: H
authors.lastname: Jovanovic
authors.forename: Bengt
authors.initials: B
authors.lastname: Andrée
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Nordstrom
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
authors.forename: Lars
authors.initials: L
authors.lastname: Farde
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010879:Piperazines / Q000378:metabolism; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D011725:Pyridines / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D013223:Statistics as Topic; D014316:Tritium / Q000378:metabolism; D055815:Young Adult
chemical_list: D010879:Piperazines; D011725:Pyridines; D050486:Serotonin Plasma Membrane Transport Proteins; D014316:Tritium; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide