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Serotonin transporter genotype is associated with cognitive performance but not regional 5-HT1A receptor binding in humans.

Artikel i vetenskaplig tidskrift
Författare Borg
Susanne Henningsson
Saijo
Inoue
Jessica Bah Rösman
Lars Westberg
Lundberg
Jovanovic
Andr?e
Nordstrom
Halldin
Elias Eriksson
Farde
Publicerad i The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)
Volym 12
Nummer/häfte 6
Sidor 783-92
ISSN 1461-1457
Publiceringsår 2009
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 783-92
Språk en
Länkar dx.doi.org/10.1017/S146114570800975...
Ämnesord Cognition, PET, serotonin, 5-HT1A, 5-HTTLPR, WCST
Ämneskategorier Farmakologi och toxikologi

Sammanfattning

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.

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