The International Journal of Neuropsychopharmacology

Research Article

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

Jacqueline Borga1 c1, Susanne Henningssona2, Tomoyuki Saijoa1a3, Makoto Inouea1a3, Jessica Baha2, Lars Westberga2, Johan Lundberga1, Hristina Jovanovica1, Bengt Andréea1, Anna-Lena Nordstroma1, Christer Halldina1, Elias Erikssona2 and Lars Fardea1

a1 Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry and Stockholm Brain Institute, Stockholm, Sweden

a2 Department of Pharmacology, Institute of Neuroscience and Physiology, Göteborg University, Göteborg, Sweden

a3 Brain Imaging Project, Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan


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.

(Received May 31 2008)

(Reviewed July 29 2008)

(Revised November 07 2008)

(Accepted November 17 2008)

(Online publication January 06 2009)


c1 Address for correspondence: Dr J. Borg, Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, Stockholm Brain Institute, 171 76 Stockholm, Sweden. Tel.: +46 8 5177 63 85 Fax: +46 8 5177 17 53 Email: