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.

Cognitive function is related to fronto-striatal serotonin transporter levels – a brain PET study in young healthy subjects

“…Genetic studies have associated attention and other executive functions to the short 5-HTTLPR allele of the SLC6A4 gene (Strobel et al 2007;Borg et al 2009;Roiser et al 2007), but we did not find gene effects in this relatively small sample for such associations. However, differences in SERT binding between short and long Fig.…”

When the Serotonin Transporter Gene Meets Adversity: The Contribution of Animal Models to Understanding Epigenetic Mechanisms in Affective Disorders and Resilience

“…Taken together, the studies in non-human primates complement the findings in human on emotionality in social settings and suggest that the 5-HTTLPR shortvariant is associated with increased attention (Roiser et al 2007) to task parameters and may contribute to improved decision making and improved cognitive flexibility (Borg et al 2009;Jedema et al 2009;Roiser et al 2006Roiser et al , 2009. Moreover, it may be linked with heightened social vigilance and, generally, sensitivity to environmental cues per se, which could result in maladaptive responsiveness when danger or social threats are absent.…”

“…At the level of cognitive flexibility, it was found that the 5-HTTLPR short-allele is associated with improved performance in trials of attentional set shifting (Borg et al 2009), which is in accord with increased attention towards task parameters (Roiser et al 2007). The cognitive enhancement is also consistent with the observation that short-allele carriers show increased processing of negative feedback (Althaus et al 2009).…”

Effects of the 5-HTTLPR Polymorphism of the Serotonin Transporter Gene on the Recognition of Mimicked Emotional Expressions in Schizophrenia

“…At the same time, the neurocognitive defi cit is more clearly apparent in carriers of the S allele. In particular, patients with the S allele showed decreased verbal learning and executive functions relative to LL homozygotes [3,9], which distinguishes patients from the general population, in which the S allele is linked with better measures of executive functions [8,62]. In the present study, the defi cit in the recognition of emotions correlated with enhancement of negative symptoms, degradation of neurocognition, and low trait anxiety, which is consistent with published data [26,32].…”