Serotonin Transporter Polymorphism Modulates N-Back Task Performance and fMRI BOLD Signal Intensity in Healthy Women

Rune Jonassen,Alexander Neumeister,Nils Inge Landrø,Kari Bente Foss Haug,Jens Petter Berg,Tor Endestad,Carles Soriano-Mas

doi:10.1371/journal.pone.0030564

Abstract

ContextExploring intermediate phenotypes within the human brain's functional and structural circuitry is a promising approach to explain the relative contributions of genetics, complex behaviors and neural mechanisms in the development of major depressive disorder (MDD). The polymorphic region 5-HTTLPR in the serotonin transporter gene (SLC6A4) has been shown to modulate MDD risk, but the neural underpinnings are incompletely understood.Objective37 right handed healthy women between 21 and 61 years of age were invited to participate in an fMRI modified n-back study. The functional polymorphism 5-HTTLPR located in the promoter region of the SLC6A4 gene was genotyped using polymerase chain reaction (PCR).ResultsShort 5-HTTLPR allele carriers showed more blood-oxygen-level-dependent (BOLD) bilateral prefrontal cortex activation in the right [F(2, 30) = 4.8, η2 = .25, p = .026] and left [F(2, 30) = 4.1, η2 = .22, p = .015] inferior frontal gyrus pars triangularis with increasing n-back task difficulty relative to long 5-HTTLPR allele carriers. Short 5-HTTLPR allele carriers had inferior task performance on the most difficult n-back condition [F(2, 30) = 4.9, η2 = .26, p = .014].ConclusionsThis activation pattern found in healthy at risk individuals resembles an activation pattern that is typically found in patients suffering from acute MDD. Altered function in these areas may reflect intermediate phenotypes and may help explain the increased risk of depression in short 5-HTTLPR allele carriers.

Highlights

Altered lateral prefrontal cortex function is one of the most consistently reported findings in major depressive disorder (MDD) [1]
Short 5-HTTLPR allele carriers had inferior task performance on the most difficult n-back condition [F(2, 30) = 4.9, g2 = .26, p = .014]. This activation pattern found in healthy at risk individuals resembles an activation pattern that is typically found in patients suffering from acute MDD
Both increased and decreased functioning in the medial- and lateral prefrontal cortex during working memory related tasks have been demonstrated in MDD relative to healthy control subjects [2], and these activation patterns appear to contribute to the development and progression of MDD

Summary

Objective

37 right handed healthy women between 21 and 61 years of age were invited to participate in an fMRI modified n-back study. The functional polymorphism 5-HTTLPR located in the promoter region of the SLC6A4 gene was genotyped using polymerase chain reaction (PCR)

Results

Conclusions

Introduction

Material and Methods

Discussion