Elsevier

Biological Psychiatry

Volume 62, Issue 6, 15 September 2007, Pages 600-606
Biological Psychiatry

Original Article
Genetic Variation in Serotonin Transporter Alters Resting Brain Function in Healthy Individuals

https://doi.org/10.1016/j.biopsych.2006.11.028Get rights and content

Background

Perfusion functional magnetic resonance imaging (fMRI) was used to investigate the effect of genetic variation of the human serotonin transporter (5-HTT) gene (5-HTTLPR, SLC6A4) on resting brain function of healthy individuals.

Methods

Twenty-six healthy subjects, half homozygous for the 5-HTTLPR short allele (s/s group) and half homozygous for the long allele (l/l group), underwent perfusion functional and structural magnetic resonance imaging during a resting state. The two genotype groups had no psychiatric illness and were similar in age, gender, and personality scores.

Results

Compared with the l/l group, the s/s group showed significantly increased resting cerebral blood flow (CBF) in the amygdala and decreased CBF in the ventromedial prefrontal cortex. The effect of functional modulation in these regions by 5-HTTLPR genotype cannot be accounted for by variations in brain anatomy, personality, or self-reported mood.

Conclusions

The 5-HTTLPR genotype alters resting brain function in emotion-related regions in healthy individuals, including the amygdala and ventromedial prefrontal cortex. Such alterations suggest a broad role of the 5-HTT gene in brain function that may be associated with the genetic susceptibility for mood disorders such as depression.

Section snippets

Participants

From a sample of 276 screened, healthy subjects, we recruited 30 subjects for the scanning (14 female subjects; all Caucasian; mean age 20.3 years, range 18 to 29 years). All subjects were neurologically intact with no reported history of head trauma and no current psychiatric diagnosis. Written informed consent was obtained in accordance with the Institutional Review Board of the University of Pennsylvania. Four subjects were excluded from the study due to problems in perfusion quantification.

Results

Study demographics and the scores of behavioral measurements of 26 subjects are listed in Table 1. No significant differences were observed between the two genotype groups (all p’s > .2). The self-reported mood ratings of anxiety (61.2 for l/l group vs. 72.3 for s/s group) and sadness (71.9 for l/l group vs. 81.2 for s/s group) also showed no significant differences between the two groups (both p’s > .1).

The quantitative resting CBF images averaged from the s/s and l/l groups are shown in

Discussion

Genomic neuroimaging studies provide emerging methods to understand human emotion and behavior. The combination of neuroimaging and genetic approaches will facilitate investigations of genotypes and the associated brain mechanisms that underlie the vulnerability to mood disorders (Drevets 2000, Hariri et al 2006, Hariri and Holmes 2006, Wurtman 2005). In line with this direction, the present study integrated perfusion-based functional MRI with genomic analysis to quantify and compare the

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