Abstract
Studies of populations at genetic risk have the potential to explore the underlying structural and functional mechanisms in the development of psychological disorders. The polymorphic region (5-HTTLPR) in the serotonin transporter gene (SLC6A4) has been associated with major depression (MDD) (Caspi et al., 2003). In healthy women, variation in the human brain white matter microstructure integrity in the uncinate fascicule (UF) has been suggested as an endophenotypes in the development of MDD. Pacheco et al. (2009) found a unique effect of age and 5-HTTLPR within the left frontal UF. The present study examined whether these associations persist along the adult life span. Thirty-seven right-handed healthy women between 21 and 61 years of age were invited for a diffusion MRI study. The functional polymorphism 5-HTTLPR located in the promoter region of the SLC6A4 gene was genotyped using polymerase chain reaction (PCR). Fractional anisotropy (FA) was generated for the UF based on Tract-Based Spatial Statistics (TBSS). Models of emotion regulation circuitry suggest that working memory is important in conscious emotion regulation (Price and Drevets, 2010). To explore if 5-HTTLPR is related to this aspects of emotion processing, a working memory pathway, the superior longitudinal fascicule (SLF) was included. The results demonstrate that age may explain the hypothesized association between 5-HTTLPR and frontal UF white matter integrity in healthy adult women. Both white matter changes associated with the aging process and those associated with growth and development may explain why the earlier reported unique effects of genotype in frontal UF FA do not persist into adulthood.
Highlights
A unique statistically significant effect of 5-HTTLPR on frontal white matter integrity has recently been reported (Pacheco et al, 2009)
The few Diffusion Tensor Imaging (DTI) studies on 5-HTTLPR are related to circuitry involved in automatic bottom-up processing of emotion, while there is a paucity of studies on white matter pathways involved in conscious top-down regulation of emotion
We tested the hypothesis that adult female short 5-HTTLPR carriers have less white matter integrity in the uncinate fascicule (UF) compared to long 5-HTTLPR carriers
Summary
A unique statistically significant effect of 5-HTTLPR on frontal white matter integrity has recently been reported (Pacheco et al, 2009). Carriers of the short 5-HTTLPR allele showed reduced fractional anisotropy (FA) in the frontal part of the left uncinate fasciculus (UF), a part of a white matter pathway which connects the amygdala to the medial and orbital prefrontal cortex (Pacheco et al, 2009). The sample in Pacheco et al (2009) consisted of adolescent females and young adults, a restricted age cohort, and did not reveal an age moderated association between FA values and 5-HTTLPR. The lateral prefrontal cortex (LPF) and the associated white matter pathway, the superior longitudinal fascicule (SLF) is important for conscious emotion regulation (Phillips et al, 2003). We tested the specificity of this association by calculating FA values within the SLF that connect the LPF to the occipital and temporal lobe, a predominantly cognitive pathway. The potential effects of age will, be of substantial interest as the effects of age are Frontiers in Human Neuroscience www.frontiersin.org
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