5-HTTLPR
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SNPedia | 25531 |
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5-HTTLPR (serotonin-transporter-linked promoter region) is a
Alleles
The polymorphism occurs in the
One study published in 2000 found 14
Some studies have found that long allele results in higher serotonin transporter
Neuropsychiatric disorders
In the 1990s it has been speculated that the polymorphism might be related to
Treatment response
With the results from one study the polymorphism was thought to be related to treatment response so that long-allele patients respond better to antidepressants.[19] Another antidepressant treatment response study did, however, rather point to the rs25531 SNP,[20] and a large study by the group of investigators found a "lack of association between response to an SSRI and variation at the SLC6A4 locus".[21]
One study could find a treatment response effect for
Amygdala
The 5-HTTLPR has been thought to predispose individuals to affective disorders such as anxiety and depression. There have been some studies that test whether this association is due to the effects of variation in 5-HTTLPR on the reactivity of the human amygdala. In order to test this, researchers gathered a group of subjects and administered a harm avoidance (HA) subset of the Tridimensional Personality Questionnaire as an initial mood and personality assessment.[23] Subjects also had their DNA isolated and analyzed in order to be genotyped. Next, the amygdala was then engaged by having the subject match fearful facial expressions during an fMRI scan (by the 3-T GE Signa scanner).[23] The results of the study showed that there was bilateral activity in the amygdala for every subject when processing the fearful images, as expected. However, the activity in the right amygdala was much higher for subjects with the s-allele, which shows that the 5-HTTLPR has an effect on amygdala activity. There did not seem to be the same effect on the left amygdala.
Insomnia
There has been speculation that the 5-HTTLPR gene is associated with insomnia and sleep quality. Primary insomnia is one of the most common sleep disorders and is defined as having trouble falling or staying asleep, enough to cause distress in one's life. Serotonin (5-HT) has been associated with the regulation of sleep for a very long time now.[5] The 5-HT transporter (5-HTT) is the main regulator of serotonin and serotonergic energy and is therefore targeted by many antidepressants.[5] There also have been several family and twin studies that suggest that insomnia is heavily genetically influenced. Many of these studies have found that there is a genetic and environment dual-factor that influences insomnia. It has been hypothesized that the short 5-HTTLPR genotype is related to poor sleep quality and, therefore, also primary insomnia. It is important to note that research studies have found that this variation does not cause insomnia, but rather may predispose an individual to experience worse quality of sleep when faced with a stressful life event.
Brummett
The effect that the 5-HTTLPR gene had on sleep quality was tested by Brummett in a study conducted at Duke University Medical Center from 2001 to 2004. The sleep quality of 344 participants was measured using The Pittsburgh Sleep Quality Index. The study found that caregivers with the homozygous s-allele had poorer sleep quality, which shows that the stress of caregiving combined with the allele gave way to worse sleep quality. Although the study found that the 5-HTTLPR genotype did not directly affect sleep quality, the 5-HTTLPR polymorphism's effect on sleep quality was magnified by one's environmental stress.[24] It supports the notion that the 5-HTTLPR s-allele is what leads to hyperarousal when exposed to stress; hyperarousability is commonly associated with insomnia.
Deuschle
However, in a 2007 study conducted by a sleep laboratory in Germany, it was found that the 5-HTTLPR gene did have a strong association with both insomnia and depression both in participants with and without lifetime affective disorders. This study included 157 insomnia patients and a control group of 836 individuals that had no psychiatric disorders. The subjects were then genotyped through polymerase chain reaction (PCR) techniques.[5] The researchers found that the s-allele was greater represented in the vast majority of patients with insomnia compared to those who had no disorder.[5] This shows that there is an association between the 5-HTTPLR genotype and primary insomnia. However, it is important to consider the fact that there was a very limited number of subjects with insomnia tested in this study.
Personality traits
5-HTTLPR may be related to
In a study published in 2009, authors found that individuals homozygous for the long allele of 5-HTTLPR paid more attention on average to positive affective pictures while selectively avoiding negative affective pictures presented alongside the positive pictures compared to their heterozygous and short-allele-homozygous peers. This biased attention of positive emotional stimuli suggests they may tend to be more optimistic.[34] Other research indicates carriers of the short 5-HTTLPR allele have difficulty disengaging attention from emotional stimuli compared to long allele homozygotes.[35] Another study published in 2009 using an eye tracking assessment of information processing found that short 5-HTTLPR allele carriers displayed an eye gaze bias to view positive scenes and avoid negative scenes, while long allele homozygotes viewed the emotion scenes in a more even-handed fashion.[36] This research suggests that short 5-HTTLPR allele carriers may be more sensitive to emotional information in the environment than long allele homozygotes.
Another research group have given evidence for a modest association between shyness and the long form in grade school children.[37] This is, however, just a single report and the link is not investigated as intensively as for the anxiety-related traits.
Neuroimaging
Associations between the polymorphism and the
Especially the amygdala brain structure has been the focus of the functional neuroimaging studies.
Electrophysiology
The relationship between the Event Related Potentials P3a and P3b and the genetic variants of 5-HTTLPR were investigated using an auditory oddball paradigm and revealed short allele homozygotes mimicked those of COMT met/met homozygotes with an enhancement of the frontal, but not parietal P3a and P3b. This suggests a frontal-cortical dopaminergic and serotoninergic mechanism in bottom-up attentional capture.[46]
Other organisms
In rats (Rattus rattus) berberine increases 5-HTTLPR activity.[47]
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Further reading
- "Serotonin Transporter-Linked Polymorphic Region (5HTTLPR) and rs25531 SNP (Mspl, LA/LG)". Archived from the original on 2017-04-07. Retrieved 2015-05-04.
- Brown GW, Harris TO (November 2008). "Depression and the serotonin transporter 5-HTTLPR polymorphism: a review and a hypothesis concerning gene-environment interaction". Journal of Affective Disorders. 111 (1): 1–12. PMID 18534686.
External links