High anxiety and migraine are associated with the s allele of the 5HTTLPR gene polymorphism

Gonda, Xénia; Rihmer, Zoltán; Juhász, Gabriella; Zsombók, Terézia; Bagdy, György

doi:10.1016/j.psychres.2006.05.014

Cited by 72 publications

(75 citation statements)

References 24 publications

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“…Using this hypothesis that multiple rare sequence variations with high penetrance have important roles in the susceptibility to complex diseases, researchers may use the findings in this study to determine the role that SERT has in emotional-behavioral disorders. Today, non-human primate research together with human research give clues that the different allele systems (rare or common alleles) may be best thought of as affecting cognitive choice, broad phenotypes such as social intrusiveness (non-human primate), 2 anxiety (human), 45 aggression (non-human primate) 46 and obsessive traits (humans), 5 and that each of these behaviors vary by both allele structure and possibly experience (some geneenvironment interaction (GxE)).…”

Section: Discussionmentioning

confidence: 99%

Identification and functional characterization of three novel alleles for the serotonin transporter-linked polymorphic region

Ehli

Lengyel-Nelson

et al. 2011

Mol Psychiatry

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A promoter polymorphism in the serotonin transporter gene (5-HTTLPR) has been reported to confer relative risk for phenotypes (depression/anxiety) and endophenotypes (amygdala reactivity). In this report, we identify and characterize three rare 5-HTTLPR alleles not previously described in the human literature. The three novel alleles were identified while genotyping 5-HTTLPR in a family-based attention deficit hyperactivity disorder clinical population. Two of the novel alleles are longer than the common 16-repeat long (L) allele (17 and 18 repeats) and the third is significantly smaller than the 14-repeat short (S) allele (11 repeats). The sequence and genetic architecture of each novel allele is described in detail. We report a significant decrease in the expression between the XL 17 (17r) allele and the L A (16r) allele. The XS 11 (11r) allele showed similar expression with the S (14r) allele. A 1.8-fold increase in expression was observed with the L A (16r) allele compared with the L G (16r) allele, which replicates results from earlier 5-HTTLPR expression experiments. In addition, transcription factor binding site (TFBS) analysis was performed using MatInspector (Genomatix) that showed the presence or absence of different putative TFBSs between the novel alleles and the common L (16r) and S (14r) alleles. The identification of rare variants and elucidation of their functional impact could potentially lead to understanding the contribution that the rare variant may have on the inheritance/susceptibility of multifactorial common diseases.

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Section: Discussionmentioning

confidence: 99%

Identification and functional characterization of three novel alleles for the serotonin transporter-linked polymorphic region

Ehli

Lengyel-Nelson

et al. 2011

Mol Psychiatry

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“…Whereas rates of anxiety-like behavior did not vary by genotype and social status, these behaviors increased over time. It is possible that as the novelty of the new group wanes, evidence of more anxiety-like behavior will not only emerge in subordinate females [57] but in s-variant females, regardless of social status [18].…”

Section: Discussionmentioning

confidence: 99%

“…Variation in serotonin (5HT) neurotransmission is one such factor, as 5HT can limit responses to acute stress [9], and its activity is compromised during chronic stress [10,11]. Indeed, the short length variant in the promoter region of the gene that encodes the serotonin reuptake transporter (5HTTLPR or SERT) is associated with diminished transcriptional activity compared to the long allele [12,13], and people with the short allele have increased incidences of anxiety and depression in response to life stressors [14][15][16][17][18]. Individuals who are homozygous for the long variant (l/l) show a greater response to SSRIs than those with either one or two short alleles (s/l, s/s) [19].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the serotonin reuptake transporter gene modify the consequences of social status on metabolic health in female rhesus monkeys

Jarrell¹,

Hoffman²,

Kaplan³

et al. 2008

Physiology & Behavior

109

163

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Individuals vary substantially in their vulnerability to physical and psychosocial stressors. The causes of such variation in susceptibility to stress are poorly understood, but are thought to relate in part to genetic factors. The present study evaluated the extent to which polymorphisms in the gene encoding the serotonin reuptake transporter (5HTTLPR or SERT) modulated physiologic responses to the imposition of psychosocial stress (social reorganization and subordinate social status) in female rhesus monkeys. Forty females, drawn from the middle ranking genealogies of several large social groups, were reorganized into eight groups containing 5 monkeys each; four groups were comprised entirely of animals homogeneous for the long promoter variant in the SERT gene (l/l), while the other four groups had monkeys with at least one allele of the short promoter variant (l/s or s/s). Females were sequentially introduced into these new groups in random order and dominance ranks were established within several days. During the ensuing 6 weeks, dominant monkeys exhibited elevated rates of aggression while subordinates displayed high rates of submission. Notably, females with the s-variant SERT genotype, collapsed across social status positions, exhibited the highest overall rates of both aggression and submission. Although neither social status nor SERT genotype influenced morning cortisol concentrations, glucocorticoid negative feedback was reduced significantly in subordinate compared to dominant females irrespective of genotype. All animals lost weight and abdominal fat across the experiment. However, decreases were greatest in subordinates, regardless of genotype, and least in dominant females with the l/l genotype. Serum concentrations of insulin, glucose, and ghrelin decreased significantly during the group formation process, effects that were independent of genotype or social status. In contrast, social status and genotype interacted to influence changes in serum concentrations of leptin and triiodothyronine (T3), as dominant, l/l females had the highest levels while subordinate s-variant females had the lowest levels. The order in which a female was introduced to her group generally predicted her eventual social rank. However, rank was additionally predicted by pre-experimental T3 and abdominal fat values, but only in the l/l animals. While these findings must be replicated with a larger sample size, the data suggest that the s-variant SERT genotype confers increased vulnerability to the adverse effects of psychosocial stress associated with subordinate status while the l/l genotype benefits the most from the absence of stress conferred by dominant social status. These findings suggest that genetic factors modify the responses of monkeys to social subordination and perhaps other psychosocial stressors.

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“…At the same time, some candidate genes that are linked to ADs are also associated with HPA axis activity. For example, a common polymorphism at the serotonin transporter (5-HTT) gene, namely 5HTTLPR, is a strong candidate genetic variation for ADs and depression [102][103], and also is significantly implicated in HPA axis activity [104]. Similar to the CCKergic system, the HPA axis system has long been recognized as a stress hormone [105,106], and plays a critical role in the pathogenesis of ADs [107,108].…”

Section: Introductionmentioning

confidence: 99%

CCKergic System, Hypothalamus-Pituitary-Adrenal (HPA) Axis, and Early-Life Stress (ELS)

Tang¹,

Joseph²,

Chen³

et al. 2012

Glucocorticoids - New Recognition of Our Familiar Friend

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High anxiety and migraine are associated with the s allele of the 5HTTLPR gene polymorphism

Cited by 72 publications

References 24 publications

Identification and functional characterization of three novel alleles for the serotonin transporter-linked polymorphic region

Identification and functional characterization of three novel alleles for the serotonin transporter-linked polymorphic region

Polymorphisms in the serotonin reuptake transporter gene modify the consequences of social status on metabolic health in female rhesus monkeys

CCKergic System, Hypothalamus-Pituitary-Adrenal (HPA) Axis, and Early-Life Stress (ELS)

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