5HTTLPR: White Knight or Dark Blight?

Murphy, Dennis L.; Maile, Michelle S.; Vogt, N.

doi:10.1021/cn3002224

Cited by 31 publications

(30 citation statements)

References 14 publications

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“…It will also be critical to explore this gene‐environment interaction in larger populations to examine other mutations affecting serotonin uptake and stress tolerance. Studies have revealed several polymorphisms on the SLC6A4 gene that have profound effects on gene expression (Murphy, Maile, & Vogt, ). For example, the rs25531 variant, in close proximity to 5‐HTTLPR, has been shown to modulate SERT expression and functionally change a long allele variant to a short allele (Hu et al, ; Wendland et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…For example, the rs25531 variant, in close proximity to 5‐HTTLPR, has been shown to modulate SERT expression and functionally change a long allele variant to a short allele (Hu et al, ; Wendland et al, ). Additional polymorphisms, such as rs25532 and STin2 VNTR, have also been discovered on the serotonin transporter gene that alter gene expression and regulate stress reactivity and risk for neuropsychiatric disorders (MacKenzie & Quinn, ; Murphy et al, ; Wendland et al, ). While the small sample in this study limited the focus on one polymorphism, future studies with larger samples will be required to examine how the full range of relevant polymorphisms may interact with prenatal stress to increase the risk for ASD along with the 5‐HTTLPR polymorphism.…”

Section: Discussionmentioning

confidence: 99%

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Maternal serotonin transporter genotype affects risk for ASD with exposure to prenatal stress

et al. 2016

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Stress exposure during gestation is implicated in several neuropsychiatric conditions, including autism spectrum disorder (ASD). Previous research showed that prenatal stress increases risk for ASD with peak exposure during the end of the second and the beginning of the third trimester. However, exposures to prenatal stress do not always result in ASD, suggesting that other factors may interact with environmental stressors to increase ASD risk. The present study examined a maternal genetic variation in the promoter region of the serotonin transporter gene (5-HTTLPR) affecting stress tolerance and its interaction with the effect of environmental stressors on risk for ASD. Two independent cohorts of mothers of ASD children recruited by the University of Missouri and Queen's University were surveyed regarding the prenatal environment and genotyping on 5-HTTLPR was performed to explore this relationship. In both samples, mothers of children with ASD carrying the stress susceptible short allele variant of 5-HTTLPR experienced a greater number of stressors and greater stress severity when compared to mothers carrying the long allele variant. The temporal peak of stressors during gestation in these mothers was consistent with previous findings. Additionally, increased exposure to prenatal stress was not reported in the pregnancies of typically developing siblings from the same mothers, regardless of maternal genotype, suggesting against the possibility that the short allele might increase the recall of stress during pregnancy. The present study provides further evidence of a specific maternal polymorphism that may affect the risk for ASD with exposure to prenatal stress. Autism Res 2016, 9: 1151-1160. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Maternal serotonin transporter genotype affects risk for ASD with exposure to prenatal stress

et al. 2016

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“…In addition to inhibition by antidepressants, SERT function is potentially modified by a number of commonly occurring human SERT gene (SLC6A4) polymorphisms (Murphy et al, 2013;Murphy and Moya, 2011). Reductions in SERT associated with low-expressing SLC6A4 alleles have most often been linked to heightened anxiety-related personality traits (eg, neuroticism), stress-sensitivity, and increased susceptibility to mood disorders (Caspi et al, 2010;Mitchell et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Perinatal vs Genetic Programming of Serotonin States Associated with Anxiety

Altieri

Yang

O'Brien

et al. 2014

Neuropsychopharmacol

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Large numbers of women undergo antidepressant treatment during pregnancy; however, long-term consequences for their offspring remain largely unknown. Rodents exposed to serotonin transporter (SERT)-inhibiting antidepressants during development show changes in adult emotion-like behavior. These changes have been equated with behavioral alterations arising from genetic reductions in SERT. Both models are highly relevant to humans yet they vary in their time frames of SERT disruption. We find that anxiety-related behavior and, importantly, underlying serotonin neurotransmission diverge between the two models. In mice, constitutive loss of SERT causes life-long increases in anxiety-related behavior and hyperserotonemia. Conversely, early exposure to the antidepressant escitalopram (ESC; Lexapro) results in decreased anxiety-related behavior beginning in adolescence, which is associated with adult serotonin system hypofunction in the ventral hippocampus. Adult behavioral changes resulting from early fluoxetine (Prozac) exposure were different from those of ESC and, although somewhat similar to SERT deficiency, were not associated with changes in hippocampal serotonin transmission in late adulthood. These findings reveal dissimilarities in adult behavior and neurotransmission arising from developmental exposure to different widely prescribed antidepressants that are not recapitulated by genetic SERT insufficiency. Moreover, they support a pivotal role for serotonergic modulation of anxiety-related behavior.

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“…Additionally, hippocampus and amygdala activation at rest correlated positively with life stress exposure in short-5-HTTLPR allele carriers, but correlated negatively with life stress in non-carriers (Canli et al, 2006). Furthermore, and refining the genotyping procedures, low and intermediate expression diplotypes of 5-HTTLPR-rs25531 were recently associated with increased amygdala reactivity to angry faces (Lonsdorf et al, 2011), a finding supporting the necessity of such diplotypes approaches in genetic studies (Murphy et al, 2013).…”

Section: Gene X Environment Interactionsmentioning

confidence: 81%