|(A;A)||2.5||short form of 5-HTTLPR. lower levels of serotonin, slightly less happy, benefits from more support|
|(G;G)||2.1||long form of 5-HTTLPR. less sensitive to pain|
The minor allele (G) of rs25531 is almost always in phase with the long (L) allele of the 5-HTTLPR, which is the most commonly studied variation in this region. The (L) long allele may be associated with lower levels of serotonin.[PMID 8929413]
The article and video from "The Atlantic" suggests that children with the short allele (A), may need and benefit greatly from more maternal support
In contrast to earlier reports linking rs25531, a SNP in the serotonin transporter SLC6A4 gene, to obsessive compulsive disorder (OCD), a March 2007 publication finds no significant association studying "the largest sample size of OCD patients (N=347) and controls (N=749) ever investigated". [PMID 17375136]
A small study (62 patients and 62 matched controls) investigated this SNP in relation to blushing. (Blushing is considered to be one of the prime pathophysiological markers of social anxiety disorder.) The less active 5-HTTLPR genotypes were nominally significantly associated with increased blushing propensity in patients with social anxiety disorder, and association remained significant even when statistically controlled for he influence of depression.[PMID 18629430]
A study of 97 "normal" individuals concluded that rs25531(G;G) individuals selectively process positive affective material alongside selective avoidance of negative affective material, in a manner absent among individuals carrying a rs25531(A) allele. To put it another way, if this conclusion drawn from a very small sample of people can be replicated, rs25531(G;G) individuals may have a tendency to be optimists and to be more resilient to stress.10.1098/rspb.2008.1788
A study published in 2011 of 2,500+ individuals followed from 1995 - 2008 as part of the US National Longitudinal Study of Adolescent Health found that twice as many respondents with two 5-HTTLPR long variants said they were very satisfied with life compared with carriers of two short versions. Conversely, 26% of those carrying two short alleles said they were dissatisfied with life, compared with 20% of people carrying two long variants.10.1038/jhg.2011.39 This blog post investigates the statistics.
A study of 135 patients with major depressive disorder (mean age 31.1+/-11.6 years, 68% females) treated with escitalopram 10-20 mg/day for 12 weeks concluded that patients carrying the rs25531(A) allele may be at increased risk for side effects (e.g. headaches), but they say no associations with efficacy.[PMID 19272758]
[PMID 19521089] Serotonin Transporter Gene Polymorphic Element 5-HTTLPR Increases the Risk of Sporadic Parkinson's Disease in Italy
Protocol for genotyping rs25531
[PMID 19570226] Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans
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[PMID 21319930] Associations between serotonin transporter gene promoter region (5-HTTLPR) polymorphism and gaze bias for emotional information
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[PMID 18441666] Extended evaluation of serotonin transporter gene functional polymorphisms in subjects with post-stroke depression.
[PMID 18444253] Additional functional variation at the SLC6A4 gene.
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[PMID 18951433] Lack of association of the serotonin transporter gene promoter region polymorphism, 5-HTTLPR, including rs25531 with cigarette smoking and alcohol consumption.
[PMID 18981341] Association of serotonin transporter gene polymorphisms with poststroke depression.
[PMID 19015103] Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting.
[PMID 19020798] Association study to evaluate the serotonin transporter and apolipoprotein E genes in frontotemporal lobar degeneration in Italy.
[PMID 19032574] Characterization of a functional polymorphism in the 3' UTR of SLC6A4 and its association with drinking intensity.
[PMID 19122845] An examination of the association between the 5-HTT promoter region polymorphism and depressogenic attributional styles in childhood.
[PMID 19125330] The serotonin transporter polymorphism rs25531 is associated with irritable bowel syndrome.
[PMID 19249159] Sex-specific association between the 5-HTT gene-linked polymorphic region and basal cortisol secretion.
[PMID 19429111] No association between polymorphism of serotonin transporter gene and depression in Parkinson's disease in Chinese.
[PMID 19541292] Accurate, Large-Scale Genotyping of 5HTTLPR and Flanking Single Nucleotide Polymorphisms in an Association Study of Depression, Anxiety, and Personality Measures.
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[PMID 19860858] Combinatorial interaction between two human serotonin transporter gene variable number tandem repeats and their regulation by CTCF.
[PMID 19884608] Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations.
[PMID 19962442] Emotion specific modulation of automatic amygdala responses by 5-HTTLPR genotype.
[PMID 19996755] Serotonin transporter triallelic genotype and response to citalopram and risperidone in dementia with behavioral symptoms.
[PMID 20406689] Serotonin transporter polymorphisms (SLC6A4 insertion/deletion and rs25531) do not affect the availability of 5-HTT to [11C] DASB binding in the living human brain.
[PMID 20450949] Serotonin transporter gene polymorphisms and treatment-resistant depression.
[PMID 20452607] Influence of serotonin transporter gene polymorphisms on clozapine response in Brazilian schizophrenics.
[PMID 20452754] Mixture regression analysis on age at onset in bipolar disorder patients: investigation of the role of serotonergic genes.
[PMID 20455953] Serotonin transporter gene, childhood emotional abuse and cognitive vulnerability to depression.
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[PMID 20515362] Genetic predictors of response to treatment with citalopram in depression secondary to traumatic brain injury.
[PMID 20584552] The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder.
[PMID 20862697] Rare genotype combination of the serotonin transporter gene associated with treatment response in severe personality disorder.
[PMID 20971165] Relationships among 5-HTT genotype, life events and gender in the recognition of facial emotions.
[PMID 21166770] Dopamine D4 receptor and serotonin transporter gene effects on the longitudinal development of infant temperament.
[PMID 21172166] Pharmacogenetics of antidepressant response.
[PMID 21232011] Serotonin transporter allelic variation in mothers predicts maternal sensitivity, behavior and attitudes toward 6-month-old infants.
[PMID 21290142] Parent of origin effect and allelic expression imbalance of the serotonin transporter in bipolar disorder and suicidal behaviour.
[PMID 21356267] 5-HTTLPR and COMTval158met genotype gate amygdala reactivity and habituation.
[PMID 21429092] Serotonin transporter gene variants and prediction of stress-induced risk for psychological distress.
[PMID 21441157] Serotonin transporter gene polymorphism in Chinese patients with poststroke depression: a case-control study.
[PMID 21453464] The influence of psychiatric screening in healthy populations selection: a new study and meta-analysis of functional 5-HTTLPR and rs25531 polymorphisms and anxiety-related personality traits.
[PMID 21497794] A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings.
[PMID 21818827] The relationship between combat-related posttraumatic stress disorder and the 5-HTTLPR/rs25531 polymorphism.
[PMID 21893641] Acute and posttraumatic stress symptoms in a prospective gene x environment study of a university campus shooting.
[PMID 22094432] Perception of a naturalistic stressor interacts with 5-HTTLPR/rs25531 genotype and gender to impact reward responsiveness.
[PMID 22348680] Somatic markers mediate the effect of serotonin transporter gene polymorphisms on Iowa Gambling Task.
[PMID 22489680] No difference in 5-HTTLPR and Stin2 polymorphisms frequency between premature ejaculation patients and controls.
[PMID 22520017] Suicide ideators and attempters with schizophrenia--the role of 5-HTTLPR, rs25531, and 5-HTT VNTR Intron 2 variants.
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[PMID 23021380] Strong effects of environmental factors on prevalence and course of major depressive disorder are not moderated by 5-HTTLPR polymorphisms in a large Dutch sample
[PMID 23499791] Resting-state cerebral blood flow in amygdala is modulated by sex and serotonin transporter genotype
[PMID 22390669] Interaction between serotonin transporter polymorphism (5-HTTLPR) and stressful life events in adolescents' trajectories of anxious/depressed symptoms.
[PMID 22623017] Serotonin transporter-linked polymorphic region (5-HTTLPR) genotype is associated with cortisol responsivity to naloxone challenge.
[PMID 22836288] 5-HTTLPR X stress in adolescent depression: moderation by MAOA and gender.
[PMID 22884012] Influence of serotonin transporter promoter variation on the effects of separation from parent/partner on depression.
[PMID 22907732] Interaction between polymorphisms in serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes predict treatment response to venlafaxine XR in generalized anxiety disorder.
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[PMID 22921508] Association between serotonin transporter promoter polymorphisms and psychological distress in a diabetic population.
[PMID 23033208] Characterization of serotonin transporter gene (SLC6A4) polymorphisms and its association with drug dependence in a Jordanian Arab population.
[PMID 23101739] The Generation R Study: A review of design, findings to date, and a study of the 5-HTTLPR by environmental interaction from fetal life onward.
[PMID 23123360] Allele-specific associations of 5-HTTLPR/rs25531 with ADHD and autism spectrum disorder.
[PMID 23149035] Association study of serotonin transporter availability and SLC6A4 gene polymorphisms in patients with major depression.
[PMID 23261136] State dependent gene-environment interaction: serotonin transporter gene-child abuse interaction associated with suicide attempt history among depressed psychiatric inpatients.
[PMID 23277270] 5-HTTLPR rs25531A > G Differentially Influence Paroxetine and Fluvoxamine Antidepressant Efficacy: A Randomized Controlled Trial.
[PMID 23313272] An association study of suicide and candidate genes in the serotonergic system.
[PMID 23510579] Worldwide population variation and haplotype analysis at the serotonin transporter gene SLC6A4 and implications for association studies.
[PMID 23630162] Common and rare alleles of the serotonin transporter gene, SLC6A4, associated with Tourette's disorder.
[PMID 24776739] Multimodal imaging of a tescalcin (TESC)-regulating polymorphism (rs7294919)-specific effects on hippocampal gray matter structure
[PMID 25214390] Interaction among childhood trauma and functional polymorphisms in the serotonin pathway moderate the risk of depressive disorders
[PMID 25564228] Population Frequencies of the Triallelic 5HTTLPR in Six Ethnicially Diverse Samples from North America, Southeast Asia, and Africa
[PMID 25671637] Relationship of Genetic Variation in the Serotonin Transporter Gene (SLC6A4) and Congenital and Acquired Cardiovascular Diseases
[PMID 25793742] An Examination of the Association between 5-HTTLPR, Combat Exposure, and PTSD Diagnosis among U.S. Veterans
[PMID 25903736] Serotonin transporter gene polymorphisms: Relation with platelet serotonin level in patients with primary Sjogren's syndrome
[PMID 25990886] Impact of monoamine-related gene polymorphisms on hippocampal volume in treatment-resistant depression
[PMID 24021217] Common selective serotonin reuptake inhibitor side effects in older adults associated with genetic polymorphisms in the serotonin transporter and receptors: data from a randomized controlled trial
[PMID 26175754] DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women
[PMID 26232751] Interaction of the 5-HTTLPR and childhood trauma influences memory bias in healthy individuals
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