SLC6A4 S/S

OBJECTIVE: To study the relationship of polymorphic variants of the SLC6A4 gene with depression among people aged 25-44 years in Novosibirsk. MATERIAL AND METHODS: Under the WHO program «MONICA-psychosocial (MOPSY)», a random representative sample of people aged 25-44 years from the population of the Oktyabrsky district of Novosibirsk (men n =725, mean age 43.4±0.4 years, response - 71.3%, women n =710, mean age 44.8±0.4 years, response - 72%)...

BACKGROUND: Food insecurity is a persistent concern in the United States and has been shown to affect child mental health and behavior. The SLC6A4 gene has been indicated as a moderator of the effects of chronic stress on anxiety in adolescents aged 14-21. However, it is unclear if SLC6A4 may also play a role in the effects of childhood food insecurity, a form of chronic stress, on adolescent mental health. This study aimed to identify effects of food insecurity on adolescents' mental health and delinquent behavior when both mom and child go hungry in the child's early years, and the potential interaction with SLC6A4 variants (SS/LL)...

BACKGROUND: Pediatric chronic intestinal pseudo-obstruction (PIPO) is a rare disease characterized by symptoms and radiological signs suggestive of intestinal obstruction, in the absence of lumen-occluding lesions. It results from an extremely severe impairment of propulsive motility. The intestinal endocrine system (IES) jointly with the enteric nervous system (ENS) regulates secreto-motor functions via different hormones and bioactive messengers/neurotransmitters. The neurotransmitter 5-hydroxytryptamine (5-HT) (or serotonin) is linked to intestinal peristalsis and secretory reflexes...

OBJECTIVE: Anorexia nervosa (AN) is a severe psychiatric disorder characterized by an intense fear of gaining weight, a relentless pursuit of thinness, and a distorted body image. Recent research highlights the substantial contribution of genetics to AN's etiology, with genes like BDNF, SLC6A4, and DRD2 implicated. However, a comprehensive genetic test for AN diagnosis is lacking. This study aims to elucidate the biological foundations of AN, examining variants in genes associated with syndromic forms, rare variants in AN patients, and candidate genes from GWAS studies, murine models, or established molecular pathways...

Pre-eclampsia (PE) is a disorder characterized by hypertension in the second trimester of pregnancy that results from abnormal placentation affecting fetal development and maternal health. Previous studies have shown the role of serotonin (5-HT) that leads to poor placental perfusion, where S/S and S/L polymorphisms promote the solute carrier family 6 member 4 (SLC6A4) gene associated with the risk of developing changes in the microvasculature of the placenta. This study looked at the association between the gene variant 5-HTTLPR (serotonin-transporter-linked promoter region) of the SLC6A4 gene and the occurrence of PE...

Prenatal exposure to maternal depression and serotonin reuptake inhibitor (SRI) antidepressants both affect the development of the hypothalamic-pituitary-adrenal (HPA) system, possibly via the neurotransmitter serotonin (5HT). In a community cohort, we investigated the impact of two factors that shape prenatal 5HT signaling (prenatal SRI [pSRI] exposure and child SLC6A4 genotype) on HPA activity at age 6 years. Generalized estimating equation (GEE) models were used to study associations between cortisol reactivity, pSRI exposure, and child SLC6A4 genotype, controlling for maternal depression, child age, and sex (48 pSRI exposed, 74 nonexposed)...

This study aimed to explore the mechanism of albiflorin in the treatment of Alzheimer's disease(AD) based on network pharmacology, molecular docking, and in vitro experiments. Network pharmacology was used to predict the potential targets and pathways of albiflorin against AD, and molecular docking technology was used to verify the binding affinity of albiflorin to key target proteins. Finally, the AD cell model was induced by Aβ_(25-35) in rat pheochromocytoma(PC12) cells and intervened by albiflorin to validate core targets and pathways...

Identifying and resolving molecular complexities underlying chronic neuropathic pain is a significant challenge. Among the numerous classes of histone deacetylases, the Class I (HDAC 1-3) and Class III (sirtuins) have been best studied in experimental pain models where inhibitor pre-treatments but not post-treatments abrogate development of pain-related behaviors. Post-treatment here in week 3 with less well-studied Class IIa HDAC4/5 selective inhibitor LMK235 diminishes the trigeminal ganglia increases of HDAC5 RNA and protein in two chronic orofacial neuropathic pain models to levels measured in naïve mice at week 10 post-model induction...

The recombinant B6.CBA-D13Mit76C mouse strain is characterized by an altered sensitivity of 5-HT1A receptors and upregulated 5-HT1A gene transcription. Recently, we found that in B6.CBA-D13Mit76C mice, chronic fluoxetine treatment produced the pro-depressive effect in a forced swim test. Since 5-HT2A receptor blockade may be beneficial in treatment-resistant depression, we investigated the influence of chronic treatment (14 days, intraperitoneally) with selective 5-HT2A antagonist ketanserin (0.5 mg/kg), fluoxetine (20 mg/kg), or fluoxetine + ketanserin on the behavior, functional activity of 5-HT1A and 5-HT2A receptors, serotonin turnover, and transcription of principal genes of the serotonin system in the brain of B6...

BACKGROUND: The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression. METHODS: Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified...

BACKGROUND: The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression. METHODS: Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified...

Behaviour has a significant heritable component; however, unpicking the variants of interest in the neural circuits and molecular pathways that underpin these has proven difficult. Here, we present a comprehensive analysis of the relationship between known and new candidate genes from identified pathways and key behaviours for survival in 109 adult rhesus macaques (Macaca mulatta). Eight genes involved in emotion were analysed for variation at a total of nine loci. Genetic data were then correlated with cognitive and observational measures of behaviour associated with wellbeing and survival using MCMC-based Bayesian GLMM in R, to account for relatedness within the macaque population...

BACKGROUND: Depression is a debilitating condition that affects the mind and the individual's body. The improving effects of saffron on depression and anxiety have long been discussed, with limited information about the molecular mechanism of action. HYPOTHESIS/PURPOSE: Investigating the effect of saffron carotenoids, Crocin and Crocetin, on depression and anxiety in rats by emphasizing some signaling pathways involved. STUDY DESIGN: Depression and anxiety were induced in rats via unpredictable chronic mild stress (UCMS)...

Post-translational modifications are an important mechanism in the regulation of protein expression, function, and degradation. Well-known post-translational modifications are phosphorylation, glycosylation, and ubiquitination. However, lipid modifications, including myristoylation, prenylation, and palmitoylation, are poorly studied. Since the early 2000s, researchers have become more interested in lipid modifications, especially palmitoylation. The number of articles in PubMed increased from about 350 between 2000 and 2005 to more than 600 annually during the past ten years...

Background. The serotonin transporter (SERT), highly expressed in the gut and brain, is implicated in metabolic processes. A genetic variant of the upstream regulatory region of the SLC6A4 gene encoding SERT, the so-called short (s) allele, in comparison with the long (l) allele, results in the decreased function of this transporter, altered serotonergic regulation, an increased risk of psychiatric pathology and type-2 diabetes and obesity, especially in older women. Aged female mice with the complete ( Sert -/- : KO) or partial ( Sert +/- : HET) loss of SERT exhibit more pronounced negative effects following their exposure to a Western diet in comparison to wild-type ( Sert +/+ : WT) animals...

AIM: To develop individualized approaches to the treatment of irritable bowel syndrome (IBS) based on the interaction of genetic and epigenetic factors, to characterize the phenotypes of the disease. MATERIALS AND METHODS: According to the formulated concept of the authors, from the cohort of patients with IBS, subgroups were distinguished - "post-infectious IBS" ( n =45), "IBS in overweight and obese people" ( n =49), "comorbid IBS" ( n =75) and "essential IBS" ( n =51)...

BACKGROUND: Nux Vomica (NV) has the effects of dredging collaterals, relieving pain, dispersing knots, and detumescence, and has a verified effect in treating ischemic stroke (IS), but its molecular mechanism for treating IS remains unclear. In this study, network pharmacology and molecular docking methods were adopted to explore the pharmacological mechanism of NV in treating IS. METHODS: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the HERB database were searched to screen the active components and targets of NV...

Prenatal adversity has been linked to later psychopathology. Yet, research on cumulative prenatal adversity, as well as its interaction with offspring genotype, on brain and behavioral development is scarce. With this study, we aimed to address this gap. In Finnish mother-infant dyads, we investigated the association of a cumulative prenatal adversity sum score (PRE-AS) with (a) child emotional and behavioral problems assessed with the Strengths and Difficulties Questionnaire at 4 and 5 years ( N = 1568, 45...

PURPOSE: The aim of this study was to assess changes in the severity of alcohol craving according to allelic variants of the 5-HTTLPR gene polymorphism during hospitalisation and their association with selected clinical variables in alcohol-dependent patients. PATIENTS AND METHODS: The study is exploratory. Participants were investigated at the 2nd and 6th week of alcohol-dependence therapy in the addiction treatment unit. Recruitment was conducted among alcohol-dependent patients from several Polish drug treatment centres...

Suicide is defined as the action of harming oneself with the intention of dying. It is estimated that worldwide, one person dies by suicide every 40 s, making it a major health problem. Studies in families have suggested that suicide has a genetic component, so the search for genetic variants associated with suicidal behavior could be useful as potential biomarkers to identify people at risk of suicide. In Mexico, some studies of gene variants related to neurotransmission and other important pathways have been carried out and potential association of variants located in the following genes has been suggested: SLC6A4 , SAT-1 , TPH-2 , ANKK1 , GSHR , SCARA50 , RGS10 , STK33 , COMT , and FKBP5...