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101. A serotonin transporter polymorphism is associated with postoperative nausea and vomiting: An observational study in two different patient cohorts. (Abstract)

A serotonin transporter polymorphism is associated with postoperative nausea and vomiting: An observational study in two different patient cohorts. Clinical risk factors for postoperative nausea and vomiting (PONV) are well described, whereas genetic findings are conflicting.The aim of this study was to investigate a possible association of genetic variants and nongenetic variables with the incidence and severity of PONV.A prospective observational study in two independent and different patient (...) ): 3.6 (2.7 to 4.8), P < 0.0001], nonsmoking status 1.8 (1.3 to 2.5), P < 0.001, the SS genotype (5-HTTLPR, rs4795541) of the promoter polymorphism in the serotonin transporter 1.5 (1.1 to 2.1), P = 0.019, and patient age 0.99 (0.98 to 0.99), P = 0.013. Analysis of Cohort B was consistent with these findings [5-HTTLPR: 1.8 (1.4 to 2.3), P < 0.00001]. Sex-specific regression models confirmed this 5-HTTLPR association in women and men.In two independent cohorts, in addition to the well known clinical

2019 European Journal of Anaesthesiology

102. The effects of serotonin modulation on medial prefrontal connectivity strength and stability: A pharmacological fMRI study with citalopram. Full Text available with Trip Pro

The effects of serotonin modulation on medial prefrontal connectivity strength and stability: A pharmacological fMRI study with citalopram. Static and dynamic functional connectivity are being increasingly used to measure the effects of disease and a range of different interventions on brain networks. While preliminary evidence suggests that static connectivity can be modulated by chronic antidepressants administration in healthy individuals and in major depression, much less is known about (...) the acute effects of antidepressants especially on dynamic functional connectivity changes. Here we examine acute effects of antidepressants on dynamic functional connectivity within the default mode network. The default mode network is a well described network with many functions in which the role of serotonin is not clear.In this work we measured acute pharmacological effects of an infusion of the selective serotonin reuptake inhibitor (SSRI) citalopram (10 mg) in a sample of thirteen healthy

2019 Progress in neuro-psychopharmacology & biological psychiatry Controlled trial quality: uncertain

103. Differential impact of endurance, strength, or combined training on quality of life and plasma serotonin in healthy older women. (Abstract)

Differential impact of endurance, strength, or combined training on quality of life and plasma serotonin in healthy older women. Aging is associated with a progressive decline in physical and neurophysiological functions, and some studies suggest that cerebral serotonin is decreased in older adults. These factors contribute to reduced ability to perform daily activities, influencing quality of life (QoL). Regular physical activity has demonstrated important benefits in reversing ageing effects (...) ; however, little is known whether different training protocols might induce differential effects on QoL. The aim of this study was to verify the effects of different types of training on QoL and its relation with plasma serotonin in healthy older women. Forty-eight older women were randomly assigned in four groups: Strength Training (ST), Endurance Training (ET), Combined Training (CT), and Control Group (CG) which was instructed not to engage in any physical exercise during the study time

2019 Aging clinical and experimental research Controlled trial quality: uncertain

104. Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway. Full Text available with Trip Pro

Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway. Our study aimed to evaluate the side effects of selective serotonin reuptake inhibitors (SSRIs) on the ocular surface.Twenty patients with depression and dry eye disease (DED) were randomly picked to receive SSRI treatment, whereas another 20 patients received placebo treatment. The serotonin, inflammatory cytokine, and proapoptotic protein levels were determined by using protein (...) chip, qRT-PCR, and ELISA analyses. A rat depression model was established, and SSRIs were applied for 3 or 6 weeks. Tear production and corneal epithelial barrier function were evaluated. The serotonin and inflammatory cytokine levels were analyzed by qRT-PCR, immunohistochemical staining, and ELISA. Human corneal epithelial cells were subjected to serotonin, a HTR antagonist, and/or an NF-κB signaling inhibitor. The inflammatory cytokine and proapoptotic protein levels were determined by qRT-PCR

2019 Investigative Ophthalmology & Visual Science

105. Potentiation of serotonin signaling leads to increased carbohydrate and lipid absorption in the murine small intestine. (Abstract)

Potentiation of serotonin signaling leads to increased carbohydrate and lipid absorption in the murine small intestine. Enteric serotonin influences intestinal homeostasis and functions as a mucosal growth factor. Previously, we demonstrated increased mucosal surface area and enhanced crypt cell proliferation in serotonin reuptake transporter (SERT)-deficient mice. Therefore, we hypothesized that serotonin-mediated mucosal growth would also result in enhanced carbohydrate and lipid (...) .Villus height and crypt depth were significantly greater in the middle and distal small intestine of SERTKO animals compared to WT. Overall absorption of D-xylose and BODIPY was greater in SERTKO animals compared to WT animals. Absorption of D-xylose was persistently elevated in SERTKO animals, while there was an initial delay in BODIPY absorption followed by a sustained and significantly greater absorption in SERTKO animals at 60-360 min after gavage.Potentiation of serotonin signaling in SERTKO

2019 Journal of Pediatric Surgery

106. Comparative Cardiac Safety of Selective Serotonin Reuptake Inhibitors among Individuals Receiving Maintenance Hemodialysis. (Abstract)

Comparative Cardiac Safety of Selective Serotonin Reuptake Inhibitors among Individuals Receiving Maintenance Hemodialysis. Individuals receiving maintenance hemodialysis may be particularly susceptible to the lethal cardiac consequences of drug-induced QT prolongation because they have a substantial cardiovascular disease burden and high level of polypharmacy, as well as recurrent exposure to electrolyte shifts during dialysis. Electrophysiologic data indicate that among the selective (...) serotonin reuptake inhibitors (SSRIs), citalopram and escitalopram prolong the QT interval to the greatest extent. However, the relative cardiac safety of SSRIs in the hemodialysis population is unknown.In this retrospective cohort study, we used data from a cohort of Medicare beneficiaries receiving hemodialysis included in the US Renal Data System registry (2007-2014). We used a new-user design to compare the 1-year risk of sudden cardiac death among hemodialysis patients initiating SSRIs

2019 Journal of the American Society of Nephrology

107. Use of a Bioinformatics-Based Toxicity Scoring System to Assess Serotonin Burden and Predict Population-Level Adverse Drug Events from Concomitant Serotonergic Drug Therapy. Full Text available with Trip Pro

Use of a Bioinformatics-Based Toxicity Scoring System to Assess Serotonin Burden and Predict Population-Level Adverse Drug Events from Concomitant Serotonergic Drug Therapy. Numerous medications interact at serotonin (5-hydroxytryptamine [5-HT]) receptors directly or through off-target interactions, causing mild to severe serotonergic adverse drug events (ADEs), particularly among older adults. Our objective was to develop a novel molecular-based toxicity scoring system to assess serotonergic (...) created for each drug exposure cohort and matched in a 4:1 ratio for age, sex, and length of enrollment.Eight 5-HT medications were screened against multiple bioactivity databases to identify their off-target interactions at 5-HT receptors and serotonin reuptake transporter protein. A computational serotonin burden score (SBS) was derived from the receptor-specific interaction propensities reported from the comprehensive bioactivity screen. Linear regression was used to characterize associations

2019 Pharmacotherapy

108. Traditional Tibetan medicine Anzhijinhua San attenuates Ovalbumin-induced diarrhea by regulating serotonin signaling system in mice. (Abstract)

Traditional Tibetan medicine Anzhijinhua San attenuates Ovalbumin-induced diarrhea by regulating serotonin signaling system in mice. Tibetan medicine has a history of 3800 years. Anzhijinhua San (AZJHS) which is a traditional Tibetan medicine was effective in the treatment of indigestion, anorexia and cold diarrhea etc. However, the effects of AZJHS on allergic diarrhea have not been reported.The aim of present study is to elucidate the effect of AZJHS on the preventive effect of experimental (...) . Immunohistochemical and histopathology were performed in gastrointestinal tract tissues. 5-HT-related gene expression was assayed in colon.Severe symptoms of allergic diarrhea were observed in the model group. AZJHS (46.7, 467.0mg/kg) ameliorated diarrhea and reduced anaphylaxis in mice. There was a very significant hyperplasia (P<0.05) in serotonin (5-HT)-related cells after the 10th challenged with OVA, and AZJHS (46.7, 467.0mg/kg) significant suppressed the increases of 5-HT-related cells. The nuclei of EC

2019 Journal of Ethnopharmacology

109. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. (Abstract)

Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. The main psychedelic component of magic mushrooms is psilocybin, which shows promise as a treatment for depression and other mental disorders. Psychedelic effects are believed to emerge through stimulation of serotonin 2A receptors (5-HT2ARs) by psilocybin's active metabolite, psilocin. We here report for the first time the relationship between intensity of psychedelic effects, cerebral

2019 Neuropsychopharmacology

110. Persistence with selective serotonin (norepinephrine) reuptake inhibitors in Germany-A retrospective database analysis. (Abstract)

Persistence with selective serotonin (norepinephrine) reuptake inhibitors in Germany-A retrospective database analysis. Selective serotonin (norepinephrine) reuptake inhibitors (SS(N)RIs) are used in the treatment of depression. The aim of this study was to assess the persistence with SS(N)RIs in outpatients treated by general practitioners (GP) or psychiatrists (PSY) in Germany, and to investigate the association between persistence and the following factors: age, gender, specialty

2019 Journal of Affective Disorders

111. Neural activity in the periaqueductal gray and other specific subcortical structures is enhanced when a selective serotonin reuptake inhibitor selectively prevents seizure-induced sudden death in the DBA/1 mouse model of sudden unexpected death in epileps (Abstract)

Neural activity in the periaqueductal gray and other specific subcortical structures is enhanced when a selective serotonin reuptake inhibitor selectively prevents seizure-induced sudden death in the DBA/1 mouse model of sudden unexpected death in epileps Sudden unexpected death in epilepsy (SUDEP) is a critical issue in epilepsy, and DBA/1 mice are a useful animal model of this devastating epilepsy sequela. The serotonin hypothesis for SUDEP proposes that modifying serotonergic function (...) significantly alters susceptibility to seizure-induced respiratory arrest (S-IRA). Agents that enhance serotonergic function, including a selective serotonin reuptake inhibitor, fluoxetine, selectively prevent S-IRA in DBA/1 mice. This study examined fluoxetine-induced changes in brain activity using manganese-enhanced magnetic resonance imaging (MEMRI) to reveal sites in the DBA/1 mouse brain where fluoxetine acts to prevent S-IRA.DBA/1 mice were subjected to audiogenic seizures (Sz) after saline

2019 Epilepsia

112. Zebrafish fin regeneration involves transient serotonin synthesis. Full Text available with Trip Pro

Zebrafish fin regeneration involves transient serotonin synthesis. The zebrafish is a vertebrate organism capable of regenerating many of its organs. Notably, it can undergo epimorphic regeneration of its fins after amputation. This process occurs through the formation of a wound epithelium and the dedifferentiation of mesenchymal and bone-forming cells, which form a proliferative blastema. Here, we report that the entry into the regenerative process involves the local synthesis of serotonin (5 (...) -hydroxytryptamine, 5-HT) in the injury-associated tissue. One day after wounding, intracellular accumulation of serotonin was induced in the stump below the amputation plane. During blastema formation, serotonin was detected in the mesenchyme at the vicinity of the amputation plane and in the apical wound epithelium. During the advanced outgrowth phase, this monoamine was no longer present in the blastema, suggesting a temporal involvement of serotonin in the postinjury area. We show the expression of two

2019 Wound Repair and Regeneration

113. The effect of serotonin reuptake inhibitors on the vaginal epithelium in postmenopausal women. Full Text available with Trip Pro

The effect of serotonin reuptake inhibitors on the vaginal epithelium in postmenopausal women. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used as alternative treatments for the vasomotor symptoms of menopause in women who are unwilling or unable to receive hormone therapy. These agents have been associated with sexual dysfunction and xerostomia (dry mouth), but the effect on the vagina has not been studied. The objective (...) of superficial vaginal epithelial cells and the total MI were higher in the SSRI/SNRI group (p = 0.006 and p = 0.047, respectively). There were no significant differences in FSFI scores, vaginal pH, or total MI values.The use of serotonin reuptake inhibiting drugs does not appear to have a negative influence on the vaginal epithelium and associated vaginal atrophy.

2019 Climacteric

114. Hypophagia induced by hindbrain serotonin is mediated through central GLP-1 signaling and involves 5-HT2C and 5-HT3 receptor activation. (Abstract)

Hypophagia induced by hindbrain serotonin is mediated through central GLP-1 signaling and involves 5-HT2C and 5-HT3 receptor activation. The overlap in neurobiological circuitry mediating the physiological and behavioral response to satiation and noxious/stressful stimuli are not well understood. The interaction between serotonin (5-HT) and glucagon-like peptide-1 (GLP-1) could play a role as upstream effectors involved in mediating associations between anorectic and noxious/stressful stimuli

2019 Neuropsychopharmacology

115. Circadian regulation of depression: a role for serotonin. (Abstract)

Circadian regulation of depression: a role for serotonin. Synchronizing circadian (24 h) rhythms in physiology and behavior with the environmental light-dark cycle is critical for maintaining optimal health. Dysregulation of the circadian system increases susceptibility to numerous pathological conditions including major depressive disorder. Stress is a common etiological factor in the development of depression and the circadian system is highly interconnected to stress-sensitive (...) neurotransmitter systems such as the serotonin (5-hydroxytryptamine, 5-HT) system. Thus, here we propose that stress-induced perturbation of the 5-HT system disrupts circadian processes and increases susceptibility to depression. In this review, we first provide an overview of the basic components of the circadian system. Next, we discuss evidence that circadian dysfunction is associated with changes in mood in humans and rodent models. Finally, we provide evidence that 5-HT is a critical factor linking

2019 Frontiers in Neuroendocrinology

116. Deficiency of ZnT8 Promotes Adiposity and Metabolic Dysfunction by Increasing Peripheral Serotonin Production. (Abstract)

Deficiency of ZnT8 Promotes Adiposity and Metabolic Dysfunction by Increasing Peripheral Serotonin Production. ZnT8 is a zinc transporter enriched in the pancreatic beta cells and its polymorphism is associated with increased susceptibility to type 2 diabetes. However, the exact role of ZnT8 in systemic energy metabolism remains elusive. In this study, we found that ZnT8 knockout mice displayed increased adiposity without obvious weight gain. We also observed the intestinal tract morphology

2019 Diabetes

117. Successful treatment of clozapine-nonresponsive refractory hallucinations and delusions with pimavanserin, a serotonin 5HT-2A receptor inverse agonist. (Abstract)

Successful treatment of clozapine-nonresponsive refractory hallucinations and delusions with pimavanserin, a serotonin 5HT-2A receptor inverse agonist. Clozapine was the widely accepted gold standard treatment for treatment resistant psychotic symptoms. Clozapine has efficacy of about 50% and some responding patients have to discontinue it due to serious adverse effects. The search for novel agents to use for clozapine-non-responders continues. One such possible agent is the non-dopaminergic (...) antipsychotic pimavanserin, an inverse agonist of serotonin 5-HT2A receptors which was recently approved for the hallucinations and delusions of Parkinson's Disease Psychosis. We report here the successful results of using pimavanserin in patients with refractory hallucinations and delusions who failed to respond to clozapine. We also report similar results in refractory psychosis patients who did not receive clozapine.We present ten cases of patients with schizophrenia and schizoaffective disorder

2019 Schizophrenia Research

118. Plasma serotonin levels are associated with antidepressant response to SSRIs. Full Text available with Trip Pro

Plasma serotonin levels are associated with antidepressant response to SSRIs. Less than half of patients with major depressive disorder (MDD) respond to their first antidepressant trial. Our understanding of the underlying mechanisms of selective serotonin reuptake inhibitors (SSRIs) remains poor, and there is no reliable method of predicting treatment response.Thirty-seven MDD subjects and 41 healthy controls, somatically healthy and medication-free for at least six weeks, were recruited (...) , and plasma serotonin (5-HT) levels were assessed at baseline. Twenty-six of the MDD subjects were then treated in an open-label manner with clinically appropriate doses of sertraline for 8 weeks, after which plasma 5-HT levels were again assessed. Response to treatment was defined as an improvement of 50% or more on the Hamilton Depression Rating Scale.Non-responders to sertraline treatment had significantly lower pre-treatment 5-HT levels compared to both healthy controls and responders (F = 4.4, p 

2019 Journal of Affective Disorders

119. Fenfluramine, a serotonin-releasing drug, prevents seizure-induced respiratory arrest and is anticonvulsant in the DBA/1 mouse model of SUDEP. (Abstract)

Fenfluramine, a serotonin-releasing drug, prevents seizure-induced respiratory arrest and is anticonvulsant in the DBA/1 mouse model of SUDEP. Prevention of sudden unexpected death in epilepsy (SUDEP) is a critical goal for epilepsy therapy. The DBA/1 mouse model of SUDEP exhibits an elevated susceptibility to seizure-induced death in response to electroconvulsive shock, hyperthermia, convulsant drug, and acoustic stimulation. The serotonin hypothesis of SUDEP is based on findings (...) that treatments which modify serotonergic function significantly alter susceptibility to seizure-induced sudden death in several epilepsy models, including DBA/1 mice. Serotonergic abnormalities have also recently been observed in human SUDEP. Fenfluramine is a drug that enhances serotonin release in the brain. Recent studies have found that the addition of fenfluramine improved seizure control in patients with Dravet syndrome, which has a high incidence of SUDEP. Therefore, we investigated the effects

2019 Epilepsia

120. Peripheral serotonin causes dengue-induced thrombocytopenia through 5HT<sub>2</sub> receptors. (Abstract)

Peripheral serotonin causes dengue-induced thrombocytopenia through 5HT2 receptors. Dengue virus (DENV) is the most prevalent vector-borne viral pathogen, infecting millions of patients annually. Thrombocytopenia, a reduction in circulating platelet counts, is the most consistent sign of DENV-induced disease, independent of disease severity. However, the mechanisms leading to DENV-induced thrombocytopenia are unknown. Here, we show that thrombocytopenia is caused by serotonin (...) , derived from mast cells (MCs), which are immune cells that are present in the perivascular space and a major peripheral source of serotonin. We show that during DENV infection, MCs release serotonin, which prompts platelet activation, aggregation and enhanced phagocytosis, dependent on 5HT2A receptors. MC-deficiency in mice or pharmacological inhibition of MCs reversed thrombocytopenia. Furthermore, reconstitution of MC-deficient mice with wild-type MCs, but not MCs lacking serotonin synthesis due

2019 Blood

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