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Serotonin

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101. 5-HT1A receptor, 5-HT2A receptor and serotonin transporter binding in the human auditory cortex in depression Full Text available with Trip Pro

5-HT1A receptor, 5-HT2A receptor and serotonin transporter binding in the human auditory cortex in depression Serotonergic system abnormalities are implicated in many psychiatric disorders, including major depression. The temporal lobe receives a high density of serotonergic afferent projections, and responses in the primary auditory cortex to sound are modulated by serotonergic tone. However, the associations between changes in serotonergic tone, disease state and changes in auditory cortical (...) function remain to be clarified.We quantified serotonin 1A (5-HT1A) receptor binding, serotonin 2A (5-HT2A) receptor binding, and serotonin transporter (SERT) binding in Brodmann areas (BA) 41/42, 22, 9 and 4 from postmortem brain sections of 40 psychiatrically healthy controls and 39 individuals who had a history of a major depressive episode (MDE).There was 33% lower 5-HT2A receptor binding in BA 41/42 in individuals who had an MDE than in controls (p = 0.0069). Neither 5-HT1A nor SERT binding in BA

2019 Journal of Psychiatry & Neuroscience

102. Citalopram overdose and severe serotonin syndrome in an intermediate metabolizing patient. (Abstract)

Citalopram overdose and severe serotonin syndrome in an intermediate metabolizing patient. Citalopram is a selective serotonin reuptake inhibitor used for treatment of depression. Metabolism is primarily through CYP3A4 and CYP2C19; activity of the latter can vary depending on genetics. Although rare after single agent exposure, large citalopram ingestions can lead to serotonin syndrome. We report a case of citalopram overdose in an intermediate CYP2C19 metabolizer complicated by severe (...) serotonin syndrome.A 25-year-old female presented after intentional citalopram overdose with seizures, tachycardia, persistent neuromuscular findings, and severe hyperthermia requiring aggressive sedation and cooling. Protracted symptoms required critical care services throughout a 14 day hospital stay despite traditional treatment of serotonin syndrome. Pharmacogenomic studies revealed intermediate CYP2C19 metabolism which reduces citalopram inactivation and may cause increased levels and toxicity.In

2019 American Journal of Emergency Medicine

103. Illicit upregulation of serotonin signaling pathway in adrenals of patients with high plasma or intraadrenal ACTH levels. Full Text available with Trip Pro

Illicit upregulation of serotonin signaling pathway in adrenals of patients with high plasma or intraadrenal ACTH levels. In the human adrenal, serotonin (5-HT), released by mast cells stimulates corticosteroid secretion through activation of type 4 serotonin receptors (5-HT4R). In primary pigmented nodular adrenocortical disease (PPNAD) cells, activation of the cAMP/protein kinase A (PKA) pathway by PRKAR1A mutations triggers upregulation of the 5-HT synthesizing enzyme tryptophan hydroxylase

2019 Journal of Clinical Endocrinology and Metabolism

104. Central serotonin prevents hypotension and hypothermia and reduces plasma and spleen cytokine levels during systemic inflammation. (Abstract)

Central serotonin prevents hypotension and hypothermia and reduces plasma and spleen cytokine levels during systemic inflammation. An exceptionally high mortality rate is observed in sepsis and septic shock. Systemic administration of lipopolysaccharide (LPS) has been used as an experimental model for sepsis resulting in an exacerbated immune response, brain neurochemistry adjustments, hypotension, and hypothermia followed by fever. Central serotonergic pathways not only modulate systemic (...) inflammation (SI) but also are affected by SI, including in the anteroventral region of the hypothalamus (AVPO), which is the hierarchically most important region for body temperature (Tb) control. In this study, we sought to determine if central serotonin (5-HT) plays a role in SI induced by intravenous administration of LPS (1.5 mg/kg) in male Wistar rats (280-350 g) by assessing 5-HT levels in the AVPO, mean arterial pressure, heart rate, and Tb up to 300 min after LPS administration, as well

2019 Brain, behavior, and immunity

105. Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule. Full Text available with Trip Pro

Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule. Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin produced within the central nervous system regulates behavior, suppresses appetite, and promotes energy expenditure by increasing sympathetic drive to brown adipose tissue. In addition to these central circuits, emerging evidence also (...) suggests an important role for peripheral serotonin as a factor that enhances nutrient absorption and storage. Specifically, glucose and fatty acids stimulate the release of serotonin from the duodenum, promoting gut peristalsis and nutrient absorption. Serotonin also enters the bloodstream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion and de novo lipogenesis in the liver and white adipose tissue, while reducing lipolysis and the metabolic

2019 Endocrine Reviews

106. Comparative Cardiac Safety of Selective Serotonin Reuptake Inhibitors among Individuals Receiving Maintenance Hemodialysis. Full Text available with Trip Pro

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. 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

108. 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

109. 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

110. Deficiency of ZnT8 Promotes Adiposity and Metabolic Dysfunction by Increasing Peripheral Serotonin Production. Full Text available with Trip Pro

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

111. 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

112. 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

113. Bioactivities of serotonin transporter mediate antidepressant effects of Acorus tatarinowii Schott. (Abstract)

Bioactivities of serotonin transporter mediate antidepressant effects of Acorus tatarinowii Schott. Acrorus tatarinowii Schott has been widely used in the treatments of neuropsychiatric and digestive disorders in clinical practices of traditional Chinese medicine for thousands of years. Both clinical and preclinical studies demonstrated antidepressant effects of A. tatarinowii. However, the possible action mechanisms of antidepressant effects of A. tatarinowii remain unraveled.The present study (...) aimed to investigate the roles of serotonin transporter (SERT) in antidepressant effects of A. tatarinowii.Antidepressant effects of water extract of A. tatarinowii were evaluated by forced swimming test (FST), tail suspension test (TST) and locomotor activity test. The water extract was analyzed by ultra high performance liquid chromatography (UPLC) method. Two major fractions of A. tatarinowii, petroleum ether extract and water extract after petroleum ether processed, were prepared and analyzed

2019 Journal of Ethnopharmacology

114. Functional connectivity of the raphe nucleus as a predictor of the response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder. Full Text available with Trip Pro

Functional connectivity of the raphe nucleus as a predictor of the response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder. Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological agents for treating obsessive-compulsive disorder (OCD). However, because nearly half of patients show insufficient SSRI responses, serotonergic dysfunction in heterogeneous OCD patients should be investigated for precision medicine. We aimed to determine whether

2019 Neuropsychopharmacology

115. Editorial: Cognitive-Behavior Therapy Versus Serotonin Reuptake Inhibitors for Pediatric Obsessive-Compulsive Disorder. (Abstract)

Editorial: Cognitive-Behavior Therapy Versus Serotonin Reuptake Inhibitors for Pediatric Obsessive-Compulsive Disorder. How should treatment be initiated for children with obsessive-compulsive disorder (OCD)? This editorial comments on an article by Melin and colleagues,1 published in this issue, from the NordLOTS study, which reports excellent outcomes from cognitive behavior therapy (CBT) for children with OCD. Children continued to improve after CBT was discontinued; at 3 year follow-up (...) , they enjoyed a 90% response rate. Such continuing improvement contrasts markedly with other studies finding, among patients treated with selective serotonin reuptake inhibitors (SSRIs), high relapse rates upon discontinuation. Evidence has accumulated that upon discontinuation of SSRIs, there is often not simply a return to baseline, but a withdrawal state for which opposites of the therapeutic effects can be prominent symptoms-these may include anxiety, dysphoria, irritability, and insomnia. The duration

2019 Journal of the American Academy of Child and Adolescent Psychiatry

116. 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

117. 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

118. 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

119. 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

120. 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

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