Serum Serotonin Levels Research Articles

Bronchial Carcinoid and Primary Hyperparathyroidism

Our patient, a 62-year-old female, presented for management of primary hyperparathyroidism. Subsequent to confirmatory lab testing, she underwent Tc-sestamibi imaging for localization of parathyroid adenoma. The imaging was suspicious for right inferior parathyroid adenoma and showed a posterior right lower lobe lung nodule (2.4 1.8 cm) (Figures 1 and 2). Biopsy of the right lung mass showed a lowgrade neuroendocrine tumor (carcinoid). An octreotide scan confirmed the presence of carcinoid in the right lower lobe. Biochemical work-up for carcinoid was unrevealing except for elevated serum serotonin levels at 394 ng/mL (normal range, 50 –220 ng/mL). Subsequent to resection of the lung mass and right inferior/left inferior and right superior parathyroid glands, her serum

Primary Carcinoid Tumors of the Pancreas: Report of Eight Cases

Context Primary pancreatic carcinoid tumors (foregut) are very rare. A typical carcinoid syndrome with diarrhea and flushing may be present. The diagnosis is based on the high urinary 5-HIAA (5-hydroxyndole acetic acid) levels (or high serum serotonin levels) or the immunostaining of serotonin (5-HT) in the tumor cells. Objective We evaluated clinical presentation, endocrine tumor markers, histology, therapeutic approach and follow up. Methods From 1986 to 2011 in our department we observed 211 neuroendocrine (NE) pancreatic tumors and 8 of them (3.8%) were primary carcinoid tumors (5 males and 3 females; averaging 55.8 years, range: 38-69 years). Follow up was updated until December 2012. Results Among the eight patients enrolled, 3 were symptomatic. Seven had high serum 5-HT or high urinary 5-HIAA, and one was asymptomatic with immunostaining of 5-HT in tumor cells. Location: 6 body-tail. All were malignant tumors: 7 liver and 1 single nodal metastases. Markers: 4 high serum 5-HT (up to 176 µmol/L), 7 high urinary 5-HIAA (up to 522 µmol/L). Surgery: 1 left pancreatectomy, 7 biopsy. Histology: 7 NE tumor, 1 negative pancreatic biopsy (liver metastases). Other therapy: 3 treated with somatostatin analogues (SST-A) and chemotherapy (CT), 1 CT and radiometabolic therapy after hepatic artery embolization (HAE), 1 HAE and SST-A, 1 CT. Follow up: 6 dead for disease progression (mean survival 52 months), 2 alive (1 without disease 78 months after surgery; 1 asymptomatic with high 5-HIAA 33 months after SST-A and CT). Conclusion Most of primary pancreatic carcinoids are locally advanced tumors or have liver metastases at time of diagnosis, then patients are not amenable to surgery. Although most patients had high 5-HIAA urinary excretion, few patients had carcinoid syndrome. A long term survival may be achieved with multimodal approach, including chemotherapy, in foregut carcinoid tumors.

Activation of Repair Processes in the Acute Period of Craniocerebral Trauma in Conditions of Neurotrophic Treatment

Emotional, cognitive, and psychoautonomic status were investigated and serum serotonin and brainderived neurotrophic factor (BDNF) levels were measured in 72 patients during the acute phase of craniocerebral trauma (CCT) during treatment using Cerebrolysin. Particular attention was paid to cerebral contusions (CC). Before treatment, patients with CC had neurological and cognitive impairments, as well as mild signs of reactive anxiety and depression, and increased humoral serotonin, related to trauma severity. After treatment, patients showed decreases in the severity of neurological impairments, along with improvements in the state of cognitive functions and in the emotional domain, which corresponded to increases in blood BDNF and serotonin. These results lead to the conclusion that the use of Cerebrolysin in the complex treatment of CC during the acute period, promoting activation of neurotrophic processes, improves the outcomes of closed CCT.

Measurement of Plasma, Serum, and Platelet Serotonin in Individuals With High Bone Mass and Mutations in LRP5

It has recently been suggested that the low-density lipoprotein receptor-related protein 5 (LRP5) regulates bone mass by suppressing secretion of serotonin from duodenal enterochromaffin cells. In mice with targeted expression of a high bone mass-causing (HBM-causing) LRP5 mutation and in humans with HBM LRP5 mutations, circulating serotonin levels have been reported to be lower than in controls whereas individuals with loss-of-function mutations in LRP5 have high blood serotonin. In contrast, others have reported that conditionally activating a knock-in allele of an HBM-causing LRP5 mutation in several tissues, or genetic deletion of LRP5 in mice has no effect on serum serotonin levels. To further explore the possible association between HBM-causing LRP5 mutations and circulating serotonin, levels of the hormone were measured in the platelet poor plasma (PPP), serum, and platelet pellet (PP) of 16 affected individuals from 2 kindreds with HBM-causing LRP5 mutations (G171V and N198S) and 16 age-matched controls. When analyzed by HPLC, there were no differences in levels of serotonin in PPP and PP between affected individuals and age-matched controls. Similarly, when analyzed by ELISA, there were no differences in PPP or PP between these two groups. By ELISA, serum levels of serotonin were higher in the affected individuals when compared to age-matched controls. A subgroup analysis of only the G171V subjects (n=14) demonstrated that there were no differences in PPP and PP serotonin between affected individuals and controls when analyzed by HPLC. PP serotonin was lower in the affected individuals when measured by ELISA but serum serotonin levels were not different. We conclude that there is no change in PPP serotonin in individuals with HBM-causing mutations in LRP5.

Serotonin: a novel bone mass controller may have implications for alveolar bone

As recent studies highlight the importance of alternative mechanisms in the control of bone turnover, new therapeutic approaches can be envisaged for bone diseases and periodontitis-induced bone loss. Recently, it has been shown that Fluoxetine and Venlafaxine, serotonin re-uptake inhibitors commonly used as antidepressants, can positively or negatively affect bone loss in rat models of induced periodontitis. Serotonin is a neurotransmitter that can be found within specific nuclei of the central nervous system, but can also be produced in the gut and be sequestered inside platelet granules. Although it is known to be mainly involved in the control of mood, sleep, and intestinal physiology, recent evidence has pointed at far reaching effects on bone metabolism, as a mediator of the effects of Lrp5, a membrane receptor commonly associated with Wnt canonical signaling and osteoblast differentiation. Deletion of Lrp5 in mice lead to increased expression of Tryptophan Hydroxylase 1, the gut isoform of the enzyme required for serotonin synthesis, thus increasing serum levels of serotonin. Serotonin, in turn, could bind to HTR1B receptors on osteoblasts and stop their proliferation by activating PKA and CREB.Although different groups have reported controversial results on the existence of an Lrp5-serotonin axis and the action of serotonin in bone remodeling, there is convincing evidence that serotonin modulators such as SSRIs can affect bone turnover. Consequently, the effects of this drug family on periodontal physiology should be thoroughly explored.

Homocysteine and serotonin: Association with postpartum depression

Postpartum depression (PPD) is a disorder of multifactorial origin with significant consequences on both maternal and child health. One of the biological factors implicated is perturbed methionine–homocysteine metabolism. Since this metabolic pathway plays a significant role in myelination of nerve fibers, the growth and development of the child would also be adversely affected. We carried out this study in 103 women (58 with PPD and 45 without PPD) who delivered their child in our institute from December 2010 to November 2011. The study group was evaluated for PPD using Edinburgh postnatal depression scale with a cut-off score of 10. Assessment of fetal well being was done by APGAR score assessed immediately after birth. Serum folic acid, vitamin B12, homocysteine and serotonin was done by ELISA. We found significantly elevated levels of homocysteine in women with PPD as compared to those without PPD, both at 24–48h as well as six weeks after delivery, although no associations were found with folate and vitamin B12 levels. Also, there was a significant negative correlation between serum homocysteine and serotonin levels in the postpartum depression group with a significant negative correlation between homocysteine and serotonin. Our study showed a significantly lower APGAR score in the infants born to mothers with PPD. Our study also shows that homocysteinemia is associated with PPD whether at the first week or sixth week, while low serum serotonin may play a role in depression during the first week, but may not have a role in depression status at the sixth week. Also, PPD in the mother is related to a low APGAR score in infants born to these mothers emphasizing the significance of both mental as well as nutritional status of the mother.

THU0342 Anti-TNF Treatment Reduces Serum Serotonin Levels in Patients with Ankylosing Spondylitis and Downregulates Serotonin Signaling in an Experimental Cell Line Model

BackgroundThe mechanisms involved in new bone formation in ankylosing spondylitis (AS) are incompletely understood. Evidence suggests that gut-derived serotonin is an inhibitor of bone formation; serotonin binds to the serotonin...

Mutations of the trypsinogen activation peptide in hereditary pancreatitis

Mutations of the trypsinogen activation peptide in hereditary pancreatitis

High-frequency transcutaneous electrical nerve stimulation reduces pain and cardio-respiratory parameters in an animal model of acute pain: Participation of peripheral serotonin

The objective of this study was to investigate the effect of high-frequency transcutaneous electrical nerve stimulation (HF-TENS) in antihyperalgesia, assessed through changes of sciatic nerve activity and its effects on cardiorespiratory parameters, using formalin-induced nociception in anesthetized rats. The animals were divided into formalin (FORM) and HF-TENS groups. All rats received injections of 5% formalin (50 μl, right hind-paw). The sciatic nerve activity and cardiopulmonary parameters (mean arterial pressure, heart rate, and respiratory frequency) were measured, and then the serum levels of serotonin (5-HT) were determined by an enzyme-linked immunosorbent assay kit. The formalin injection was able to increase the sciatic nerve activity, heart rate, and respiratory frequency. The treatment with HF-TENS significantly reduced the sciatic nerve activity and respiratory frequency 20 minutes after formalin injection and was able to increase serum 5-HT. Furthermore, when comparing the groups, reductions in the mean arterial pressure, heart rate, respiratory frequency, and sciatic nerve activity were shown at different times. Thus, we concluded that HF-TENS was capable of inducing analgesia, which was most likely related to increased serotonin release. Moreover, we demonstrated that TENS was able to block the adverse cardiovascular and respiratory changes induced by pain. Further neurophysiological studies are necessary to clarify the intrinsic mechanisms underlying HF-TENS-induced analgesia.

An exploration of the serotonin system in antisocial boys with high levels of callous-unemotional traits.

BackgroundThe serotonin system is thought to play a role in the aetiology of antisocial and aggressive behaviour in both adults and children however previous findings have been inconsistent. Recently, research has suggested that the function of the serotonin system may be specifically altered in a sub-set of antisocial populations – those with psychopathic (callous-unemotional) personality traits. We explored the relationships between callous-unemotional traits and functional polymorphisms of selected serotonin-system genes, and tested the association between callous-unemotional traits and serum serotonin levels independently of antisocial and aggressive behaviour.MethodParticipants were boys with antisocial behaviour problems aged 3–16 years referred to University of New South Wales Child Behaviour Research Clinics. Participants volunteered either a blood or saliva sample from which levels of serum serotonin (N = 66) and/or serotonin-system single nucleotide polymorphisms (N = 157) were assayed.ResultsFunctional single nucleotide polymorphisms from the serotonin 1b receptor gene (HTR1B) and 2a receptor gene (HTR2A) were found to be associated with callous-unemotional traits. Serum serotonin level was a significant predictor of callous-unemotional traits; levels were significantly lower in boys with high callous-unemotional traits than in boys with low callous-unemotional traits.Conclusion Results provide support to the emerging literature that argues for a genetically-driven system-wide alteration in serotonin function in the aetiology of callous-unemotional traits. The findings should be interpreted as preliminary and future research that aims to replicate and further investigate these results is required.

Clinical-Biochemical Studies of the Mechanisms of Formation of Chronic Lumbosacral Pain

A total of 78 patients with chronic vertebrogenic pain in the lower part of the spine were studied: 23 (29.5%) with lumbar root syndromes and 55 (70.5%) with reflex lumbar syndromes not in exacerbation. Patients with lumbar dorsopathy and root compression syndromes were characterized by high pain levels with a marked neuropathic component, lower quality of life, and significantly lower serum serotonin levels, which correlated with the severity of neuropathic pain and depression.

Tryptophan Hydroxylase Autoantibodies as Markers of a Distinct Autoimmune Gastrointestinal Component of Autoimmune Polyendocrine Syndrome Type 1

Autoantibodies to tryptophan hydroxylase (TPHAbs) directed against serotonin-producing enterochromaffin cells (EC) have been reported in autoimmune-polyendocrine-syndrome type 1 (APS-1) patients with gastrointestinal dysfunction (GID). Serotonin plays a critical role in enteric function and its peripheral blood levels reflect serotonin release from the gastrointestinal tract. We test the hypothesis that TPHAbs mark a distinct autoimmune component of APS-1 characterized by an autoimmune attack toward EC, which results in clinical GID. TPHAbs were measured in 64 APS-1 patients. Endoscopy with gastric (antrum/body) and duodenal biopsy was carried in 16 TPHAbs+ patients (8 with and 8 without GID) and in 2 TPHAbs- patients (without GID). Immunohistochemistry of biopsy specimens was carried out using antibodies to serotonin, chromogranin-A, CD3, CD4, CD8, and CD20. Serotonin serum levels were measured in TPHAbs+ and TPHAbs- patients who had endoscopy. Thirty-seven of 64 patients were TPHAbs+ (11/12 with GID and 26/52 without GID; P < .001). Gastric and duodenal biopsies in all 8 TPHAb+ patients with GID showed lymphocytic infiltration with increased CD3+CD8+ intraepithelial lymphocytes and absence of EC. Furthermore, mean serotonin serum levels were below the normal range in TPHAb+ patients with GID (P < .01). In 8 TPHAb+ patients without GID gastric and duodenal biopsies showed different grades of inflammatory infiltration and reduced number of EC. Mean serotonin serum levels were near the lower limit of the normal range. In all TPHAbs+ patients the biopsies showed a reduced number of chromogranin-A positive cells consistent with enteroendocrine cells depletion. TPHAbs- patients without GID showed normal gastrointestinal mucosa and serotonin serum levels. TPHAbs appear to be markers of a distinct autoimmune component of APS-1. Progressive involvement of the gastrointestinal EC leads to the transition from preclinical to clinical disease, characterized by GID and reduced serotonin serum levels.

Antidepressant-like effects of tea polyphenols on mouse model of chronic unpredictable mild stress

Tea polyphenols (TPs), which are the natural compounds extracted from tea leaves, possess a number of beneficial properties, such as reducing the risks of cancer and heart diseases, alleviating cognitive impairments and showing antidepressant-like activity in the forced swim test (FST) and tail suspension test (TST). The present study was designed to investigate the protective effect of TPs on the chronic unpredictable mild stress (CUMS)-induced depression model in mice and to elucidate the related underlying mechanisms. With the daily exposure to stressor for 5 consecutive weeks, TPs were administered in mice at a daily dose of 25mg/kg or 50mg/kg by gavage for 3 consecutive weeks from the 3rd week. Our results showed that CUMS significantly decreased the levels of serum serotonin (5-HT) and norepinephrine (NE) in the hippocampus, the prefrontal cortex and serum, and the activities of superoxide dismutase (SOD) and catalase (CAT), with an increase in lipid peroxidation level as well as a reduction in glutathione (GSH) level and an elevation in the production of malondialdehyde (MDA) in the hippocampus and the prefrontal cortex. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. TPs administration could effectively reverse the alterations in the concentrations of 5-HT and NE, elevate the activities of SOD and CAT as well as the level of GSH, reduce the MDA level and inhibit lipid peroxidation. Moreover, TPs could effectively reverse alterations in immobility duration, sucrose consumption and open-field activity. In conclusion, TPs administration has exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of TPs might be related to the alteration of monoaminergic responses and antioxidant defenses.

Adjuvant Use of Melatonin with Fluoxetine for Management of Fibromyalgia

Fibromyalgia (FMS) is a chronic musculoskeletal disorder characterized by generalized muscular pain and tenderness at specific anatomical sites. Although melatonin was effective in treating the pain associated with this syndrome, no defined clinical evidence supports this claim. The present study was designed to evaluate the clinical significance of using melatonin, alone or in combination with fluoxetine in FMS. A double-blind clinical study was conducted on 45 patients with FMS randomized into 4 groups; group A, treated with fluoxetine 20mg/day alone; group B, treated with melatonin 5mg alone; group C, treated with combination of fluoxetine 20 mg+3 mg melatonin; group D treated with combination of fluoxetine 20 mg+5 mg melatonin. Both fluoxetine and melatonin were given once daily in the morning and night time respectively for 8 weeks. Each patient clinically evaluated using Fibromyalgia Impact Questionnaire (FIQ). Serum levels of serotonin, malondialehyde and nitric oxide were also evaluated. Using melatonin (3 and 5mg/day) in combination with 20mg/day fluoxetine significantly decreased total FIQ score values; the combination therapy significantly decreased serum serotonin level associated with reduction in the oxidative stress parameters (MDA and NO). In conclusion, adjuvant use of melatonin with fluoxetine improves the biochemical and clinical parameters of FMS patients.

Effect of Antiepileptic Drugs on Serum Serotonin Level among Children with Idiopathic Epilepsy

Effect of Antiepileptic Drugs on Serum Serotonin Level among Children with Idiopathic Epilepsy

The relationship between serum serotonin levels and cytotoxic drugs adverse effects in cancer patients

The relationship between serum serotonin levels and cytotoxic drugs adverse effects in cancer patients

Differences in serotonin serum concentration between aggressive English cocker spaniels and aggressive dogs of other breeds

Aggression is one of the most common behavioral problems in dogs and may have important negative effects on public health, human–animal bond, and animal welfare. There is ample evidence showing a negative correlation between serum serotonin concentration and aggressive behavior in a variety of species, including the domestic dogs. This negative correlation is particularly pronounced in dogs that show impulsive aggression. Data obtained in some previous studies suggest that the English cocker spaniel (ECS) is more likely to show impulsive aggression than other breeds. Therefore, the aim of this study was to analyze possible differences in serum serotonin levels between aggressive ECS and aggressive dogs of other breeds. Nineteen ECSs presented for aggression at the Animal Behavior Service (School of Veterinary Science, Barcelona, Spain) were evaluated and compared with 20 aggressive dogs of other breeds attended at the same center. Serum serotonin levels were measured using an enzyme-linked immunosorbent assay method. Statistical analysis was done using the SPSS 15.0 for Windows. Aggressive ECSs had significantly (P < 0.001) lower levels of serum serotonin than aggressive dogs of other breeds (318.6 ± 67.1 and 852.77 ± 100.58 ng/mL, respectively). Variances were not significantly different between ECSs and other breeds (standard deviation = 449.84 ng/mL vs. 292.47 ng/mL, P > 0.05). This finding may explain why ECSs are more likely to show impulsive aggression than other breeds, and suggests that the ECS could be a good model to study the neurophysiologic mechanisms underlying impulsive aggression.

Correlation between serum serotonin and endoscopy inflammation scores in patients with ileal pouches

BackgroundInflammatory and functional complications are common in patients with inflammatory bowel disease (IBD) after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). The pathogenesis of these complications remains poorly understood, and there is discrepancy between the clinical symptoms and objective endoscopic inflammation scores in these patients. While serum serotonin level has been reported to be associated with symptoms of irritable bowel syndrome, its association with ileal pouch disorders has not been studied. AimTo investigate the association between serum serotonin level and symptoms and endoscopic inflammation in patients with IPAA. MethodsA total of 185 consecutive eligible IPAA patients who presented to a specialized Pouchitis Clinic from Jan 2009 to May 2009 were prospectively recruited. Patients were divided into 4 groups: normal pouch, irritable pouch syndrome (IPS), inflammatory pouch disorders (Crohn's disease, acute and chronic pouchitis, and cuffitis), and surgical complications. Serum serotonin level was measured and analyzed for correlation with clinical and endoscopic inflammation scores. ResultsDemographic and clinical variables were evaluated, including age, gender, smoking history, duration of UC, duration of the pouch, and disease category of the pouch. The median fasting serum serotonin level was comparable among the 4 groups: 94.0ng/ml (interquartile range [IQR], 70.0, 128.1), 89.2ng/ml (IQR 54.2, 155.9), 90.3ng/ml (IQR 49.7, 164.1), 77.9ng/ml (IQR 54.7, 129.0), for normal pouch, irritable pouch, inflammatory pouch disorders, and surgical complication groups, respectively (p=0.91). A significant association between serum serotonin level and the Pouchitis Disease Activity Index (PDAI) endoscopy subscore of the pouch (odds ratio [OR]=1.9, 95% confidence interval [CI]: 1.2, 2.9, p<0.05) and total PDAI endoscopy score (OR=1.8; 95% CI: 1.2, 2.8, p<0.05) in the inflammatory complication group were noted. ConclusionsSerum serotonin level appears to correlate with the PDAI endoscopy subscores and total PDAI score in patients with inflammatory complications suggesting that the hormone may be involved in mechanisms of mucosal inflammation. These findings may promote future treatment strategies for patients with pouch inflammation.

A laboratory inter-comparison of the importance of serum serotonin levels in the measurement of a range of radiation-induced bystander effects: Overview of study and results presentation

Purpose: Recent research has suggested that serotonin may play an important role in the expression of radiation-induced bystander effects. Serotonin levels in serum were reported to range from 6–22 μM and to correlate inversely with the magnitude of cellular colony-forming ability in medium transfer bystander assays. That is, high serotonin concentration correlated with a low cloning efficiency in cultures receiving medium derived from irradiated cells.Methods: Because of the potential importance of this observation, the European Union's Non-targeted Effects Integrated Project (NOTE) performed an inter-comparison exercise where serum samples with high and low serotonin levels were distributed to seven laboratories which then performed their own assay to determine the magnitude of the bystander effect.Results: The results provided some support for a role for serotonin in four of the laboratories. Two saw no difference between the samples and one gave inconclusive results. In this summary paper, full data sets are presented from laboratories whose data was inconclusive or insufficient for a full paper. Other data are published in full in the special issue.Conclusion: The data suggest that there may be multiple bystander effects and that the underlying mechanisms may be modulated by both the culture conditions and the intrinsic properties of the cells used in the assay.

The involvement of serum serotonin levels producing radiation-induced bystander effects for an in vivo assay with fractionated high dose-rate (HDR) brachytherapy

Purpose: The primary goal of this investigation was to observe whether measurable levels of bystander factor(s) can be detected in esophageal carcinoma patients’ urine samples taken after undergoing high dose rate (HDR) intraluminal brachytherapy (ILBT). However, a small pilot study was developed to evaluate whether serotonin [5-Hydroxytryptamine (5-HT)] serum levels play an active role in the mechanisms of radiation-induced bystander effects (RIBE) at high doses.Materials and methods: In the present study, a colony-forming in vivo assay was developed and used for the detection of non-targeted effects. Samples of urine were collected from five esophageal carcinoma patients undergoing fractionated HDR-ILBT. To observe whether 5-HT modulates the bystander effect at higher doses, different batches of foetal bovine serum (FBS) and 5-HT were tested on the same urine samples before and after brachytherapy.Results: Some of our data suggests statistically significant evidence for serotonin playing an active role as a signalling molecule at higher doses when patients underwent HDR-ILBT.Conclusion: However, a more thorough investigation, with a larger sample size, is warranted before serotonin can be known to play a role in bystander effects at this particular dose range and treatment regime.