Blood Serotonin Levels Research Articles

Blood serotonin levels and male infertility.

Seventy men, aged 20-40 years, who were attending an infertility clinic were studied to evaluate associations between seminal quality, whole blood serotonin, and serum testosterone levels. Men with blood serotonin levels greater than 100 ng/ml showed lower sperm counts and sperm motility than those with normal levels of blood serotonin (less than 90 ng/ml). Seminal volume, pH, sperm morphology, fructose, citric acid, and serum testosterone values were similar between groups of patients with different levels of blood serotonin. The levels of blood serotonin correlated best with sperm motility when using a cubic regression analysis. When blood serotonin increased from 50 to 90 ng/ml (normal range), there was an increase in the percentage of spermatozoa with excellent motility. However, when serotonin was above 90 ng/ml the percentage of sperm with excellent motility decreased. An inverse exponential relationship was observed between blood serotonin and sperm count. The sperm count reached values of oligozoospermia when blood serotonin was over 100 ng/ml. It would appear that blood serotonin in the normal range is important for sperm motility. Values of serotonin above the normal range could affect negatively both sperm count and motility. These effects were observed in the absence of changes in serum testosterone levels.

Tryptophan loading test in premenstrual syndrome

SummaryAn oral tryptophan loading test (SOmg/kg) was performed in both women with premenstrual syndrome and controls. In controls at all sampling intervals, and the premenstrual syndrome subjects in the follicular and mid-luteal phases, tryptophan loading consistently increased whole blood serotonin levels. By contrast, during the late luteal phase, in subjects with premenstrual syndrome there was a decrease in blood serotonin.

In vivo and in vitro Effects of Adrenocorticotrophic Hormone on Serotonin Receptors in Neonatal Rat Brain

The molecular basis of the antimyoclonic and antiepileptic properties of ACTH is unknown. Direct actions at neurotransmitter receptors have been hypothesized. Abnormalities of serotonergic neurotransmission have been suggested in the ACTH-responsive disorder infantile spasms based on elevated blood or platelet serotonin (5-HT) levels and induction of infantile spasms in Down's syndrome by the 5-HT precursor 5-hydroxytryptophan. To pursue these and other clinical and basic links between ACTH and 5-HT, the activity of ACTH at 5-HT receptors was determined n vitro and in vivo. Neonatal rats were treated for 30 consecutive days with a pharmacologic dose (40 IU/kg) of lyophilized porcine ACTH1-39 reconstituted in normal saline or with saline alone. ACTH administration impaired the weight gain of rat pups. In saturation receptor binding studies of rats treated as neonates (n = 7/group), ACTH significantly reduced receptor density (Bmax) of 5-HT2 sites in the cortex (-13%) compared to controls without a change in receptor affinity. Regional 5-HT1 receptor sites and 5-HT and 5-HIAA levels were not altered. Cortical tryptophan concentrations were significantly decreased (-29%) in rats treated neonatally with ACTH. In competition experiments in vitro using naive 7- to 10-day-old neonatal rat forebrain, ACTH1-39 displaced 5-HT1 and 5-HT2 sites only with 100 micromolar IC50 values. The small effects of ACTH at 5-HT receptors even at a supraclinical dose may not explain its potent clinical antimyoclonic properties.

Contraction of canine stomach and small bowel by intravenous administration of serotonin. A physiologic response?

Serotonin is found in large quantities in the gastrointestinal tract, where it can increase gastrointestinal motility. Whether this response represents a physiologic event has not previously been shown. In our investigation eight conscious dogs were fitted with strain gauges to monitor motility responses to serotonin. When infused intravenously, serotonin significantly increased the contraction rate and force of canine stomach, small bowel, and isolated Thirty-Vella loops. Whole blood serotonin levels monitored by radioimmunoassay showed no significant increase in levels during these infusions. Serotonin may have a physiologic function in the mediation of gastrointestinal motility.

Serotonin and measured intelligence.

Blood serotonin (5HT) has been shown to be elevated in 30% of autistic children and 50% of severely mentally retarded children. Ninety-eight normal adult subjects were studied to determine if there was an inverse relationship between whole blood 5HT in normal adults of average and above-average intelligence. There was a trend toward a negative correlation between whole blood 5HT and Vocabulary scores that would not account for hyperserotonemia in autistic or mentally retarded individuals. Female subjects had significantly greater whole blood 5HT than male subjects. There was no difference in whole blood 5HT collected before and after volume depletion of 450 ml, providing further evidence of the intraindividual stability of whole blood serotonin levels. There was no relationship between age and whole blood 5HT in a group of normal adult subjects.

Distinguishing Features of Idiopathic Flushing and Carcinoid Syndrome

We compared the clinical and biochemical profiles of 11 patients with idiopathic flushing (IF) with those of eight patients with carcinoid syndrome (CS). Patients with IF were more often women, had a longer duration of symptoms, and were younger. Palpitations, syncope, and hypotension occurred only in patients with IF, while wheezing and abdominal pain occurred only with CS; diarrhea occurred in both types of patients. Elevated blood serotonin levels were present primarily in CS. Increased levels of urine 5-hydroxyindoleacetic acid was specific for CS but unsufficiently sensitive to detect all cases. Abnormalities of gut and vasoactive peptides failed to distinguish the two conditions. Flushing in carcinoid patients responds uniformly to octreotide (Sandostatin), but only one third of the patients with IF are relieved of the symptom. Patients with IF have features that distinguish them from individuals with flushing from other causes, such as CS, postmenopausal state, chlorpropamide-alcohol flush, panic attacks, medullary thyroid carcinoma, and autonomic epilepsy. Familiarity with the clinical and biochemical features of IF should facilitate evaluation and identification of these patients.

Influence of experimental hyperthyroidism on blood and myocardial serotonin in rats.

Recent reports suggest a role for serotonin in the pathogenesis of primary hypertension and left ventricular (LV) hypertrophy. In this study, we have induced LV hypertrophy by oral feeding of thyroxine at increasing dosages (150-450 micrograms/kg b.wt.) over a 5-week period. The effects of hyperthyroidism on cardiovascular parameters, blood and myocardial serotonin concentrations were assessed. Water-fed rats and formerly hyperthyroid recovered animals served as controls. Thyroxine caused a significant LV hypertrophy: hyperthyroid rats 2.19 +/- 0.16*; controls 1.65 +/- 0.13 g/kg b.wt. (mean +/- SD; *P less than 0.05). An almost complete regression of LV hypertrophy occurred in the recovery group (1.66 +/- 0.20 g/kg b.wt.) 3 weeks after cessation of thyroid hormone application. Thyroxine-treated animals showed a significant increase of serotonin blood levels (thyroxine rats: 2108 +/- 781*, recovery: 1132 +/- 726, controls: 705 +/- 480 ng/ml; *P less than 0.05). The concentrations of serotonin in left ventricular myocardium were increased after thyroid hormone application, whereas the highest levels were found in the recovery group (thyroxine rats: 139.1 +/- 30.4, recovery: 167.2 +/- 43.1, controls: 68.9 +/- 27.9 mg/ml homogenate). Serotonin-containing cells in the left ventricular myocardium were stained immunohistochemically. They were localized perivascularly and were assumed to represent tissue mast cells. In experimental hyperthyroidism the serotonin levels in blood and heart are increased possibly indicating an interaction of both hormones in thyroxine-induced cardiomyopathy.

Brief report: does fenfluramine treatment enhance the cognitive and communicative functioning of autistic children?

In 1982, a biomedical research team reported success in altering some of the cognitive, behavioral, and communicative deficits in three autistic children (GeUer, Ritvo, Freeman, & Yuwiler, 1982). Symptomatic improvements were attributed to fenfluramine medication which, according to the investigators, substantially reduced circulating levels of serotonin (see Holm & Varley, 1988, for a comprehensive review). The results of two follow-up studies (Ritvo, Freeman, Geller, & Yuwiler, 1983; Ritvo et al., 1986) appeared to confirm Geller's initial hypothesis. Several recent studies have also confirmed the effectiveness of fenfluramine in reducing blood serotonin levels (August, Raz, & Baird, 1985; Groden, Groden, Dondey, & Zane, in press; Ho et al., 1986; Klykylo, Feldis, O'Gredy, Ross, & Halloran, 1985; Stubbs, Budden, Jack-

Autism

In 1982, three autistic children with hyperserotoninemia were reported to have had an impressive clinical response to treatment with fenfluramine—a finding that generated considerable hope and excitement. Now, well-designed studies have evaluated both the relationship of serotonin levels to autism and the clinical and biochemical effects of fenfluramine. Blood serotonin levels are not universally elevated in children with autism, and mean blood serotonin concentrations in autistic children are not significantly different from those in normal or in nonautistic retarded children. Treatment with fenfluramine does cause significant decreases in blood serotonin concentrations in autistic children, but such biochemical changes are not associated with changes in psychometric measurements of general intelligence.

Gabapentin augments whole blood serotonin in healthy young men.

It has been previously demonstrated that gabapentin, a gamma-amino butyric acid analogue, inhibits monoaminergic neurotransmitter release from rabbit caudate nucleus slices and from rat cortex. In humans this drug has been shown to have anti-epileptogenic activity. Serotonin may act as an inhibitory neurotransmitter and its interaction with blood platelets is thought to reflect its central actions. We investigated sleep stages, whole blood serotonin levels, and serum melatonin in healthy men after the administration of gabapentin. With increasing serum gabapentin levels six healthy subjects showed an increase in sleep stages 3 and 4 and in whole blood serotonin (P less than 0.05) Serum melatonin levels were not influenced. On account of these results we speculate that gabapentin modulates the release of serotonin from blood platelets. The increase in peripheral serotonin points paradigmatically to an increase in the bioavailability of serotonin which may account for the increase in sleep stages 3 and 4.

The pentagastrin test as an indicator of a cure in surgically treated patients with advanced carcinoid disease

A unique case of midgut carcinoid with advanced disease, engaging lymph nodes and liver but still accessible to curative surgery, is reported. Besides elevated urinary levels of 5-hydroxyindoleacetic acid, the diagnosis was based on a positive provocation test with pentagastrin, i.e., basally elevated levels of serotonin in peripheral whole blood increased twofold 3 min postinjection related to the appearance of carcinoid symptoms. After removal of primary and secondary lesions in a two-step procedure carcinoid symptoms disappeared completely. Biochemically, urinary excretion of 5-hydroxyindoleacetic acid and serotonin levels in peripheral blood before and during provocation with pentagastrin were both normalized after surgery and have remained so during 27 months of follow-up. Computed tomographies of the abdomen at regular intervals do not indicate recurrent disease. Histologically, the carcinoid lesions displayed a mixed growth pattern and signs of local aggressiveness. Immunocytochemically, the majority of the tumour cells (positive against neuron specific enolase) showed a positive reaction with serotonin antisera. Substance P-like immunoreactivity was also found in a large proportion of these cells.

Treatment of porcine Pseudomonas ARDS with combination drug therapy.

A combination drug therapy (Poly-5: ibuprofen 12.5 mg/kg, methylprednisolone 30 mg/kg, cimetidine 150 mg, diphenhydramine 10 mg/kg, and ketanserin 0.2 mg/kg) given at 20 and 120 minutes after starting continuous intravenous Pseudomonas (Ps, 5 X 10(8) CFU/20 kg/min) was studied in three groups of swine: saline control (C, n = 9), Ps alone (Ps, n = 8), and Ps plus Poly-5 (n = 5). PaO2, systemic (SAP) and pulmonary arterial (PAP) pressures, cardiac index (CI), thermal-cardiogreen extravascular lung water (EVLW), pulmonary albumin flux (slope index, SI), and arterial blood serotonin levels (5-HT) were measured. Ps produced significant (p less than 0.05) increases in PAP, EVLW, and SI with decreases in PaO2, CI, and SAP. 5-HT fell significantly compared to baseline. Poly-5 prevented (p less than 0.05) the rise in EVLW and SI and the fall in PaO2 and CI compared to Ps. PAP and SI were maintained at C until 90 and 150 minutes, respectively. SAP fell significantly from C at 30, 60, and 180 minutes. 5-HT was significantly lower than Ps throughout, and significantly lower than baseline at 180 minutes. Combined blockade of arachidonic acid metabolites, histamine, and serotonin receptors prevented hypoxemia, increased pulmonary capillary permeability, and cardiovascular deterioration in this porcine septic ARDS model.

Vervet monkey ([formula omitted]) whole blood serotonin level is determined by platelet uptake sites

Whole blood serotonin levels in adult male vervet monkeys living in social groups are sensitive to the animals' social environment. The mechanisms that translate different behavioral and environmental cues into altered whole blood serotonin levels are unknown. In this study, we have measured platelet number, size, serotonin content, and serotonin uptake, as well as the serum concentrations of tryptophan, Mg+2 and Ca+2. Results showed that whole blood serotonin levels, platelet serotonin content, and the serotonin uptake parameter Vmax were stable within animals on repeated sampling. The whole blood serotonin level was highly positively associated with platelet serotonin content, and the platelet serotonin content was highly positively associated with Vmax. These findings suggested that whole blood serotonin levels were a function of the number of platelet uptake sites.

Serotonin receptor blockade improves cardiac output and hypoxia in porcine ARDS

The effects of the serotonin receptor blocker, ketanserin, were studied in a porcine Pseudomonas adult respiratory distress syndrome model. Swine, weighing 14–30 kg, were anesthetized and ventilated with 0.5 FiO 2 and 5 cm H 2O positive end expiratory pressure. Three groups were studied: saline control (C, n = 9), continuous intravenous Pseudomonas aeruginosa, 5.0 × 10 8 CFU/kg/min (Ps, n = 8), and Pseudomonas and intravenous ketanserin, 0.2 mg/kg, given at 20 and 120 min after the onset of the Pseudomonas infusion (KET, n = 5). Pulmonary arterial (PAP) and systemic arterial (SAP) pressures, cardiac index (CI), thermal Cardio-Green extravascular lung water (EVLW), pulmonary albumin flux (slope index, SI), arterial blood gases, and whole blood serotonin levels were measured and pulmonary shunt and pulmonary (PVRI) and systemic (SVRI) vascular resistance indices were calculated. At 3 hr the Ps group demonstrated significant ( P < 0.05) increases in PAP (34 ± 1 vs C 13 ± 2 mm Hg), EVLW (14.4 ± 2.2 vs C 4.3 ± 1.2 ml/kg), SI (2.05 ± 0.23 × 10 −3 vs C 0.38 ± 0.09 × 10 −3 U/min), pulmonary shunt (67 ± 15% vs C 9 ± 3%), PVRI (1599 ± 89 vs C 184 ± 14 dyn · sec · cm −5/m 2), and SVRI (4542 ± 774 vs C 2087 ± 129 dyn · sec · cm −5/m 2) and decreases in CI (0.9 ± 0.1 L/min/m 2 vs C 2.8 ± 0.2 L/min/m 2), P aO 2 (93 ± 17 Torr vs C 203 ± 15 Torr) and arterial blood serotonin concentration (23.5 ± 13% decrease from basal). Treatment with ketanserin was associated with maintenance of P aO 2 (KET 207 ± 5 mm Hg vs C 203 ± 15 mm Hg), pulmonary shunt (KET 8 ± 3% vs C 9 ± 3%), and CI (KET 2.3 ± 0.1 L/min/m 2 vs C 2.8 ± 0.2 L/min/m 2) at control levels and attenuated the Pseudomonas-induced increase in PVRI (873 ± 37 vs Ps 1599 ± 89 dyn · sec · cm −5/m 2) and SVRI (2089 ± 287 vs Ps 4542 ± 774 dyn · sec · cm −5/m 2), but did not alter the development of pulmonary edema. These data indicate that serotonin plays a role in the development of the V Q mismatch and arterial hypoxemia observed in this model by a mechanism independent of changes in microvascular injury and permeability and was probably a result of reduced peripheral bronchiolar constriction.

A simple procedure for reliability growth modeling : John Healy. Proc. a. Reliab. Maintainab. Symp., 171 (1987)

The excess and deficit of serotonin can be the cause of somatic and mental disorders. The aim of this study was to evaluate serotonin levels in blood and ascitic fluid as well as excretion of 5-hydroxyindoleacetic acid (5-HIAA) in urine in patients with hepatic encephalopathy (HE).The study included 75 alcoholic cirrhotic patients divided into 3 groups (HE1, HE2, HE3), 25 patients each, with grade 1, 2 and 3 of hepatic encephalopathy according to West-Haven classification. The control group (C) included 25 clinically healthy volunteers. Venous blood and ascitic fluid were collected in fasting. On the same day a 24-hour urine collection was performed. Immunoenzymatic method was used to determine the serotonin level in serum and ascitic fluid, and 5-HIAA in urine (IBL-RE-59121, RE-59131).In the control group, mean serum serotonin level (ng/ml) was 155.5±38.1 and in the 3 study groups: HE1 – 175.2±32.4 (NS), HE2 – 137.2±28.6 (NS), HE3 – 108.3±46.3 (p<0.001). Serotonin concentration in ascitic fluid was on the average about 25% of its level in serum. The excretion of 5-HIAA in urine (mg/24h) in all groups, was: C – 5.9±2.1, HE1 – 5.8±1.8 (NS), HE2 – 4.8±1.2(NS), HE3 – 4.3 ±1.3 (p<0.05).The results of our study indicate that serum and ascitic fluid level of serotonin and urine excretion of 5-HIAA depends on the grade of hepatic encephalopathy. In patients with severe hepatic encephalopathy serotonin concentration in blood is decreased which can affect some clinical manifestation of this disease.

Carcinoid in a gastrointestinal duplication

This is a report of a 12-year-old boy having gastric duplication with foci of carcinoid. He complained of right abdominal pain. Physical examination showed a cystic mass in the right abdomen. It was excised operatively. The mass was a duplication cyst composed of gastric mucosa with a muscle layer. Foci of carcinoid was detected in the muscle layer. The tumor cells involved nerve fibers but did not extend to the subserosa. Postoperative blood serotonin and histamine levels were normal. The patient is healthy without signs of recurrence 17 months after operation. This is the second case of gastrointestinal duplication with foci of carcinoid. The findings indicate that careful histologic examination is necessary to determine the exact nature of the cyst.

Measurement of whole blood serotonin as a guide in prescribing psychostimulant medication for children with attentional deficits.

A retrospective study was made of a series of 73 children who presented at the Diagnostic and Developmental Center, Northbrook, IL, U.S.A. between February 1, 1983 and July 1, 1984 with learning disabilities, impulsivity, short attention span, and in some cases, hyperactivity as well. Ninety-eight percent of the patients with low whole blood serotonin levels (below 90 ng/ml) improved in their ability to pay attention and learn and diminished in impulsivity when the psychostimulant medication pemoline was administered, while the patients with higher levels (above 100 ng/ml) did not benefit from the drug. Thus, the measurement of serotonin levels in whole blood appears to have predictive value as to which children can be helped by treatment with pemoline. Based on the data presented, we recommend the use of the whole blood serotonin test at the time of initial evaluation to determine whether children should be treated with pemoline, thereby sparing those who would not respond favorably from an ineffectual trial of the drug.

Blood serotonin concentrations and fenfluramine therapy in autistic children

Whole-blood serotonin concentrations of 31 autistic children, aged 2 1/2 to 16 years, 10 non-autistic retarded children, and 18 children with Down syndrome were measured by a fluorometric method and compared with those of normal children of similar age range. No significant difference in the serotonin concentration per milliliter of whole blood or per 1000 platelets was found between groups for autistic, retarded, or normal children, but the values for those with Down syndrome were significantly lower. A double-blind cross-over study on the effect of fenfluramine versus placebo in seven autistic boys over a period of 8 months demonstrated a significant decrease in blood serotonin levels during the fenfluramine phase in all subjects. Slight improvements were found in short-term auditory memory and some measures of receptive language skills, particularly in children functioning at a high level. There was no significant change in global psychometric measurements of general intelligence during therapy. No adverse clinical effect was observed other than weight loss of 6% in one child. We conclude that fenfluramine may have some selective favorable effects on increasing attention in high-functioning autistic children. Blood serotonin concentration may be followed as an indication of drug compliance during fenfluramine therapy, but does not appear to reflect clinical efficacy.

Side Effects of Fenfluramine in Autistic Children

This study reports fenfluramine side effects in autistic children. Eight individuals (age range 4-15 years) were initially enrolled in this part of the multicenter study. Four of the children developed side effects which included decreased appetite, lethargy, and irritability. Side effects were eliminated in three when dosage was reduced from the initial 1.5 mg/kg dose. One child severely regressed, then recovered when fenfluramine was discontinued. Some plateauing of weight gain was noted during the active medication phase. Height did not appear affected. Variation was noted in medication-free blood serotonin levels.

Plasma free tryptophan concentration in autistic Children

The plasma free and total tryptophan (TRP) and blood serotonin levels in autistic children were examined simultaneously in order to establish a relationship between these parameters and the pathophysiology of infantile autism. The subjects were 37 autistic children, 28 normal adults and 12 normal children. Quantitative evaluation of the global severity, hyperkinetic behavior and intellectual function was performed by means of the Children's Psychiatric Rating Scale (CPRS-1), the Werry-Weiss-Peters Activity Scale (WWPAS) and the Developmental Quotient (DQ), respectively. The mean total TRP level in autistic children was not significantly different from those in normal children and adults. The mean plasma free TRP level in autistic children was significantly higher than those in normal children and adults. A significant positive correlation was found between the plasma free TRP level and CPRS-1 or WWPAS score in autistic children. Moreover, there tended to be a negative correlation between the plasma free TRP level and DQ. These findings suggest the presence of some defect in the metabolic system for TRP-serotonin in the brain of autistic children.