Neurotransmitter Metabolites In Cerebrospinal Fluid Research Articles

Low serotonin and dopamine metabolite concentrations in cerebrospinal fluid from bulimic patients with frequent binge episodes.

Cerebrospinal fluid neurotransmitter metabolite levels were studied to assess whether measures of central serotonin, dopamine, or norepinephrine function are associated with severity of abnormal eating patterns in patients with bulimia nervosa. In comparison with healthy controls (N = 17), hospitalized bulimic patients with a history of binge eating more frequently than twice daily (N = 11) had significantly lower CSF concentrations of 5-hydroxyindoleacetic acid and homovanillic acid. For the total patient group (N = 29), levels of both metabolites were significantly inversely correlated with binge frequency. On the basis of preclinical studies, these results were examined in the context of speculative models in which low central serotonin function might contribute to blunted satiety responses in bulimic patients, while low central dopamine activity might play a role in abnormal hedonic responses to food.

Changes in CSF neurotransmitters during the first year of life

Changes in cerebrospinal fluid neurotransmitter metabolites in 25 children younger than 1 year of age were analyzed to assess maturation of the central nervous system and were compared to cerebrospinal fluid from older children and adults. Significant inverse correlations ( P < .05) with aging were observed for tryptophan, 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, kynurenine, tyrosine, dopa, dopamine, dihydroxyphenylacetic acid, homovanillic acid, norepinephrine, and 3-methoxy-4-hydroxyphenylglycol concentrations. There were no significant differences observed with respect to age in the cerebrospinal fluid serotonin, 3-hydroxykynurenine, and 3-methoxytyramine concentrations. This study suggests that changes in the major cerebrospinal fluid neurotransmitters occur with increasing age during the neonatal period. Because these findings are preliminary, additional patients require study.

Lack of seasonal variation in pediatric lumbar cerebrospinal fluid neurotransmitter metabolite concentrations

Seasonal variation of cerebrospinal fluid (CSF) monoamines, particularly 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) has been reported for psychiatrically ill and normal adults. Circannual variability was examined for a group of 72 children (mean age = 159.4 +/- 40.3 (SD), range 77-238 months), with a primary diagnosis of obsessive-compulsive disorder (OCD) or disruptive behavior disorder (DBD) (attention deficit disorder, oppositional disorder and/or conduct disorder), from whom CSF had been obtained systematically. There were no seasonal differences in mean concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), HVA, or 5-HIAA, either for the group as a whole, for the separate diagnostic (OCD vs DBD) categories or for the pre-pubertal subgroup. Log-corrected HVA concentrations for the Tanner IV and V subgroup differed by season with summer concentrations less than those of fall (P = 0.06) and winter (P = 0.005). The results suggest that pubertal changes may play a role in any expression of circannual variability.

Analysis of equine cisterna magna cerebrospinal fluid for the presence of some monoamine neutrotransmitters and transmitter metabolites

Small volumes (0.05 ml) of cisterna magna cerebrospinal fluid (CSF) from 23 neurologically normal horses were analysed for the monoamine neurotransmitters dopamine, norepinephrine, epinephrine, serotonin and their metabolites using high pressure liquid chromatography and electrochemical detection. Two metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were present in all CSF samples. The deaminated and methylated metabolite of dopamine, HVA, was present at a mean concentration of 42.33 +/- 3.14 ng/ml of CSF. The deaminated metabolite of serotonin, 5-HIAA, was present at a mean concentration of 45.52 +/- 3.65 ng/ml of CSF. A positive correlation was found between the CSF concentrations of HVA and 5-HIAA (r = 0.72, p = 0.0003). The mean ratio of HVA to 5-HIAA concentrations was 1.07 +/- 0.05. The ratios of HVA to 5-HIAA concentrations were found to be more indicative of the serotonergic metabolite 5-HIAA (r = -0.62, p = 0.0016) than the dopaminergic metabolite HVA (r = 0.11, p = 0.60). There was a stronger relationship between the concentrations of 5-HIAA and the ratios of HVA to 5-HIAA in male CSF (r = -0.85, p = 0.0006) than in female CSF (r = -0.54, p = 0.01). Concentrations of CSF neurotransmitter metabolites were evaluated in horses grouped by age (0-4, 5-9 and 10-13 years). The youngest group of horses had a significantly (p = 0.003) greater CSF concentration of HVA than of 5-HIAA. The 10-13-year-old horses had a significantly (p = 0.02) lower mean CSF HVA concentration than the 0-4-year-old horses. No age-related differences in CSF 5-HIAA concentrations were detected.

Neurological deterioration in adult phenylketonuria

A 28-year-old man with classical phenylketonuria had increased seizure frequency and rapidly progressive spasticity. There was a marked reduction of biogenic amine neurotransmitter metabolites in cerebrospinal fluid. Dietary therapy reduced serum phenylalanine levels, improved symptoms of hypertonicity, and cerebrospinal fluid neurotransmitter metabolites became normal. An adolescent male with classical phenylketonuria, treated by dietary restriction until age 6 years, was assessed for decreasing school performance at 18 years. Cerebrospinal fluid biogenic amine neurotransmitter metabolites were significantly reduced. Magnetic resonance imaging in both subjects showed multiple areas of increased signal intensity in cerebral white matter. Neuropathological changes in classical phenylketonuria have been characterized as a dysmyelinating or demyelinating process. Neurochemical studies show a defect in brain lipids and biogenic amine metabolism. In the past, dietary therapy was directed at reducing hyperphenylalaninaemia only during the first decade of life. This report, as well as other studies, indicates that dietary therapy should be lifelong in patients with classical phenylketonuria, in order to prevent progressive and insidious neurological deterioration in later life.

Endogenous opioid peptide modulation of LH secretion in the ewe lamb: possible involvement of 5-hydroxytryptamine.

Evidence from several species suggest that the endogenous opioid peptides participate in the regulation of gonadotrophin and prolactin secretion. The aim of the present study involving intact and ovariectomized prepubertal ewe lambs was to compare the effects in vivo of an opioid peptide agonist [D-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33-824) and antagonist, naloxone, on concentrations of LH and prolactin in plasma, and levels of neurotransmitter metabolites in cerebrospinal fluid (CSF), with their effects in vitro on the release of gonadotrophin-releasing hormone (GnRH) and neurotransmitters from isolated median eminences. Infusion of FK 33-824 (0.5 mg/30 min) in vivo depressed plasma LH levels in both intact and ovariectomized lambs; this effect could be reversed by naloxone. In ovariectomized lambs, the inhibitory action of FK 33-824 on plasma LH levels was associated with a 13% rise in the concentration of the metabolite of 5-hydroxytryptamine, 5-hydroxyindolacetic acid (5-HIAA). Concurrent administration of naloxone resulted in an abrupt 33% fall in CSF levels of 5-HIAA. No significant changes in plasma concentrations of prolactin or CSF concentrations of the metabolites of dopamine were observed in response to the administration of FK 33-824 or FK 33-824 plus naloxone. That FK 33-824 inhibited LH release through a central mechanism was confirmed using superfused median eminences in vitro. Thus FK 33-824 (1 mumol/l) greatly diminished the release of GnRH induced by the introduction of a depolarizing stimulus (36 mmol K+/l) in tissue obtained from both intact and ovariectomized ewe lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of amitriptyline and imipramine on brain amine neurotransmitter metabolites in cerebrospinal fluid.

The effects of amitriptyline (AMI) or imipramine (IMI) on levels of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) (the major brain metabolites of the neurotransmitters norepinephrine [NE], serotonin [5-HT], and dopamine [DA]) in cerebrospinal fluid were determined in 66 subjects with unipolar and bipolar depression. There were significant reductions in MHPG and 5-HIAA levels for the depressed group taken as a whole, but levels of HVA did not change significantly. The changes were similar when subjects were grouped as treated with AMI and IMI and with unipolar and bipolar depression. Reductions in MHPG and 5-HIAA levels were greater in women than in men. In all subjects with depression and in those treated with AMI and IMI, amine metabolite changes did not differ significantly between those who had a positive clinical response to drug therapy and those who did not. Responders with bipolar depression had smaller reductions in MHPG levels than did responders with unipolar depression. The similar effects of AMI and IMI on MHPG and 5-HIAA differ from the dissimilar effects of the two drugs on NE and 5-HT amine uptake systems reported in animal and in in vitro studies. Results provide conclusive evidence of the effects of AMI and IMI on noradrenergic and serotonergic (but not dopaminergic) systems in patients with depression.

Seasonal variations of human lumbar CSF neurotransmitter metabolite concentrations

While circadian rhythms of many biological processes have been well characterized in humans, variations throughout the year have been little studied. Lumbar cerebrospinal fluid (CSF) neurotransmitter metabolite levels for homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) were determined in patients with schizophrenia and Alzheimer's disease. Samples from both groups taken during October through March had significantly higher levels of HVA and 5-HIAA, but not MHPG, than samples from April through September.

Monitoring of transmitter metabolites by voltammetry in cerebrospinal fluid following neural pathway stimulation.

AN in vivo voltammetry technique has been developed which enables direct and continuous measurement to be made of the release of neurotransmitter metabolites in cerebrospinal fluid (CSF) after electrical stimulation or pharmacological manipulations of neural pathways. The measurement is very simple in principle. A potential is applied to a micro carbon electrode stereotaxically placed in a lateral ventricle. One then measures the minute current which results from the oxidation or reduction of small molecular weight constituents near the sensor electrode. The potential at which the electrolysis occurs serves as a qualitative indication of the constituent being monitored and the current itself is directly proportional to the concentration of this component in CSF.