Liquid chromatographic monitoring of CSF metabolites.
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3,4-Dihydroxyphenylacetic Acid↗
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CSF monoamine metabolites in children with minimal brain dysfunction: evidence for alteration of brain dopamine. A preliminary report.
Epidemiologic and pharmacologic evidence suggests that abnormalities of catecholaminergic systems in the brain play a role in the pathogenesis of minimal brain dysfunction, but previous attempts to document a neurochemical abnormality have been unsuccessful. To better define central nervous system mechanisms in children with MBD, we have utilized the probenecid loading technique to determine the concentrations of metabolites in the CSF of a clinically homogeneous group of children with MBD. CSF concentrations of homovanillic acid, the principal metabolite of dopamine, correlated directly with CSF probenecid in 26 control subjects (r = 0.05, p less than 0.01) and in six children with MBD (r = 0.91, p less than 0.05). Concentration of HVA (ng/ml) per unit of probenecid (mug/ml) was found to be significantly lower in children with MBD (9.8 +/- 1.5, mean +/- SEM) compared to those in control subjects (16.5 +/- 1.5), suggesting reduced turnover of brain dopamine in the MBD group. CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the principle metabolite of serotonin, did not differ significantly between the groups. Our findings indicate that there may be a neurochemical abnormality in MBD.
Attention Deficit Disorder with Hyperactivity↗
Causal effect of three autoimmune diseases on brain functional networks and cerebrospinal fluid metabolites to underlie the pathogenesis of autoimmune psychosis: a two-sample mendelian randomization analysis.
BACKGROUND: Autoimmune diseases such as Systemic Lupus Erythematosus (SLE), Sjögren's Syndrome (SS), and Hashimoto's Thyroiditis (HT) frequently exhibit neuropsychiatric manifestations, including cognitive impairment, depression, anxiety, and so on, yet the exact pathogenesis underlying this association remain incompletely understood. Dysfunction of brain resting-state functional networks and cerebrospinal fluid (CSF) metabolite disturbances have been widely reported in psychiatric disorders. However, the application of resting-state functional magnetic resonance imaging (rsfMRI) and CSF metabolomics in the diagnosis and monitoring of autoimmune psychosis is still limited. METHODS: A two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationships between three autoimmune diseases (SLE, SS, and HT, n = 14,267 to 402,090 individuals) and 191 rsfMRI phenotypes (n = 47,276 individuals), as well as 338 CSF metabolites. The genome-wide association study (GWAS) of three autoimmune diseases was used as the exposure, whereas rsfMRI phenotypes and 338 CSF metabolites were treated as the outcome. Inverse variance weighted (IVW) with P value < 0.05 was regarded as the primary approach for calculating causal estimates. Additionally, the false discovery rate (FDR)-adjusted P value (PFDR) < 0.05 was utilized to account for multiple testing. MR Egger method, weighted median method, simple mode method and weighted mode method were used for sensitive analysis. RESULTS: Our analyses identified 5 causal relationships between SLE and the 191 rsfMRI phenotypes, 48 between SS and the 191 rsfMRI phenotypes, and 4 between HT and the 191 rsfMRI phenotypes. Additionally, we found 8 causal relationships between HT and CSF metabolites. Furthermore, all three diseases were significantly associated with the temporal lobe and triple networks (default mode network (DMN), salience network (SN), and central executive network (CEN)), which are the core brain regions and functional networks for cognition. Following FDR correction, 6 causal relationships between SS and the 191 rsfMRI phenotypes were further validated. CONCLUSIONS: Our study pinpoints important brain functional networks and CSF metabolites potentially implicated in the pathogenesis of psychiatric disorders associated with autoimmune diseases and highlights critical brain regions for the development of novel therapeutics.
Humans↗
The effect of propranolol treatment in shizophrenia on CSF amine metabolites and prolactin.
Recent reports have suggested that high doses of propranolol may be an effective treatment in schizophrenia. To determine whether such treatment has effects on cerebrospinal fluid (CSF) amine metabolites and prolactin similar to the effects of the neuroleptic drugs, we studied CSF from ten patients before and after propanolol therapy. The initial CSF sample was removed after a drug-free period and propranolol dosage was then increased over 1 week to 1000 mg daily in all ten patients. A second CSF sample was removed after 3 weeks of propranolol therapy. Propranolol levels and prolactin in CSF were measured by radioimmunoassay. Homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were measured by gas chromatography-mass spectrometry. Propranolol had no effect on the prolactin or amine metabolite concentrations. CSF propranolol levels averaged 40 ng/ml (range less than 1--78).
Adult↗
In vivo voltammetry: monitoring of dopamine metabolites in CSF following release by electrical stimulation.
An in vivo electrochemical system which continuously records the concentration of metabolites of biogenic amines in small animal CSF is described. A small electrode, immersed in lateral ventricle CSF through a guide cannula, measures the amine metabolites by voltammetric oxidation. The detailed results of HVA release following electrical stimulation of the nigrostriatal pathway in rats are presented and compared with previous perfusion data. All the electrochemical results are verified by independent liquid chromatographic (chemical) analysis.
3,4-Dihydroxyphenylacetic Acid↗
MAO activity, csf amine metabolites, and drug-free improvement in schizophrenia.
Platelet monoamine oxidase (MAO) activity and amine metabolites in cerebrospinal fluid were compared in 22 schizophrenic patients, 8 of whom improved during a 30-day drug-free period. CSF 5-hydroxyindoleacetic acid and homovanillic acid did not distinguish between drug-free improvers and nonimprovers. However, drug-free improvers had lower platelet MAO activities than did normal controls. The authors suggest that looking at clinical variables in patients with low MAO activity might provide a means of biologically subtyping schizophrenic patients.
Adolescent↗
Alcohol, sleep and cerebrospinal fluid changes in alcoholics: cyclic AMP and biogenic amine metabolites in CSF.
Relative to baseline, one day of alcohol ingestion by chronic alcoholics demonstrated significant increases in SWS, decreases in REM sleep and decreases in CSF levels of cyclic AMP and 5-HIAA.
Adult↗
Effects of haloperidol and probenecid on plasma and CSF dopamine metabolites in the rhesus monkey (Macacca mulatta).
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3,4-Dihydroxyphenylacetic Acid↗
Changes in the metabolism of biogenic amines in alcoholism--especially regarding CSF monoamine metabolites and serum DBH activity.
Concentrations of the major metabolites of biogenic amines in cerebrospinal fluid and activity of serum dopamine-beta-hydroxylase in abstinent alcoholics were measured, suggesting that withdrawal symptoms of alcoholics were based on the abnormality of serotonin and dopamine metabolism in the body.
Adult↗
[Cerebrospinal fluid metabolism of biogenic amines in Huntington chorea].
CSF metabolites of dopamine (HVA), norepinephrine (MHPG) and serotonine (5HIAA) in 9 patients affected by Huntington's Chorea before and after therapy with phenotiazine derivatives (Fluphenazine) have been studied. A close relationship seems to exist between therapeutical results and CSF HVA modifications: improvement of choreatic movements is associated with marked increase in CSF HVA values. Biochemical bases of Huntington's Chorea are discussed.
Adult↗
Alcohol and central serotonin metabolism in man.
Animal studies and some of thephenomena associated with alcoholism in humans suggest that some central effects of alcohol may involve serotonergic systems. The CSF metabolites of serotonin and dopamine, 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were studied in hospitalized alcoholics. There were no significant differences in HVA levels between groups. The level of 5HIAA of alcoholics in the abstinence phase, 28 to 63 days after their last drink, was significantly lower (21.8 +/- 1.9 ng/mL) than both a nonalcoholic comparison group (31.7 +/- 2.0 ng/mL) and alcoholics in the immediate postintoxication phase, within one to two days after their last drink (32.3 +/- 2.9 ng/mL).
Adult↗
Hypersomnia with simultaneous waking and sleep patterns in the electroencephalogram. A case report with neurotransmitter studies.
A mildly dyslexic boy of 11 years, with no neurological deficit or history of epileptic seizures, had marked hypersomnia for 2 years, which was most pronounced in the morning hours. Repeated EEG studies and power spectral analysis revealed simultaneous posterior alpha rhythm and sleep patterns (spindles, vertex waves, K complexes) over vertex and frontocentral regions, while the patient was behaviorally awake. Bilateral synchronous anterior spikes were frequently noted in association with sleep patterns. A polysomnogram over 24 h confirmed excessive sleep, night and day (especially morning hours) and there was evidence of a large REM sleep percentage (on EMG and EOG basis) while the EEG had predominantly non-REM sleep patterns. Special neurotransmitter studies were performed in view of a presumed disturbance affecting the neurobiochemical sleep regulation. These studies were based on CSF metabolite levels and provided evidence for a high serotonin metabolite (5HIAA) level. It is tempting to hypothesize that the biochemical disturbance has led to encroachment of non-REM sleep patterns on both wakefulness and REM sleep. Further discussion deals with the bilateral-synchronous spike activity and its relationship to arousal patterns in sleep.
Child↗
Monoamine metabolites in the CSF of epileptic patients.
To assess the possible role of amine neurotransmitters in human epilepsy, we measured metabolites of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), dopamine (homovanillic acid [HVA]), and norepinephrine (3-methoxy-4-hydroxyphenylethylene glycol [MHPG]) in the lumbar cerebrospinal fluid (CSF) of patients with partial complex seizures and in neurologic controls. Untreated epileptic patients had lower concentrations of 5-HIAA and HVA in the lumbar CSF than the controls, but the differences were not statistically significant. Among epileptic patients receiving effective antiepileptic drug treatment, the HVA concentration was within the control range. Mean MHPG concentrations were similar in patients and controls. From the epileptic patients whose CSF was obtained at pneumoencephalography we obtained a second sample of CSF that was originally in the basal cisterns. No significant differences between treated and untreated patients were found for any of the three metabolites. The concentrations of HVA and 5-HIAA were higher in cisternal than in lumbar CSF, but there was no such gradient for MHPG.
Adolescent↗
CSF acid monoamine metabolites in psychotic syndromes: what might they signify?
Research thus far indicates that CSF 5HIAA and HVA may be correlated with state components of psychotic syndromes. HVA may be positively correlated with a component of arousal or activity. The negative correlation between 5HIAA and state variables of activity or agitation in one study suggests an inhibitory deficit in some acute psychoses or a circulating psychotomimetic substance acting on 5HT receptors. Low CSF HVA values in some psychotic patients could be a manifestation of DA receptor supersensitivity which may antedate and promote the occurrence of acute psychosis. The low CSF HVA is also consistent with a Type B monoamine oxidase deficiency in chronic patients. Such a deficiency could theoretically play a role in either (or both) state or trait behavioral components of psychotic illnesses. Decreased CSF HVA could also be related to trait behaviors in psychoses as a possible reflection of MBD. An increasingly important aspect of biological research in psychotic states in the recognition that biological studies should relate to the component behaviors which make up particular psychotic disorders.
Homovanillic Acid↗
Chronic, multiple tics of Gilles de la Tourette's disease. CSF acid monoamine metabolites after probenecid administration.
Central nervous system metabolism in six children and one adult with the syndrome of chronic multiple tics was studied by measuring the accumulation of acid metabolites of dopamine and serotonin (homovanillic acid [HVA] and 5-hydroxyindole-acetic acid [5-HIAA], respectively) in the CSF following probenecid administration. The accumulation of 5-HIAA was reduced in patients with multiple tics in contrast with other pediatric patients (N = 27). The degree of reduction in 5-HIAA relative to HVA appeared to be associated with the severity of the tic disorder. With dextroamphetamine, tic symptoms worsened, CSF HVA level decreased, and CSF 5-HIAA concentration increased. These findings suggest an association in Gilles de la Tourette's disease of reduced functioning of inhibitory serotonergic mechanisms and functional dopaminergic overactivity.
Adolescent↗
Naloxone (Narcan) treatment in depression: clinical observations and effects on CSF endorphins and monoamine metabolites.
Various dysphoric states are seen both in mood depression and on taking opiates. On the hypothesis that opiate antagonists would alter mood level, naloxone (Narcan), 0.4--0.8 mg t.i.d., was given to five depressed patients in six trials for a duration of 6--12 days. The CSF endorphin and monoamine metabolite content was analyzed before and after naloxone treatment. We observed no positive effect on mood level. However, an abrupt worsening of symptoms was noted in two cases on discontinuation of treatment. Decreasing values of endorphin Fraction I as a result of treatment was noted as a general trend. Fraction II, although elevated, showed no distinct trend. 5HIAA increased in four of the six trials. The results suggest that naloxone treatment changes endorphin and serotonin activity, though not to a clinically observable extent.
Adult↗
Selected ion monitoring assay for biogenic amine metabolites and probenecid in human lumbar cerebrospinal fluid.
Details are presented of an improved selected ion monitoring assay for the major biogenic amine metabolites and probenecid in human lumbar cerebrospinal fluid (CSF). The metabolites and probenecid are simultaneously extracted with ethyl acetate from an acidified aqueous phase, and are simultaneously converted to pentafluoropropionyl esters by reaction with pentafluoropropionic anhydride and pentafluoropropanol. The esters of the metabolites are analyzed following a single injection of the derivatized sample onto the gas chromatographic column, while the ester of probenecid is analyzed following a separate injection onto the gas chromatographic column. Quantitation is achieved using for internal standards dueterated analogues of the metabolites and a chemical analogue of probenecid. Data are presented on the concentration of free and conjugated forms of the metabolites in lumbar CSF taken from healthy volunteers.
Biogenic Amines↗
Biogenic amines in 47, XYY syndrome.
47, XYYs represent a high percentage of patients admitted in security settings for aggressiveness. By using a polygraphic technique and amine metabolite estimation in the cerebrospinal fluid (CSF), an attempt was made to evaluate the functional activity of the central aminergic system of these patients. No drastic change was observed in sleep patterns of XYYs. The estimation of CSF amine metabolites revealed a normal value for homovanillic acid, but a significant decrease of 5-hydroxyindoleacetic acid turnover.
Adult↗