CSF monoamine metabolites in schizophrenic patients

The monoamine metabolites 3-methoxy-4-hydroxyphenyglycol (MHPG), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the cerebrospinal fluid (CSF) of 16 psychiatrically health controls and in 28 schizophrenic patients. There was no difference in CSF MHPG and HVA levels between the group of patients and the controls. CSF levels of 5-HIAA were significantly lower in schizophrenic patients than in controls. Differential analysis of patients with and without neuroleptics revealed that these findings were not due to drug treatment. Positive correlations were found between the level of 5-HIAA and the items: hallucinatory behaviour, grandiosity, and tension as rated on the Brief Psychiatric Rating Scale. As 5-HIAA CSF data are controversial for nosological entities, the search for correlations between 5-HIAA and individual psychopathological variables could provide more specific indices for psychiatric diagnosis, treatment or prophylaxis.     

CSF monoamine metabolites in patients with progressive supranuclear palsy]

Neurochemical abnormalities in the patients with progressive supranuclear palsy (PSP) are not well understood. We investigated CSF levels of the monoamine metabolites HVA, 5HIAA and MHPG in 5 patients with PSP in order to investigate, especially dopaminergic, serotonergic and noradrenergic metabolism. Results were as follows (value; mena +/- S.D.). [table: see text] The levels of HVA were significantly lower than those in controls. These findings suggest that there is a hypofunction of dopaminergic neurons in PSP patients.     

CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters.

Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a subgroup of MID patients characterised by dilated ventricles and disturbed CSF hydrodynamics. These data suggest that a low CSF outflow conductance may facilitate the clearance of acidic substances from the arachnoid space at the probenecid sensitive active transport site. Alternative explanations would be that a pathologically low CSF outflow conductance is accompanied by an inverse caudorostral flow of CSF or a compromised trans-ependymal diffusion.     

CSF monoamine metabolites in mania

As part of the National Institute of Mental Health Clinical Research Branch Collaborative Program on the Psychobiology of Depression, the authors compared concentrations of CSF monoamine metabolites (the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol [MHPG], the dopamine metabolite homovanillic acid [HVA], and the serotonin metabolite 5-hydroxyindoleacetic acid [5-HIAA]) from 14 hospitalized manic patients with concentrations from 62 healthy comparison subjects. The manic patients had significantly higher levels of MHPG. Levels of 5-HIAA and HVA did not differ between the manic patients and the comparison male subjects, but they were elevated in the female manic patients. MHPG was the only metabolite that correlated significantly with mania symptom ratings. These data are consistent with findings that have shown abnormal, perhaps excessive, central noradrenergic activity in patients with mania, but not with those suggesting deficits in serotoninergic function.     

CSF monoamine metabolites in melancholia

The neurotransmitter metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenyl glycol (HMPG) in cerebrospinal fluid (CSF) were measured by mass fragmentography in 83 patients with melancholia (diagnosed by the Newcastle Inventory and the Research Diagnostic Criteria), and 66 healthy volunteer controls. After adjustment by analysis of covariance for differences between the subject groups in body height, age and sex distribution, significantly (P less than 0.001) lower concentrations of 5-HIAA and HVA were found in the melancholia patients than in the controls. HMPG did not differ between the groups. The differences could not be accounted for by differences in timing or examination techniques, and not by previously administered drugs (all patients were drug-free at the examination, but a minority had taken small amounts of psychotropic drugs prior to the wash-out period). The differences persisted after excluding the suicidal patients. There were no clear-cut differences between unipolar and bipolar patients. It is suggested that the reduced concentrations of 5-HIAA and HVA in the melancholic patients may be due to altered serotonin and/or dopamine functions in the central nervous system, which may be connected with an increased vulnerability to certain types of affective illness.     

CSF neurotransmitter metabolites and neuropsychiatric symptomatology in patients with normal pressure hydrocephalus

Patients with normal pressure hydrocephalus (NPH) may exhibit certain neuropsychiatric symptomatology, possibly related to alterations in central neurotransmitter activity. The aim of this study was to relate psychiatric distress, as expressed by the scores in the SCL-90 subscales, to CSF levels of the main metabolites of noradrenaline (MHPG), serotonin (5-HIAA), and dopamine (HVA) in NPH patients. The metabolite levels were estimated in CSF samples taken during the tap test in 19 patients with probable NPH, and compared to 19 sex- and age-matched controls. Cognitive impairment was evaluated by the MMSE. Compared to controls, NPH patients had similar MHPG and 5-HIAA levels, and significantly elevated HVA levels, a notable difference from patients with dementias. There were no significant correlations of metabolite levels to the scores in the nine SCL-90 subscales. MMSE score was not related either to metabolite levels, or to the SCL-90 subscale scores. Patients scored higher than controls in most SCL-90 subscales, more pronounced being the difference in obsessive-compulsive symptomatology. Serotonergic neurotransmitter activity seems not to be altered in NPH patients, and this may explain the reported lack of beneficial effect of serotonergic drugs for obsessive-compulsive symptoms in NPH patients.     

CSF monoamine metabolites in child and adult psychiatric patients. A developmental perspective

Concentrations of acid metabolites of dopamine and serotonin were measured in lumbar CSF of a diagnostically heterogeneous group of 154 psychiatric patients following oral probenecid loading. The patients ranged in age from 2 to 67 years old. No patients had received psychoactive medications for at least two weeks prior to the lumbar puncture. Children had higher mean CSF homovenillic acid (HVA) levels, higher mean CSF HVA-probenecid ratios, higher CSF HVA-log probenecid ratios, and lower mean CSF probenecid levels than adults. Age was negatively correlated with CSF HVA level and with CSF HVA-probenecid ratio. These correlations were more pronounced in male patients than in female patients.     

The changes of monoamine metabolites in CSF of patients with cerebral stroke]

For understanding of the role of monoamines in cerebral ischemia, 3-methoxy-4-hydroxyphenylglycol (MHPG), hydroxyindoleacetic acid (5HIAA) homovanillic acid (HVA) the three major monoamine metabolites in CSF of 33 patients and 18 controls were measured with high-performance liquid chromatography. Results showed MHPG was more sensitive to cerebral ischemia than the two others. All three metabolites were elevated in patients with severe ischemia but only MHPG and 5-HIAA were significantly elevated. A positive correlation between any two of metabolites was found in controls and in patients in the first week after stroke but altered at the end of the second week. Computer assisted multivariate analysis indicated 5-HIAA might contribute more to the state of illness in the acute stage while HVA the least. Clinically, MHPG appeared to be the most significant element on reflecting the degree of the damage and the prognosis of the disease among the metabolites.     

CSF monoamine metabolites in old age dementias

Cerebrospinal Fluid (CSF) levels of the main metabolites of monoamines (HMPG, 5-HIAA, and HVA) were measured in patients with early onset (AD) and late-onset (SDAT) Alzheimer’s disease, vascular dementia (VD), and elderly controls. Psychobehavioral assessment was carried out by means of MMSE and GBS. Mean HMPG levels did not differ from controls; 5-HIAA was lower in VD when compared to both controls and SDAT. HVA was decreased in AD, SDAT, and VD with respect to controls. Significant correlations between HVA and psychobehavioral parameters were observed in SDAT and VD groups, whereas no relationship was documented in AD. The SDAT group was divided in SDAT-A (age at onset: >65≤80 yr) and SDAT-B (age at onset: >80 yr). SDAT-A had significantly lower CSF HVA values than SDAT-B (165±64 vs 235.7±85). SDAT-B HVA levels were similar to those observed in controls. Correlation analysis between HVA and neuropsychological variables was significant in SDAT-A, but not in SDAT-B. These results might support the evidence of SDAT heterogeneity.     

Concentration gradients of monoamine metabolites in human cerebrospinal fluid.

The monamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), vanillylmandelic acid (VMA), and 4-hydroxy-3-methoxyphenylglycol (HMPG) were analysed in CSF from different regions of the CSF system to study the caudocranial concentration gradient of the metabolites. Four consecutive 10 ml fractions of CSF were withdrawn in 17 patients during the course of four minutes. The CSF pressure was monitored through a lumbar cannula because of suspected adult hydrocephalus. A pronounced gradient of the HVA concentration was found with a ratio between the last and the first fraction of 1,7. 5-HIAA showed a slight increase while HMPG and VMA showed no increase at higher levels of the CSF system. The results suggest that lumbar HVA reflects dopaminergic activity in the brain, whereas lumbar 5-HIAA and HMPG/VMA reflect the activity of 5-hydroxytryptamine and noradrenaline secreting neurones in both the brain and the spinal cord.     

CSF monoamine metabolites of depressed patients during illness and after recovery

Repeated lumbar punctures in 16 healthy volunteers showed reproducible concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid (CSF). In seven depressed patients, studied during two or three illness periods, the metabolite concentrations were also fairly stable. In 11 patients CSF concentrations of 5-HIAA, but not of HVA, were higher after recovery than during depression. This increase of 5-HIAA after recovery was confined to patients whose initial serotonin metabolite levels were low. The finding constitutes further evidence of a biochemical heterogeneity within the depressive disorders, and suggests that patients whose CSF 5-HIAA is low during a depressive episode may have a less stable serotonin system than other patients with depressive illness.     

CSF levels of receptor-active endorphins in schizophrenic patients: correlations with symptomatology and monoamine metabolites

Cerebrospinal fluid (CSF) levels of an opioid receptor-active, chromatographically separated endorphin fraction (Fraction I) were measured in 45 schizophrenic patients and 18 healthy volunteers. Significantly increased levels of Fraction I differentiated the patient group from controls, with no difference being found between newly admitted untreated and chronic previously neuroleptic-treated subjects. Fraction I levels did not correlate with age, weight, height, duration of illness, total time hospitalized, or age when symptoms first appeared. No differences were found between patients with or without a family history of schizophrenia. Fraction I levels were negatively correlated with "hallucinations" and "indecision" on the Comprehensive Psychopathological Rating Scale. Increased levels of Fraction I were associated with low levels of the dopamine metabolite homovanillic acid in drug-free schizophrenics. This relationship was not present after neuroleptic treatment or in healthy controls. No relationship was found between Fraction I and the serotonin metabolite 5-hydroxyindoleacetic acid. Neuroleptic treatment did not significantly change Fraction I levels; when only patients above the control range were considered, however, a significant decrease was observed. The data support our previous hypothesis of an increased opioid activity in schizophrenia and further indicate a concomitant dysfunction of brain endorphin and dopamine activity in schizophrenic patients.     

CSF monoamine metabolites and neuropeptides in depressed patients before and after electroconvulsive therapy

Antidepressant drugs affect monoamines and neuropeptides in human cerebrospinal fluid (CSF) and in rodent brain. The purpose of this study was to investigate if also electroconvulsive therapy (ECT) affects these compounds in a similar manner in the CSF of depressed patients. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and corticotropin-releasing hormone (CRH)-like immunoreactivity (-LI) and neuropeptide Y (NPY)-LI were determined in CSF in six drug resistant patients with major depression. Lumbar puncture was performed at baseline and after completion of eight ECTs. ECT was associated with an increase in NPY-LI (p=0.009) and a decrease in CRH-LI (p相似文献   

Vasopressin levels in CSF of Alzheimer patients: correlations with monoamine metabolites and neuropsychological test performance

Concentrations of vasopressin (AVP) and monoamine metabolites (HVA, 5-HIAA, MHPG) in cerebrospinal fluid (CSF) were measured and compared with memory functions in patients with dementia of Alzheimer type (DAT) and control subjects. CSF concentrations did not differ between the DAT patients and the controls, or between patients with different degrees of dementia. There were no correlations between concentrations of vasopressin and monoamine metabolites in CSF or between the CSF measures and psychological test scores, except for a correlation between CSF HVA and immediate and delayed story recall. These data suggest that probable damage to the vasopressinergic and monoaminergic systems in DAT is not reflected in the CSF of patients in early stages of the disease, nor is a deficit in these systems or their interaction the primary cause of cognitive impairment in DAT.     

CSF monoamine metabolites and somatostatin in Alzheimer's disease and major depression.

Decreased cerebrospinal fluid (CSF), somatostatinlike immunoreactivity (SLI) and alterations in the CSF monamine metabolites 3-methoxy-4-hydroxyphenylethylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) have been reported in patients with probable Alzheimer's disease (AD) and in patients with major depression. In this study, we found CSF SLI to be significantly lower in a large group of AD patients (n = 60) and in a group of age-matched patients with major depression (n = 18) as compared with normal controls (n = 12). Mean CSF, MHPG, 5-HIAA, and HVA levels were not significantly different among diagnostic groups. Within a group of "depressed" AD patients, CSF levels of 5-HIAA showed a significant positive correlation (p = 0.03) with CSF SLI; a similar relationship was found within the group of patients with major depression. Further exploration of the relationship between the somatostatin and serotonin systems may provide clues as to how neuropeptides interact with monoamine neurotransmitters and what role they have in depression.     

Concentration gradients for monoamine metabolites in lumbar cerebrospinal fluid

Summary Concentration gradients in lumbar cerebrospinal fluid (CSF) for the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were studied in 9 healthy controls and 47 neuropsychiatric patients without diseases causing disturbed CSF circulation. In a serial sampling of the first 24 ml of CSF, steep concentration gradients between the first (0–4 th ml) and last (21th–24th ml) portions of CSF were found for HVA (99±59% increase; p<0.001) and 5-HIAA (88±54% increase; p<0.001), while the concentration gradient was slight for HMPG (11±7% increase; p<0.001). The existence of marked concentration gradients for the monoamine metabolites HVA and 5-HIAA gives further evidence for an active transport system for these metabolites and indicates that the lumbar CSF-HVA and 5-HIAA levels reflect the dopamine and serotonin metabolism in the brain. Moreover, the existence of pronounced concentration gradients for HVA and 5-HIAA levels reflect the dopamine and serotonin metabolism in the brain. Moreover, the existence of pronounced concentration gradients for HVA and 5-HIAA stresses the importance of making analyses on a standardized volume of CSF.     

Concentration gradient of CSF monoamine metabolites in children and adolescents

Whether the lumbar cerebrospinal fluid (CSF) concentration gradient of monoamine metabolites found in adults is influenced by age or pubertal status was studied in 26 children ranging from 6.5 to 17.3 years of age. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were assayed by high-power liquid chromatography (HPLC) with electrochemical detection. Eight patients were prepubertal (Tanner stage I). The slopes in units of picomoles/milliliter/milliliter for regression lines for CSF monoamine metabolite concentrations versus milliliter of CSF collected were 5.07 +/- 0.65, 10.13 +/- 2.0, and 0.67 +/- 0.22 for 5-HIAA, HVA, and MHPG, respectively, for the group as a whole. Significant correlations with age, height, weight, or Tanner stage were not found for the HVA or MHPG concentration gradients. Tanner stage and 5-HIAA slope were significantly correlated. Three of eight prepubertal patients had nonsignificant 5-HIAA gradients. CSF studies in pediatric populations must control for aliquot collected, as the size of the gradient could produce differences sufficient to mimic a "positive" clinical study if the aliquots collected are not the same.     

Effects of monoamine oxidase inhibition by selegiline on concentrations of noradrenaline and monoamine metabolites in CSF of patients with Alzheimer's disease

Summary A double-blind, cross-over trial with 12 patients with Alzheimer's disease (AD) was carried out primarily to test the suitability of this design in the investigation of the clinical, effects of selegiline (10 mg/day) in AD. Cerebrospinal fluid (CSF) samples for the determination of concentrations of noradrenaline (NA) and several monoamine metabolites were collected at baseline and at the end of both four-week treatment periods (placebo and selegiline). The severity of dementia was assessed using Ferm's and Gottfries-Bråne-Steen (GBS) dementia scales. The concentrations of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and the NA metabolites, 3,4-dihydroxyphenylglycol (DHPG), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) decreased significantly during selegiline treatment. There was a clear trend of reduction in concentrations of homovanillic acid (HVA) during selegiline treatment, whereas the concentrations of NA, 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan did not differ significantly. The study design was not suitable for the analysis of the clinical results as there was a significant carry-over effect in both scales. As only the first period data could be used in the analysis, there were no significant differences in the scores of Ferm's or GBS scales, but clear positive trends could be detected in favour of selegiline.