CSF monoamine metabolite levels in Alzheimer's and Parkinson's disease

Levels of the monoamine metabolites homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in lumbar CSF from 32 patients with a clinical diagnosis of Alzheimer's disease (AD) and from 21 patients with Parkinson's disease (PD). The baseline CSF metabolite values did not differ significantly between the two groups of patients, although HVA levels were lowest in patients with PD and in the more severely demented patients with AD. Levels of all three metabolites increased significantly in both patient groups during probenecid administration, but HVA levels were significantly higher in patients with AD than in patients with PD. Within the AD group, those with the most severe dementia had the greatest rise in MHPG levels. Alterations in monoamine metabolite levels in the CSF detected during probenecid administration aid in the differential diagnosis of neurodegenerative diseases such as AD.     

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.     

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.     

CSF amine metabolites in depression.

The amine metabolites, namely homovanillic acid (HVA) and 5-hydroxy indoleacetic acid (5-HIAA) were measured in cerebrospinal fluid (CSF) of depressives (n = 30) and controls (n = 30). Depressed patients had significantly lower HVA levels than controls. No significant differences were noted between the two groups in 5-HIAA levels. However, the differences between the groups for the CSF HVA/5-HIAA ratio were larger than those for the CSF HVA alone (p less than 0.01 versus p less than 0.025, respectively). HVA levels correlated positively with monoamine oxidase activity and adenosine deaminase activity.     

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.     

The dexamethasone suppression test in Alzheimer's disease and major depression: relationship to dementia severity, depression, and CSF monoamines.

Patients with Alzheimer's disease (AD) have been reported to have a rate of nonsuppression on the dexamethasone suppression test (DST) comparable to that of patients with major depression. With symptoms of depression being increasingly recognized in patients with AD, studying their DST response may provide clues to the etiology of the abnormal response in both diagnostic groups. A correlation between dementia severity and post-dexamethasone cortisol was found within the group of male, but not female AD patients. Within the group of elderly depressives, a correlation between post-dexamethasone cortisol and ratings of depression was found. Serum dexamethasone levels were not significantly lower in the nonsuppressors as compared with suppressors in either diagnostic group. Within the AD group, dexamethasone levels themselves correlated significantly with ratings of dementia severity and with the Wechsler Memory Scale score. Cerebrospinal fluid (CSF) 3-methoxy-4-hydroxyphenylglycol (MHPG) correlated positively with 4:00 pm post-dexamethasone cortisol level and with ratings of dementia severity in the AD patients. Findings are discussed in light of the known clinical and other biological similarities between AD and major depression, followed by a review of theories regarding the etiology of the hypothalamic-pituitary-adrenal abnormalities in these two illnesses.     

CSF corticotropin-releasing factor (CRF) in Alzheimer's disease: its relationship to severity of dementia and monoamine metabolites

The concentration of corticotropin-releasing factor-like immunoreactivity (CRF-LI) in the cerebrospinal fluid (CSF) of 15 probable Alzheimer's disease (AD) patients with mild to moderate dementia and 10 neurologically normal age-matched controls was examined. There were no significant alterations in the mean CSF CRF-LI concentration in AD compared to controls. However, in the AD group, CSF CRF-LI correlated significantly with the global neuropsychological impairment ratings, suggesting that greater cognitive impairment was associated with lower CSF CRF-LI concentrations. There was a significant reduction in the CSF concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the AD patients, and there was a positive correlation between the concentration of CRF-LI and 5-HIAA in CSF. This latter finding suggests that serotoninergic neuronal systems may interact with CRF-containing neurons.     

抑郁症患者脑脊液生长抑素及单胺代谢产物的测定

目的 探讨抑郁症可能的生化病理机制,方法 采用放射免疫测定法及高效液相色谱法,分别测定２７例抑郁症患者和２７例对照者脑脊液（ＣＳＦ）生长抑素（ＳＳ）及单胺代谢产物水平。结果抑郁症组ＧＳＦ中ＳＳ水平和３－甲氧－４羟苯乙二醇（ＭＨＰＧ）水平（Ｐ〈０．０５）和５－羟吲哚乙酸水平（Ｐ〈０．０１）,均低于对照组,而抑制症组ＣＳＦ中高香草酸含量与对照组间的差异无显著性（Ｐ〉０．０５）;抑郁症组ＣＳＦ中ＳＳ与Ｍ     

Relationship between CSF neurotransmitter metabolites and aggressive behavior in Alzheimer's disease

To assess neurochemical correlates of aggressive behavior in Alzheimer's disease (AD) we examined concentrations of homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) in lumbar cerebrospinal fluid (CSF) of 11 clinically diagnosed Alzheimer's disease (AD) patients and 12 non-demented age-equivalent controls. There were no significant differences between AD patients and controls in CSF HVA concentrations. However, the CSF 5-HIAA content was significantly lower in AD patients compared to controls. Patients without aggressive behavior had significantly lower concentrations of HVA and 5-HIAA than those with aggression, in whom concentrations were preserved compared to non-demented controls.     

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.     

The TRH stimulation test in Alzheimer's disease and major depression: relationship to clinical and CSF measures

A blunted thyroid-stimulating hormone (TSH) response to exogenous thyrotropin-releasing hormone (TRH) has been reported to occur consistently in patients with major depression and less consistently in patients with Alzheimer's disease (AD). In this study we compared the TSH response to TRH in a large group (n = 40) of AD patients, elderly patients with major depression (n = 17), and age-matched controls (n = 14) to further characterize how it may relate to clinical variables, baseline thyroid function tests, and cerebrospinal fluid measures. Comparisons of TRH stimulation test response across all three groups revealed that patients with major depression had lower stimulated TSH levels (delta maxTSH) (p less than 0.02) and higher (though still within normal limits) mean thyroxine (T4) levels (p less than 0.05) than the AD patients or controls. AD patients with a blunted TSH response had a significantly higher mean free T4 (FT4) level (p less than 0.03) and tended to be more severely demented (p less than 0.01) than those with a nonblunted response.     

CSF amine metabolites and depression

Cerebrospinal fluid (CSF) amine metabolites were measured in 37 male subjects with major depressive disorder. Scores on the Hamilton Rating Scale for Depression (HRSD) correlated significantly with 5-hydroxyindoleacetic acid (5HIAA) and with homovanillic acid (HVA). In addition, the single suicide item of the HRSD correlated significantly with 5HIAA. Further, 5HIAA and HVA correlated significantly with each other. There was a significant positive correlation between HVA and two HRSD items, the depersonalization/derealization item and the paranoid item. Since lumbar CSF metabolite concentrations may reflect central nervous system activity of parent amines, these data suggest a relationship between depression and decreased dopaminergic and serotonergic activity.     

On the relationship between l-DOPA therapy and CSF monoamine metabolites in parkinson's disease

Summary HVA, the main dopamine catabolite, was shown to be decreased in CSF of parkinsonian patients. A significant relationship was also shown between clinical improvement and HVA concentration increase in CSF. It was, however, recently claimed that such increase was not specific.A study on the CSF concentrations of HVA and 5-HIAA (the main serotonin metabolite) was undertaken on 10 parkinsonian patients. The determinations were made before and after l-DOPA therapy, when a satisfactory clinical status was achieved. The results obtained clearly demonstrate that a large increase of HVA was found in CSF during l-DOPA therapy, but no relationship was found between HVA levels and clinical improvement. A decrease of 5-HIAA in CSF during l-DOPA treatment was found.These results are discussed in the light of a relationship between dopamine and serotonin during l-DOPA therapy.     

Platelet membrane fluidity in Alzheimer's disease and major depression

Double-blind fluorescence studies of platelet membrane fluidity were conducted at 37 degrees C for 51 patients with Alzheimer-type dementia, 24 nondemented depressed patients, and 50 neurologically healthy subjects. The fluidity of the hydrocarbon region of platelet membranes from the demented group, as reflected by the steady-state anisotropy of the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), was significantly greater than that for the depressed and normal control subjects. Within the demented group, platelet membrane fluidity was significantly correlated with severity of dementia but not with duration of illness or age at onset. Demented patients with "increased" platelet membrane fluidity had an earlier onset, were more severely demented, and deteriorated more rapidly.     

Differentiation of geriatric major depression from Alzheimer's disease with CSF tau protein phosphorylated at threonine 231

OBJECTIVE: Differentiation of geriatric major depression from Alzheimer's disease is hampered by overlapping symptoms. Increased CSF concentrations of tau protein phosphorylated at threonine 231 (p-tau(231)) have been suggested as a biomarker for Alzheimer's disease. The authors asked whether p-tau(231) levels improve the differential diagnosis between geriatric major depression and Alzheimer's disease. METHOD: Included were 34 depression subjects, 64 with probable Alzheimer's disease, 17 with possible Alzheimer's disease, and 21 healthy comparison subjects. P-tau(231) concentrations were measured with an enzyme-linked immunosorbent assay. RESULTS: P-tau(231) levels were significantly higher in Alzheimer's disease than in geriatric major depression patients and healthy comparison subjects. For differentiation of probable Alzheimer's disease from major depression, p-tau(231) correctly allocated 87% of subjects. When possible mild Alzheimer's disease was compared to major depression, p-tau(231) correctly allocated 78% of subjects. CONCLUSIONS: CSF p-tau(231) should be evaluated as a potential biological marker for differentiation of geriatric depression from Alzheimer's disease.