Intraspinal pressure influences CSF disposition of tryptophan and 5-HIAA.

Cerebrospinal fluid (CSF) concentrations of monoamine compounds are influenced by factors such as age, gender, height, body weight, tapping time, and atmospheric pressure. We have now examined the role of intraspinal pressure. Thirteen male volunteers underwent lumbar puncture in the right decubitus position without preceding strict bed rest. The intraspinal pressure was recorded, and monoamine precursors, transmitters, and metabolites were analyzed in two consecutively collected CSF fractions. Tryptophan in 12 ml of CSF and the 5-hydroxyindoleacetic acid concentration ratio [fraction II (7--12 ml CSF)/fraction I (0--6 ml CSF)] correlated with the intraspinal pressure. Hypothetically, the intraspinal pressure may be a confounding factor for a correct interpretation of CSF tryptophan and 5-hydroxyindoleacetic acid concentrations, and this is an issue that has to be addressed in future CSF studies.

Monoamine compounds in cerebrospinal fluid of healthy subjects punctured without preceding strict bed rest: a pilot study.

The interpretation of data on compounds in the lumbar cerebrospinal fluid (CSF) is limited by several confounding factors, e.g. motor activity for which strict bed rest prior to lumbar puncture is recommended for standardisation. Now we report data from 14 healthy males employing the standardised procedure except for the requirement of strict bed rest. The levels of serotonin, noradrenaline, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid and 4-hydroxy-3-methoxyphenylglycol in the second CSF fraction (7-12 ml) were significantly higher than those in the first fraction (0-6 ml), indicating the presence of concentration gradients. 5-HIAA was negatively influenced by age and the neuraxis distance in the lying position and positively by atmospheric pressure. Storage time and atmospheric pressure contributed to the variance in dopamine. Both tyrosine, tryptophan and dopamine were linearly correlated with storage time. We also found a significant curvilinear correlation between tapping time and atmospheric pressure. On comparing with previous studies, the results support the notion that the issue of strict bed rest or not prior to lumbar puncture might have to be taken into consideration when interpreting lumbar monoamine CSF data.

CSF collection time at lumbar puncture is influenced by plasma cholesterol and triglycerides.

It is a fairly well-known fact that the CSF collection time (tapping time) at lumbar puncture may influence CSF levels of monoamine compounds (e.g. the serotonin metabolite 5-hydroxyindoleacetic acid, 5-HIAA) and some neuropeptides. Since serum levels of cholesterol and triglycerides and low CSF levels of 5-HIAA have been linked to violent behaviour and impulsivity, we investigated retrospectively whether serum cholesterol and triglycerides affect CSF collection time. The series consists of 14 healthy males lumbar punctured at the L(4-5) level. We found that both serum cholesterol and serum triglycerides influenced the CSF collection time for 12 ml of CSF (R = 0.77; p = 0.0067). There was no correlation between cholesterol in serum and CSF, nor between cholesterol in the CSF and collection time. However, we accidentally found a correlation between cholesterol in the CSF and age. The proposed hypothesis tries to explain why cholesterol- and triglyceride-rich lipoprotein particles modify the CSF collection time and influence endothelial function with a subsequent effect on CSF production and/or intraspinal pressure. Thus, it may be of interest to pay attention to serum cholesterol and triglycerides, their effect on CSF collection time and, in the next step, their putative impact on levels of various compounds in the CSF.

Cerebrospinal fluid levels of monoamine compounds and cholecystokinin peptides after exposure to standardized barometric pressure.

BACKGROUND: Connections between mood changes and weather have been described throughout the ages, and in more recent years, there have been reports on a relationship between atmospheric pressure and neurotransmitter levels in cerebrospinal fluid. METHODS: To further investigate this issue under strictly standardized conditions, we have lumbar-punctured 8 healthy males under low (963 hPa) and high (1064 hPa) barometric pressure, using a pressure chamber. RESULTS: Under high pressure, the tyrosine concentrations in the cerebrospinal fluid (CSF) were lower, while the cholecystokinin tetrapeptide (CCK-4) levels were higher. No differences between low and high pressure were found for tryptophan, 5-hydroxyindolacetic acid (5-HIAA), dopamine (DA), and sulphated cholecystokinin octapeptide (CCK-8S). The serum level of CCK-8S was higher under high pressure. On comparing concentration ratios between the second and the first CSF fraction, we found significantly increased ratios for homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylglycol (HMPG), but a decreased ratio for tyrosine under high pressure. The difference in the concentration ratios of HVA between low and high pressure correlated negatively with age. Intraspinal pressure correlated negatively with tapping time at low pressure. CONCLUSION: Our results are in line with the hypothesis that atmospheric pressure influences CSF levels of monoamine compounds and cholecystokinin peptides.

Serum and cerebrospinal fluid concentrations of melatonin: a pilot study in healthy male volunteers.

Melatonin was determined in serum and cerebrospinal fluid (CSF) obtained from 13 healthy males lumbar-punctured in the sitting position without preceding bed rest. There was a significant correlation between the levels of melatonin in serum and the CSF. The serum concentration was lower than that in the CSF, a finding that calls in question the theory that melatonin is mainly released from the pineal gland into the bloodstream. In conclusion, serum levels of melatonin in healthy male volunteers, mirror the CSF concentrations when lumbar puncture is carried out using the described technique.

Cholecystokinin peptides in cerebrospinal fluid: a study in healthy male subjects lumbar-punctured without preceding strict bed-rest.

In a recent study we analysed the concentrations of two forms of cholecystokinin (CCK), CCK-8S (sulphated) and CCK-4 in cerebrospinal fluid (CSF) obtained from 14 healthy male volunteers lumbar-punctured after a minimum of eight hours of strict bed-rest. We have now lumbar-punctured another group of 14 healthy males, using the same procedure except for the requirement of strict bed-rest prior to puncture. In contrast to our previous study, the concentration of CCK-4 (but not CCK-8S) was significantly higher in the second CSF fraction (7-12 ml) than in the first one (0-6 ml). On using the concentration ratio between the second and first fraction, CCK-8S (but not CCK-4) correlated positively with the atmospheric pressure, which is in contrast to our previous study in which a significant negative correlation was found. When the lumbar CSF concentrations were expressed as the concentration per minute of tapping-time (an estimate of the mass flow), atmospheric pressure, age and the neuraxis distance in the lying position made significant contributions to the variance in CCK-8S. A significant positive correlation with atmospheric pressure was found for CCK-4. In conclusion, the results indicate that the question of strict bed-rest or not prior to lumbar puncture may have to be considered when interpreting data on lumbar CSF concentrations of CCK. A controlled study is warranted.

Altered CSF 5-HIAA Disposition in Pathologic Male Gamblers.

Previous reports concerning the cerebrospinal fluid (CSF) of pathologic gamblers have described disturbed norepinephrine and dopamine (but not serotonin) functioning in the central nervous system. We analyzed neurotransmitter metabolites in two consecutive 6-mL samples of CSF obtained from 10 pathologic male gamblers punctured at the L4-5 level following 8 hours of fasting along with strict bed rest. Data were compared with those for healthy male controls. In conformity with findings in healthy male controls, we found gradients in CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), but not 4-hydroxy-3-methoxyphenyl glycol (HMPG). Expressing the CSF concentrations as nmol x L-1 x min-1 of tapping time (an estimate of the mass flow through the needle), the levels of 5-HIAA and HMPG (but not HVA) were found to be significantly lower in gamblers. Levels of 5-HIAA and HVA showed a significant correlation in gamblers but not in healthy controls. Taking tapping time into account, the CSF levels of HMPG and 5-HIAA were significantly lower in gamblers. We concluded that, in light of previous CSF findings of disturbed norepinephrine and dopamine function, altered indolamine function cannot be fully ruled out.

Cholecystokinin peptides in cerebrospinal fluid: a study in healthy male subjects.

The clinical reliability of measuring cholecystokinin (CCK) peptides in the cerebrospinal fluid (CSF) has not been fully elucidated. Therefore, we have assayed CCK-8S and CCK-4 in CSF obtained from 14 healthy male subjects, lumbar-punctured at the L4-5 level following a strictly standardised procedure. CSF concentrations of free CCK-8S and free CCK-4 were used as dependent variables while age, height, body weight, atmospheric pressure and some other factors served as independent variables. It was shown that the CCK-8S ratio between the second (7-12 ml) and first (0-6 ml) CSF fractions, correlated significantly with the atmosphere pressure at the time of puncture. Neither CCK-8S nor CCK-4 displayed concentration gradients in CSF. The CCK-4 levels, expressed as pmol l-1 in the total amount of CSF were found to be positively correlated with the neuraxis distance in the lying position and negatively with the neuraxis distance in the sitting position. Furthermore, CCK-4, expressed as pmol l-1 per min of tapping-time (pmol l-1 min-1), showed a negative correlation with storage time, presumably mirroring a proteolytic process. CCK-8S and CCK-4 intercorrelated positively independently of whether expressed as pmol l-1 or pmol l-1 min-1. In conclusion, the results of this exploratory study indicate that the neuraxis distance (in the sitting and lying positions) and storage-time have to be accounted for when interpreting data on CSF levels of CCK-4. Attention has to be paid to the potential influence of atmospheric pressure on the concentration ratio of CCK-8S.

Monoamine precursors, transmitters and metabolites in cerebrospinal fluid: a prospective study in healthy male subjects.

In order to elucidate methodological aspects of CSF investigations, 14 healthy male subjects were lumbar-punctured at the L4-5 level following a standardised procedure. CSF concentrations of precursors, transmitters and transmitter metabolites were used as dependent variables, while age, height, body weight, atmospheric pressure and some other factors served as independent variables. 5-HIAA and HVA (but not HMPG) have pronounced concentration gradients. We also found CSF gradients for the precursors tryptophan and tyrosine, as well as for serotonin, dopamine and the dopamine metabolite DOPAC. Dopamine and atmospheric pressure showed a positive intercorrelation. Age correlated curvilinearly (convex upward) with tryptophan but showed a negatively directed linear correlation with serotonin. Serotonin and 5-HIAA showed no intercorrelation. Our results suggest an age-dependent disposition of tryptophan in the CSF. The absence of a correlation between serotonin and 5-HIAA might be inconsistent with the notion that 5-HIAA is a marker of central serotonin turnover. The comparatively high body weight of our volunteers might explain the lack of a gradient for HMPG.

Patterns of drug treatment of schizophrenic patients in Estonia, Spain and Sweden.

1. Patterns of drug treatment and the use of polypharmacy in schizophrenic in-patients were compared and evaluated in the University Teaching Hospitals of Psychiatry in Badajoz, Spain, Huddinge, Sweden, and Tartu, Estonia. 2. The medical records of up to 100 consecutively admitted patients were retrospectively reviewed using a standardized data form. 3. The male patients were significantly younger than females in all study locations, but there were no age differences between the locations. The length of stay was equal for the two series in the same hospital, but considerably longer in Tartu than in Badajoz and Huddinge. 4. The neuroleptic drugs used most commonly in Badajoz and Tartu were similar in prescription frequency and in the doses prescribed, but different from those used in Huddinge. Haloperidol was the most frequently prescribed neuroleptic in Badajoz and Tartu, accounting for one third of all neuroleptic prescriptions. In Huddinge the choice of neuroleptics was more evenly spread over several compounds. Intramuscular injections other than depot preparations were commonly used in Tartu and Badajoz, but not in Huddinge. 5. At least two neuroleptics were prescribed simultaneously on 73% of treatment days in Badajoz and 46% in both Huddinge and Tartu. The average cumulative daily doses of concomitant multiple neuroleptic treatment, expressed in chlorpromazine equivalents, were lower in Huddinge than in the other study locations and higher for male patients in Badajoz and Tartu. 6. Anticholinergics were used together with neuroleptics in 42% of treatment days in Badajoz and 30% in Huddinge as compared with 75% in Tartu. The use of anticholinergics increased in parallel to the increase in the number and the cumulative dose of concomitant neuroleptics in all study locations. 7. About 15% of patients in Badajoz and Tartu, but only 1% in Huddinge, received concomitant treatment with antidepressant drugs. The simultaneous use of antidepressants and benzodiazepines was inversely related to the number and the cumulative dose of neuroleptics in Badajoz and Tartu. In contrast, the cumulative dose and number of neuroleptics were greater, when additional benzodiazepines were prescribed in Huddinge. 8. The study in schizophrenic in-patients revealed that polypharmacy with concomitant multiple neuroleptics, additional anticholinergics and other psychotropics is an international phenomenon.

Gradients of CSF monoamine metabolites: a comparison between male and female volunteers.

Lumbar puncture at the L4-5 level was performed on 12 healthy male and 12 healthy female volunteers. Confirming previous results, we found pronounced gradients in cerebrospinal fluid (CSF) 5-HIAA and HVA (5-hydroxyindoleacetic acid and homovanillic acid). We also found a gradient in 4-hydroxy-3-methoxyphenylglycol (HMPG), but only in the male volunteers. We also found that tapping-time was significantly longer in females than in males. One reason for this discrepancy may be that an estimate of the spinal distance was greater in males, which might indicate that a hydrodynamic factor plays a role. On taking tapping-time into consideration, the 5-HIAA and HMPG concentrations were significantly higher in males than in females.

Influence of tapping-time and atmospheric pressure on concentrations of monoamine metabolites in the cerebrospinal fluid: a prospective study in female volunteers.

Lumbar puncture was performed on 12 healthy female volunteers at the L4-5 level. CSF concentrations of 5-HIAA, HVA and HMPG were included in turn as dependent variables in repeated analyses of covariance with age, height, tapping-time, atmospheric pressure and the distance on the spine in the lying position as regressors. Use or non-use of oral contraceptives was included as a nominal variable. Results obtained were confirmed by nonparametric statistics. We found significant relationships between 5-HIAA and HVA, respectively, and height when the concentrations per minute of tapping-time (nM/min) were used as dependent variables. Hypothetically, the tapping-time mirrors the transport of concentrated CSF from the cranial to the caudal region when sitting up. We also found significant influences of atmospheric pressure and the use or non-use of oral contraceptives on HMPG. The role of atmospheric pressure is not clear but it might contribute to the transport of HMPG from the periphery to the CSF or affect the outflow of HMPG from the lumbar CSF compartment. The contribution of oral contraceptives might reflect interactions in the cerebral catecholamine metabolism.