Annette Gjerris

5-HT and 5-HIAA in cerebrospinal fluid in depression

CSF 5-HT and 5-HIAA were measured in endogenously depressed patients (ICD-9) (n = 23) and controls (n = 11). Distribution of sex, age and body height was similar in the two groups. Non-parametric statistics were used. In depressed patients CSF 5-HT concentrations were found to be higher (P less than or equal to 0.01) than in controls. A further classification of the depressed patients by the Newcastle Scale showed that the highest values were found in the endogenous group compared to the non-endogenous group (P less than or equal to 0.02). CSF 5-HIAA was found to be equal in the two groups, even when pairs matched for height were compared. No relation between clinical recovery due to drug treatment and changes in CSF 5-HT was seen. Our data support a possible involvement of 5-HT in the biology of depression, but the anatomical and functional levels of a serotonin derangement are still unknown.

CSF-amine metabolites in depression, dementia and in controls

ABSTRACT— Lumbar CSF concentration of 5‐HIAA, MHPG, and HVA were measured in patients with depression, dementia due to normal pressure hydrocephalus (NPH) and in controls. Moreover, ventricular concentrations of the metabolites were measured in patients with NPH. It was aimed to match patients and controls for age, sex, and body height. Non‐parametric statistics were used throughout the study. No differences in lumbar concentrations of CSF 5‐HIAA, MHPG and HVA were found between the different diagnostic groups. A ventriculolumbar gradient of 5‐HIAA and HVA being 4:1 and 5:1, respectively, was found in patients with NPH. No correlation between the difference in ventricular and lumbar concentrations and body height was found, suggesting that body height may be an inaccurate measure for the rostro‐caudal gradient. Moreover, no correlation between ventricular and lumbar levels of 5‐HIAA and HVA was seen.

CSF dopamine increased in depression: CSF dopamine, noradrenaline and their metabolites in depressed patients and in controls

Some studies report reduced levels of the dopamine metabolite HVA in CSF in depression. In the present study including 24 depressed patients and 10 controls, we found significantly increased concentrations of total CSF dopamine in depressed patients. This finding suggests a dysfunction in central dopamine turnover in depression. No differences in CSF levels of noradrenaline or the amine metabolites homovanillic acid and 3-methoxy-4-hydroxy-phenylglycol were seen when comparing depressed patients with controls.

Increased cerebrospinal fluid concentrations of C-but not N-terminal cholecystokinin fragments in multiple sclerosis

The sulfated N-terminus and the carboxyamidated C-terminus of cholecystokinin octapeptide (CCK-8) were radioimmunoassayed in cerebrospinal fluid from 19 patients with multiple sclerosis (MS) and 17 control subjects. While the N-terminal immunoreactivity was normal in all phases of MS, the concentration of C-terminal CCK immunoreactivity was significantly increased from 3.7 +/- 0.3 to 7.9 +/- 1.0 pmol/l (mean +/- S.E.M.) in both progressive and stable phases. The results indicate that C-terminal forms of CCK are released at an increased rate or that increased amounts of CCK-8 are released together with enhanced aminopeptidase activity in MS.

Cholecystokinin and other neuropeptides in the cerebrospinal fluid (CSF) in psychiatric disorders

CCK function has been hypothesized to be diminished in schizophrenia. It is well-known that there are several fractions of CCK, and it is now possible to determine at least two fractions of CCK-8 in CSF. We have measured CCK-8 in CSF by the use of two antisera, Antiserum 278 and Antiserum G160, in patients with schizophrenia and depressive disorders. 47 patients with schizophrenia, endogenous and non-endogenous depression and 15 controls entered the study. CSF was obtained by lumbar puncture. The antisera used to measure CCK have the following characteristics: Antiserum 278 detects small bioactive C-terminal fragments and Antiserum G 160 binds all larger molecular forms of CCK, both with significantly higher potency than the sera previously used. Comparison of CSF-CCK level did not show significant differences between the different diagnostic groups. A significant correlation between CSF-CCK level and age was demonstrated for all patients examined for both CCK fractions. When comparing the CSF-CCK level m...

MAO-Inhibitors Revisited II: Clinical Implications

For nearly forty years clinicians have had the feeling that there were types of depressions responding better or only to MAO-inhibitors. But whenever it was tried to prove this tenet by comparisons in well-planned studies, the results were disappointing. The most notorious case was the British Medical Research Council from 1965 where the MAO-inhibitor phenelzine was inferior not only to electroconvulsive therapy (ECT) and to imipramine, but also to placebo, — the latter difference was, fortunately enough, not statistically significant (Shepherd, 1965). Ever since, many clinicians has argued that it was indeed the ‘atypical’ depressive patients who were candidates for MAO-inhibitor treatment and that such patients did rarely enter psychiatric hospitals and departments and that it therefore was not surprising that the results with hospitalized patients were rather disappointing (Quitkin et al., 1981).

Psychiatry in Denmark in the 1990s

In Denmark an extreme reduction in the number of psychiatric beds has taken place over the last 15 years - from 2.4/1000 inhabitants in 1976 to 0.9/1000 inhabitants in 1991. With a substantial delay, community psychiatric services have been organized in the country. Concomitantly, the social services are working hard to take over the responsibility of treating psychiatric patients. In spite of severe opposition from the Danish Society of Psychiatry they have succeeded in several regions in Denmark. However, the Danish Parliament has now recommended a stop in the further reduction of psychiatric beds, and The National Board of Health has stated in their status on psychiatry and plans for the future that psychiatry still has its place among the medical specialities.

The biological pathogenesis of depression

The pathogenesis of endogenous depression is still unknown. However, several studies seem to indicate an imbalance between different transmitter systems in the central nervous system in depression more than a deficiency in an isolated amine. This imbalance may reflect single symptoms of depression such as suicidality, somatic anxiety and hypochondriasis rather than the depressive syndrome as such.□ Biological markers, Depression, Pathogenesis, Serotonin.

Mao-Inhibitors Revisited I: Adrenaline (A) and Noradrenaline (NA) in Cerebrospinal Fluid (CSF) in Isocarboxazide treated Rats

For many years the research on biology of depressions has focused on noradrenaline and serotonin. However, it has been known for nearly 10 years that adrenalineis present in neurons in the brain (Hokfelt et al., 1974), and experimental studies indicate that hypothalamic adrenaline is of central origin (Mefford et al., 1981). Using a highly specific and sensitive isotope derivative technique we are now able to measure adrenaline in CSF and brain (Christensen et al., 1980; Gjerris et al., 1981; Christensen et al., 1983). Before entering clinical studies of depressed patients to test a possible relation between changes in central adrenaline and clinical outcome of treatment with different antidepressant principles, we found it valuable first to investigate the influence of antidepressant drugs on adrenaline and noradrenaline in rat brains and to see, whether a change in brain concentrations was reflected in the CSF.

Neurotransmitters and Their Metabolites in CSF in Depression and Under the Influence of Antidepressant Drugs

In the search for a possible deficiency in the monoaminergic systems in depressive illness, most interest has been concentrated on the amine metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3-hydroxy-4-methoxyphenylglycol (MHPG), and to a lesser extent homovanillic acid (HVA) in cerebrospinal fluid (CSF). The reason for measuring the metabolites and not the amines themselves has been the lack of proper analytical methods.