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Cerebrospinal fluid (CSF), thyrotropin releasing hormone (TRH), CSF-vasopressin (AVP), plasma-AVP, CSF-osmolality, plasma-osmolality, CSF-adrenaline (A) and -noradrenaline (NA) were measured in psychiatric patients and controls. Psychiatric patients were classified according to ICD-9 and grouped into endogenous depression, non-endogenous depression, mania and schizophrenia. The depressive groups were classified according to the Newcastle Rating Scale for Depression 1965. Severity of disease was quantified by BRMES, BRMS and BPRS. No difference in CSF-TRH levels was seen among the different diagnostic groups and controls. A positive correlation between CSF-TRH and CSF-A was demonstrated. CSF-AVP concentrations were significantly lowered in both endogenous and non-endogenous depression; no correlation with CSF-A or -NA was seen. Neither did any difference between plasma levels of AVP, plasma-osmolality or CSF-osmolality appear among the groups investigated.

Diazepam-binding inhibitor (DBI) is a neuromodulatory peptide for gamma-aminobutyric acid (GABA) neurotransmission. Cerebrospinal fluid (CSF) levels of DBI have been found to be elevated in depression. CSF levels of the peptide corticotropin-releasing hormone (CRH) have also been found to be elevated in depression. Therefore, we examined for a relationship between DBI and CRH in human CSF. We found significant positive correlations between CSF levels of DBI and CRH in depressed patients, pathological gamblers, and normal controls. These data, along with the elevated CSF levels of DBI in depression, suggest the possibility that DBI may have a role in coordinating responses to stress in humans in addition to its possible role in the pathophysiology of depression.

Neuropeptide Y (a recently discovered brain peptide that is colocalized with norepinephrine within some adrenergic central nervous system neurons) was measured in the cerebrospinal fluid (CSF) from patients with major affective disorder, chronic schizophrenia, and in normal volunteers. No differences between diagnostic groups were found, suggesting that if this neuropeptide is involved in the pathogenesis of these disorders, an abnormality is not detectable in the CSF.

Cerebrospinal fluid levels of norepinephrine and six monoamine metabolites were measured in 28 medication-free depressed patients. Patients with a major depressive episode with melancholia (n = 15) had significantly lower levels of the three dopamine metabolites: homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), and conjugated dihydroxyphenylacetic (CONJDOPAC), when compared with a combined group of patients with a major depressive episode or dysthymic disorder (n = 13). In patients with major depressive episode with melancholia, levels of HVA and of the serotonin metabolite 5-hydroxyindoleacetic acid significantly correlated with the severity of depression. In the total group of 28 depressed patients, cerebrospinal fluid (CSF) levels of norepinephrine significantly correlated with symptoms of anxiety. In both patients with major depressive episode and major depressive episode with melancholia, those who were non-suppressors on the dexamethasone suppression test had significantly higher CSF levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol compared to those who were suppressors.

The concentration of somatostatinlike immunoreactivity in cerebrospinal fluid (CSF) from normal, healthy volunteers (n = 10) and patients with DSM-III diagnoses of major depression (n = 17), schizophrenia (n = 11), or dementia (n = 29) was measured by a sensitive and specific radioimmunoassay. Statistically significant decreases in CSF concentrations of somatostatinlike immunoreactivity were seen in all three patient populations when compared with controls. These findings confirm previous reports of decreased concentrations of somatostatinlike immunoreactivity in the CSF of patients with depression and dementia and extend this observation to patients with schizophrenia as well. These findings are concordant with the view that reductions in somatostatinlike immunoreactivity concentrations are associated with diseases in which cognitive function is disturbed.

A group of 20 inpatients with moderate to severe primary affective disorder received 14 days of placebo treatment and were then randomly allocated to receive mianserin 10 mg 3 times daily or identical amitriptyline 25 mg 3 times daily for 1 week followed by 60 mg mianserin or 150 mg amitriptyline daily for a second week. Patients were rated for side-effects and depression (Hamilton Depression Scale) on days 0, 7, 14, 21 and 28. Probenecid 100 mg/kg was administered in 3 divided doses on days 13/14 and on days 27/28 of the trial, followed by collection of CSF. Blood samples for determination of antidepressant levels were collected on day 27. Both mianserin and amitriptyline produced a significant decrease in CSF levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), but only amitriptyline significantly lowered CSF levels of 5-hydroxyindole-3-acetic acid (5-HIAA). Neither drug affected CSF levels of homovanillic acid (HVA). Both mianserin and amitriptyline produced significant but indistinguishable improvement in mean Hamilton scores over 2 weeks of treatment. There was no relationship between therapeutic response and either plasma antidepressant levels or pre-treatment CSF monoamine metabolite levels in his small group of patients. The reductions of CSF levels of metabolites of NA (MHPG) and 5-HT (5-HIAA) are consistent with the known effects of amitriptyline on amine uptake. Mianserin may reduce CSF MHPG levels as a result of its effects upon NA release and/or uptake, but it appears to be devoid of influence upon central 5-HT metabolism.

The effects of electroconvulsive therapy (ECT) on sleep and cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were studied in 11 male patients suffering from major depressive disorders severe enough to require ECT. Total sleep time and sleep efficiency index increased significantly after ECT, while the number of awakenings, the ratio wake/total sleep time, and the time of intermittent awake decreased, indicating that sleep continuity improved after treatment. Sleep architecture was also favorably influenced by ECT as shown by a significant increase in time of stage 2 and rapid eye movement (REM) sleep. REM latency and REM density also normalized after ECT. CSF 5HIAA increased significantly after ECT, but this was not the case for CSF HVA. These results demonstrate a positive effect of ECT on sleep EEG and CSF neurochemical markers for depressive illness.

Empirical study of suicide began early in this century from the sociological (Durkheim 1951) and psychological (Freud 1956) perspective. A decade ago, a biological dimension was added, focusing on two major issues, i.e., are disturbances in brain functioning instrumental in the occurrence of suicidal behavior and/or do such disturbances increase the likelihood of suicidal behavior in an individual exposed to stressful events? Biological suicide research has developed as an offshoot of biological depression research. This is a logical development, as depression is a major precursor of both attempted (Weissman et al. 1973; van Praag 1982a) and completed (Guze and Robins 1970; Miles 1977) suicide. The major biochemical research targets are similar: monoamines and hormones. This paper will review the main findings in suicidal behavior, discuss the methodological shortcomings of this research, and indicate ways of avoiding them.