Neurochemical studies on tardive dyskinesia. I. Urinary homovanillic acid and plasma prolactin.

Forty-two schizophrenic patients under chronic neuroleptic treatment (11-24 years) were studied, 20 without and 22 with tardive dyskinetic symptomatology. Blood and urine samples were collected on 3 consecutive days. Plasma prolactin (PRL) and urinary homovanillic acid (HVA) values were higher in both tardive dyskinetic and nontardive dyskinetic groups, compared to normals. The increased PRL and HVA values were not related to tardive dyskinesia but to the actual neuroleptic dose. The subgroup of patients with actual dose under 900 chlorpromazine equivalents had normal PRL values and increased HVA at low significance level compared to normals, while the subgroup with doses over 900 equivalents had highly significant (p less than 0.001) increased PRL and HVA values. Thus, the actual neuroleptic dose determines plasma PRL and urinary HVA excretion in patients chronically treated with neuroleptics.

Neurochemical studies on tardive dyskinesia. II. Urinary methoxyhydroxyphenylglycol and plasma dopamine-beta-hydroxylase.

The noradrenergic correlates 3-methoxy-4-hydroxy-phenylglycol (MHPG) in urine and dopamine-beta-hydroxylase (DBH) in plasma were estimated on 3 consecutive days in chronic schizophrenic patients under neuroleptic treatment, 20 without and 22 with tardive dyskinetic symptomatology. Compared to normals, no differences in DBH activities were found, but MHPG excretion was higher in both patient groups. Dichotomy of DBH and MHPG values according to their medians for the 42 patients revealed a higher incidence of low DBH activities and low MHPG excretion in the tardive dyskinesia group, while there were no differences in relation to low or high actual neuroleptic dose.

Physical activity and plasma cyclic adenosine monophosphate levels in manic-depressive patients and healthy adults.

Intense exercise for one hour induced a significant increase in plasma cyclic adenosine monophosphate (cAMP) in 5 healthy volunteers. In 44 manic-depressive patients, cAMP levels correlated more strongly with mood ratings than with activity scores. The authors conclude that physical activity is one of the factors which contribute to changes of cAMP levels in affective illness.

Plasma cyclic AMP in manic-depressive illness.

The postulated disturbance of cyclic AMP (cAMP) in manic-depressive illness was investigated by using plasma as the biological material. Cyclic AMP was measured by a protein-binding assay, which was found very satisfactory for the purpose of this study. In the drug-free state, depressed patients (n = 28) had significantly lower and manic patients (n = 9) significantly higher plasma concentrations of cAMP than controls. Unmedicated manic-depressive subjects had normal cAMP levels during normothymic phases (n = 7). Cyclic AMP was reduced by neuroleptics in mania and elevated by tricyclics in depression. Lithium exerted a normalizing effect on cAMP in both phases of the illness. It is concluded that manic-depressive illness is associated with a disturbance in the cAMP system. The use of plasma rather than urine for the investigation of the state of cAMP in psychiatric disorders is advocated.

Elevated blood serotonin concentrations in unmediated chronic schizophrenic patients: a preliminary study.

The authors found higher serotonin concentrations in the blood of unmedicated chronic schizophrenic patients than in the blood of medicated schizophrenic patients or normal control subjects. This finding is consistent with the previous observation that the level of monoamine oxidase activity is low in the platelets of chronic schizophrenics.

Gradients of concentrations of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF).

CSF from neurological and other patients was analyzed for its content of tryptophan, 5-HIAA and homovanilic acid (HVA). The gradients of concentration of these substances from ventricular spaces to lumbar sac indicate that tryptophan and 5-HIAA probably enter the CSF from all levels of the nervous system, but that HVA originates entirely in the brain. A study of CSF tryptophan in patients with hepatic cirrhosis provided no support for theories which implicate abnormal tryptophan metabolism as a cause of hepatic coma.

Use of cerebrospinal fluid drawn at pneumoencephalography in the study of monoamine metabolism in man.

Concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly higher in CSF obtained after injection of air during pneumoencephalography (PEG) than in lumbar CSF, as drawn before the injection. There was a high correlation between levels in the `mixed' and lumbar samples of CSF in the case of each of the two acids. The concentration of lumbar HVA, but not that of 5-HIAA, was negatively correlated with CSF pressure. 5-HIAA levels were low in both samples of CSF in a group of epileptics, by comparison with controls. In two patients with Kufs disease and in one with Niemann-Pick disease, the concentration of HVA was very low in the lumbar sample. The application of a standardized PEG technique in the study of monoamine metabolism in man is suggested.

Cyclic adenosine monophosphate: selective increase in caudate nucleus after administration of L-dopa.

Treatment with the dopamine precursor L-dopa produced a significant accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in the caudate nucleus of the rat. In contrast, there was no change in the amount of cyclic AMP in the cerebellum. Accumulation of cyclic AMP in the caudate nucleus after administration of L-dopa was prevented by prior treatment with the decarboxylase inhibitor RO 4-4602. These observations and those in other laboratories support the assumption that dopamine formed from L-dopa selectively activates striatal adenylate cyclase. The in vivo activation of adenylate cyclase after treatment with L-dopa may be a useful model for studying neurological and psychiatric disorders that are thought to involve the dopaminergic system of the brain.

Sites of origin in the central nervous system of monoamine metabolites measured in human cerebrospinal fluid.

The concentrations of homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) were measured in five cases with partial or complete block of CSF circulation, at various levels. Determinations were made in both a lumbar and a cisternal, or `mixed', sample obtained during pneumoencephalography. Most of the HVA appears to enter the ventricular system at the lateral ventricles, whereas much of the 5-HIAA in CSF originates in lower neuronal structures, including the spinal cord. The spinal contribution to the 5-HIAA content of lumbar CSF is of the order of 23-37%.