ABSTRACT
Concentrations of norepinephrine, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA) were quantified in the CSF of 28 drug-free schizophrenic patients. Fifteen patients provided more than one drug-free sample on separate occasions. Considerable intraindividual variability over time was found in the concentrations of norepinephrine and these major monoamine metabolites in the repeated samples. This was not explained by assay errors or changes in the patient's global psychosis ratings. The variability in the present sample for CSF 5-HIAA concentrations was almost twice as wide as has been reported for patients with affective disorder. Variables that contribute much of the variability of norepinephrine and major monoamine metabolite concentrations in drug-free CSF samples from schizophrenic patients remain unknown and cannot be controlled.
Subject(s)
Glycols/cerebrospinal fluid , Homovanillic Acid/cerebrospinal fluid , Hydroxyindoleacetic Acid/cerebrospinal fluid , Methoxyhydroxyphenylglycol/cerebrospinal fluid , Norepinephrine/cerebrospinal fluid , Phenylacetates/cerebrospinal fluid , Schizophrenia/cerebrospinal fluid , Adult , Chronic Disease , Female , Hospitalization , Humans , Male , Schizophrenic Psychology , Spinal Puncture , Time FactorsABSTRACT
Continuous exposure of Jensen tumor cells in vitro to 1 mM inosine following a 1 hr exposure to 5-fluorouracil resulted in a 5-fold potentiation of growth inhibition. This effect was abolished by the simultaneous presence of 1 mM cytidine and was attributable to altered metabolic processing of drug anabolites after the uptake of 5-fluorouracil had ceased. In contrast, antagonism to 5-fluorouracil was seen when the cells were exposed successively to 1 mM inosine for 1.5 hr and to 5-fluorouracil for 1 hr. In this case the inhibitory action of the drug was diminished by nearly one-half. Quantitation of the potentiation and antagonism was based upon growth delays measured from growth curves obtained by serial photomicrography.
Subject(s)
Fluorouracil/pharmacology , Inosine/pharmacology , Neoplasms, Experimental/metabolism , Animals , Cell Division/drug effects , Cells, Cultured , Cytidine/pharmacology , Drug Synergism , Fluorouracil/antagonists & inhibitors , RatsABSTRACT
Local cerebral uptake of deoxyglucose labeled with fluorine 18 was measured by positron-emission tomography in eight patients with schizophrenia who were not receiving medication and in six age-matched normal volunteers. Subjects sat in an acoustically treated, darkened room with eyes closed after injection of 3 to 5 mCi of deoxyglucose 18F. After uptake, seven to eight horizontal brain scans parallel to the canthomeatal line were done. Scans were treated digitally, with a 2.3-cm strip peeled off each slice and ratios to whole-slice activity computed. Patients with schizophrenia showed lower ratios in the frontal cortex, indicating relatively lower glucose use than normal control subjects; this was consistent with previously reported studies of regional cerebral blood flow. Patients also showed diminished ratios for a 2.3-cm square that was positioned over central gray-matter areas on the left but not on the right side. These findings are preliminary; issues of control of mental activity, brain structure identification, and biologic and anatomic heterogeneity of schizophrenia remain to be explored.
Subject(s)
Blood Glucose/metabolism , Brain/metabolism , Schizophrenia/diagnosis , Tomography, Emission-Computed/methods , Adolescent , Adult , Cerebral Cortex/diagnostic imaging , Cerebral Ventricles/diagnostic imaging , Cerebrovascular Circulation , Deoxyglucose/metabolism , Female , Frontal Lobe/metabolism , Humans , Male , Mesencephalon/diagnostic imaging , Schizophrenia/metabolismABSTRACT
gamma-Aminobutyric acid (GABA) levels in CSF were not significantly different in 30 drug-free schizophrenic patients and in 39 normal control subjects, because the control subjects were significantly older. Schizophrenic women had significantly lower levels than age-matched normal control women (less than 30 years). The GABA levels increased with duration of illness, number of hospitalizations, and months of hospitalizations, as well as with age. They correlated nonsignificantly with psychosis levels. After short-term pimozide treatment, GABA levels in all patients were raised, albeit nonsignificantly. The date suggest that low GABA levels may be observed only in the early years of the illness, particularly in female schizophrenic patients, and that these levels increase with time and with long-term neuroleptic treatment.
Subject(s)
Schizophrenia/cerebrospinal fluid , gamma-Aminobutyric Acid/cerebrospinal fluid , Adult , Double-Blind Method , Female , Humans , Male , Pimozide/therapeutic use , Psychotic Disorders/cerebrospinal fluid , Schizophrenia/drug therapyABSTRACT
The authors measured total opioid activity by radioreceptor assay in the CSF of 41 normal subjects and 89 unmedicated psychiatric patients, including schizophrenic, schizoaffective, depressed, and manic diagnostic groups. Schizophrenic men had significantly lower levels of opioid activity than the normal men, although these levels did not significantly differ from levels of other male patients. The authors observed higher opioid activity during mania than during depression in paired samples for 4 manic-depressive patients. beta-Endorphin immunoreactivity in a subsample of the same subjects was no different in the patient group than in the normal group, suggesting that the differences in CSF opioid activity between schizophrenic men and normal patients may be related to opioids other than beta-endorphin.
