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The significance of endorphins, endogenous morphine-like agents, in some psychiatric disorders was investigated. Samples of cerebrospinal fluid were taken by lumbar puncture from healthy volunteers and from patients with schizophrenic, manic-depressive and puerperal psychosis and analyzed for two major fractions of endorphins (Fractions I and II). In 19 healthy volunteers the levels of the two fractions fell within a fairly narrow range. In contrast, six out of nine drug-free and symptom-rich schizophrenics showed elevated levels of Fraction I, which returned to normal or slightly supranormal values after treatment with neuroleptics or propranolol. This decrement was paralleled by a clinical improvement in four of six responding patients. In four manic-depressive patients, serial samples of cerebrospinal fluid revealed elevated endorphin levels, particularly Fraction I during the manic stage. In three out of four patients with puerperal psychosis, the levels of endorphins (either Fraction I or II) were elevated in the acute drug-free stage. During a later symptom-free stage, after treatment with ECT and/or neuroleptics, the endorphin levels were within the normal range. The present data lend credit to the hypothesis that endorphins are involved in some psychotic states in the human.
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