Cerebrospinal Fluid Content of Endorphins in Schizophrenia

The discovery that human brain contains peptides with opioid activity has created a worldwide research effort. Since opiate alkaloids have a profound influence on pain, mood, and behavior in man, the hypothesis has arisen that certain mental disorders could be connected with a dysfunction of the endorphin systems. The first direct evidence for this hypothesis was obtained from a small group of schizophrenic patients, who were found to have increased concentrations of two endorphin fractions in the cerebrospinal fluid (CSF) in a drug-free state (Terenius et al., 1976). This finding was supported by later studies (Lindstrom et al., 1978; Rimon et al., 1980); furthermore, patients with manic-depressive disorders and puerperal psychosis have been found to have increased levels of endorphins in CSF (Terenius et al., 1977; Lindstrom et al., 1978) and plasma (Pickar et al., 1980). Indirect support for the hypothesis comes from studies with the opiate antagonist naloxone. A decrement especially of auditory hallucinations has been reported in selected patients (Gunne et al., 1977; Emrich et al., 1977; Watson et al., 1978), but others have failed to replicate these results (Table 1). A relationship between endorphins and mental disturbances has also been suggested by several investigators (Bloom et al., 1976; Jacquet and Marks, 1976; Herz, 1976; Byck, 1976; for a review see Verebey et al., 1978; Watson et al., 1979; Davis et al., 1979).