Circadian and sleep-related endocrine rhythms in schizophrenia
E. Van Cauter, P. Linkowski, M. Kerkhofs, P. Hubain, M. L'Hermite-Baleriaux, R. Leclercq, M. Brasseur, G. Copinschi and J. Mendlewicz
Department of Medicine, University of Chicago, IL 60637.
Plasma levels of prolactin, growth hormone, corticotropin, and cortisol
were measured at 15-minute intervals for 24 hours in nine unmedicated male
schizophrenic patients and in nine age-matched normal male subjects. Each
study was preceded by 3 days of habituation to the laboratory environment.
Sleep was polygraphically recorded. The circadian and pulsatile variations
present in each hormonal profile were quantitatively characterized with the
use of computer algorithms specifically designed for analyses of hormonal
fluctuations. The major abnormality of neuroendocrine release that was
observed in the schizophrenic patients was an almost threefold enhancement
of the sleep-related increase in the prolactin level, associated with an
intensified frequency of nocturnal prolactin pulses. This increased
stimulatory effect of sleep on prolactin secretion was evident immediately
after sleep onset. The normal inhibition of cortisol secretion during early
sleep was absent in schizophrenic patients. The major sleep abnormalities
were a prolonged sleep latency and a reduction in total rapid eye movement
stage sleep. During wakefulness, prolactin and cortisol levels were normal.
The 24-hour profile of growth hormone was unaltered in schizophrenic
patients, and a sleep-onset growth hormone pulse was observed in all
patients. No abnormalities were noted in the levels or temporal
organization of corticotropin secretion. Both the amplitude and the timing
of the cortisol rhythm were normal. We conclude that, in schizophrenic men,
pituitary-adrenal function and circadian time-keeping are normal but
prolactin secretion is hyperresponsive to the physiologic stimulus of sleep
onset. Schizophrenia thus appears to be characterized by a subset of
neuroendocrine disturbances distinct from that observed in major endogenous
depression.
