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Abstract
Somatostatin is a tetradecapeptide that is assuming increasing importance as a regulator
of central nervous system activity. Originally identified as the hypothalamic growth
hormone release-inhibiting factor, somatostatin has subsequently been shown to be
extensively and selectively distributed throughout the central nervous system, to
alter neuron excitability, to regulate and be regulated by the activity of classical
neurotransmitters and neuropeptides, to exert a number of direct behavioral actions,
and to display neuropsychiatric disorder-related alterations. In this article, a three-part
study of cerebral spinal fluid (CSF) somatostatin in affective illness and schizophrenia
is presented. In part 1, significant reductions in CSF somatostatin were observed
in 49 bipolar and unipolar depressed patients relative to 47 controls. Values during
depression were also significantly lower than those observed in affective disorder
during the improved state or in schizophrenia. Diurnal studies involving paired am
and pm lumbar punctures revealed that depressed patients and normal volunteers had
similar somatostatin values in the evening, despite having significantly different
values in the morning. In part 2, the effects of several psychopharmacological agents
on CSF somatostatin were examined, particularly the tricyclic anticonvulsant carbamazepine.
A significant reduction of CSF somatostatin during treatment with carbamazepine was
observed. The effect of carbamazepine on somatostatin could be related to its anticonvulsant,
analgesic, or psychotropic effects. Part 3 deals with somatostatin as a major regulator
of hypothalamic-pituitary-adrenal (HPA) axis activity. Somatostatin affects HPA activity
by inhibiting, at a number of cellular levels, the stimulated release of adrenocorticotrophic
hormone (ACTH) from the pituitary. A significant negative relationship between CSF
somatostatin and the postdexamethasone plasma cortisol level in 22 depressed and 16
schizophrenic patients was observed. This relationship between low CSF somatostatin
and escape from dexamethasone suppression was observed irrespective of diagnosis (i.e.,
depression or schizophrenia). Thus, there is indirect supporting evidence for a role
for somatostatin dysregulation in the most consistently observed biological abnormality
in depression, escape from dexamethasone suppression. Further study of somatostatin
in neuropsychiatric disorders, and particularly depressive illness, offers great promise
for better understanding their underlying affective, vegetative, cognitive, and physiological
dysregulations.
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Article info
Publication history
Received:
July 22,
1985
The author gratefully acknowledges the invaluable contributions to the studies described in this paper of Alan Doran, M.D., Seymour Reichlin, M.D., Robert Post, M.D., Phillip W. Gold, M.D., and David Pickar, M.D.Footnotes
☆Recipient of 1985 A. E. Bennett Award for Clinical Science.
Identification
Copyright
© 1986 Published by Elsevier Inc.
