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Pyridostigmine-induced growth hormone responses in healthy and depressed subjects: evidence for cholinergic supersensitivity in depression

Published online by Cambridge University Press:  09 July 2009

V. O'Keane
Affiliation:
Trinity College Medical School, St James's Hospital, Dublin, Ireland
K. O'Flynn
Affiliation:
Trinity College Medical School, St James's Hospital, Dublin, Ireland
J. Lucey
Affiliation:
Trinity College Medical School, St James's Hospital, Dublin, Ireland
T. G. Dinan*
Affiliation:
Trinity College Medical School, St James's Hospital, Dublin, Ireland
*
1 Address for correspondence: Dr Ted Dinan, Psychiatric Unit, St James's Hospital, Dublin 8, Ireland.

Synopsis

Theorists have extrapolated the cholinergic supersensitivity theory of affective disorder from a convincing and broad spectrum of clinical observation and research. This hypothesis is tested using a neuroendocrine probe approach with the challenge drug pyridostigmine, an indirect cholinergic agent thought to release growth hormone (GH) by decreasing inhibitory somatostatin tone. The consequent increments in plasma GH were considered to reflect central acetylcholine responsivity. Fifty-four volunteers were tested: 27 DSM-III-R major depressives (18 women and 9 men) and 27 age- and sex-matched healthy controls. Subjects were cannulated at 9.00 h following an overnight fast and two baseline samples were taken at 15 min intervals. Pyridostigmine 120 mg was administered orally and thereafter samples were taken at the time points +60, +90, +120 and +180 min. GH responses were significantly greater in depressives than controls and this effect was more marked for men than women. These results support the proposal that muscarinic upregulation and/or supersensitivity is associated with depression.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 1992

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