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Studying brain receptor function: a neuroendocrine approach

Published online by Cambridge University Press:  13 June 2014

Timothy G Dinan
Timothy G Dinan*
Affiliation:
Department of Psychological Medicine, St. Bartholomew's Hospital, London EC1
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Abstract

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A significant component of psychiatric practice relates to the management of patients with behavioural disturbance whose aetiology lies in the subtle alteration of brain biochemistry. The major handicap in assessing such patients, both from a clinical and a research point of view has been a lack of suitably sophisticated technology for studying brain function. Despite significant improvements in imaging technique and the development of positron emission tomography we are still lacking tools which assess brain receptor functioning. The neuroendocrine axis provides us with the means of assessing specific neurotransmitters in a safe and relatively inexpensive way. Such an approach is now widely used in research and has considerable potential within a clinical setting.

The fact that classic monoamine neurotransmitters are implicated both in affective disorders and schizophrenia and at the same time control hypothalmic-anterior pituitary function provides the basis for many psychoneuroendocrine investigations. The stimulation of certain central neurotransmitter systems results in the elevation of anterior pituitary hormones. If a pharmacologically selective drug is used, the rise in the anterior pituitary hormone gives some index of the integrity of the neurotransmitter pathway and the sensitivity of its receptor system. This approach is heavily dependent on the development of selective drugs for challenging specific receptor systems. As there are a myriad of potential confounding variables it is essential that there be rigorous control over such factors as gender, age, psychotropic drug exposure, weight loss etc.

The release of growth hormone (GH) from the anterior pituitary is under the control of 2 peptides, namely growth hormone releasing hormone (GHRH) and somatostatin (SS). Noradrenaline acting via the GHRH containing neurones stimulates the release of GH (1,2). We now know that the stimulated release of GH through this mechanism is significantly blunted in patients with major depression (3,4,5). When sone suppression and noradrenergic mediated GH release are both investigated in depressed patients, those subjects who show dexamethasone non-suppression are more likely to demonstrate blunted GH release than those with normal dexamethasone responses (5).

Acetylcholine (ACh) stimulates growth hormone release via the SS method (6). It is now clear that depressed patients show enhanced release when their cholinergic system is challenged with pyridostigmine (7). Overall therefore, depressed patients seem to have a downregulation or under activity of their NA receptors and an up-regulation or over-activity of their ACh receptors.

GH release is also under GABAergic control. In a study of patients with major depression baclofen the GABA-B agonist was used to induce GH release. Baclofen (20 mg) significantly elevated GH levels in all healthy subjects but a blunting of response was seen in those patients with major depressive illness. The finding indicates diminished responsivity of the GABA-B receptor system in depression (7a).

The release of prolactin from the anterior pituitary is under the inhibitory control of dopamine (DA) which acts directly on the lactotrophs of the pituitary. The release of prolactin is stimulated by serotonin (8,9). There is now unequivocal evidence to indicate that 5-HT mediated prolactin release is blunted in major depression (10,11). Such blunting has been demonstrated with a wide variety of probe drugs including 1-tryptophan and fenfluramine. The abnormality is however not entirely specific to depression as patients with obsessive compulsive disorder and sociopathic personality disorder also demonstrate such blunting even in the absence of mood disturbance (12,13).

The first evidence to emerge that central DA receptors might in some way control GH release was demonstrated by the administration of 1-dopa which led to an increase in GH levels (14). GH responses to the DA agonist apomorphine have been reported to be greater in patients with first rank symptoms of schizophrenia, but to be blunted in those patients with significant egative symptoms such as emotional flattening and social withdrawal (15,16).

The very complex neurotransmitter control of such hormones as GH and prolactin provides a window to the biology of neuro-behavioural disturbance. As a tool psychoneuroendocrinology is of relevance not just to the researcher but to the practicing psychiatrist as well.

Type
Editorial
Information
Irish Journal of Psychological Medicine , Volume 10 , Issue 1 , February 1993 , pp. 4 - 5
Copyright
Copyright © Cambridge University Press 1993

References

1.Lovinger, R, Holland, J, Kaplan, S, et al.Pharmacological evidence for stimulation of growth hormone secretion by a central noradrenergic system in dogs. Neuroscience 1976; 1: 443–50.CrossRefGoogle ScholarPubMed
2.Katakami, H, Kato, Y, Matsushita, N, Imura, H. Effects of neonatal treatment with monosodium glutamate on growth hormone release induced by Clonidine and prostaglandin E1 in conscious male rats. Neuroendocrine 1984; 38: 1–5.CrossRefGoogle ScholarPubMed
3.Checkley, SA, Slade, AP, Shur, P. Growth hormone responses and other responses to Clonidine in patients with endogenous depression. Br J Psychiatry 1981; 138: 51–5.CrossRefGoogle ScholarPubMed
4.Charney, DS, Henninger, GR, Sternberg, DE. Alpha 2 adrenergic receptor sensitivity and the mechanism of action of antidepressant therapy. Br J Psychiatry 1983; 142: 265–75.CrossRefGoogle ScholarPubMed
5.Dinan, TG, Barry, S. Responses of growth hormone to desimpramine in endogenous and non-endogenous depression. Br J Psychiatry 1990; 156: 680–4.CrossRefGoogle Scholar
6.Casaneuva, FF, Betti, R, Cella, SG, et al.Effects of agonists and antagonists of cholinergic neurotransmission on growth hormone release in the dog. Acta Endocrinol 1983; 103: 15–20.Google Scholar
7.O'Keane, V, O'Flynn, K. Lucey, J. Dinan, TG. Pyridostigmine induced growth hormone responses in healthy and depressed subjects: evidence for cholinergic supersensitivity in depression. Psychol Med 1992; 22: 55–60.CrossRefGoogle ScholarPubMed
7a.O'Flynn, K, Dinan, TG. Baclofen induced growth hormone release in major depression: relationship to dexamethasone suppressor status. Am J Psychiatry. In press.Google Scholar
8.Charney, DS, Henninger, JR, Sternberg, DE. Serotonin function and mechanism of action of antidepressant treatment: effects of amitriptyline and desipramine. Arch Gen Psychiatry 1984; 41: 359–65.CrossRefGoogle ScholarPubMed
9.O'Keane, V, O'Hanlon, M, Webb, M. Dinan, TG. d-fenfluramine/prolactin response throughout the menstrual cycle: evidence for an oestrogen induced alteration. Clin Endocrinol 1991; 34: 289–92.CrossRefGoogle ScholarPubMed
10.Coccaro, E, Siever, LJ, Kalar, HM, et al.Serotoninergic studies in patients with affective and personality disorders. Arch Gen Psychiatry 1989; 46: 587–99.CrossRefGoogle Scholar
11.O'Keane, V, Dinan, TG. Prolacting and Cortisol responses to d-fenfluramine in major depression: evidence for diminished responsivity of central serotoninergic function. Am J Psychiatry 1991; 148: 1009–15.Google Scholar
12.O'Keane, V, Maloney, E, O'Neill, H, et al.Blunted prolactin responses to d-fenfluramine in sociopathy: evidence for sub-sensitivity of central serotoninergic function. Br J Psychiatry 1992; 160: 643–6.CrossRefGoogle Scholar
13.Lucey, JV, O'Keane, V, Butcher, G, et al.Prolactin and Cortisol responses to d-fenfluramine in obsessive compulsive disorder: a comparison with depressives and healthy controls. Br J Psychiatry 1992; 161: 512–7.CrossRefGoogle ScholarPubMed
14.Boyd, AE, Lebovitz, HE, Pfeiffer, JB. Stimulation of growth hormone secretion by 1-dopa. N Engl J Med 1970; 183: 1425–9.CrossRefGoogle Scholar
15.Whalley, LJ, Christie, JE, Brown, S, Arbuthontt, GW, Schneider's first rank symptoms of schizophrenia: an association with increased growth hormone response to apomorphine. Arch Gen Psychiatry 1984; 41: 103–4.CrossRefGoogle ScholarPubMed
16.Ferrier, N, Johnstone, EC, Crow, TJ, Rodriguez, IR. Anteriro pituitary hormone secretion in chronic schizophrenics. Arch Gen Psychiatry 1986; 4: 755–61.Google Scholar