Neuroendocrinology and mental illness

The interactions between the brain and endocrine system have long been the subject of study. Treatment of psychiatric patients with glandular extracts has been essayed on innumerable occasions, but the hormones 'have often been used indiscriminately and without endocrinological investigation of the patient, in the expectation of miraculous results which rarely occurred' (Reiss, 1951). Nevertheless, at that time studies of the relationship between the nervous system and endocrine glands showed great promise in the understanding and treatment of mental illness. Has this promise been justified ? Not entirely, although the reasons underlying the early disappointments are now becoming clear. As in so many other fields, progress in neuroendocrinology has had to wait upon the development of sensitive and practical methods of hormone assay. And particularly upon the invention of methods that require such small volumes of blood and tissue fluids that changes in hormone secretion can be followed over long periods of time by the collection of serial samples. Newly refined radio immunological assay methods now make it possible to trace the blood level of many hormones in this way, and the information being collected is both fascinating and of great importance. The lability of hormone secretion is striking. The existence of a circadian variation in the release of pituitary and adrenal hormones has long been known, but when the intervals between sample collection from an individual are shortened it becomes evident that hormones seldom flow from a gland at a particular rate, but tend to be ejected in spurts. Thus assay of the corticosteroid content of plasma collected every 20 minutes over a period of 26 hours has clearly demonstrated the occurrence of oscillations in corticosteroid concentration superimposed upon the familiar circadian (nycthemeral) rhythm. The frequency and amplitude of the oscillations increased during the night. Curiously, similar oscillations persisted in cases of Cushing's syndrome, although the circadian rhythm was lost (Sederberg-Olsen et ah, 1973). The realization that hormone secretion is often episodic in character is particularly applicable to the pituitary gland, from which it follows that procedures for assessing the secretion of a trophic hormone may need to be revised. Because of the pulsatile nature of the secretion of luteinizing hormone (LH), for example, the collection of a single sample may coincide with a transiently high plasma concentration, with a nadir in output, or any point between these two extremes. Misleading conclusions may be drawn in this form of lucky dip, so that if only an indication of the level of gonadotrophin secretion is required, measurement of the 24 hour urinary excretion may be more reliable. In a recent study, Santen and Bardin (1973) found that at least three hours of observation, with the collection of blood samples every 20 minutes, was required to determine the mean level of luteinizing hormone in serum with 95% confidence limits of ± 18%. Alternatively, nine consecutive daily samples were needed to provide 95% confidence limits of less than +25%. More surges of LH occurred during the follicular phase of the menstrual cycle than during the luteal phase, although the spikes of LH observed during the luteal phase were bigger than those seen earlier in the cycle. Observations of this kind help to account for the wide range of normal values recorded for the blood level of this gonadotrophin, while the continued occurrence of a pulsatile release of LH in cases of enhanced or depressed release of gonadotrophin needs to be borne in mind. Changes in the pattern of hormone secretion may be of greater significance. Interestingly, Santen and Bardin (1973) recorded secretory spikes of LH, like those normally seen during the luteal phase of the menstrual cycle, in women with psychogenic amenorrhoea, whereas there was relatively little fluctuation in the serum of patients with anorexia nervosa. As is also demonstrable in animal studies, the hypersecretion of gonadotrophin in agonadal or