These preliminary data reveal that our patients’ basal hormonal levels and responses to usual stimuli are partly similar to those of subjects with MAD and partly to those of patients with panic disorder. In fact, basal levels of GH and PRL were as high as in panic attacks, levels of b-EP and b-LPH were high and TSH, FSH, and LH levels were tendentially normal as has been ascertained in MAD. Administration of RH induced generally normal physiological responses, with the exception of the TSH response to TRH, which was blunted, as in both MAD and panic attacks. The unusual AP responses to RH administration were present in our patients and had the characteristics described for MAD, however, they occurred with a lower frequency. Since we examined only a small number of patients, it is possible that the investigation of a larger group cf subjects would reveal a higher frequency of these phenomena.
The analysis of the correlations between abnormal responses to RH admin­istration and clinical symptomatology did not show any correlation with in­somnia. Consequently, we can exclude a link between neuroendocrine alterations and impairments of the circadian secretion of the hormones owing to variations of sleep architecture, as suggested by Caroffet al. (11). Similarly, they cannot be the expression of an aspecific stress reaction, because they do not correlate with the degree of anxiety. The lack of an association between degree of depression and the unusual AP hormone responses to RH administration is not unexpected. In fact, we observed the same phenomena in depressed patients during phases of remission of the disease and in first-degree relatives, and with a total absence of depressive symp­tomatology (7). Our present and previous data suggest that the abnormal AP responses to RH administration are a trait marker of a spectrum of depressive disorders. They are probably the expression of neurotransmitter-neuromodulator alterations that are the common basis of various subtypes of affective disorders, possibly rep­resenting a continuum along the course of the mental disease, independent of its clinical manifestations and, in particular, of anxiety and sleep disorders. (more…)

We examined 10 outpatients, 1 man and 9 women (6 fertile and 3 post­menopausal), aged 23 to 51 years, with 2- to 20-year histories of depression associated in the last 2 years with severe anxiety. None of these subjects had panic disorders; seven had a family history of depression. Ten healthy subjects, matched for sex and age, served as controls. Informed consent was obtained from patients and controls. The Hamilton Rating Scale for Depression (HRSD) and the Hamilton Rating Scale for Anxiety (HRSA) were used to quantify the patients’ symptomatology. Sleep efficiency was rated by electroencephalographic measures modified ac­cording to an analogical scale. Patients and controls were given TRH (500 meg i.v. as a bolus) and LHRH (150 meg i.v. as a bolus) 48 hr later. The tests started at 9:00 a.m. after an overnight fast and 1 hr of bed rest. At 8:30 a.m., a 19-gauge butterfly needle was inserted into a forearm vein, kept patent by saline infusion. Heparinized blood samples were drawn for AP hormone assays, and trasylol (1000 U/ml) was added to the samples for /3-EP and /3-LPH assays. Blood was drawn at 9:00 a.m., before administration of TRH and LHRH, and, thereafter, at 15 and 30 min intervals for 150 min. Blood samples were immediately centrifuged, and plasma was stored at — 20 °C until assayed. A com­plete description of methodology and criteria used to define abnormal AP re­sponses to RH has been given previously (5,8). Data were analyzed statistically by the Student Mest and Pearson’s linear correlation. RESULTS Results are reported in Table 1 and Figs. 1 to 6. Baseline GH levels were elevated in 4 patients (mean ± SEM = 9.3 ± 2.2 ng/ml) and normal in the others. Mean values for the whole group were significantly higher than those of
controls (Table 1). GH levels rose after TRH administration in 2 cases, 1 of whom had a high basal value, whereas LHRH administration did not change them (Fig. 1). Two patients had elevated baseline PRL levels (18.5 and 32.0 ng/ml, respec­tively), whereas those of the others were normal. Mean values for the whole group were not significantly different from those of controls (Table 1). TRH (more…)

1. American Psychiatric Association. (1980): Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. American Psychiatric Association, Washington, D.C.

2. Appleby, I. L., Klein, D. F., Sachar, E., and Levitt, M. (1981): In: Anxiety: New Research and Changing Concepts, edited by D. F. Klein, and J. Rabkin, pp. 411-422. Raven Press, New York. 3. Beumont, P. J. V., Abraham, S. F., and Turtle, J. (1980): / Clin. Endocrinol. Metab., 51:1283-1285. 4. Brambilla, F., Cocchi, D., Nobile, P., and Muller, E. E. (1981): Neuropsychobiology, 7:225-237. 5. Brambilla, F., Petraglia, F., Facchinetti, F., and Genazzani, A. R. (1986): Acta Endocrinol, 112: 481-486. 6. Brambilla, F., Pugnetti, L., Scarone, S., Gambini, O., Maggioni, M., and Nobile, P. (1985): In: Chronic Treatments in Neuropsychiatry, edited by D. Kemali, and G. Racagni, pp. 69-79. Raven Press, New York. 7. Brambilla, F., Smeraldi, E., Bellodi, L., Sacchetti, E., and Muller, E. E. (1980): In: Progress in Psychoneuroendocrinology, edited by F. Brambilla, G. Racagni, and D. De Wied, pp. 235-245. Elsevier, Amsterdam. 8. Brambilla, F., Smeraldi, E., Sacchetti, E., Cocchi, D., and Muller, E. E. (1978): Arch. Gen. Psychiatry. 35:1231-1238. 9. Bridges, M., Yeragani, V. K., Rainey, J. M., and Pohl, R. (1986): Biol. Psychiatry, 21:849-853. 10. Cantalamessa, L., Catania, A., Silva, A., Orsatti, A., Motta, P., and Cazzullo, С L. (1985): Psychoneuroendocrinology, 10:481-484. 11. Caroff, S., Winokur, A., Snyder, P. J., and Amsterdam, J. (1984): Psychosom. Med, 46:59-66. 12. Carr, D. В ., Fishman, S. M., Kasting, N. W., and Sheehan, D. V. (1986): Functional Neurology, 1:123-127. 13. Carr, D. В ., Sheehan, D. V., Surman, O. S., Coleman, J. H., Greenblatt, D. J., Heninger, G. R., Jones, K. J., Levine, P. H., and Watkins, W. D. (1986): Am. J. Psychiatry, 143:483-494. 14. Fredrikson, M., Sundin, O., and Frankenauser, M. (1985): Psychosom. Med., 47:313-319. 15. Gil-Ad, I., Dickerman, Z., Weizman, R., Tyano, S., and Laron, Z. (1981): Am. J. Psychiatry, 138:357-360. 16. Gold, M. S., Pottash, A. L., Extein, I., Martin, D. M., Howard, E., Mueller, E. A., and Sweeney, D. R. (1981): Psychoneuroendocrinology, 6:159-169. 17. Kiecolt-Glaser, J. K, Ricker, D., George, J., Messick, G, Speicher, С E., Garner, W., and Glaser, R. (1984): Psychosom. Med., 46:15-23. 18. Liebowitz, M. R., Gorman, J. M., Fyer, A. J., Levitt, M., Dillon, M., Davies, S., and Klein, D. F. (1985): Arch. Gen. Psychiatry, 42:709-719. 19. Maeda, K., Kato, Y., Ohgo, S., Chihara, K., Yoshimoto, Y., Yamaguchi, N., Kuromaru, S., and Imura, H. (1975): J. Clin. Endocrinol. Metab., 40:501-505. 20. Maeda, K., Kato, Y., Yamaguchi, N., Chihara, K, Ohgo, S., Iwasaki, Y., Yoshimoto, Y., Moridera, K., Kuromaru, S., and Imura, H. (1976): Acta Endocrinol, 81:1-8. 21. Mendlewicz, J., Linkowski, P., Desmedt, D., Goldstein, J., Copinschi, C, and Van Cauter, E. (1985): J. Clin. Endocrinol. Metab., 60:505-512. 22. Naeije, R., Goldstein, J., Zegers De Beyl, D., Linkowski, P., Mendlewicz, J., Copinschi, C, Badawi, M., Leclerq, R., L’Hermite, M., and Vanhaelst, L. (1978): Clin. Endocrinol, 9:49-58. 23. Ramseier, F., Gastpar, M., and Girard, J. (1980): Acta Psychiatr. Belg., 80:399-409. 24. Schlienger, J. L., Kapfer, M. Т ., Singer, L., and Stephan, F. (1980): Acta Psychiatr. Belg., 80: 584-599. 25. Sheehan, D. V., Claycomb, J. В ., Surman, O. S., Baer, L., Coleman, J., and Gelles, L. (1983): Am. J. Psychiatry, 140:1063-1064. 26. Spitzer, R. L., Endicott, J., and Robins, E. (1978): Arch. Gen. Psychiatry, 35:773-782. 27. Takahashi, S., Kondo, H., and Yoshimura, M. (1975): Folia Psychiatr. Neurol. Jpn., 29:215-220. 28. Takahashi, Y. (1979): In: The Function of Sleep, edited by R. Drucker-Colin, M. Shkuvovich, and M. B. Sterman, pp. 113-145. Academic Press, New York. 29. Weizman, R., Abraham, W., Gil-Ad, Y., Tyano, S., and Laron, Z. (1982): Br. J. Psychiatry, 141: 582-585. 30. Winokur, A., Amsterdam, J., Oler, J., Mendels, J., Snyder, P., Caroff, S., and Brunswick, D. J-(1983): Arch. Gen. Psychiatry, 40:525-531. 31. Yamaguchi, N., Tanimoto, D. J., and Kuromaru, S. (1980): Psychoneuroendocrinology, 5:253-260.
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*Paolo Pini Psychiatric Hospital, 20161 Milan, Italy; ** Department of Psychiatry, University of Milan Medical School, 20161 Milan, Italy; t Institute of Obstetrics and Gynecology, University of Modena, 41100 Modena, Italy
In previous studies we observed that patients with Primary Affective Disorders (PAD), according to RDC (26), or Major Affective Disorders (MAD), according to DSM-III (1), responded to thyrotropin-releasing hormone (TRH) adminis­tration with abnormal rises of growth hormone (GH), follicle-stimulating hor­mone (FSH), luteinizing hormone (LH), and /3-endorphin ((3-EP) and jS-lipo-thropin (/3-LPH) plasma levels, and to luteinizing hormone-releasing hormone (LHRH) with rises of GH, prolactin (PRL), /3-EP, and 0-LPH (5-8). The ab­normal GH, FSH, and LH responses to TRH administration occurred not only in depression, but also in anorexia nervosa, schizophrenia and drug addiction (3,4,10,15,16,19,20,22-24,27,29-31). This would suggest that the phenomenon is not specifically related to the basic brain impairments of depression, but to still undefined alterations of neurotransmitter-neuromodulator secretory patterns in the central nervous system that may occur in various mental disorders. It has been suggested that abnormal GH response to stimulation with releasing hormones (RH) may be owing to impairments of the rest/activity cycle and of sleep architecture, which frequently occur in mental disorders (21) since they are also present in normal humans after prolonged periods of wakefulness (11,28). Severe anxiety may be another factor that can elicit hormonal alterations and may be present in several mental disorders. Patients suffering from generalized anxiety, panic disorders, or phobias have been observed to have multiple neu­roendocrine abnormalities. Higher than normal basal plasma levels of GH, PRL, adrenocorticotropic hormone (ACTH), and Cortisol, blunted thyroid-stimulating hormone (TSH) and PRL responses to TRH stimulation, blunted ACTH-cortisol responses to corticotropin-releasing hormone (CRH) stimulation, and positive Dexametha-sone Suppression Test (DST) have been reported to occur in the aforementioned psychopathologies (9,13,14,17,18,25). Lactate infusion, which induces the appearance of panic attacks exclusively in patients with panic disorder, stimulates in these subjects GH and PRL secre­tion, whereas Cortisol, /?-EP, LH, and vasopressin levels do not change or are increased slightly. GH and PRL rises never occur in control subjects under the same experimental conditions (2,12,18). We have investigated the influence of severe anxiety and sleep disorders on the responses of anterior pituitary (AP) hormones to RH stimulation in a group of subjects with anxious depression, defined, according to DSM-III, as Dysthymic Disorder. The aim of this study was to see whether the neuroendocrine alterations ob­served in PAD were present also in this subgroup of depressive disorders and to determine if their presence could be attributed to anxiety and/or reduced sleep efficiency. (more…)