Psychopathological aspects of neuroendocrine diseases: Possible parallels with the psychoendocrine aspects of normal aging

Psychoneuroendocrinology,Vol.17.No.4, pp.283-291,1992

0306-4530/92$5.00+0.00 ©1992PergamonPressLtd.

PrintedinGreatRritain

PSYCHOPATHOLOGICAL ASPECTS OF NEUROENDOCRINE DISEASES: POSSIBLE PARALLELS WITH THE PSYCHOENDOCRINE ASPECTS OF NORMAL AGING FRANCESCA BRAMBILLA Cen~o di Psiconeuroendocrinologia,Ospedale Psichiatrico "Paolo Pini", Milano, Italy Received 18 March 1992; in final form 10 April 1992)

SUMMARY Psychological impaarments can occur during the course of major endocrine diseases. These impairments range from mild affective-cognitive-behavioral disturbances to frank psychoses. The former are rather specific for each hormonal disorder and disappear with the hormonal correction. The latter, instead, seem to be quite nonspecific and include depression, mania, schizophrenia-like and organic brain syndromes which appear at random in each endocrinopathy, not always regressing with hormonal recovery, and apparently correlating more with the severity than with the nosographic classification of the metabolic disturbances. It is suggested that age-related physiological changes of hormonal and psychological patterns mimic those occurring in neuroendocrine diseases and that, possibly, common brain biochemical changes may underlie the two phenomena.

INTRODUCTION INVESTIGATIONOF MAJOR ENDOCRINEDISEASEShas revealed that functional and organic psychopathologies may develop concomitantly with hormonal dysfunctions and regress after recovery from the metabolic disturbances. This is not unexpected, since the central nervous system (CNS) secretes hormones that act either on specific brain receptors with a neurotransmitter-like mechanism or by modulating production, release, and receptor sensitivity of neurotransmitters. Peripherally secreted hormones are also known to influence brain biochemistry by acting through a feedback m e c h a n i s m on n e u r o t r a n s m i t t e r - n e u r o m o d u l a t o r systems. Dysfunctions in these biochemical circuits may be at the basis of the psychopathologies that develop in the course of endocrine diseases. It has been observed, however, that affective, cognitive and behavioral disturbances occurring concomitantly with the metabolic impairments do not always disappear when the hormonal disorders are successfully treated and sometimes persist in spite of complete endocrine recovery, thus requiring specific psychopharmacological treatment. This suggests that the relationship between hormonal and psychological dysfunction is modulated by a complex system of intervening factors and that their global impairment and recovery are mandatory for the development and regression of the mental disturbances. Address correspondence and reprint requests to: Prof. Francesca Brambilla, Centro di Psiconeuroendocrinologia, Ospedale Psichiatrico Pini, Via Ippocrate 45, 1-20161 Milano, ITALY 283

284

E BRAMBILLA

The study of the psychoneurological aspects of endocrine diseases has yielded important information on the physiological-pathological effects exerted by central and peripheral hormones on the CNS. The results, in part, may be extrapolated to the psychoneuroendocrine study of normal aging, since the endocrine and psychological changes that occur physiologically in elderly subjects may be similar to the impairments occurring in endocrinopathies of younger individuals. Thus, it may be hypothesized that psychological alterations occurring during endocrine diseases and in normal elderly subjects may share similar etiopathogenic substrates. HYPOTHALAMO-PITUITARY-ADRENAL (HPA) DISORDERS Psychopathological symptoms develop frequently during the course of HPA secretory impairments, particularly in Cushing's and Addison's diseases. Cushing's disease may have different bases, from excessive stimulation of the axis by hypothalamic corticotropin-releasinghormone (CRH), with ensuing ACTH, 13-endorphin (13-EP), and cortisol hypersecretion, to ACTH hyperproduction due to pituitary or ectopic adenomas/carcinomas, with ensuing cortisol hypersecretion and blunted CRH production, to increased cortisol concentrations linked to adrenal adenomas or therapeutic administration of the hormone, with blunted CRH, ACTH, and 13-EP production. The different hormonal secretory pattems may be at the basis of the variability in psychopathological symptomatology that characterizes the disorder. Mild impairments, ranging from apathy, negativism, and social withdrawal to euphoria, irritability, anger, and reduced memory, concentration, and comprehension occur in most patients in the course of the disease. However, a large group of patients display full psychopathologies, in particular depression. This may be so severe as to lead to suicide attempts. It is worth to remember that in iatrogenic Cushingoid syndrome, euphoria and manic excitement occur more frequently than does depression. The different effect of spontaneous or iatrogenic Cushing's disease suggests that the psychological impairments in the former are not due to increased cortisol concentrations, but possibly are modulated by the variable impairments of CRH, ACTH and 13-EPsecretion, each of these neuropeptides being responsible for different behaviors. Cognitive disturbances occur less frequently in Cushing's disease. They include acute schizophrenia-like syndrome, with hallucinations, delusions, and thought disorder, and organic brain syndrome. With respect to the latter, it is worth remembering that in experimental animals excessive and prolonged cortisol secretion and/or administration induces anatomical alterations of limbic neurons, in particular in the hippocampus, which may be at the basis of the organic brain syndrome. Along this line, brain imaging procedures have revealed that, in the course of Cushing's disease or during prolonged corticoid therapy, a reversible brain atrophy may develop (Momose et al., 1971; Brown, 1975; Jeffcoate et al., 1979; Okuno et al., 1980; Starkman et al., 1981a, 1981b, 1986; Carpenter & Gruen, 1982; Fava et al., 1987; Wolkowitz et al., 1988). In Addison's disease the decreased adrenal secretion of cortisol also may be related to different pathologies, including tumors, surgery, fibrosis and atrophy of the gland. As a consequence of peripheral hypofunction, the HPA axis is activated and hypersecretion of CRH, ACTH and I~-EP ensues. In Addisonian patients, affective and cognitive disturbances are similar to those occurring in Cushing's disease and include apathy, negativism, social withdrawal, irritability, reduced memory and concentration, and slowing of thought production. Depression occurs frequently, while schizophrenia-like and organic brain syndromes are rather rare. This symptomatological

PSYCHOPATHOLOGIES IN ENDOCRINOPATHIES

285

overlapping of Cushing's and Addison's diseases is not unexpected, since excessive CRH, ACTH, and ~-EP secretion may occur in both syndromes, with cortisol production being increased in Cushing's and decreased in Addison's disease as the only difference (Brown, 1975; Whybrow & Hurwitz, 1976; Chatelanat, 1978; Fava et al., 1978). In hyperaldosteronism due to adrenal adenoma, depression may develop, possibly as a consequence of the profound electrolyte imbalance which characterizes both diseases (Avery, 1984). Psychological impairments concomitant with adrenogenital syndrome are very rare, mainly represented by paranoid psychosis or by depression (Allen & Broster, 1945; Feldman et al., 1987). HYPOTHALAMO-PITUITARY-THYROID (HPT) DISORDERS Hyperthyroidism may be caused by generalized thyroid hyperfunction, with ensuing elevated levels of T3 and T4, or by hyperproduction of the two hormones by a single thyroid adenoma in the context of a normally functioning gland. In both cases, the elevated concentrations of the two peripheral hormones blunt the secretion of TRH from the hypothalamus and TSH from the pituitary. Very infrequently, the disease may be caused by hypothalamic dysfunction, with increased secretion of TRH, TSH, T4 and T3. The endocrinopathy is characterized by severe anxiety and aggressivity, and only occasionally by apathy, negativism, and social withdrawal (apathetic hyperthyroidism), which occurs generally in elderly subjects. Emotional-affective disturbances may include depression and mania, and less frequently, panic disorder. The cognitive impairments include hyperactive mentation, conceptual disorganization and confusion and, rarely, a schizophrenia-like syndrome (Brown, 1975; Whybrow & Hurwitz, 1976; Chatelanat, 1978; Fava et al., 1987). Hypothyroidism may be of central origin, with reduced secretion of TRH, TSH, T4 and T3, or of peripheral origin, with reduced thyroid hormone concentrations and increased levels of TRH and TSH. Hypothyroidism induces profound psychological impairments, especially when it starts in pre-perinatal life, where it results in cretinism. Even when the onset of the disorder is delayed until a young-adult age, mental retardation with reduced memory, concentration, and thought production, apathy, negativism, and social withdrawal consistently occur. Depression, mania, and organic brain syndrome also can develop. In the past, when thyroid substitution therapy was not properly administered, the so-called "myxedematous madness" was frequently observed, which was a schizophrenia-like syndrome reversible under hormonal therapy. This psychosis is very rare today (Brown, 1975; Fava et al., 1987). PARATHYROIDDISORDERS Parathyroid impairments lead to alterations of circulating available calcium ion, the importance of which as a second messenger at cellular levels is well recognized. As such, calcium can participate in the regulation of neurotransmitter secretion, release and receptor response, thus possibly modulating dependent psychological functions. Hyperparathyroidism can be caused by hyperfunction of the gland due to hyperplasia or to adenomas. In both cases, parathormone (PTH) secretion is increased, with ensuing increased plasma and cerebrospinal fluid (CSF) levels of calcium ion. Minor psychological imbalances such as apathy, lethargy, moroseness, or, alternatively, nervousness, tension, irritability, and reduced concentration and memory are reported in one-third of the patients. Major psychiatric

286

E BRAMB1LLA

disturbances are represented by depression with suicidal ideation, hypomania, disturbed cognition, catatonic or paranoid symptomatology, and acute organic psychosis, all correlated with increased plasma concentrations of calcium and possibly magnesium, but not with PTH levels (Gatewood et al., 1975; Whybrow & Hurwitz, 1976; Chatelanat, 1978; Alargon & Franceschini, 1984; Rastad et al., 1991). Hypoparathyroidism may be idiopathic, or related to ablation of the glands or to peripherally reduced sensitivity to PTH (pseudohypoparathyroidism). In the former two cases, the plasma PTH decreases, while in pseudohypoparathyroidism it is normal. In all cases, plasma concentration of calcium is decreased and that of phosphorus is increased. The most prominent symptom of the disease at the level of the CNS is tetany, due to excessively low plasma and CSF calcium levels. Psychological impairments are mainly represented by defective cognition and reduced memory, both of which appear in hypo- and pseudohypoparathyroidism. Depression, obsessive-compulsive disorder, catatonic stupor, schizophrenia-like syndrome, and dementia are rather frequent in both pathologies (Kitis, 1976; Whybrow & Hurwitz, 1976; Chatelanat, 1978; Mikkelsen & Reider, 1979). ANTERIOR-POSTERIOR PITUITARYDISORDERS Global hypopituitarism occurs in Sheehan syndrome due to pituitary necrosis consequent to thrombosis or embolism, or to ablation of the gland. As a result, not only are all the pituitary hormones deficient, but the peripheral glands, whose secretion is regulated by the hypophyseal hormones, also show decreased function. Reduced. memory, apathy, depression or mania, schizophrenia-like, and organic brain syndromes may develop, possibly as consequence of multiple deficiencies of both pituitary and peripheral hormones (Kitis, 1976; Jeffcoate et al., 1979). Isolated hormone deficiencies can occur for ACTH, with the appearance of depressive symptomatology, and for GH, with reduction of memory, impulsiveness, inappropriate affect, and idleness (Endo et al., 1981). Excessive sec.retion of isolated pituitary hormones is mainly represented by GH-producing adenomas with ensuing acromegaly/gigantism, or by prolactinomas with ensuing prolactin hypersecretion. During acromegaly-gigantism, apathy, negativism or anxiety, and irritability are rather frequent and generally have been considered to be a consequence of the physical impairment. However, depression or a schizophrenia-like syndrome may develop concomitantly with the metabolic alteration (Margo, 1981 ; Abed et al., 1987; Fava et al., 1987). Hyperprolactinemia may be due to prolactin (PRL)-secreting adenomas or be iatrogenic, related to therapies with dopamine-antagonist or serotonin-agonist drugs. Anxiety, hostility, distress, decreased libido, and impotence are frequently present in hyperprolactinemic patients. Severe depression and psychotic disturbances are more rare (Franks et al., 1978; Kellner et al., 1984; Koppelman et al., 1984; Fava et al., 1987). Inappropriate vasopressin secretion may be idiopathic or iatrogenic, mainly linked to neuroleptic or antidepressant administration. Depression, psychotic disturbances and organic brain syndrome have been described concomitantly with the endocrine disease. It has been suggested that electrolyte and/or vasopressin alterations are at the basis of the disorders (Fava et al., 1987). HYPOTHALAMO-PITUITARY-GONADAL (HPG) DISORDERS Psychological impairments can occur with physiological changes of the HPG axis during the

PSYCHOPATHOLOGIESIN ENDOCRINOPATHIES

287

lifespan. Emotional instability, reduced memory and concentration, anxiety, irritability, hostility, neuroticism, hypomania, depression, and periodic psychosis can occur at puberty, during pregnancy, the postpartum period, lactation, the premenstruum, and at a menopausal/andropausal age; they are variably related to fluctuations of HPG hormones (Taylor & Levine, 1969; Adler et al., 1986). Among the HPG dysfunctions, diseases related to sex chromosome aberrations are prominent, including Klinefelter's and Tumer's syndromes. Klinefelter's syndrome, or tubular fibrosis of the testis with aspermiogenesis, reduced testosterone, and increased gonadotropin secretion, frequently is associated with mental retardation and reduced spatial ability, possibly linked to both chromosomal and hormonal alterations. Various sexual impairments, anxiety, and social withdrawal are frequent in the course of the disease. In some cases, depression, mania, and or a schizophrenia-like syndrome can develop (Campbell et al., 1972; Nyborg et al., 1981a; Schiavi et al., 1988). Turner's syndrome is characterized by ovarian atrophy, with reduced estrogen-progesterone and increased gonadotropin secretion. Mental retardation with reduced spatial ability may be present, together with social withdrawal, anxiety, and depression (Tchertkoff, 1966; Gorzynski & Katz, 1977; Nyborg et al., 1981b). Hypersecretion of androgens from the ovary occurs in androgenizing ovarian tumors and in polycystic ovarian syndrome. Subjects generally display only an increased sexual drive, but a schizophrenia-like syndrome also has been described in a few patients (Tchertkoff, 1966; Gorzynski & Katz, 1977). Hyposecretion of androgens in men may be linked to primary testicular alterations, resulting in reduced plasma testosterone and increased gonadotropin concentrations. Alternatively, it may be due to hypothalamo-pituitary deficiency of LHRH, LH, and FSH, with ensuing decreased testosterone secretion. The former includes Klinefelter's syndrome, andropause, and castration, and the latter includes hypogonadotropic hypogonadism. In both cases, irritability, nervousness, self-reproachfulness, tearfulness, apathy, loss of libido, lack of drive, psychomotor retardation, poor concentration and memory, neuroticism, and depression are often present (Hermann & Beach, 1976). GLUCOSE- INSULIN DISORDERS In diabetes mellitus, psychological impairments may vary according to the age of onset of the disease. In children-adolescents, submissiveness and dependence on the family, frustration, rebelliousness, hostility, negativistic behavior, and provocative attitudes and behavior may be variably present. In adulthood, diabetic patients are generally insecure, tense, glum, fearful of physical complications, and depressed (Crammer & Gillies, 1981; Tattersall, 1981). No consistent psychiatric abnormalities seem to develop in patients with insulinoma. In a few cases, decreased memory and concentration, apathy, manic-depressive states, paranoia, schizophrenia-like and organic brain syndromes, and dementia have been described (De Muth & Taft, 1964; Boyd & Cleveland, 1967; Chatelanat, 1978). PHEOCHROMOCYTOMA An association between pheochromocytoma and depression or psychotic-like symptoms has been described, even though the coexistence of the two pathologies seems to be rather infrequent (Lulu, 1969; Fava et al., 1987).

288

F. BRAMBILLA DISCUSSION AND CONCLUSIONS

The data reported above clearly demonstrate that the correlation between endocrinopathies and psychopathologies is a very complex one, and that the cause-effect link between the two disorders is far from having been proved. Analysis of the data in the literature revealed phenomena that seem to occur rather frequently in the context of the endocrinologically-related psychological disorders. First, psychopathologies seem to overlap from one endocrine disease to another, with the same impairments occurring in totally different hormonal disorders. A clear example of this is represented by depression, which occurs, despite a different frequency, in most of the endocrinopathies. The study of the various reports suggests a possible explanation for this contradiction. Frank psychoses, either of the predominantly affective or cognitive type, seem to be more related to the severity than to the nosographic classification of the metabolic disorder. In other words, while each endocrinopathy displays mild psychopathological symptoms which are specific for the single diseases, as they become more severe the same psychological disorders develop in each one, going from depression to cognitive clouding-up, to a schizophrenia-like or an organic brain syndrome. Alternatively, it may be that psychopathologies are not linked to, and thus are not specific for, the primary hormonal impairments, but depend on the alterations of second messengers or other metabolic changes which can occur as a consequence of different hormonal alterations. Finally, the primary hormonal alterations can start a cascade of dysmetabolic events, leading to a final alteration, hormonal or metabolic in general, common to different endocrinopathies and responsible for the psychological changes. These are, obviously, some of the hypotheses which can be advanced to explain the apparent lack of specificity of the psychological impairments occurring during the course of endocrinopathies. The second intriguing phenomenon which appears from the data in the literature is represented by the occurrence of totally different and sometimes frankly opposite psychopathologies during the same hormonal disorder. A typical example is represented by the development of either depression or mania in Cushing's disease. As mentioned earlier, it may be that the former is linked to alterations of CRH, ACTH, and 13-EP secretion and the latter to cortisol hypersecretion, with blunted CRH, ACTH, and 13-EP production. In other words, in any endocrine disorder the type of psychological alteration displayed by individual patients may be linked to varying impairments of different levels of the hormonal axis involved. The last observation which stems from the above-reviewed psychoendocrine studies is that frank psychoses occur rather infrequently in the course of endocrinopathies, and in some cases they may persist after the recovery from the hormonal disorder. This suggests that the endocrine-psychological relationship is not a simple "one cause - one effect" phenomenon, and that hormonal dysfunctions are necessary, but not sufficient, to induce the onset and development of a psychological disorder. The studies reported up to now have not taken into account parameters which may intervene in modulating the endocrine and psychological disorders. Genetic, socio-familial, and metabolic alterations might be necessary to modulate the development of specific endocrineconnected psychological disturbances. In this case, a proper treatment of the double pathology should include not only a specific hormonal correction, but also the manipulation of the modulating cofactors. Thus psychoneuroendocrine studies of endocrinopathies must be reviewed, taking into consideration the temporal relationship between development of the metabolic and the psychological disorders, which hints at the connection between the two phenomena but

PSYCHOPATHOLOGIES1N ENDOCRINOPATHIES

289

does not offer a sufficient pathogenic explanation for it. All possible intervening factors must be evaluated and included in the studies in order to offer a definite explanation of the phenomenon. We already have proposed that psychoendocrine research of hormonal disorders may offer some paradigms for the investigation and understanding of hormonal-psychological correlations in normal aging. Increased function of the HPA axis, elevated ADH and PRL secretion, and decreased GH, somatomedin, gonadotropin, and gonadal steroid secretion, and a balanced decline in thyroid hormone production and degradation with loss of the TSH diumal variation have been observed in the normal aging of experimental animals and humans (Bemardini et al., 1988; Cramer, 1988; Emerson & Wiener, 1988; Hoffman et al., 1988; Legros, 1988). These changes mimic the hormonal hyper- and hyposecretions occurring in the course of specific endocrinopathies, even though being physiological in elderly subjects. In turn, the psychopathological aspects of endocrinopathies make us recall some of the mental characteristics of normal aging. This coincidence enforces the hypothesis that hormonally induced psychological alterations do exist and that common metabolic changes might be at the basis of some psychopathologies similarly occurring in endocrine diseases and aging subjects.

REFERENCES Abed RT, Clark J, Elbadawy MHF, Cliffe MJ (1987) Psychiatric morbidity in acromegaly. Acta Psychiat Scand 75: 635-639. Alarqon RD, Franceschini JA (1984) Hyperparathyroidism and paranoid psychosis. Br J Psychiatry 145: 477-486. Alder EM, Cook A, Davidson D, West C, Bancroft J (1986) Hormones, mood and sexuality in lactating women. Br J Psychiatry 148: 74-79. Allen C, Broster RL (1945) A further case of paranoid psychosis successfully treated by adrenalectomy. Brit MedJ h 696-701. Avery TL (1984) Primary hyperaldosteronism and depression. NZ Med J 97: 537. Bernardini R, Rabin D, Calogero AE, Margioris A, Grino M, Gold P, Pavlov EP, Chrousos GB (1988) The hypothalamo-pituitary-adrenal axis in aging. In: Valenti G (Ed) Psychoneuroendocrine Control of Aging: Basic and Clinical Aspects. Liviana Press, Padova, pp 75-82. Boyd IH, Cleveland SE (1967) Psychiatric symptoms masking an insulinoma. Dis Nerv Syst 28: 457-458. Brown GM (1975) Psychiatric and neurologic aspects of endocrine disease. Hosp Pract (Aug): 71-79. Campbell M, Wolman SR, Breuer H, Miller FT, Perlman BK (1972) Klinefelter's syndrome in a three-year-old severely disturbed child. Autism Child Schiz 2: 34-48. Carpenter WT, Gruen PH (1982) Cortisol's effects on human mental functioning. J Clin Psychopharmacol 2: 34--48. Chatelanat P (1978) Troubles mentaux symptomatiques d'affections medicales. Schweiz Rundschau Med 67: 518-526. Cramer H (1988) Pathological aging brain and pituitary hormone pattern: Alzheimer type and multiinfart dementia. In: Valenti G (Ed) Psychoneuroendocrine Control of Aging: Basic and Clinical Aspects. Liviana Press, Padova, pp 97-112. Crammer J, Gillies C (1981) Psychiatric aspects of diabetes mellitus: diabetes and depression. Br J Psychiatry 139: 171-172. Dennerstein L, Burrows G (1979) Affect and the menstrual cycle. JAffectDisord 1: 77-92. Dennerstein L, Spencer-Gardner C (1983) The menstrual cycle and mood changes. In: Dennerstein L, Burrows G (Eds) Handbook of Psychosomatic Obstetrics and Gynecology. Elsevier Biomedical Press, Amsterdam, pp 149-171. De Muth WE, Taft WC (1964) Insulinoma: neuropsychiatric manifestations. Penn MedJ 67: 43-45. Donas E, Donas W (1977) Paranoid schizophrenia in a 47,XYY male. Am J Psychiatry 134: 687-689.

290

E BRAMBILLA

Emerson CH, Wiener R (1988) Psychoneuroendocrine control of pituitary TSH secretion and aging. In: Valenti G (Ed) Psychoneuroendocrine Control of Aging: Basic and Clinical Aspects. Liviana Press, Padova, pp 29-42. Endo M, Daiguji M, Asano Y, Yamashita I, Takahashi S (1978) Periodic psychosis recurring in association with menstrual cycle. J Clin Psychiat 39: 456-466. Endo M, Endo J, Notsu K, Note S, Yamane K (1981) Mental symptoms of patients with isolated pituitary hormone deficiencies. Proc III World Congr Biol Psychiat, Stockholm, Sweden. Fava GA, Sonino N, Murphy MA (1987) Major depression associated with endocrine disease. Psychiat Develop 4: 321-348. Feldman SR, Krishnan KRR, McPearson H, Meglin DE (1987) Organic affective disorder in a patient with congenital adrenal hyperplasia. Biol Psychiat 22: 767-770. Franks S, Jacobs HS, Martin N, Nabarro JDN (1978) Hyperprolactinemia and impotence. Clin Endocrinol 8: 277-287. Frigus JP, Kleczkowska A, Kubien E, Dmoch E, van den Berghe H (1991) Turner syndrome - mental performance and psychological problems in 218 patients diagnosed in Leuven, in the period 1965-1989. Biol Psychiat 29: 720. Gatewood JW, Organ CH (1975) Mental changes associated with hyperparathyroidism. Arch Gen Psychiatry 32: 129-132. Gorzynski G, Katz JL (1977) The polycystic ovary syndrome: psychosexual correlates. Arch Sex Behav 6: 212-222. Herman WM, Beach RC (1976) Psychotropic effects of androgens: a review of clinical observations and new human experimental findings. Pharmakopsychiat 9: 205-219. Hoffman AR, Griffin C, Kalinyak J, Perkins S, Ceda GP (1988) The hypothalamic-somatotroph-somatomedin axis and aging. In: Valenti G (Ed) Psychoneuroendocrine Control of Aging: Basic and Clinical Aspects. Liviana Press, Padova, pp 43-60. Kellner R, Buckman MT, Fava GA, Pathak D (1984) Hyperprolactinemia, distress and hostility. Am J Psychiatry 141: 759-763. Kitis G (1976) Sheehan syndrome with psychosis. Proc Roy Soc Med 69: 43-44. Koppelman MCS, Parry BL, Hamilton JA, Alagna SW, Loriaux DL (1987) Effect of bromocriptine on affect and libido in hyperprolactinemia. Am J Psychiatry 144: 1037-1041. Jarrahi-Zadeh A, Kane FJ, Van de Castle RL, Lachenbruch PA, Ewing JA (1969) Emotional and cognitive changes in pregnancy and early puerperium. Br J Psychiatry 115: 797- 805. Jeffcoate WJ, Silverstone JT, Edwards CRW, Besser GM (1979) Psychiatric manifestations of Cushing's syndrome: response to lowering of plasma cortisol. Quart J Med 191: 465-472. Legros JJ (1988) Physiological aging brain and psychoneuroendocrine control of ADH secretion. In: Valenti G (Ed) Psychoneuroendocrine Control of Aging: Basic and Clinical Aspects. Liviana Press, Padova, pp 8390. Lesage J, Chouinard G (1978) Manic-depressive illness associated with Klinefelter's syndrome and essential tremors. Am J Psychiatry 136: 757-758. Lulu DJ, (1969) Pheochromocytoma of the organs of Zuckerkandl. Arch Surg 99: 641-644. Margo A (1981) Acromegaly and depression. Br J Psychiatry 139: 467-468. Mikkelsen EJ, Reider AA (1979) Post-parathyroidectomy psychosis: clinical and research implications. J Clin Psychiat 40: 352-357. Momose KJ, Kjellberg RN, Kliman B (1971) High incidence of cortical atrophy of the cerebral and cerebellar hemispheres in Cushing's disease. Neuroradiology 99: 341-348. Nott PN, Franklin M, Armitage C, Gelder MG (1976) Hormonal changes and mood in puerperium. Br J Psychiatry 128: 379-383. Nyborg H, Nielsen J (1981a) Spatial ability of men with karyotype 47,XXY, 47,XYY or normal controls. In: Schmid W, Nielsen J (Eds) Human Behavior and Genetics. Elsevier/North Holland, Amsterdam, pp 85106. Nyborg H, Nielsen J (1981b) Sex hormone treatment and spatial ability in women with Turner's syndrome. In: Schmid W, Nielsen J (Eds) Human Behavior and Genetics. Elsevier/North Holland, Amsterdam, pp 167. Okuno T, Ito M, Konishi Y, Yoshioka M, Nakano Y (1980) Cerebral atrophy following ACTH therapy. J Comput Assist Tomogr 4: 20-23.

PSYCHOPATHOLOGIESIN ENDOCRINOPATHIES

291

Peri G, Molinari E (1983) Psychological aspects in gonadal dysgenesis. Acta Med Auxol 15: 75-84. Pomeroy JC, (1980) Klinefelter's syndrome and schizophrenia. Br J Psychiatry 136: 597-599. Rastad J, Joborn C, Akerstrom G, Ljunghall S (1991) Neurobehavioral disturbances of primary hyperparathyroidism. J Endocrinol Invest 14 (Suppi 3): 35-??. Reid RL, Yen SSC (1981) Premenstrual syndrome. Am J Obst Gynecol 139: 85-104. Schiavi RC, Theilgaard A, Owen DR, White D (1988) Sex chromosome anomalies, hormones and sexuality. Arch Gen Psychiatry 45: 19-24. Sonnendecker EWW, Polakow ES, Gerdes L (1981) Psychoendocrine differences and correlations in symptomatic and asymptomatic climacteric women -- the possible role of prolactin. SA Med J 61: 661-665. Starkman MN, Schteingart DE (1981a) Neuropsychiatric manifestations of patients with Cushing's syndrome. Relationship to cortisol and adrenocorticotropic hormone levels. Arch lnt Med 141: 215-219. Starkman MN, Schteingart DE, Schork MA (1981b) Depressed mood and other psychiatric manifestations of Cushing's syndrome: relationship to hormone levels. Psychiatry Res 43: 3-18. Starkman MN, Schteingart DE, Schork MA (1986) Cushing's syndrome after treatment: changes in cortisol and ACTH levels, and amelioration of the depressive syndrome. Psychiatry Res 19:177-188. Tattersall RB (1981) Psychiatric aspects of diabetes: a physician's review. Br J Psychiatry 139: 485-493. Taylor MA, Levine R (1969) Puerperal schizophrenia: a physiological interaction between mother and fetus. Biol Psychiat 1: 97-101. Tchertkoff V (1966) Hirsutism and schizophrenia in post-menopausal women. NY State J Med ?: 2440-2446. Whybrow PC, Hurwitz T (1976) Psychological disturbances associated with endocrine disease and hormone therapy. In: Sachar EJ (Ed) Hormones, Behavior and Psychopathology. Raven Press, New York, pp 125143. Wolkowitz OM, Breier A, Doran A, Rubinow D, Berrettini W, Coppola R, Gold P, Pickar D (1988) Prednisoneinduced behavioral changes in medically healthy volunteers. Psychopharmacol Bull 24: 492-494.