In 1972 it was reported that in some euthyroid depressed patients the serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was deficient. Since then, 41 reports describing 917 ...depressed patients have confirmed this finding. Although it is useful to report differences between mean response values of patient populations, it is necessary to identify those individuals in whom the fault occurs so that sensitivity, specificity, state-trait distribution, and clinical correlates can be determined. Present data allow some tentative conclusions: 1) the fault usually reflects a defect in central regulation of the pituitary-thyroid axis, 2) in some patients the fault may be a trait marker, and 3) it may represent a biological bridge between some depressed patients and some patients with other mental disorders.
1. The authors examined the effect of total sleep deprivation (SD) in combination with nortriptyline in 20 patients with major depressive disorder (MDD). Patients underwent a 36-hour SD procedure ...followed by nortriptyline started on the evening after SD, with ratings for two weeks. 2. Eleven (55%) patients were responders; they showed a rapid and sustained remission after SD, whereas non-responders demonstrated the delayed results expected with nortriptyline. 3. High initial depression scores and absence of depersonalization were associated with response to SD, while being female and middle insomnia were associated with response to the combined regimen. 4. The combination of SD with antidepressants proves to be an effective and safe treatment modality.
Although relationships between hormones of the hypothalamic-pituitary-thyroid (HPT) axis and behavior have been suspected for more than two centuries, there existed no framework within which they ...could be understood. It now appears that disturbances in the HPT-axis have more to do with affective state than with any other aspect of mentation, save possibly cognition. First, depression is the most frequently observed psychiatric symptom in patients suffering from hypothyroidism. Second, approximately 30% of euthyroid patients with major depression show a blunted, i.e., attenuated TSH response after TRH administration. Third, it is now well established that a small dose of thyroid hormone will accelerate the antidepressant effect of tricyclic antidepressants (TCA) in women, and convert TCA non-responders into responders in both sexes. Fourth, administration of TRH may induce an increased sense of well-being and relaxation in some patients and healthy volunteers. However, little is known about the pathophysiologic mechanism whereby evocative emotional factors express their effect on the HPT axis, or whereby thyroid gland alterations express their behavioral effects. Longitudinal, prospective studies of both patients with thyroid disease and patients with depression (through close collaboration between endocrinology and psychiatry) are most likely to separate cause and effect in most instances.
The effects of acute gonadal suppression on sexual function and behavior were studied in eight normal men. Administration of a newly developed, potent gonadotropin-releasing hormone antagonist ...induced azoospermia and reduced levels of serum testosterone, luteinizing hormone, and follicle-stimulating hormone. These effects coincided with a reduction in outward-directed aggression in all men. Self-reported measures of anxiety and sexual desire revealed less consistent change over time. Measures of anger control, inward-directed anger, and affective state were unaffected.
Twenty-nine alcoholic men who had been abstinent for more than 2 years were evaluated behaviorally and neuroendocrinologically and then followed for 2 years. Mean length of abstinence at intake was ...shorter in the eight patients with histories of depression (3.3 years) than in the patients without such histories (6.8 years). Six patients relapsed during follow-up, all of whom had been sober less than 5 years. None of the neuroendocrine variables studied was predictive of outcome. In summary, abstinence of less than 5 years and comorbidity with depression were most predictive of poor outcome.
The psychoneuroendocrinology of mood disorders and alcoholism is reviewed here. For reasons of both space and clarity, the article focuses on the clinical data and largely omits the basic science ...data.
Objective: We hypothesized that abnormal entry of glucose into the central nervous system (CNS) might exist in some chronic binge eaters of carbohydrates, as either a cause or consequence of binge ...eating. The purpose of this study was thus to determine fasting and postprandial glucose concentrations in the cerebrospinal fluid (CSF) of healthy women, and to obtain similar data in an obese, irritable woman with chronic binge eating of postpartum onset. Method: CSF was sampled continuously at 0.1 ml/min from 1100 hr to 1700 hr from the binge eating patient, who consumed 5,000 to 10,000 calories per day (preferentially binging on refined carbohydrates), and 4 healthy women via an indwelling, flexible spinal canal catheter. CSF aliquots were obtained at 10-min intervals for measurement of glucose concentrations. Simultaneously, blood was withdrawn at 30-min intervals to obtain serum for glucose assay. A glucose-rich mixed liquid meal was consumed by participants at 1300 hr. Results: In striking contrast to the normal women, our bulimic patient showed no postprandial rise whatever in CSF glucose concentrations. Fasting CSF glucose concentrations were slightly lower whereas fasting serum glucose levels were normal in the bulimic patient, compared with the normal women. After eating, serum glucose levels increased in all participants, but less so in our patient. Discussion: This is the first description of a lack of postprandial elevation in CSF glucose concentration in a patient with a binge eating disorder. Defective transport of glucose across the blood-brain barrier might account for the observed abnormality. While considering other possibilities, we conjecture that our patient's binge eating was an attempt to compensate for impaired postprandial entry of glucose into her CNS.
Despite strong evidence of a physiologic relationship between cholecystokinin (CCK) and corticotropin‐releasing hormone (CRH) in the rat central nervous system (CNS), evidence of such a relationship ...between the two hormones in the human CNS is lacking. A post hoc analysis of serial concentrations of immunoreactive CCK and CRH, obtained every ten minutes from CSF continuously collected over six hours, was performed. A total of 30 subjects were studied: 15 normal volunteers, 10 patients with major depression, and 5 recently‐abstinent, alcohol‐dependent patients. Overall, we observed an average intra‐subject correlation of +.273 (P<0.001) between CSF CRH and CCK. Inter‐subject correlations between mean CSF levels of CRH and CCK were +.948 (P=0.0001) and +.959 (P=0.005) in the depressed and abstinent alcoholic patients, respectively. These inter‐individual correlations were significantly greater than that seen within the group of normal volunteers ® = + .318, n.s.). The present data suggest that interactions between CCK and CRH are significant in the human CNS, particularly perhaps in depressed and alcoholic patients, and that CSF samples may be used to assess elements of the relationship between these hormones. Depression and Anxiety 10:77–80, 1999. Published 1999 Wiley‐Liss, Inc.
Cushing's disease (pituitary ACTH-dependent Cushing's syndrome) has been described in association with the syndrome of multiple endocrine neoplasia type I (MEN-I). Cushing's disease is uncommon in ...MEN-I and has not been reported in more than one member of a kindred. Here we describe a mother and her daughter with Cushing's disease and major depressive disorder. The mother, her other daughter, and two other relatives also had primary hyperparathyroidism. We believe this to be the first reported instance of hereditary Cushing's disease as a manifestation of MEN-I.
Certain neuroendocrine abnormalities (e.g., blunted plasma adrenocorticotropic hormone ACTH response to corticotropin-releasing hormone CRH administration and blunted serum TSH response to ...thyrotropin-releasing hormone TRH administration) are common in alcoholic patients. It was the objective of this study to evaluate whether they are centrally mediated: that is, whether they are secondary to increased activity of CRH and/or TRH neurons. We evaluated the nocturnal secretion (2200 hours to 1000 hours, q 15 min) of plasma ACTH, serum cortisol, and serum TSH, and their responses to the combined administration of CRH and TRH, in 28 acutely abstinent alcoholic (age range: 32 to 57 years; mean: 42.4 years) and 19 normal men (age range: 21 to 52 years; mean: 32.1 years). To assess the validity of administering CRH and TRH simultaneously, we gave 10 additional abstinent alcoholic men (age range: 36 to 53 years; mean: 45.8 years), in random order and at least 4 days apart, either CRH, TRH, placebo, or CRH plus TRH. Nocturnal ACTH, cortisol, and TSH secretion, as well as cortisol and TSH responses after CRH plus TRH administration, were similar in alcoholic and normal men. However, ACTH peak responses to CRH plus TRH were reduced in the alcoholic men (p < 0.05). The ACTH, but not cortisol, response was greater after combined CRH plus TRH administration than after CRH alone (p < .002). The blunted ACTH response does not appear to be the result of increased endogenous CRH activity, because all parameters of nocturnal ACTH pulsatility were normal in the alcoholics. It rather appears to be secondary to an intrinsic defect in the CRH responsiveness of the pituitary corticotroph, possibly due to genetic vulnerability or to the toxic effects of prolonged alcohol abuse.
PDF