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Several risk factors have been proposed for the development of Alzheimer’s disease (AD), among them, a family history of dementia (1) and prior thyroid disease (2). The results of a recent case–control study from Greece suggested that depression, when combined with a family history of dementia, was the main risk factor for the development of dementia of the Alzheimer type (3). The present study searched for correlations among Dexamthasone Suppression Test (DST) cortisol levels, thyroid indices, and family history of dementia in depression patients. To our knowledge, this is the first study that explores this possible relation. Material and MethodsThirty patients entered the study. There were 10 men and 20 women (mean age 42.43 years, SD 11.82 years; range 21 to 60 years). All suffered from major depressive disorder diagnosed according to DSM-IV criteria. All had been free of any medication for at least 2 weeks prior to entering the study. They were physically healthy, with normal clinical and laboratory findings (specifically, EEG, blood and biochemical testing, and testing for pregnancy, B12, and folic acid). All patients provided written informed consent before participating in the study. The hospital’s investigational review board approved the protocol. We used the Schedule for Clinical Assessment in Neuropsychiatry, Version 2.0 (4,5), and the International Personality Disorders Examination (6–9) for clinical diagnosis. Data concerning the family history of dementia of any kind were registered according to the family history method (10). Assessment of Thyroid Function We assessed serum levels of free T3 (FT3), free T4 (FT4), thyroid-stimulating hormone (TSH), thyroid-binding inhibitory immunoglobulines (TBII), thyroglobulin antibodies (TAs), and thyroid microsomal antibodies (TMAs) for all patients. We also calculated the FT4/FT3 ratio. Table 1 shows the technical details of the measurement methods. The Dexamethasone Suppression Test The DST (11) protocol demands the oral administration of 1 mg dexamethasone at 23.00 hours on the first day and determination of cortisol serum levels simultaneously and on the following day at 16.00 and 23.00 hours. Cortisol levels (in mg/dL) were measured by luminance immunoassay (intraassay reliability, 4.9%; interassay reliability, 7.5%). The nonsuppression cut-off level was 5 mg/dL cortisol. The statistical analysis included 1-way multiple analysis of covariance with age as the covariate and t test as the post hoc test. ResultsThree patients (10%) had a family history of dementia and manifested significantly higher TMA levels (P < 0.001, see Table 1). We found no significant differences concerning the other thyroid indices and cortisol values. No patient had FT3, FT4, or TA levels outside the normal range. Four patients (13.3%) had increased TSH levels; 12 patients (26.6%) had increased TMA levels; and 5 patients (16.6%) had increased TBII levels. Of the patients, 8 (26.6%) were DST nonsuppressors; 6 (22.22%) had no positive family history of dementia; and 1 (33.33%) had a positive family history. The difference in percentages is small and not significant.
DiscussionMany authors suggest that depression may be characterized by a “low thyroid function syndrome” (12–14). However, screening tests are often routinely applied for inpatients with depression, and data suggest that thyroid screening adds little to the diagnostic evaluation. Concerning the hypothalamo–pituitary–thyroid axis, Musselman and Nemeroff (15) have reported that patients suffering from depression show altered TSH response to thyrotropin-releasing hormone (TRH), an abnormally high rate of antithyroid antibodies, and elevated TRH concentrations in cerebrospinal fluid. Moreover, triiodothyronine has been shown conclusively to augment the efficacy of various antidepressants (16). Other authors report that autoimmune thyroiditis associated with a mild subclinical form of hypothyroidism is more pronounced in patients with AD. There are also direct reports that high values of antithyroglobulin and antimicrosomial autoantibodies are present in AD patients (17). Our study reports that, while serum levels of FT3, FT4, and TSH are generally within the normal range in patients suffering from depression, significantly higher thyroid microsomal antibodies (TMAs) were present in patients having a positive family history of dementia. Microsomal antibodies are frequently present in patients with chronic lymphocytic thyroiditis, while thyroid-binding inhibitory immunoglobulines inhibit the binding of TSH to its receptor and lead to hypothyroidism. The main advantage of our study was the deep and thorough clinical and laboratory investigation of patients who constituted a natural population. Its major disadvantage was the small number of patients in the group with a positive family history of dementia. ConclusionThe current study confirms that overt thyroid dysfunction is not common in depression patients. However, an autoimmune process may characterize a subgroup of patients, and this process may be even more pronounced in patients with a family history of dementia. In patients suffering from depression, the mechanism that could relate the severity of an autoimmune process to family history of dementia remains unknown. References1. Graves A, White E, Koepsel T. The association between head trauma and Alzheimer’s disease. Am J Epidemiol 1990;131:491–501. 2. Heyman A, Wilkinson W, Stafford J. Alzheimer’s disease: a study of epidemiological aspects. Ann Neurol 1984;15:335–41. 3. Tsolaki M, Fountoulakis K, Chantzi H, Kazis A. Risk factors for clinically diagnosed Alzheimer’s disease: a case–control study in a Greek elderly population. Int Psychogeriatr 1997;3:327–41. 4. Wing J, Babor T, Brugha T. SCAN: Schedules for Clinical Assessment in Neuropsychiatry. Arch Gen Psychiatry 1990;47:589–93. 5. Mavreas V. Greek version of the World Health Organisation: Schedules for Clinical Assessment in Neuropsychiatry-SCAN. Version 2.0. 1995. Located at: Research University Institute for Mental Health, Athens. 6. Loranger A, Sartorious N, Andreoli A. The World Health Organisation/Alcohol, Drug Abuse and Mental Health Administration International Pilot Study of Personality Disorders. Arch Gen Psychiatry 1994;51:215–24. 7. World Health Organisation. International Personality Disorders Examination. Geneva: WHO; 1995. 8. Fountoulakis K, Iacovides A, Kaprinis G, Ierodiakonou C. Greek translation of the World Health Organisation: International Personality Disorders Examination. 1998. Located at: 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Thessaloniki, Greece. 9. Fountoulakis K, Iacovides A, Ioannidou C, Bascialla F, Nimatoudis I, Kaprinis G, and others. Reliability and cultural applicability of the Greek version of the International Personality Disorders Examination. BMC Psychiatry 2002;2(1):6. 10. Andreasen N. The measurment of genetic aspects of depression. In: Marsella A, Hirschfeld R, Katz M, editors. The measurement of depression. New York: John Wiley & Sons; 1987. p 87–108. 11. Carroll B, Martin F, Davies B. Resistance of suppression by dexamethasone of plasma 11-OHCS levels in severe depressive illness. BMJ 1968;3:285–7. 12. Staner L, De La Fuente J, Kerkhofs M, Linkowski P, Mendlewicz J. Biological and clinical features of recurrent brief depression: a comparison with major depressed and healthy subjects. J Affect Disord 1992;26:241–5. 13. Legros S, Mendlewicz J, Wybran J. Immunoglobulins, autoantibodies and other serum protein fractions in psychiatric disorders. Eur Arch Psychiatry Neurol Sci 1985; 235(1):9–11. 14. Rao M, Ruhrmann S, Retey B, Liappis N, Fuger J, Kraemer M, and others. Low plasma thyroid indices of depressed patients are attenuated by antidepressant drugs and influence treatment outcome. Pharmacopsychiatry 1996;29:180–6. 15. Musselman DL, Nemeroff CB. Depression and endocrine disorders: focus on the thyroid and adrenal system. Br J Psychiatry Suppl 1996;(30):123–8. 16. Aronson R, Offman HJ, Joffe RT, Naylor CD. Triiodothyronine augmentation in the treatment of refractory depression: a meta-analysis. Arch Gen Psychiatry 1996;53:842–8. 17. Genovesi G, Paolini P, Marcellini L, Vernillo E, Salvati G, Polidori G, and others. Relationship between autoimmune thyroid disease and Alzheimer’s disease. Panminerva Med 1996; 38(1):61–3. Author(s)Manuscript received June 2003, revised, and accepted March 2004. 1. Lecturer in Psychiatry, Laboratory of Psychophysiology, 3rd Department of Psychiatry, Aristotle University of Thessaloniki, University Hospital AHEPA, Thessaloniki, Greece. 2. Lecturer in Psychiatry, 3rd Department of Psychiatry, Aristotle University of Thessaloniki, University Hospital AHEPA, Thessaloniki, Greece. 3. Associate Professor of Psychiatry, 3rd Department of Psychiatry, Aristotle University of Thessaloniki, University Hospital AHEPA, Thessaloniki, Greece. 4. Associate Professor of Psychiatry and Director, 2nd Department of Psychiatry, Aristotle University of Thessaloniki, University Hospital AHEPA, Thessaloniki, Greece. 5. Director, 3rd Department of Psychiatry, Aristotle University of Thessaloniki, University Hospital AHEPA, Thessaloniki, Greece. Address for correspondence: Dr KN Fountoulakis, 53 Chrysostomou Smyrnis Street, 55132 Aretsou, Thessaloniki, Greece e-mail: kfount@med.auth.gr
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