1. ¹Department of Psychiatry, Teikyo University School of Medicine, Tokyo, Japan
2. ²Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
3. ³Department of Psychiatry and Human Behavior, Gunma University Graduate School of Medicine, Gunma, Japan
4. ⁴Department of Psychiatry, Showa University School of Medicine, Tokyo, Japan
5. ⁵Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan
6. ⁶Department of Neuropsychiatry, Graduate School of Medicine and Engineering, Yamanashi University, Yamanashi, Japan
7. ⁷Department of Psychiatry and Neural Function, Hokkaido University Graduate School of Medicine, Sapporo, Japan
8. ⁸Department of Psychiatry, National Center of Neurology and Psychiatry Kohnodai Hospital, Ichikawa, Japan
9. ⁹Department of Psychiatry, National Center of Neurology and Psychiatry Musashi Hospital, Tokyo, Japan
10. ¹⁰Department of Environmental Health and Safety, Division of Psychiatry and Neurology, Kobe University Graduate School of Medicine, Kobe, Japan
11. ¹¹Department of Neuropsychiatry, Oita University Faculty of Medicine, Oita, Japan
12. ¹²Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Correspondence: Dr H Kunugi, Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. Tel/Fax: +81 423 46 1714; E-mail: hkunugi@ncnp.go.jp

Received 29 March 2005; Revised 9 June 2005; Accepted 10 June 2005; Published online 17 August 2005.

Abstract

There is compelling evidence for the involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in depression. Growing evidence has suggested that the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test is highly sensitive to detect HPA axis abnormalities. We organized a multicenter study to assess the DEX/CRH test as a state-dependent marker for major depressive episode in the Japanese population. We conducted the DEX/CRH test in 61 inpatients with major depressive episode (Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)) and 57 healthy subjects. In all, 35 patients were repeatedly assessed with the DEX/CRH test on admission and before discharge. The possible relationships between clinical variables and the DEX/CRH test were also examined. Significantly enhanced pituitary–adrenocortical responses to the DEX/CRH test were observed in patients on admission compared with controls. Such abnormalities in patients were significantly reduced after treatment, particularly in those who underwent electroconvulsive therapy (ECT) in addition to pharmacotherapy. Age and female gender were associated with enhanced hormonal responses to the DEX/CRH test. Severity of depression correlated with DEX/CRH test results, although this was explained, at least in part, by a positive correlation between age and severity in our patients. Medication per se was unrelated to DEX/CRH test results. These results suggest that the DEX/CRH test is a sensitive state-dependent marker to monitor HPA axis abnormalities in major depressive episode during treatment. Restoration from HPA axis abnormalities occurred with clinical responses to treatment, particularly in depressed patients who underwent ECT.