The Dexamethasone Suppression Test and Sleep Electroencephalogram in Nonbipolar Major Depressed Inpatients: A Multivariate Analysis Phillipe P. Hubain, Luc Staner, Michele Dramaix, Myriam Kerkhofs, Georges Papadimitriou, Julien Mendlewicz, and Paul Linkowski Background: The present study further examined rela- tionships between postdexamethasone cortisol plasma val- ues and sleep electroencephalogram (EEG) parameters. Methods: The dexamethasone suppression test (DST) and polysomnographic recordings were perJbrmed in a sample of 300 inpatients with primary major depressive disorder (MDD) (102 men and 198 women, mean age 44 ± 12 years, range 20-74 years) consecutively admitted to Erasme Hospital (Brussels, Belgium) between 1981 and 1992. Results: The DST was abnormal in 40% of the sample. Postdexamethasone cortisol plasma values at 4:00 PM were significantly influenced by age, but not by gender. They were also sign~cantly and positively correlated with weight loss, total scores on the Hamilton Depression Rating Scale, total scores on the Newcastle Scale, percent- age of awakenings during sleep, and percent of stage 1. They were significantly and negatively' correlated with percent of stage 2, slow-wave sleep, and REM sleep. Multiple regression analyses were conducted in two suc- cessive steps. First among clinical variables, only age and depressive symptom severity remained correlated with postdexamethasone plasma cortisol values. In the second step, with age and severity held constant, postdexametha- sone plasma cortisol values were positively associated with amount of wake time and stage 1, and negatively with amount of slow-wave sleep. Conclusions: These findings provide further indirect support for an overarousal state in MDD with sympa- thoadrenal system hyperactivity and impaired sleep continuity. They also underline the importance of taking into account various clinical confounding factors in the interpretation of both DST and sleep EEG results. From the Department of Psychiatry, Erasme Hospital, University of Brussels, Belgium (PPH, MK, JM, PL); Department of Psychiatry, Centre Hospitalier, Luxemburg (LS); Department of Biostatistics, School of Public Health, University of Brussels, Brussels, Belgium (MD); and Athens University Medical School, Department of Psychiatry, Greece (GP). Address reprint requests to Dr. Phillipe P. Hubain, Department of Psychiatry, Erasme Hospital, Route de Lennik, 808, 1070 Brussels, Belgium. Received December 30, 1994; revised April 17, I996; revised October 15, 1996; accepted January 27, 1997. Biol Psychiatry 1998;43:220-229 © 1998 Society of Biological Psychiatry Key Words: Stress, major depressive disorder, DST, sleep, overarousal, Hamilton Rating Scale for Depression Introduction S ince the pioneering studies by Stokes (1966) and Carroll et al (1968) performed in patients suffering from melancholia, abnormalities of the dexamethasone suppression test (DST), which was introduced by Liddle (1960) for the diagnosis of Cushing's disease, have been proposed as a biological correlate specific to endogenous depression (Carroll et al 1981; Mendlewicz et al 1982; Feinberg and Carroll 1984; Zimmerman et al 1986a). In their extensive studies, Carroll and coworkers postulated that the DST is useful to evaluate the hypothalamo- pituitary-adrenal (HPA) axis dysregulation supposed to reflect a noradrenergic dysfunction in endogenous depres- sion (Carroll et al 1976, 1981). Over the years, the DST has become one of the most thoroughly studied biological tests in psychiatry (for reviews see Arana et al 1985; APA Task Force on Laboratory Tests in Psychiatry 1987) and has been pro- posed as a routine psychiatric diagnostic procedure (Car- roll et al 1981; Kalin et al 1981; Carroll 1982); however, the sensitivity of the DST in overall major depression seems moderate (about 44%, Arana et al 1985), even if it rises to about 65% in some subtypes of depression (i.e., psychotic) or in specific conditions (i.e., hospitalized endogenous depressed patients) (Arana et al 1985). In the meantime, the specificity of the DST has been the subject of great debate (Arana et al 1985; Berger et al 1988). Multiple clinical factors influence postdexamethasone plasma cortisol levels, including age (Oxenkrug et al 1983; Davis et al 1984; Feinberg and Carroll 1984; Lewis et al 1984; Stokes et al 1984; Arana et al 1985; Sharma et al 1988), depressive symptom severity (Brown and Shuey © 1998 Society of Biological Psychiatry 0006-3223/98/$19.00 PII S0006-3223(97)00017-6