LETTER TO THE EDITOR

The WFSBP Task Force report on biological markers in depression is unduly pessimistic in failing to find diagnostically helpful measures (WJBP 2007, 8:141 174). The task force considered numerous candidates (e.g., neurotrophic factors, serotonergic and immunological markers, evoked potentials) and concluded none warranted inclusion as criteria in DSM-V. The reviewers, however, only briefly commented on the hypothalamic-pituitary-adrenal perturbations that have been identified in depressive illness and did not assess the literature on sleep EEG. Despite its dismissal, the task force wrote: ‘‘The dexamethasone/CRH test is one of the most reliable neuroendocrine function tests for hypothalamicpituitary-adrenal (HPA) system dysregulation in depression. Persistent overdrive of HPA system activities after successful antidepressant treatment predicts an enhanced risk for relapse of a depressive episode’’. Carroll and his co-workers originally demonstrated that abnormal cortisol metabolism was found among severely depressed patients who met ICD criteria for ‘‘melancholic depression’’ (Carroll et al. 1980; Carroll 1982). The abnormality was a sign of melancholia, resolved with effective treatment but persisted as a predictor of relapse. Extensive studies over almost four decades verify these findings (Taylor et al. 2006). Two tests define cortisol abnormality, the Dexamethasone Suppression Test (DST) and the DexCRH tests. The DST abnormality has been recommended as a specific marker of melancholia that form of major depression of abnormal mood, motor activity, and vegetative functions, with high suicide risk. Such patients commonly fall into the groups defined as psychotic, post partum, or catatonic forms of illness, usually severe enough to warrant hospital care. The specificity and reliability of the DST among patients with a melancholic depression is 70%, which compares favourably to other biological test markers. In the assessment of seizure disorders, for example, the presence of an abnormality in the EEG is used to verify the diagnosis based on clinical symptoms, signs and course of illness. The EEG is found positive in 80% of patients with clinical signs of seizure disorder (Kupfer et al. 1978). Sleep EEG recordings also accompany depressive moods. The measures show reduced sleep time, prolonged latency to sleep, reduced slow wave and non-rapid eye movement periods, and similar identifiable markers (Kupfer et al. 1978; Armitage 2001; Taylor et al. 2006). The Task Force examined the role of biological markers within the context of present DSM criteria of depression. The lack of clear findings, however, is not due to limitations of the biological abnormalities but in the poor specificity of the DSM designation of major depression resulting in substantial heterogeneity in the samples selected for study. The lack of diagnostic reliability of the present diagnostic systems is clearly reflected in the poor outcomes of the large national multi-site trials of antidepressant and antipsychotic agents (Lieberman et al. 2005; Rush et al. 2006a). Rejection of hypercortisolemia and sleep-EEG as biological markers of diagnostic value in depressive illness is unwarranted. It is a valid verifier of the diagnosis of melancholia. For such patients, treatments are available with high specificity for relief. The report should be amended.