Assessment of the dexamethasone/CRH test as a state-dependent marker for hypothalamic-pituitary-adrenal (HPA) axis abnormalities in major depressive episode: a Multicenter Study.

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.

Combined DEX/CRH test among Japanese patients with major depression.

There is compelling evidence for an important role of the hypothalamus-pituitary-adrenal (HPA) axis abnormalities in the pathophysiology of major depressive disorder. Growing evidence has suggested that the combined dexamethasone (DEX)/CRH test is much more sensitive than the conventional DEX suppression test in order to detect HPA axis abnormalities. However, little data is currently available on DEX/CRH results for Asian populations, which prompted us to examine the sensitivity of the DEX/CRH test among Japanese subjects with major depression. The DEX/CRH test was administered in 20 inpatients with major depressive episode and 30 healthy controls. Significantly increased cortisol responses were observed for the patients, compared to the controls. There was a substantial difference in the distribution of non-suppressor, intermediate suppressor, and suppressor, which were defined in terms of cortisol response, was observed between the patients and controls (10, 60, and 30% in the patients vs. 0, 27, and 73% in the controls, P<0.01). Responses of ACTH showed a trend in the same direction. Within the depressed patients, individuals with a history of attempted suicide, in particular, tended to have enhanced responses to the DEX/CRH test, compared to those without such a history. Our results confirmed that the DEX/CRH test is a sensitive test to detect HPA axis abnormalities among Japanese patients with major depression. In addition, a possible relationship between suicidal acts and enhanced HPA axis abnormalities was suggested.

Prenatal underdevelopment and schizophrenia: a case report of monozygotic twins.

A case is described herein of monozygotic twins discordant for schizophrenia that illustrates possible causal events of prenatal underdevelopment, morphological changes in the brain, poor premorbid functioning, and the development of schizophrenia. The affected twin was born with a birthweight of 1620 g, whereas the unaffected twin weighed 2300 g at birth. Marked differences in sociability and intelligence were observed between the twins from early childhood. Magnetic resonance imaging of the brain revealed high-intensity signals in the white matter and enlarged ventricles in the affected twin, while no such abnormality was detected in the well twin. This twin pair suggests a possibility that hypoxic brain damage associated with prenatal underdevelopment may be a causal factor for abnormalities in psychosocial development and subsequent schizophrenia.