Subject(s)
Antimanic Agents/pharmacology , Brain/drug effects , Brain/pathology , Lithium Carbonate/pharmacology , Antimanic Agents/adverse effects , Bipolar Disorder/drug therapy , Bipolar Disorder/pathology , Humans , Lithium Carbonate/adverse effects , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neurologic Examination/methodsABSTRACT
Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis is one of the most prominent neurobiological findings in major depressive disorder (MDD). The relationship of regional brain metabolism to HPA axis dysfunction in depressed patients, however, is still unclear. In this study, to examine the clinical pharmacotherapeutic effects on HPA axis function and brain metabolism in MDD patients, we performed the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test on 24 antidepressant-free patients with MDD a few days after positron emission tomography (PET) with a radiotracer, [(18)F]-fluorodeoxyglucose (FDG). Moreover, 10 patients who responded to pharmacotherapy were re-tested. 75% of unmedicated MDD patients exhibited a heightened cortisol response to the DEX/CRH test, and thus were defined as non-suppressors. Non-suppressors showed a marked hypometabolism in the medial prefrontal cortex as compared with suppressors. After successful pharmacotherapy, enhanced cortisol responsiveness normalized. Prior to treatment of the unmedicated MDD, a significant hypometabolism in various frontal regions and a significant hypermetabolism in the right hippocampus and parahippocampal gyrus were observed compared with controls. Metabolic activity in treatment responders showed a normalizing pattern in almost all the areas that had been characterized by metabolic abnormality at baseline except for the medial prefrontal cortex. These results indicate that depressed patients remitted with antidepressant treatment were accompanied by resolution of HPA dysregulation and alteration of regional glucose metabolism in the prefrontal cortical, limbic and paralimbic regions.
Subject(s)
Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/physiopathology , Hypothalamo-Hypophyseal System/physiopathology , Limbic System/physiopathology , Nerve Net/physiopathology , Pituitary-Adrenal System/physiopathology , Prefrontal Cortex/physiopathology , Adult , Aged , Corticotropin-Releasing Hormone , Dexamethasone , Female , Fluorodeoxyglucose F18 , Glucocorticoids , Humans , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Limbic System/metabolism , Male , Middle Aged , Nerve Net/metabolism , Pituitary-Adrenal System/metabolism , Prefrontal Cortex/metabolism , RadiopharmaceuticalsABSTRACT
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.
Subject(s)
Corticotropin-Releasing Hormone , Depressive Disorder, Major/physiopathology , Dexamethasone , Hypothalamo-Hypophyseal System/physiopathology , Pituitary-Adrenal System/physiopathology , Adult , Age Factors , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Sex CharacteristicsABSTRACT
The goal of this study was to assess the spikes systematically and to clarify an epileptc abnormality induced by electroconvulsive therapy (ECT). Our subjects were 20 psychotic patients with no spikes on prior EEGs. ECT was performed by applying electrical current to both sides of the patient's temple every 2 or 3 days for a period of between 1-4 weeks. The first EEG examination was performed either on the day that the ECT course was completed or on the following day. Subsequent EEG examinations were performed at intervals of 2 or 3 days. Thirteen of the 20 patients showed spikes. There were no significant differences in age, gender, diagnosis, or type of ECT. Patients with spikes had significantly more ECT sessions than those without spikes. The spikes were present in the frontal, temporal and central areas, predominantly frontal, anterior temporal and mid-temporal region, and almost disappeared in 1-3 weeks. The occurrence of spikes immediately after ECT was demonstrated. Although this abnormality was transient, it could indicate that in humans ECT causes the early stage of kindling phenomenon as a result of repeated application, and that the temporal lobe seems to play a major role in order to induce the phenomenon.
