Immune-endocrine host response to endotoxin in major depression.

OBJECTIVE: An impaired hypothalamic-pituitary-adrenocortical (HPA) function is a well-established finding in major depression (MD), but it is still unclear how this dysfunction affects immune responses in this disorder. METHOD: To further examine the relationship between immune and endocrine responses in MD, 0.4ng/kg body weight endotoxin [LPS] or 100mug hCRH were sequentially applied to 12 patients with MD and to 12 age- and gender-matched healthy controls after pre-treatment with 1.5mg dexamethasone (DEX). Immune (TNF-alpha, IL-6, rectal temperature) and endocrine (ACTH, cortisol) parameters were examined as area under the curve (AUC) levels. RESULTS: After pre-treatment with DEX, LPS evoked an immune response in all participants of the study with most immune parameters significantly related to the endotoxin challenge. However, only a marked immune response resulted in an additional endocrine reaction. Subsequently, the quantitative extent of the endocrine reaction was related to the extent of the immune response after DEX/LPS challenge. Pre-LPS AUC levels of cortisol, ACTH and post-LPS levels of IL-6 as well as the post-CRH AUC levels of cortisol and ACTH were related to the depressive symptomatology as measured by the Beck depression inventory (BDI). In depressive patients who showed increased cortisol plasma levels before LPS, the later increase in IL-6 was reduced. CONCLUSIONS: The challenge with DEX/LPS did not reveal major impairments of evoked immune functions in MD. Only the endocrine parameters and the IL-6 response were related to the depressive symptomatology, suggesting a limited interaction between immune and endocrine dysfunctions in MD.

The Munich vulnerability study on affective disorders: premorbid polysomnographic profile of affected high-risk probands.

BACKGROUND: The most characteristic alterations in the sleep electroencephalogram (EEG) during major depression are a shortened latency to rapid eye movement (REM) sleep and an elevated REM density. Because these changes persist in remission, they might represent vulnerability markers. To identify vulnerability markers, we investigated premorbid sleep EEG parameters in healthy high-risk probands (HRPs) with a positive family history of affective disorders. METHODS: We identified 136 depressed inpatients from referrals to our hospital who had first-degree relatives with an affective disorder as well as first-degree relatives with no current or lifetime history of psychiatric disorders. The latter (the HRP group) were investigated by polysomnography. During the follow-up period, 20 HRPs developed an affective disorder. Their premorbid sleep data were analyzed. RESULTS: Premorbid sleep EEG of affected HRPs showed an increased REM density (total night and first REM period) compared with the control group without personal or family history of a psychiatric disorder. CONCLUSIONS: Increased REM density can be observed not only in patients with depression, but also in their healthy relatives. Moreover, it is predictive for the onset of a psychiatric disorder. Therefore, it can be recommended as a possible endophenotype of these diseases.