A diagnosis of asthma may be associated with current clinically significant levels of depressive symptoms and a lifetime psychiatric disorder. The current report adds to the existing literature in this area by assessing both current and lifetime symptoms and by using a large and diverse population. The findings highlight the clinical importance of considering the possibility of psychiatric illness in asthma patients and suggest further research in this area is needed.
The findings suggest that patients with more severe asthma and depression symptomatology may have a positive response, in terms of both asthma and depressive symptom reduction, to antidepressant treatment.
Preclinical and clinical research indicates that excess corticosteroid is associated with adverse effects on the hippocampus. Animal model data suggest that N-methyl-D-aspartate (NMDA) receptor antagonists may block corticosteroid effect on the hippocampus. This translational clinical trial investigated the effect of memantine vs. placebo on hippocampal subfield volume in humans receiving chronic corticosteroid therapy. Men and women (N = 46) receiving chronic prescription corticosteroid therapy were randomized to memantine or placebo in a double-blind, crossover design (two 24-week treatment periods, separated by a 4-week washout) for 52 weeks. Structural magnetic resonance imaging was obtained at baseline and after each treatment. Data were analyzed using repeated measures analysis of variance. Mean corticosteroid dose was 7.69 ± 6.41 mg/day and mean duration 4.90 ± 5.61 years. Controlling for baseline volumes, the left DG/CA3 region was significantly larger following memantine than placebo (p = .011). The findings suggest that an NMDA receptor antagonist attenuates corticosteroid effect in the same hippocampal subfields in humans as in animal models. This finding has both mechanistic and clinical implications. Attenuation of the effect of corticosteroids on the human DG/CA3 region implicates the NMDA receptor in human hippocampal volume losses with corticosteroids. In addition, by suggesting a drug class that may, at least in part, block the effects of corticosteroids on the human DG/CA3 subfield, these results may have clinical relevance for people receiving prescription corticosteroids, as well as to those with cortisol elevations due to medical or psychiatric conditions.
Purpose/Background
Glucocorticoids are a class of hormones that include naturally occurring cortisol and corticosterone, as well as prescription drugs commonly used to manage inflammatory, autoimmune, and allergic conditions. Adverse effects, including neuropsychiatric symptoms, are common. The hippocampus appears to be especially sensitive to the effects of glucocorticoids. However, to our knowledge, no studies to date have examined hippocampal subfields in humans receiving glucocorticoids. We examined patients on chronic glucocorticoid regimens to determine relationships between dose and duration of treatment, and hippocampal subfields, and related regions volumes.
Methods/Procedures
The study included adult men and women receiving at least 5 mg daily of prednisone equivalents for at least 6 months. Volumes of brain regions were measured via magnetic resonance imaging. A multivariate general linear model was used for analysis, with brain volumes as dependent variables and age, sex, and cumulative corticosteroid exposure, as predictors.
Findings/Results
The study population consisted of 81 adult outpatients (43 male) on corticosteroids (mean dose, 7.88 mg; mean duration, 76.75 months). Cumulative glucocorticoid exposure was negatively associated with left and right hippocampal dentate gyrus/CA3 volume. In subsequent subgroup analysis, this association held true for the age group older than the median age of 46 years but not for the younger age group.
Implications/Conclusions
This finding is consistent with previous studies showing detrimental effects of elevated glucocorticoids on the hippocampus but further suggests that the dentate gyrus and CA3 regions are particularly vulnerable to those effects, which is consistent with animal models of chronic stress but has not been previously demonstrated in humans.
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