Bright light in elderly subjects with nonseasonal major depressive disorder: a double blind randomised clinical trial using early morning bright blue light comparing dim red light treatment

<p>Abstract</p> <p>Background</p> <p>Depression frequently occurs in the elderly. Its cause is largely unknown, but several studies point to disturbances of biological rhythmicity. In both normal aging, and depression, the functioning of the suprachiasmatic nucleus (SCN) is impaired, as evidenced by an increased prevalence of day-night rhythm perturbations, such as sleeping disorders. Moreover, the inhibitory SCN neurons on the hypothalamus-pituitary adrenocortical axis (HPA-axis) have decreased activity and HPA-activity is enhanced, when compared to non-depressed elderly. Using bright light therapy (BLT) the SCN can be stimulated. In addition, the beneficial effects of BLT on seasonal depression are well accepted. BLT is a potentially safe, nonexpensive and well accepted treatment option. But the current literature on BLT for depression is inconclusive.</p> <p>Methods/Design</p> <p>This study aims to show whether BLT can reduce non-seasonal major depression in elderly patients. Randomized double blind placebo controlled trial in 126 subjects of 60 years and older with a diagnosis of major depressive disorder (MDD, DSM-IV/SCID-I). Subjects are recruited through referrals of psychiatric outpatient clinics and from case finding from databases of general practitioners and old-people homes in the Amsterdam region. After inclusion subjects are randomly allocated to the active (bright blue light) vs. placebo (dim red light) condition using two Philips Bright Light Energy boxes type HF 3304 per subject, from which the light bulbs have been covered with bright blue- or dim red light- permitting filters. Patients will be stratified by use of antidepressants. Prior to treatment a one-week period without light treatment will be used. At three time points several endocrinological, psychophysiological, psychometrically, neuropsychological measures are performed: just before the start of light therapy, after completion of three weeks therapy period, and three weeks thereafter.</p> <p>Discussion</p> <p>If BLT reduces nonseasonal depression in elderly patients, then additional lightning may easily be implemented in the homes of patients to serve as add-on treatment to antidepressants or as a stand-alone treatment in elderly depressed patients. In addition, if our data support the role of a dysfunctional biological clock in depressed elderly subjects, such a finding may guide further development of novel chronobiological oriented treatment strategies.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: NCT00332670</p

Prevention of depression and sleep disturbances in elderly with memory-problems by activation of the biological clock with light - a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Depression frequently occurs in the elderly and in patients suffering from dementia. Its cause is largely unknown, but several studies point to a possible contribution of circadian rhythm disturbances. Post-mortem studies on aging, dementia and depression show impaired functioning of the suprachiasmatic nucleus (SCN) which is thought to be involved in the increased prevalence of day-night rhythm perturbations in these conditions. Bright light enhances neuronal activity in the SCN. Bright light therapy has beneficial effects on rhythms and mood in institutionalized moderate to advanced demented elderly. In spite of the fact that this is a potentially safe and inexpensive treatment option, no previous clinical trial evaluated the use of long-term daily light therapy to prevent worsening of sleep-wake rhythms and depressive symptoms in early to moderately demented home-dwelling elderly.</p> <p>Methods/Design</p> <p>This study investigates whether long-term daily bright light prevents worsening of sleep-wake rhythms and depressive symptoms in elderly people with memory complaints. Patients with early Alzheimer's Disease (AD), Mild Cognitive Impairment (MCI) and Subjective Memory Complaints (SMC), between the ages of 50 and 75, are included in a randomized double-blind placebo-controlled trial. For the duration of two years, patients are exposed to ~10,000 lux in the active condition or ~300 lux in the placebo condition, daily, for two half-hour sessions at fixed times in the morning and evening. Neuropsychological, behavioral, physiological and endocrine measures are assessed at baseline and follow-up every five to six months.</p> <p>Discussion</p> <p>If bright light therapy attenuates the worsening of sleep-wake rhythms and depressive symptoms, it will provide a measure that is easy to implement in the homes of elderly people with memory complaints, to complement treatments with cholinesterase inhibitors, sleep medication or anti-depressants or as a stand-alone treatment.</p> <p>Trial registration</p> <p>ISRCTN29863753</p

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

Citation: Shi, Z. Z., Chapes, S. K., Ben-Arieh, D., & Wu, C. H. (2016). An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data. Plos One, 11(8), 39. doi:10.1371/journal.pone.0161131We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as "sepsis". Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-a ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies

Light therapy for better mood and insulin sensitivity in patients with major depression and type 2 diabetes: a randomised, double-blind, parallel-arm trial

Background: Major depression and type 2 diabetes often co-occur. Novel treatment strategies for depression in type 2 diabetes patients are warranted, as depression in type 2 diabetes patients is associated with poor prognosis and treatment results. Major depression and concurrent sleep disorders have been related to disturbances of the biological clock. The biological clock is also involved in regulation of glucose metabolism by modulating peripheral insulin sensitivity. Light therapy has been shown to be an effective antidepressant that 'resets' the biological clock. We here describe the protocol of a study that evaluates the hypothesis that light therapy improves mood as well as insulin sensitivity in patients with a major depressive episode and type 2 diabetes. Methods/design: This study is a randomised, double-blind, parallel-arm trial in 98 participants with type 2 diabetes and a major depressive episode, according to DSM-IV criteria. We will assess whether light therapy improves depressive symptoms and insulin sensitivity, our primary outcome measures, and additionally investigate whether these effects are mediated by restoration of the circadian rhythmicity, as measured by sleep and hypothalamic-pituitary-adrenal axis activity. Participants will be randomly allocated to a bright white-yellowish light condition or dim green light condition. Participants will undergo light therapy for half an hour every morning for 4 weeks at home. At several time points, namely before the start of light therapy, during light therapy, after completion of 4 weeks of light therapy and after 4 weeks follow-up, several psychometrical, psychophysiological and glucometabolic measures will be performed. Discussion: If light therapy effectively improves mood and insulin sensitivity in type 2 diabetes patients with a major depressive episode, light therapy may be a valuable patient friendly addition to the currently available treatment strategies. Additionally, if our data support the role of restoration of circadian rhythmicity, such an observation may guide further development of chronobiological treatment strategies in this patient population