Feature-expression heat maps – A new visual method to explore complex associations between two variable sets

AbstractIntroductionExisting methods such as correlation plots and cluster heat maps are insufficient in the visual exploration of multiple associations between genetics and phenotype, which is of importance to achieve a better understanding of the pathophysiology of psychiatric and other illnesses. The implementation of a combined presentation of effect size and statistical significance in a graphical method, added to the ordering of the variables based on the effect-ordered data display principle was deemed useful by the authors to facilitate in the process of recognizing meaningful patterns in these associations.Materials and methodsThe requirements, analyses and graphical presentation of the feature-expression heat map are described. The graphs display associations of two sets of ordered variables where a one-way direction is assumed. The associations are depicted as circles representing a combination of effect size (color) and statistical significance (radius).ResultsAn example dataset is presented and relation to other methods, limitations, areas of application and possible future enhancements are discussed.ConclusionThe feature-expression heat map is a useful graphical instrument to explore associations in complex biological systems where one-way direction is assumed, such as genotype-phenotype pathophysiological models

A protocol for light therapy in bipolar disorder

BACKGROUND There is no national protocol for the use of light therapy in bipolar depression. AIM The chronotherapy collaboration group of the Foundation for Bipolar Disorders intended to write a protocol for light therapy in bipolar depressive episodes. METHOD Narrative review of several systematic reviews, two clinician’s guides and deliberation with the sub-commission Guidelines of the Dutch Ophthalmologic Society. RESULTS The following indication was established: depressive episode, with or without seasonal features, in bipolar I or II disorder, including subsyndromal (depressive) seasonal complaints. The list of relative contra-indications (pre-existent retinal illnesses, systemic illnesses with effect on the retina and use of photosensitive medication) was shortened. In this case the medical professional discusses the possibility of an ophthalmologic consultation with the patient. Use of a mood stabilizer/antimanic medication in order to prevent mania or a mixed episode is only necessary in a depressive episode in bipolar I, but not in bipolar II disorder. Standard treatment is 10.000 lux white light during 30 minutes in the morning. CONCLUSION There is sufficient evidence to propose light therapy in a bipolar depressive episode with or without seasonal features.</p

Inflammatory monocyte gene expression:Trait or state marker in bipolar disorder?

BACKGROUND: This study aimed to examine whether inflammatory gene expression was a trait or a state marker in patients with bipolar disorder (BD). METHODS: 69 healthy controls (HC), 82 euthymic BD patients and 8 BD patients with a mood episode (7 depressed, 1 manic) were included from the MOODINFLAME study. Six of the eight patients who had a mood episode were also investigated when they were euthymic (6 of the 82 euthymic patients). Of these participants the expression of 35 inflammatory genes was determined in monocytes using quantitative-polymerase chain reaction, of which a total gene expression score was calculated as well as a gene expression score per sub-cluster. RESULTS: There were no significant differences in inflammatory monocyte gene expression between healthy controls and euthymic patients. Patients experiencing a mood episode, however, had a significantly higher total gene expression score (10.63 ± 2.58) compared to healthy controls (p = .004) and euthymic patients (p = .009), as well as when compared to their own scores when they were euthymic (p = .02). This applied in particular for the sub-cluster 1 gene expression score, but not for the sub-cluster 2 gene expression score. CONCLUSIONS: Our study indicates that in BD inflammatory monocyte, gene expression is especially elevated while in a mood episode compared to being euthymic

Implications of controlled short-wavelength light exposure for sleep in older adults

<p>Abstract</p> <p>Background</p> <p>Environmental and physiological conditions make older adults more likely to lose synchronization to their local time and experience sleep disturbances. A regular, 24-hour light/dark cycle promotes synchronization. It is now well established that the circadian system is maximally sensitive to short-wavelength (blue) light. The purpose of the present study was to measure dose effectiveness (amounts and durations) of short-wavelength (blue) light for stimulating the circadian systems of older adults. We investigated the impact of six corneal irradiances (0.7 to 72 μW/cm²) of 470-nm light on nocturnal melatonin production. Nine participants, each over 50 years of age completed a within-subjects study. Each week, participants were exposed to one of the six irradiances of 470-nm light for 90 minutes.</p> <p>Findings</p> <p>A two-factor (6 corneal irradiances × 10 exposure durations), within-subjects analysis of variance (ANOVA) was conducted using the melatonin suppression levels. The ANOVA revealed a significant main effect of corneal irradiance (F_{5, 30}= 9.131, p < 0.0001), a significant main effect of exposure duration (F_{9, 54}= 5.731, p < 0.0001), and a significant interaction between these two variables (F_45,270= 1.927, p < 0.001). Post hoc t-tests revealed that corneal irradiances as low as 2 μW/cm²reliably suppressed melatonin after 90-minute exposure whereas 0.7 μW/cm²did not.</p> <p>Conclusions</p> <p>Sleep disorders are common and a serious problem for millions of older adults. The present results showed that comfortable, precise and effective doses of light can be prescribed to older adults to reliably stimulate the circadian system that presumably would promote entrainment and, thus, regular sleep. Field studies on the impact of short-wavelength-light doses on sleep efficiency in older adults should be performed.</p

Bright light therapy in pregnant women with major depressive disorder: Study protocol for a randomized, double-blind, controlled clinical trial

Background: Depression during pregnancy is a common and high impact disease. Generally, 5-10 % of pregnant women suffer from depression. Children who have been exposed to maternal depression during pregnancy have a higher risk of adverse birth outcomes and more often show cognitive, emotional and behavioural problems. Therefore, early detection and treatment of antepartum depression is necessary. Both psychotherapy and antidepressant medication, first choice treatments in a non-pregnant population, have limitations in treating depression during pregnancy. Therefore, it is urgent and relevant to investigate alternative treatments for antepartum depression. Bright light therapy (BLT) is a promising treatment for pregnant women with depressive disorder, for it combines direct availability, sufficient efficacy, low costs and high safety, taking the safety for the unborn child into account as well. Methods: In this study, 150 pregnant women (12-18 weeks pregnant) with a DSM-V diagnosis of depressive disorder will be randomly allocated in a 1:1 ratio to one of the two treatment arms: treatment with BLT (9.000 lux) or treatment with dim red light therapy (100 lux). Both groups will be treated for 6 weeks at home on a daily basis for 30 min, within 30 min of habitual wake-up time. Follow-up will take place after 6 weeks of therapy, 3 and 10 weeks after end of therapy, at birth and 2, 6 and 18 months postpartum. Primary outcome will be the average change in depressive symptoms between the two groups, as measured by the Structured Interview Guide for the Hamilton Depression Scale - Seasonal Affective Disorder version and the Edinburg Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time will be analysed using generalized linear mixed models. Secondary outcomes will be the changes in maternal cortisol and melatonin levels, in maternal sleep quality and gestational age, birth weight, infant behaviour, infant cortisol exposure and infant cortisol stress response. Discussion: If BLT reduces depressive symptoms in pregnant women, it will provide a safe, cheap, non-pharmacological and efficacious alternative treatment for psychotherapy and antidepressant medication in treating antepartum depression, without any expected adverse reactions for the unborn child. Trial registration: Netherlands Trial Register NTR5476. Registered 5 November 2015

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