Mathematical models of bipolar disorder

We use limit cycle oscillators to model bipolar II disorder, which is characterized by alternating hypomanic and depressive episodes and afflicts about 1% of the United States adult population. We consider two non-linear oscillator models of a single bipolar patient. In both frameworks, we begin with an untreated individual and examine the mathematical effects and resulting biological consequences of treatment. We also briefly consider the dynamics of interacting bipolar II individuals using weakly-coupled, weakly-damped harmonic oscillators. We discuss how the proposed models can be used as a framework for refined models that incorporate additional biological data. We conclude with a discussion of possible generalizations of our work, as there are several biologically-motivated extensions that can be readily incorporated into the series of models presented here

Blue-blocking glasses as adjunctive treatment for bipolar mania - and exploration of motor activity patterns in serious mental disorders

Background: There is a need for more effective treatments of bipolar mania. Promising reports of the effects of dark therapy on bipolar disorder symptoms and the discovery of a mainly blue-light sensitive daylight-signaling retinal ganglion cells has resulted in the utility of BB glasses to create a virtual darkness condition for the brain. Changes in activation or aberrant motor activity is present in all serious mental disorders. Actigraphy is a non-invasive and simple means of assessing motor activity, but is still mostly used to assess sleep outcomes. Before the utility of actigraphy can be broadened, there is need for further exploration of daily activity pattern characteristics for the diagnostic entities. Aims: By means of the Virtual Darkness as Additive Treatment in Mania (VATMAN) trial, we aimed to test the effectiveness and feasibility of BB glasses as an adjunctive treatment for mania compared to placebo glasses. As part of the Agitation at Admittance to a Psychiatric Acute Department Study, we aimed to characterize the motor activity patterns among a new sample of patients with psychotic disorders, and compare these characteristics to the motor activity patterns of patients with affective disorders and with healthy controls. Methods: Eligible patients for the VATMAN trial (hospitalized with bipolar disorder mania and otherwise fulfilling inclusion criteria) were randomized to receive either BB-glasses or clear-lensed placebo glasses. The glasses were worn as an adjunctive treatment from 6:00 p.m. to 8:00 a.m. for seven consecutive days. Manic symptoms were rated daily using the Young Mania Rating Scale. Motor activity was measured using wrist-worn actigraphs. Feasibility was assessed using a self-report patient experience questionnaire together with the clinical observation of side-effects. Sleep was assessed using actigraphy-derived sleep parameters. In the Agitation at Admittance to a Psychiatric Acute Department study, all hospitalized patients in the acute psychiatric ward in Østmarka Hospital, Trondheim were asked to wear an actigraph for 24 h. The motor activity patterns of patients diagnosed with schizophrenia and other psychotic disorders were compared to those of patients with mania, motor-retarded unipolar depression, and healthy controls. Linear and non-linear analytical methods were used to describe and compare motor activity variability and complexity (irregularity) for a 24 h period as well as in morning and evening sequences. Results: Out of 32 randomized patients in the VATMAN trial, 12 patients in the BB-group and 11 patients in the placebo-group were included in the analyses. After seven days, the Cohen’s d effect size was 1.86. There was a significant group difference in YMRS scores after three days (p = 0.042) and the group difference increased steadily throughout the intervention. Observed side effects included headache in one patient and rapidly reversible depressive symptoms in two patients. Actigraphy-derived sleep outcomes at night five showed significantly higher sleep efficiency, lower motor activity and less minutes of wake after sleep onset in the BB group as compared to the placebo group. Several patients in both groups displayed a 48 h-like rhythm of shorter or disrupted sleep. The schizophrenia spectrum group shared the characteristic of high motor activity variability with the unipolar depressed group, but differed with respect to more irregular (complex) activity pattern in the morning sequence. The schizophrenia spectrum and the mania groups could not be separated using formal statistical analyses, being most similar with regards to high morning activity irregularity. The mania group was the only one to show a blunted morning-to-evening activity fluctuation, while the normal morning-to-evening decline was more preserved in the schizophrenia spectrum group. Conclusions: BB-glasses were found to be both effective and feasible as an adjunctive treatment for mania. The BB-group showed actigraphy-derived sleep parameters reflecting less activated sleep compared with the placebo-group. The use of actigraphy data to characterize diurnal motor activity patterns, by use of the combination of linear and non-linear analytical approaches, seems to have potential for assessment of symptoms and for diagnostic support

Chronobiology and psychiatry : development of a conceptual model and integrative approach for South African psychiatrists

Bibliography: leaves 78-91.Chronobiology developed slowly after it was recognised that rhythmicity was a fundamental property of life. However, the principles of chronobiology are not well integrated in clinical practice. Therefore, this dissertation aims to integrate neuroscientific knowledge in a curriculum for chronobiology to be presented to South African psychiatrists in training at UCT, and is one of several steps in a programme to promote the concept of chronobiology in psychiatry

Exercise and Mood: Exploring the Role of Exercise in Regulating Stress Reactivity in Bipolar Disorder

Bipolar Disorder (BD) is a recurrent and debilitating psychological disorder characterized by a chronic dysregulation of mood with fluctuations between extremely low (e.g., depression) and extremely elevated mood states (e.g., mania), and ranks as the 6th leading cause of disability in the world. Although research has consistently shown that exercise may have antidepressant and stress-attenuating benefits in other psychiatric illnesses (e.g., depression, anxiety), these benefits have not been directly investigated for BD. The current study represents the first known investigation to examine this relationship. Single-participant designs, with crossover and interaction treatment components (i.e., A/B/A/B/A, A/C/A/C/A, A/B/A/C/A, or A/C/A/B/A) were utilized to investigate the impact of participation in a prescribed regimen of exercise (EP) versus standard behavioral activation (SBA; i.e., non-exercise activity) has on stress perception and reactivity, and mood stability in a sample of individuals with BD. Individuals completed four total weeks of treatment, and psychophysiological measures of reactivity were recorded during a laboratory stress task (i.e., backward counting task) prior to and following each two-week intervention phase. No appreciable differences were found between levels of exercise participation between treatment groups. Interestingly, symptoms of depressed mood (BDI-II scores) decreased at similar rates following 4 weeks of treatment for all participants. BDI-II decreases were found to be most correlated with elective exercise participation, although this relationship was not significant. Regarding stress reactivity, elective participation in mild to moderate intensity exercise was found to reduce an individual’s perception of stress reactivity to an acute stressor, while participation in a prescribed program of exercise was more effective in reducing physiological response to the same task. Utilizing multiple forms of behavioral activation simultaneously was found to be most effective in decreasing perception of stress reactivity, and may also result in a positive change in the use of adaptive versus maladaptive coping strategies. Participation in a 4-week program of exercise appeared to provide the most benefit, consistent with exercise habituation theories. Overall, current findings provide preliminary support for the prophylactic benefits of including a prescribed and monitored program of exercise as an adjunct treatment for individuals with BD. Larger scale research is needed to more clearly determine the impact of exercise on stress reactivity and mood episode relapse in individuals with BD

Deletion of Crtc1 leads to hippocampal neuroenergetic impairments associated with depressive-like behavior.

Mood disorders (MD) are a major burden on society as their biology remains poorly understood, challenging both diagnosis and therapy. Among many observed biological dysfunctions, homeostatic dysregulation, such as metabolic syndrome (MeS), shows considerable comorbidity with MD. Recently, CREB-regulated transcription coactivator 1 (CRTC1), a regulator of brain metabolism, was proposed as a promising factor to understand this relationship. Searching for imaging biomarkers and associating them with pathophysiological mechanisms using preclinical models can provide significant insight into these complex psychiatric diseases and help the development of personalized healthcare. Here, we used neuroimaging technologies to show that deletion of Crtc1 in mice leads to an imaging fingerprint of hippocampal metabolic impairment related to depressive-like behavior. By identifying a deficiency in hippocampal glucose metabolism as the underlying molecular/physiological origin of the markers, we could assign an energy-boosting mood-stabilizing treatment, ebselen, which rescued behavior and neuroimaging markers. Finally, our results point toward the GABAergic system as a potential therapeutic target for behavioral dysfunctions related to metabolic disorders. This study provides new insights on Crtc1's and MeS's relationship to MD and establishes depression-related markers with clinical potential