A standardized workflow for long-term longitudinal actigraphy data processing using one year of continuous actigraphy from the CAN-BIND Wellness Monitoring Study.

Monitoring sleep and activity through wearable devices such as wrist-worn actigraphs has the potential for long-term measurement in the individual's own environment. Long periods of data collection require a complex approach, including standardized pre-processing and data trimming, and robust algorithms to address non-wear and missing data. In this study, we used a data-driven approach to quality control, pre-processing and analysis of longitudinal actigraphy data collected over the course of 1 year in a sample of 95 participants. We implemented a data processing pipeline using open-source packages for longitudinal data thereby providing a framework for treating missing data patterns, non-wear scoring, sleep/wake scoring, and conducted a sensitivity analysis to demonstrate the impact of non-wear and missing data on the relationship between sleep variables and depressive symptoms. Compliance with actigraph wear decreased over time, with missing data proportion increasing from a mean of 4.8% in the first week to 23.6% at the end of the 12 months of data collection. Sensitivity analyses demonstrated the importance of defining a pre-processing threshold, as it substantially impacts the predictive value of variables on sleep-related outcomes. We developed a novel non-wear algorithm which outperformed several other algorithms and a capacitive wear sensor in quality control. These findings provide essential insight informing study design in digital health research.

Longitudinal Changes in Sleep, Biological Rhythms, and Light Exposure From Late Pregnancy to Postpartum and Their Impact on Peripartum Mood and Anxiety.

Objective: In one of the largest and most comprehensive studies investigating the link between objective parameters of sleep and biological rhythms with peripartum mood and anxiety to date, we prospectively investigated the trajectory of subjective and objective sleep and biological rhythms, levels of melatonin, and light exposure from late pregnancy to postpartum and their relationship with depressive and anxiety symptoms across the peripartum period.Methods: One hundred women were assessed during the third trimester of pregnancy, of whom 73 returned for follow-ups at 1-3 weeks and 6-12 weeks postpartum. Participants were recruited from an outpatient clinic and from the community from November 2015 to May 2018. Subjective and objective measures of sleep and biological rhythms were obtained, including 2 weeks of actigraphy at each visit. Questionnaires validated in the peripartum period were used to assess mood and anxiety.Results: Discrete patterns of longitudinal changes in sleep and biological rhythm variables were observed, such as fewer awakenings (F = 23.46, P < .001) and increased mean nighttime activity (F = 55.41, P < .001) during postpartum compared to late pregnancy. Specific longitudinal changes in biological rhythm parameters, most notably circadian quotient, activity during rest at night, and probability of transitioning from rest to activity at night, were most strongly linked to higher depressive and anxiety symptoms across the peripartum period.Conclusions: Biological rhythm variables beyond sleep were most closely associated with severity of depressive and anxiety symptoms across the peripartum period. Findings from this study emphasize the importance of biological rhythms and activity beyond sleep to peripartum mood and anxiety.

Comorbid Premenstrual Dysphoric Disorder and Bipolar Disorder: A Review.

Bipolar disorder (BD) differs in its clinical presentation in females compared to males. A number of clinical characteristics have been associated with BD in females: more rapid cycling and mixed features; higher number of depressive episodes; and a higher prevalence of BD type II. There is a strong link between BD and risk for postpartum mood episodes, and a substantial percentage of females with BD experience premenstrual mood worsening of varying degrees of severity. Females with premenstrual dysphoric disorder (PMDD)-the most severe form of premenstrual disturbances-comorbid with BD appear to have a more complex course of illness, including increased psychiatric comorbidities, earlier onset of BD, and greater number of mood episodes. Importantly, there may be a link between puberty and the onset of BD in females with comorbid PMDD and BD, marked by a shortened gap between the onset of BD and menarche. In terms of neurobiology, comorbid BD and PMDD may have unique structural and functional neural correlates. Treatment of BD comorbid with PMDD poses challenges, as the first line treatment of PMDD in the general population is selective serotonin reuptake inhibitors, which produce risk of treatment-emergent manic symptoms. Here, we review current literature concerning the clinical presentation, illness burden, and unique neurobiology of BD comorbid with PMDD. We additionally discuss obstacles faced in symptom tracking, and management of these comorbid disorders.

Sleep, biological rhythms and anxiety in the perinatal period: a systematic review protocol.

INTRODUCTION: Pregnancy and new parenthood is an exciting time, but also a stressful life event that can predispose to mental health challenges. Perinatal anxiety is one such challenge, and is an important contributor to parental distress and other negative outcomes. Sleep and biological rhythms are often disrupted in the perinatal period. These disruptions have been associated with postpartum depression, and in some cases with perinatal anxiety. However, the literature concerning the association with perinatal anxiety is inconsistent and may be methodologically limited. To our knowledge, there has been no comprehensive review published characterising the relationships between sleep, biological rhythms, and perinatal anxiety and related disorders to date. In this systematic review, we will summarise the current state of the literature concerning these relationships, allowing us to highlight gaps and potentially inform clinical understanding of perinatal anxiety, sleep and biological rhythms. METHODS AND ANALYSIS: Primary research articles will be eligible for inclusion if they assess perinatal anxiety or related disorders using validated criteria (self-report or diagnostic), assess sleep and biological rhythms in the perinatal period, include >4 participants and meet other inclusion/exclusion criteria. We will conduct comprehensive searches of MEDLINE, PsycINFO, Embase and CINAHL, with coverage spanning from database conception to search date (August 1, 2021). Key search concepts include (1) the perinatal period, (2) sleep/biological rhythms and (3) anxiety. Risk of bias will be evaluated using the Cochrane Risk of Bias Tool. Data will be narratively synthesised, with quantitative synthesis included if possible. When relevant, strength of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation criteria, and potential publication bias will be assessed. ETHICS AND DISSEMINATION: Research ethics approval is not required. Study results will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results will be disseminated to relevant stakeholders as conference presentation(s) and submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: 200166.

Obsessive-compulsive and related disorders.

Obsessive-compulsive and related disorders (OCRDs), sometimes referred to as obsessive-compulsive spectrum disorders, cause significant impairment and share similar features across several domains, including clinical course, risk factors, and response to treatment. Generally, individuals meeting criteria for one or more OCRDs present with symptoms focused on preoccupations and repetitive behaviors. Sex differences emerge in the clinical presentation of OCRDs, and the associated. Literature emphasizes the importance of considering sex when investigating causal factors, prognosis, and outcomes of OCRDs. Understanding sex-specific phenotypes can help clinicians and healthcare providers to screen for and recognize relevant symptoms, and to create a more tailored approach for care of males and females. In this chapter, we review sex differences in obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), hoarding disorder, trichotillomania (hair-pulling disorder), and excoriation (skin-picking) disorder. Here, we provide an updated review on the sex differences in the prevalence, symptomatology, illness course and prognosis, comorbidity, risk factors, and treatment outcomes associated with OCRDs, and highlight gaps in the current literature on sex differences in these disorders.

Association of functioning and quality of life with objective and subjective measures of sleep and biological rhythms in major depressive and bipolar disorder.

OBJECTIVE: Disruptions in biological rhythms and sleep are a core aspect of mood disorders, with sleep and rhythm changes frequently occurring prior to and during mood episodes. Wrist-worn actigraphs are increasingly utilized to measure ambulatory activity rhythm and sleep patterns. METHODS: A comprehensive study using subjective and objective measures of sleep and biological rhythms was conducted in 111 participants (40 healthy volunteers [HC], 38 with major depressive disorder [MDD] and 33 with bipolar disorder [BD]). Participants completed 15-day actigraphy and first-morning urine samples to measure 6-sulfatoxymelatonin levels. Sleep and biological rhythm questionnaires were administered: Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), Munich Chronotype Questionnaire (MCTQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Actigraph data were analyzed for sleep and daily activity rhythms, light exposure and likelihood of transitioning between rest and activity states. RESULTS: Mood groups had worse subjective sleep quality (PSQI) and biological rhythm disruption (BRIAN) and higher objective mean nighttime activity than controls. Participants with BD had longer total sleep time, higher circadian quotient and lower 6-sulfatoxymelatonin levels than HC group. The MDD group had longer sleep onset latency and higher daytime probability of transitioning from rest to activity than HCs. Mood groups displayed later mean timing of light exposure. Multiple linear regression analysis with BRIAN scores, circadian quotient, mean nighttime activity during rest and daytime probability of transitioning from activity to rest explained 43% of variance in quality-of-life scores. BRIAN scores, total sleep time and probability of transitioning from activity to rest explained 52% of variance in functioning (all p < 0.05). CONCLUSIONS: Disruption in biological rhythms is associated with poorer functioning and quality of life in bipolar and MDD. Investigating biological rhythms and sleep using actigraphy variables, urinary 6-sulfatoxymelatonin and subjective measures provide evidence of widespread sleep and circadian system disruptions in mood disorders.

Prospective Assessment of Daily Patterns of Mood-Related Symptoms.

Background: The Mood Rhythm Instrument (MRI) is a new self-report questionnaire that aims to assess, the presence, and timing of daily patterns of mood-related symptoms. Here, we examined the reliability of the MRI against a prospective daily investigation over the course of 15 days. As a secondary aim, we examined whether the number of items with a perceived daily pattern correlated with severity of depressive symptoms and psychological well-being. Methods: Thirty-two participants recruited from the general population were asked to prospectively fill out a daily version of the MRI (MRI-d) for 15 days. On the 16th day, they filled out the MRI, the Beck Depression Inventory (BDI) and the World Health Organization 5-item well-being index (WHO-5). Results: The MRI showed high agreement with the MRI-d, which suggests that the MRI is a valid tool to assess daily patterns of mood symptoms. The number of mood symptoms perceived as having daily peaks correlated positively with BDI scores and negatively with WHO-5 scores. Conclusions: The MRI might be a valid tool to investigate the presence of daily patterns and the timing of mood-related factors.The MRI does not seem to be influenced by recall or recency biases. Future studies should test the usefulness of this new clinical instrument in individuals with mood disorders, as well as its ability to detect changes in the daily timing of mood symptoms before and after treatment.

The Role of Circadian Rhythms in Postpartum Sleep and Mood.

Women often experience sleep disturbances and worsening sleep quality throughout pregnancy and postpartum. Circadian rhythms are closely linked to sleep problems and mood disorders. This systematic review provides a summary of studies of circadian rhythms and associated sleep problems and maternal distress, among postpartum women. Articles were idenitfied through a systematic literature search. Circadian rhythm disturbances were strongly correlated with depression, social factors and mothers`s exposure to light postpartum. Future research should include larger, prospective studies as well as randomized controlled trials for measuring effect of circadian rhythm interventions on postpartum mental health outcomes.

The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis.

Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways. In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop. This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders.

Subtle persistent working memory and selective attention deficits in women with premenstrual syndrome.

As a recurrent, cyclical phenomenon, premenstrual syndrome (PMS) affects a significant proportion of women of the reproductive age, and leads to regular monthly days of functional impairment. Symptoms of PMS include somatic and psychological symptoms, such as headaches, sleep disturbances, social withdrawal and mood changes, during the late luteal phase of the menstrual cycle, which alleviate during the follicular phase. This study investigated neurocognitive functioning in women with moderate to severe PMS symptoms (n=13) compared to women with mild/no PMS (n=27) through administration of a battery of neuropsychological tests during the asymptomatic follicular phase of the menstrual cycle. Relative to women with mild/no PMS symptoms, women with moderate to severe PMS showed significantly poorer accuracy and more errors of omission on the N-0-back, as well as more errors of omission on the N-2-back task, indicating the presence of impairment in selective attention and working memory. This study provides evidence of persistent, subtle working memory and selective attention difficulties in those with moderate to severe PMS during the follicular phase of the menstrual cycle.

Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities.

BACKGROUND: Persistent low-grade immune-inflammatory processes, oxidative and nitrosative stress (O&NS), and hypothalamic-pituitary-adrenal axis activation are integral to the pathophysiology of major depressive disorder (MDD). The microbiome, intestinal compositional changes, and resultant bacterial translocation add a new element to the bidirectional interactions of the gut-brain axis; new evidence implicates these pathways in the patho-aetiology of MDD. In addition, abnormalities in the gut-brain axis are associated with several chronic non-communicable disorders, which frequently co-occur in individuals with MDD, including but not limited to irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), obesity, and type 2 diabetes mellitus (T2DM). METHODS: We searched the PubMed/MEDLINE database up until May 1, 2016 for studies which investigated intestinal dysbiosis and bacterial translocation (the 'leaky gut') in the pathophysiology of MDD and co-occurring somatic comorbidities with an emphasis on IBS, CFS, obesity, and T2DM. RESULTS: The composition of the gut microbiota is influenced by several genetic and environmental factors (e.g. diet). Several lines of evidence indicate that gut-microbiota-diet interactions play a significant pathophysiological role in MDD and related medical comorbidities. Gut dysbiosis and the leaky gut may influence several pathways implicated in the biology of MDD, including but not limited to immune activation, O&NS, and neuroplasticity cascades. However, methodological inconsistencies and limitations limit comparisons across studies. CONCLUSIONS: Intestinal dysbiosis and the leaky gut may constitute a key pathophysiological link between MDD and its medical comorbidities. This emerging literature opens relevant preventative and therapeutic perspectives.

Intestinal Dysbiosis, Gut Hyperpermeability and Bacterial Translocation: Missing Links Between Depression, Obesity and Type 2 Diabetes.

The comorbid prevalence of major depressive disorder (MDD) with obesity and type II diabetes mellitus reflects the existence of a subset of individuals with a complex common pathophysiology and overlapping risk factors. Such comorbid disease presentations imply a number of difficulties, including: decreased treatment responsivity and adherence; altered glycemic control and increased risk of wider medical complications. A number of factors link MDD to metabolic-associated disorders, including: higher rates of shared risk factors such as poor diet and physical inactivity and biological elements including increased inflammation; insulin resistance; oxidative and nitrosative stress; and mitochondrial dysfunction. All of these biological factors have been extensively investigated in the pathophysiology of obesity and type 2 diabetes mellitus as well as MDD. In this review, we aim to: (1) overview the epidemiological links between MDD, obesity and type 2 diabetes mellitus; (2) discuss the role of synergistic neurotoxic effects in MDD comorbid with obesity, and type 2 diabetes mellitus; (3) review evidence of intestinal dysbiosis, leaky gut and increased bacterial translocation, in the pathophysiology of MDD, obesity and type 2 diabetes mellitus; and (4) propose a model in which the gut-brain axis could play a pivotal role in the comorbidity of these disorders.

The Gut-Brain Axis, Including the Microbiome, Leaky Gut and Bacterial Translocation: Mechanisms and Pathophysiological Role in Alzheimer's Disease.

Alzheimer's disease (AD), the most common form of dementia, is a progressive disorder manifested by gradual memory loss and subsequent impairment in mental and behavioral functions. Though the primary risk factor for AD is advancing age, other factors such as diabetes mellitus, hyperlipidemia, obesity, vascular factors and depression play a role in its pathogenesis. The human gastrointestinal tract has a diverse commensal microbial population, which has bidirectional interactions with the human host that are symbiotic in health, and in addition to nutrition, digestion, plays major roles in inflammation and immunity. The most prevalent hypothesis for AD is the amyloid hypothesis, which states that changes in the proteolytic processing of the amyloid precursor protein leads to the accumulation of the amyloid beta (Aß) peptide. Aß then triggers an immune response that drives neuroinflammation and neurodegeneration in AD. The specific role of gut microbiota in modulating neuro-immune functions well beyond the gastrointestinal tract may constitute an important influence on the process of neurodegeneration. We first review the main mechanisms involved in AD physiopathology. Then, we review the alterations in gut microbiota and gut-brain axis that might be relevant to mediate or otherwise affect AD pathogenesis, especially those associated with aging. We finally summarize possible mechanisms that could mediate the involvement of gut-brain axis in AD physiopathology, and propose an integrative model.

T helper 17 cells may drive neuroprogression in major depressive disorder: Proposal of an integrative model.

The exact pathophysiology of major depressive disorder (MDD) remains elusive. The monoamine theory, which hypothesizes that MDD emerges as a result of dysfunctional serotonergic, dopaminergic and noradrenergic pathways, has guided the therapy of this illness for several decades. More recently, the involvement of activated immune, oxidative and nitrosative stress pathways and of decreased levels of neurotrophic factors has provided emerging insights regarding the pathophysiology of MDD, leading to integrated theories emphasizing the complex interplay of these mechanisms that could lead to neuroprogression. In this review, we propose an integrative model suggesting that T helper 17 (Th17) cells play a pivotal role in the pathophysiology of MDD through (i) microglial activation, (ii) interactions with oxidative and nitrosative stress, (iii) increases of autoantibody production and the propensity for autoimmunity, (iv) disruption of the blood-brain barrier, and (v) dysregulation of the gut mucosa and microbiota. The clinical and research implications of this model are discussed.

Gut emotions - mechanisms of action of probiotics as novel therapeutic targets for depression and anxiety disorders.

A priority clinical and research agenda in mood and anxiety disorders is to identify determinants that influence illness trajectory and outcome. Over the past decade, studies have demonstrated a bidirectional relationship between the gut microbiome and brain function (i.e., the microbiota-gut-brain axis). Probiotic treatments and developmental analysis of the microbiome may provide potential treatments and preventative measures for depressive and anxiety disorders. This systematic literature review aims to identify original studies linking the gut microbiota to major depressive disorder and anxiety disorders. Furthermore, this review searched for original reports focusing on possible therapeutic and preventative effects of probiotics for these debilitating conditions. Accumulating data indicate that the gut microbiota communicates with the CNS through neural, endocrine and immune pathways. Studies in germ-free animals indicate that the microbiota is involved in the regulation of the stress response (e.g., hypothalamic-pituitary-adrenal axis) and in CNS development at critical stages. Probiotics attenuate anxiety and depressive-like behaviors in experimental animal models. Notwithstanding some inconsistencies and methodological limitations across trials, clinical studies suggest that probiotics may mitigate anxiety symptoms. However, future studies should investigate the anxiolytic and antidepressant effects of probiotics in more phenotypically homogeneous populations. In conclusion, the emerging concept of a gut microbiota-brain axis suggests that the modulation of the gut microbiota may provide a novel therapeutic target for the treatment and/or prevention of mood and anxiety disorders.