The digital redesign of mental health: leveraging connected digital technologies for agency-driven patient-focused care.

Digital psychiatry could empower individuals to navigate their context-specific experiences outside healthcare visits. This editorial discusses how leveraging digital health technologies could dramatically transform how we conceptualise mental health and the mental health professional's day-day practice, and how patients could be enabled to navigate their mental health with greater agency.

Correction: An Alternative to the Light Touch Digital Health Remote Study: The Stress and Recovery in Frontline COVID-19 Health Care Workers Study.

[This corrects the article DOI: 10.2196/32165.].

An Alternative to the Light Touch Digital Health Remote Study: The Stress and Recovery in Frontline COVID-19 Health Care Workers Study.

BACKGROUND: Several app-based studies share similar characteristics of a light touch approach that recruit, enroll, and onboard via a smartphone app and attempt to minimize burden through low-friction active study tasks while emphasizing the collection of passive data with minimal human contact. However, engagement is a common challenge across these studies, reporting low retention and adherence. OBJECTIVE: This study aims to describe an alternative to a light touch digital health study that involved a participant-centric design including high friction app-based assessments, semicontinuous passive data from wearable sensors, and a digital engagement strategy centered on providing knowledge and support to participants. METHODS: The Stress and Recovery in Frontline COVID-19 Health Care Workers Study included US frontline health care workers followed between May and November 2020. The study comprised 3 main components: (1) active and passive assessments of stress and symptoms from a smartphone app, (2) objective measured assessments of acute stress from wearable sensors, and (3) a participant codriven engagement strategy that centered on providing knowledge and support to participants. The daily participant time commitment was an average of 10 to 15 minutes. Retention and adherence are described both quantitatively and qualitatively. RESULTS: A total of 365 participants enrolled and started the study, and 81.0% (n=297) of them completed the study for a total study duration of 4 months. Average wearable sensor use was 90.6% days of total study duration. App-based daily, weekly, and every other week surveys were completed on average 69.18%, 68.37%, and 72.86% of the time, respectively. CONCLUSIONS: This study found evidence for the feasibility and acceptability of a participant-centric digital health study approach that involved building trust with participants and providing support through regular phone check-ins. In addition to high retention and adherence, the collection of large volumes of objective measured data alongside contextual self-reported subjective data was able to be collected, which is often missing from light touch digital health studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04713111; https://clinicaltrials.gov/ct2/show/NCT04713111.

Development and validation of a risk calculator for major mood disorders among the offspring of bipolar parents using information collected in routine clinical practice.

BACKGROUND: Family history is a significant risk factor for bipolar disorders (BD), but the magnitude of risk varies considerably between individuals within and across families. Accurate risk estimation may increase motivation to reduce modifiable risk exposures and identify individuals appropriate for monitoring over the peak risk period. Our objective was to develop and independently replicate an individual risk calculator for bipolar spectrum disorders among the offspring of BD parents using data collected in routine clinical practice. METHODS: Data from the longitudinal Canadian High-Risk Offspring cohort study collected from 1996 to 2020 informed the development of a 5 and 10-year risk calculator using parametric time-to-event models with a cure fraction and a generalized gamma distribution. The calculator was then externally validated using data from the Lausanne-Geneva High-Risk Offspring cohort study collected from 1996 to 2020. A time-varying C-index by age in years was used to estimate the probability that the model correctly classified risk. Bias corrected estimates and 95% confidence limits were derived using a jackknife resampling approach. FINDINGS: The primary outcome was age of onset of a major mood disorder. The risk calculator was most accurate at classifying risk in mid to late adolescence in the Canadian cohort (n = 285), and a similar pattern was replicated in the Swiss cohort (n = 128). Specifically, the time-varying C-index indicated that there was approximately a 70% chance that the model would correctly predict which of two 15-year-olds would be more likely to develop the outcome in the future. External validation within a smaller Swiss cohort showed mixed results. INTERPRETATION: Findings suggest that this model may be a useful clinical tool in routine practice for improved individualized risk estimation of bipolar spectrum disorders among the adolescent offspring of a BD parent; however, risk estimation in younger high-risk offspring is less accurate, perhaps reflecting the evolving nature of psychopathology in early childhood. Based on external validation with a Swiss cohort, the risk calculator may not be as predictive in more heterogenous high-risk populations. FUNDING: The Canadian High-Risk Study has been funded by consecutive operating grants from the Canadian Institutes for Health Research, currently CIHR PJT Grant 152796 he Lausanne-Geneva high-risk study was and is supported by five grants from the Swiss National Foundation (#3200-040,677, #32003B-105,969, #32003B-118,326, #3200-049,746 and #3200-061,974), three grants from the Swiss National Foundation for the National Centres of Competence in Research project "The Synaptic Bases of Mental Diseases" (#125,759, #158,776, and #51NF40 - 185,897), and a grant from GlaxoSmithKline Clinical Genetics.

High Blood Pressure and Risk of Dementia: A Two-Sample Mendelian Randomization Study in the UK Biobank.

BACKGROUND: Findings from randomized controlled trials have yielded conflicting results on the association between blood pressure (BP) and dementia traits. We tested the hypothesis that a causal relationship exists between systolic BP (SBP) and/or diastolic BP (DBP) and risk of Alzheimer's disease (AD). METHODS: We performed a generalized summary Mendelian randomization (GSMR) analysis using summary statistics of a genome-wide association study meta-analysis of 299,024 individuals of SBP or DBP as exposure variables against three different outcomes: 1) AD diagnosis (International Genomics of Alzheimer's Project), 2) maternal family history of AD (UK Biobank), and 3) paternal family history of AD (UK Biobank). Finally, a combined meta-analysis of 368,440 individuals that included these three summary statistics was used as final outcome. RESULTS: GSMR applied to the International Genomics of Alzheimer's Project dataset revealed a significant effect of high SBP lowering the risk of AD (ßGSMR = -0.19, p = .04). GSMR applied to the maternal family history of AD UK Biobank dataset (SBP [ßGSMR = -0.12, p = .02], DBP [ßGSMR = -0.10, p = .05]) and to the paternal family history of AD UK Biobank dataset (SBP [ßGSMR = -0.16, p = .02], DBP [ßGSMR = -0.24, p = 7.4 × 10-4]) showed the same effect. A subsequent combined meta-analysis confirmed the overall significant effect for the other SBP analyses (ßGSMR = -0.14, p = .03). The DBP analysis in the combined meta-analysis also confirmed a DBP effect on AD (ßGSMR = -0.14, p = .03). CONCLUSIONS: A causal effect exists between high BP and a reduced late-life risk of AD. The results were obtained through careful consideration of confounding factors and the application of complementary MR methods on independent cohorts.

Stress-related consequences of the coronavirus disease 2019 pandemic on symptoms of Crohn's disease.

OBJECTIVES: A link between stress and Crohn's disease activity suggests an association, but results have been conflicting. The purpose of this study was to assess whether the stress related to the coronavirus disease 2019 (COVID-19) pandemic affected disease activity in patients with Crohn's disease. BASIC METHODS: An anonymous survey was distributed to patients through gastroenterology clinics and networks. Patients were asked to report their Crohn's disease symptoms in the months prior to the COVID-19 pandemic and again during the early stages of the COVID-19 pandemic using the Manitoba inflammatory bowel disease index in addition to questions about stress, perception of reasons for symptom change and personal impact. MAIN RESULTS: Out of 243 individuals with a confirmed diagnosis of Crohn's disease, there was a 24% relative increase in active symptoms between the pre-COVID-19 period to the during-COVID-19 period (P < 0.0001) reflecting an absolute change from 45 to 56%, respectively. The most frequent reported reason for a change in symptoms was 'Increased stress/and or feeling overwhelmed' (118/236), and personal impact of the pandemic was, 'I'm worrying a lot about the future' (113/236), both reported by approximately half of respondents. PRINCIPAL CONCLUSIONS: This study serves as a 'proof of concept' demonstrating the impact of a significant and uniquely uniform stressor as a natural experiment on Crohn's disease activity. The severity of symptoms of Crohn's disease increased during the COVID-19 pandemic. The primary reported reason for symptom change was an increase in stress, not a change in diet, exercise or other lifestyle behaviours, corroborating the hypothesis that stress affects Crohn's disease activity.

The True Colours Remote Symptom Monitoring System: A Decade of Evolution.

The True Colours remote mood monitoring system was developed over a decade ago by researchers, psychiatrists, and software engineers at the University of Oxford to allow patients to report on a range of symptoms via text messages, Web interfaces, or mobile phone apps. The system has evolved to encompass a wide range of measures, including psychiatric symptoms, quality of life, and medication. Patients are prompted to provide data according to an agreed personal schedule: weekly, daily, or at specific times during the day. The system has been applied across a number of different populations, for the reporting of mood, anxiety, substance use, eating and personality disorders, psychosis, self-harm, and inflammatory bowel disease, and it has shown good compliance. Over the past decade, there have been over 36,000 registered True Colours patients and participants in the United Kingdom, with more than 20 deployments of the system supporting clinical service and research delivery. The system has been adopted for routine clinical care in mental health services, supporting more than 3000 adult patients in secondary care, and 27,263 adolescent patients are currently registered within Oxfordshire and Buckinghamshire. The system has also proven to be an invaluable scientific resource as a platform for research into mood instability and as an electronic outcome measure in randomized controlled trials. This paper aimed to report on the existing applications of the system, setting out lessons learned, and to discuss the implications for tailored symptom monitoring, as well as the barriers to implementation at a larger scale.

Investigating the association between anxiety symptoms and mood disorder in high-risk offspring of bipolar parents: a comparison of Joint and Cox models.

BACKGROUND: Anxiety is associated with mood disorders including bipolar disorder. Two statistical modelling frameworks were compared to investigate the longitudinal relationship between repeatedly measured anxiety symptoms and the onset of depression and bipolar disorder in youth at confirmed familial risk. METHODS: Prospectively collected data on 156 offspring of a parent with confirmed bipolar disorder participating in the Canadian Flourish high-risk offspring longitudinal cohort study were used for this analysis. As part of the research protocol at approximately yearly visits, a research psychiatrist completed the HAM-A and a semi-structured diagnostic research interview following KSADS-PL format. Diagnoses using DSM-IV criteria were made on blind consensus review of all available clinical information. We investigated two statistical approaches, Cox model and Joint model, to evaluate the relationship between repeated HAM-A scores and the onset of major depressive or bipolar disorder. The Joint model estimates the trajectory of the longitudinal variable using a longitudinal sub-model and incorporates this estimated trajectory into a Cox sub-model. RESULTS: There was evidence of an increased hazard of major mood disorder for high-risk individuals with higher HAM-A scores under both modelling frameworks. After adjusting for other covariates, a one-unit increase in log-transformed HAM-A score was associated with a hazard ratio of 1.74 (95% CI (1.12, 2.72)) in the Cox model compared to 2.91(95% CI (1.29, 6.52)) in the Joint model. In an exploratory analysis there was no evidence that family clustering substantially affected the conclusions. CONCLUSIONS: Estimated effects from the conventional Cox model, which is often the model of choice, were dramatically lower in this dataset, compared to the Joint model. While the Cox model is often considered the approach of choice for analysis, research has shown that the Joint model may be more efficient and less biased. Our analysis based on a Joint model suggests that the magnitude of association between anxiety and mood disorder in individuals at familial risk of developing bipolar disorder may be stronger than previously reported.

Epigenetic markers in inflammation-related genes associated with mood disorder: a cross-sectional and longitudinal study in high-risk offspring of bipolar parents.

Bipolar disorder is highly heritable and typically onsets in late adolescence or early adulthood. Evidence suggests that immune activation may be a mediating pathway between genetic predisposition and onset of mood disorders. Building on a prior study of mRNA and protein levels in high-risk offspring published in this Journal, we conducted a preliminary examination of methylation profiles in candidate immune genes from a subsample of well-characterized emergent adult (mean 20 years) offspring of bipolar parents from the Canadian Flourish high-risk cohort. Models were adjusted for variable age at DNA collection, sex and antidepressant and mood stabilizer use. On cross-sectional analysis, there was evidence of higher methylation rates for BDNF-1 in high-risk offspring affected (n = 27) and unaffected (n = 23) for mood disorder compared to controls (n = 24) and higher methylation rates in affected high-risk offspring for NR3C1 compared to controls. Longitudinal analyses (25 to 34 months) provided evidence of steeper decline in methylation rates in controls (n = 24) for NR3C1 compared to affected (n = 15) and unaffected (n = 11) high-risk offspring and for BDNF-2 compared to affected high-risk. There was insufficient evidence that changes in any of the candidate gene methylation rates were associated with illness recurrence in high-risk offspring. While preliminary, findings suggest that longitudinal investigation of epigenetic markers in well-characterized high-risk individuals over the peak period of risk may be informative to understand the emergence of bipolar disorder.

Unlocking stress and forecasting its consequences with digital technology.

Chronic stress is a major underlying origin of the top leading causes of death, globally. Yet, the mechanistic explanation of the association between stress and disease is poorly understood. This stems from the inability to adequately measure stress in its naturally occurring state and the extreme heterogeneity by inter and intraindividual characteristics. The growth and availability of digital technologies involving wearable devices and mobile phone apps afford the opportunity to dramatically improve measurement of the biological stress response in real time. In parallel, the advancement and capabilities of artificial intelligence (AI) and machine learning could discern heterogeneous, multidimensional information from individual signs of stress, and possibly inform how these signs forecast the downstream consequences of stress in the form of end-organ damage. The marriage of these tools could dramatically enhance the field of stress research contributing to impactful and empowering interventions for individuals bridging knowledge to practice, and intervention to real-world use. Here we discuss this potential, anticipated challenges, and emerging opportunities.

Coping strategies and self-esteem in the high-risk offspring of bipolar parents.

OBJECTIVES: This study investigated whether there were differences in coping strategies and self-esteem between offspring of parents with bipolar disorder (high-risk) and offspring of unaffected parents (control), and whether these psychological factors predicted the onset and recurrence of mood episodes. METHODS: High-risk and control offspring were followed longitudinally as part of the Flourish Canadian high-risk bipolar offspring cohort study. Offspring were clinically assessed annually by a psychiatrist using semi-structured interviews and completed a measure of coping strategies and self-esteem. RESULTS: In high-risk offspring, avoidant coping strategies significantly increased the hazard of a new onset Diagnostic and Statistical Manual of Mental Disorders, 4th Edition twice revised mood episode or recurrence (hazard ratio: 1.89, p = 0.04), while higher self-esteem significantly decreased this hazard (hazard ratio: 2.50, p < 0.01). Self-esteem and avoidant coping significantly interacted with one another ( p < 0.05), where the risk of a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition twice revised new onset mood episode or recurrence was only significantly increased among high-risk offspring with both high avoidant coping and low self-esteem. CONCLUSION: A reduction of avoidant coping strategies in response to stress and improvement of self-esteem may be useful intervention targets for preventing the new onset or recurrence of a clinically significant mood disorder among individuals at high familial risk.

Daily and weekly mood ratings using a remote capture method in high-risk offspring of bipolar parents: Compliance and symptom monitoring.

OBJECTIVES: To determine the compliance and clinical utility of weekly and daily electronic mood symptom monitoring in adolescents and young adults at risk for mood disorder. METHODS: Fifty emerging adult offspring of bipolar parents were recruited from the Flourish Canadian high-risk offspring cohort study along with 108 university student controls. Participants were assessed by KSADS/SADS-L semi-structured interviews and used a remote capture method to complete weekly and daily mood symptom ratings using validated scales for 90 consecutive days. Hazard models and generalized estimating equations were used to determine differences in summary scores and regularity of ratings. RESULTS: Seventy-eight and 77% of high-risk offspring and 97% and 93% of controls completed the first 30 days of weekly and daily ratings, respectively. There were no differences in drop-out rates between groups over 90 days (weekly P = 0.2149; daily P = 0.9792). There were no differences in mean summary scores or regularity of weekly anxiety, depressive or hypomanic symptom ratings between high-risk offspring and control groups. However, high-risk offspring compared to controls had daily ratings indicating lower positive affect, higher negative affect and lower self-esteem (P = 0.0317). High-risk offspring with remitted mood disorder compared to those without had more irregularity in weekly anxiety and depressive symptom ratings and daily ratings of lower positive affect, higher negative affect, and higher shame and self-doubt (P = 0.0365). CONCLUSIONS: Findings support that high-resolution electronic mood tracking may be a feasible and clinically useful approach in monitoring emerging psychopathology in young people at high-risk offspring of mood disorder onset or recurrence.

The Cumulative Incidence of Self-Reported Suicide-Related Thoughts and Attempts in Young Canadians.

OBJECTIVE: To estimate the cumulative incidence of self-reported suicide-related thoughts (SRTs) and suicide attempts (SAs) in males and females from 11 to 25 years of age in Canada. METHODS: A cohort study was conducted by linking cycles 2 to 8 from the National Longitudinal Survey of Children and Youth, a representative survey of Canadians aged 11 to 25 years conducted from 1996 to 2009. The 11- to 25-year cumulative incidence of self-reported SRTs and SAs (with suicidal intent) was estimated in males and females using a novel application of a counting process approach to account for discontinuous risk intervals between survey cycles. RESULTS: The risk of SRTs was 29% (95% confidence interval [CI], 26% to 31%) in females and 19% (95% CI, 16% to 23%) in males. The risk of SAs was 16% (95% CI, 14% to 19%) in females and 7% (95% CI, 6% to 8%) in males. Over 70% of SRTs and SAs first occur between 11 and 16 years of age and 30% between 11 and 13 years of age, respectively. CONCLUSIONS: The risk of SRTs and SAs is high in young Canadians, with most events first occurring in early to mid-adolescence and possibly earlier. Females are at a higher risk compared to males. This research underscores the need for better longitudinal surveillance of SRTs and SAs in the population. A counting process framework could be useful for future research using existing longitudinal surveys suffering from design limitations relating to gaps in respondent follow-up. Furthermore, these findings have implications for younger SRT and SA risk management by clinicians and earlier implementation of suicide prevention programs.

Efficacy and tolerability of lithium for the treatment of acute mania in children with bipolar disorder: A systematic review: A report from the ISBD-IGSLi joint task force on lithium treatment.

OBJECTIVES: To assess the efficacy and tolerability of lithium for the treatment of acute mania in children and adolescent diagnosed with bipolar disorder. METHODS: A systematic literature search up to August 2017 was conducted for clinical trials that included lithium in males and females up to 18 years of age with a diagnosis of bipolar disorder and experiencing a manic or mixed episode according to standardized diagnostic criteria. The protocol was registered in PROSPERO (CRD42017055675). RESULTS: Four independent studies described in seven manuscripts met the inclusion criteria. Overall, 176 patients were treated with lithium either as a monotherapy or adjunct to risperidone. Efficacy results suggest that lithium may be superior to placebo (standardized mean difference [SMD] -0.42, 95% confidence interval [CI] -0.88 to 0.04), comparable to sodium divalproex (SMD -0.07, 95% CI: -0.31 to 0.18), but significantly less effective than risperidone for treating protracted manic/mixed episodes and comorbid attention-deficit hyperactivity disorder (ADHD) in prepubertal children (SMD 0.85, 95% CI: 0.54 to 1.15). Lithium was not associated with serious adverse events, and was generally well tolerated with common side effects similar to those reported in adults. CONCLUSIONS: Limited data suggests that lithium may be an effective and tolerable treatment for some forms of paediatric mania. However, lithium is clearly inferior in efficacy to risperidone in prepubertal patients diagnosed with protracted manic/mixed episodes and comorbid ADHD. There is a lack of data concerning the efficacy and tolerability of lithium as an acute treatment for classical mania in adolescents and important clinical issues remain unaddressed.

Repeated salivary daytime cortisol and onset of mood episodes in offspring of bipolar parents.

BACKGROUND: Differences in cortisol secretion may differentiate individuals at high compared to low genetic risk for bipolar disorder (BD) and predict the onset or recurrence of mood episodes. The objectives of this study were to determine if salivary cortisol measures are: (1) different in high-risk offspring of parents with BD (HR) compared to control offspring of unaffected parents (C), (2) stable over time, (3) associated with the development of mood episode onset/recurrence, and (4) influenced by comorbid complications. METHODS: Fifty-three HR and 22 C completed salivary cortisol sampling annually for up to 4 years in conjunction with semi-structured clinical interviews. The cortisol awakening response (CAR), daytime cortisol [area under the curve (AUC)], and evening cortisol (8:00 p.m.) were calculated. RESULTS: There were no differences in baseline CAR, AUC and evening cortisol between HR and C (p = 0.38, p = 0.30 and p = 0.84), respectively. CAR, AUC and evening cortisol were stable over yearly assessments in HR, while in Cs, evening cortisol increased over time (p = 0.008), and CAR and AUC remained stable. In HR, AUC and evening cortisol increased the hazard of a new onset mood disorder/recurrence by 2.7 times (p = 0.01), and 3.5 times (p = 0.01), respectively, but this was no longer significant after accounting for multiple comparisons. CONCLUSIONS: Salivary cortisol is stable over time within HR offspring. However, between individuals, basal salivary cortisol is highly variable. More research is needed, with larger samples of prospectively studied HR youth using a more reliable method of cortisol measurement, to determine the potential role of cortisol in the development of mood disorders.