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.</p

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.</p

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 &lt; 0.01). Self-esteem and avoidant coping significantly interacted with one another (p &lt; 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.</br

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.</p

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

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 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 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 78% 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 (high‐risk p=0.2149; controls p=0.9792). There were no differences in mean summary scores or regularity of weekly anxiety, depressive or hypomanic symptom ratings between high‐risk and control groups. However, high‐risk offspring compared to controls had daily ratings indicating lower positive affect and higher negative affect (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 symptom tracking may be a feasible and clinically useful approach to monitoring emerging psychopathology in young people at high‐risk of mood disorder onset or recurrence