Digital Phenotyping for Mood Disorders: Methodology-Oriented Pilot Feasibility Study.

BACKGROUND: In the burgeoning area of clinical digital phenotyping research, there is a dearth of literature that details methodology, including the key challenges and dilemmas in developing and implementing a successful architecture for technological infrastructure, patient engagement, longitudinal study participation, and successful reporting and analysis of diverse passive and active digital data streams. OBJECTIVE: This article provides a narrative rationale for our study design in the context of the current evidence base and best practices, with an emphasis on our initial lessons learned from the implementation challenges and successes of this digital phenotyping study. METHODS: We describe the design and implementation approach for a digital phenotyping pilot feasibility study with attention to synthesizing key literature and the reasoning for pragmatic adaptations in implementing a multisite study encompassing distinct geographic and population settings. This methodology was used to recruit patients as study participants with a clinician-validated diagnostic history of unipolar depression, bipolar I disorder, or bipolar II disorder, or healthy controls in 2 geographically distinct health care systems for a longitudinal digital phenotyping study of mood disorders. RESULTS: We describe the feasibility of a multisite digital phenotyping pilot study for patients with mood disorders in terms of passively and actively collected phenotyping data quality and enrollment of patients. Overall data quality (assessed as the amount of sensor data obtained vs expected) was high compared to that in related studies. Results were reported on the relevant demographic features of study participants, revealing recruitment properties of age (mean subgroup age ranged from 31 years in the healthy control subgroup to 38 years in the bipolar I disorder subgroup), sex (predominance of female participants, with 7/11, 64% females in the bipolar II disorder subgroup), and smartphone operating system (iOS vs Android; iOS ranged from 7/11, 64% in the bipolar II disorder subgroup to 29/32, 91% in the healthy control subgroup). We also described implementation considerations around digital phenotyping research for mood disorders and other psychiatric conditions. CONCLUSIONS: Digital phenotyping in affective disorders is feasible on both Android and iOS smartphones, and the resulting data quality using an open-source platform is higher than that in comparable studies. While the digital phenotyping data quality was independent of gender and race, the reported demographic features of study participants revealed important information on possible selection biases that may result from naturalistic research in this domain. We believe that the methodology described will be readily reproducible and generalizable to other study settings and patient populations given our data on deployment at 2 unique sites.

Assessing mental health apps marketplaces with objective metrics from 29,190 data points from 278 apps.

OBJECTIVE: Utilizing a standard framework that may help clinicians and patients to identify relevant mental health apps, we sought to gain a comprehensive picture of the space by searching for, downloading, and reviewing 278 mental health apps from both the iOS and Android stores. METHODS: 278 mental health apps from the Apple iOS store and Google Play store were downloaded and reviewed in a standardized manner by trained app raters using a validated framework. Apps were evaluated with this framework comprising 105 questions and covering app origin and accessibility, privacy and security, inputs and outputs, clinical foundation, features and engagement style, and interoperability. RESULTS: Our results confirm that app stars and downloads-even for the most popular apps by these metrics-did not correlate with more clinically relevant metrics related to privacy/security, effectiveness, and engagement. Most mental health apps offer similar functionality, with 16.5% offering both mood tracking and journaling and 7% offering psychoeducation, deep breathing, mindfulness, journaling, and mood tracking. Only 36.4% of apps were updated with a 100-day window, and 7.5% of apps had not been updated in four years. CONCLUSION: Current app marketplace metrics commonly used to evaluate apps do not offer an accurate representation of individual apps or a comprehensive overview of the entire space. The majority of apps overlap in terms of features offered, with many domains and other features not well represented. Selecting an appropriate app continues to require personal matching given no clear trends or guidance offered by quantitative metrics alone.

Digital phenotyping of student mental health during COVID-19: an observational study of 100 college students.

Objective: This study assessed the feasibility of capturing smartphone based digital phenotyping data in college students during the COVID-19 pandemic with the goal of understanding how digital biomarkers of behavior correlate with mental health. Participants: Participants were 100 students enrolled in 4-year universities. Methods: Each participant attended a virtual visit to complete a series of gold-standard mental health assessments, and then used a mobile app for 28 days to complete mood assessments and allow for passive collection of GPS, accelerometer, phone call, and screen time data. Students completed another virtual visit at the end of the study to collect a second round of mental health assessments. Results: In-app daily mood assessments were strongly correlated with their corresponding gold standard clinical assessment. Sleep variance among students was correlated to depression scores (ρ = .28) and stress scores (ρ = .27). Conclusions: Digital Phenotyping among college students is feasible on both an individual and a sample level. Studies with larger sample sizes are necessary to understand population trends, but there are practical applications of the data today.

Similarity matrix-based anomaly detection for clinical intervention.

The use of digital phenotyping methods in clinical care has allowed for improved investigation of spatiotemporal behaviors of patients. Moreover, detecting abnormalities in mobile sensor data patterns can be instrumental in identifying potential changes in symptomology. We propose a method that temporally aligns sensor data in order to achieve interpretable measures of similarity between time points. These computed measures can then be used for anomaly detection, baseline routine computation, and trajectory clustering. In addition, we apply this method on a study of 695 college participants, as well as on a patient with worsening anxiety and depression. With varying temporal constraints, we find mild correlations between changes in routine and clinical scores. Furthermore, in our experiment on an individual with elevated depression and anxiety, we are able to cluster GPS trajectories, allowing for improved understanding and visualization of routines with respect to symptomology. In the future, we aim to apply this method on individuals that undergo data collection for longer periods of time, thus allowing for a better understanding of long-term routines and signals for clinical intervention.

Anomaly detection to predict relapse risk in schizophrenia.

The integration of technology in clinical care is growing rapidly and has become especially relevant during the global COVID-19 pandemic. Smartphone-based digital phenotyping, or the use of integrated sensors to identify patterns in behavior and symptomatology, has shown potential in detecting subtle moment-to-moment changes. These changes, often referred to as anomalies, represent significant deviations from an individual's baseline, may be useful in informing the risk of relapse in serious mental illness. Our investigation of smartphone-based anomaly detection resulted in 89% sensitivity and 75% specificity for predicting relapse in schizophrenia. These results demonstrate the potential of longitudinal collection of real-time behavior and symptomatology via smartphones and the clinical utility of individualized analysis. Future studies are necessary to explore how specificity can be improved, just-in-time adaptive interventions utilized, and clinical integration achieved.

Altering leukocyte recruitment following traumatic brain injury with ghrelin therapy.

BACKGROUND: Traumatic brain injury (TBI)-induced cerebral inflammation involves several mediators including activation of resident microglia, infiltration of leukocytes, and release of proinflammatory cytokines and chemokines at the site of injury. Invading leukocytes, mainly neutrophil and inflammatory monocytes, contribute to ongoing post-TBI cerebral edema and neuronal injury. Based on the beneficial effect of ghrelin hormone treatment following TBI, we hypothesized that ghrelin may alter the infiltrating inflammatory cell profile. METHODS: A weight drop model was used to create severe TBI. C57 mice were divided into three groups: sham, no TBI or ghrelin treatment; TBI, TBI only; TBI/ghrelin, animals were treated with ghrelin 20 µg (intraperitoneally) immediately following TBI and again 1 hour later. Seven days after injury, brain sections were immunostained with Iba-1 and CD11b to assess the recruitment and activation of resident microglia and infiltrated leukocytes. Alternatively, brain dissociates were isolated, and flow cytometry was used to gate for microglia (CD11b, CD45 cells), monocytes (CD11b, CD45, F4/80 cells), and neutrophils (CD11b, CD45, F4/80 cells) to measure their recruitment to injury site. RESULTS: TBI resulted in a rapid invasion (16-fold) of inflammatory leukocytes to the site of injury, which persisted for at least 1 week. Ghrelin treatment significantly reduced infiltration of peripheral leukocytes (2.8-fold). In particular, recruitment of CD11bCD45 inflammatory monocytes (2.4-fold) and CD11bCD45F4/80 neutrophils (1.7-fold) was reduced following ghrelin treatment. There were no observed ghrelin-mediated changes in either the number of CD11bCD45 resident microglia or its activation state. CONCLUSION: Together, our data demonstrate that ghrelin attenuated leukocyte recruitment, which correlates with improved histologic outcome following TBI.