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ABSTRACT Pharmacogenetics is a promising strategy to facilitate individualized care for patients with Major Depressive Disorder (MDD). Research is ongoing to identify the optimal genetic markers for predicting outcomes to antidepressant therapies. The primary aim of this systematic review was to summarize antidepressant pharmacogenetic studies to enhance understanding of the genes, variants, datatypes/methodologies, and outcomes investigated in the context of MDD. The secondary aim was to identify clinical genetic panels indicated for antidepressant prescribing and summarize their genes and variants. Screening ofN = 5793 articles yieldedN = 390 for inclusion, largely comprising adult (≥ 18 years) populations. Top‐studied variants identified in the search were discussed and compared with those represented on theN = 34 clinical genetic panels that were identified. Summarization of articles revealed sources of heterogeneity across studies and low rates of replicability of pharmacogenetic associations. Heterogeneity was present in outcome definitions, treatment regimens, and differential inclusion of mediating variables in analyses. Efficacy outcomes (i.e., response, remission) were studied at greater frequency than adverse‐event outcomes. Studies that used advanced analytical approaches, such as machine learning, to integrate variants with complimentary biological datatypes were fewer in number but achieved higher rates of significant associations with treatment outcomes than candidate variant approaches. As large biological datasets become more prevalent, machine learning will be an increasingly valuable tool for parsing the complexity of antidepressant response. This review provides valuable context and considerations surrounding pharmacogenetic associations in MDD which will help inform future research and translation efforts for guiding antidepressant care. 

Abstract Pharmacogenomic (PGx) biomarkers integrated using machine learning can be embedded within the electronic health record (EHR) to provide clinicians with individualized predictions of drug treatment outcomes. Currently, however, drug alerts in the EHR are largely generic (not patient‐specific) and contribute to increased clinician stress and burnout. Improving the usability of PGx alerts is an urgent need. Therefore, this work aimed to identify principles for optimal PGx alert design through a health‐system‐wide, mixed‐methods study. Clinicians representing multiple practices and care settings (N = 1062) in urban, rural, and underserved regions were invited to complete an electronic survey comparing the usability of three drug alerts for citalopram, as a case study. Alert 1 contained a generic warning of pharmacogenomic effects on citalopram metabolism. Alerts 2 and 3 provided patient‐specific predictions of citalopram efficacy with varying depth of information. Primary outcomes included the System's Usability Scale score (0–100 points) of each alert, the perceived impact of each alert on stress and decision‐making, and clinicians' suggestions for alert improvement. Secondary outcomes included the assessment of alert preference by clinician age, practice type, and geographic setting. Qualitative information was captured to provide context to quantitative information. The final cohort comprised 305 geographically and clinically diverse clinicians. A simplified, individualized alert (Alert 2) was perceived as beneficial for decision‐making and stress compared with a more detailed version (Alert 3) and the generic alert (Alert 1) regardless of age, practice type, or geographic setting. Findings emphasize the need for clinician‐guided design of PGx alerts in the era of digital medicine. 

BackgroundThe occupational burnout epidemic is a growing issue, and in the United States, up to 60% of medical students, residents, physicians, and registered nurses experience symptoms. Wearable technologies may provide an opportunity to predict the onset of burnout and other forms of distress using physiological markers. ObjectiveThis study aims to identify physiological biomarkers of burnout, and establish what gaps are currently present in the use of wearable technologies for burnout prediction among health care professionals (HCPs). MethodsA comprehensive search of several databases was performed on June 7, 2022. No date limits were set for the search. The databases were Ovid: MEDLINE(R), Embase, Healthstar, APA PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection via Clarivate Analytics, Scopus via Elsevier, EBSCOhost: Academic Search Premier, CINAHL with Full Text, and Business Source Premier. Studies observing anxiety, burnout, stress, and depression using a wearable device worn by an HCP were included, with HCP defined as medical students, residents, physicians, and nurses. Bias was assessed using the Newcastle Ottawa Quality Assessment Form for Cohort Studies. ResultsThe initial search yielded 505 papers, from which 10 (1.95%) studies were included in this review. The majority (n=9) used wrist-worn biosensors and described observational cohort studies (n=8), with a low risk of bias. While no physiological measures were reliably associated with burnout or anxiety, step count and time in bed were associated with depressive symptoms, and heart rate and heart rate variability were associated with acute stress. Studies were limited with long-term observations (eg, ≥12 months) and large sample sizes, with limited integration of wearable data with system-level information (eg, acuity) to predict burnout. Reporting standards were also insufficient, particularly in device adherence and sampling frequency used for physiological measurements. ConclusionsWith wearables offering promise for digital health assessments of human functioning, it is possible to see wearables as a frontier for predicting burnout. Future digital health studies exploring the utility of wearable technologies for burnout prediction should address the limitations of data standardization and strategies to improve adherence and inclusivity in study participation. 

Background Mental health disorders are a leading cause of medical disabilities across an individual’s lifespan. This burden is particularly substantial in children and adolescents because of challenges in diagnosis and the lack of precision medicine approaches. However, the widespread adoption of wearable devices (eg, smart watches) that are conducive for artificial intelligence applications to remotely diagnose and manage psychiatric disorders in children and adolescents is promising. Objective This study aims to conduct a scoping review to study, characterize, and identify areas of innovations with wearable devices that can augment current in-person physician assessments to individualize diagnosis and management of psychiatric disorders in child and adolescent psychiatry. Methods This scoping review used information from the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of several databases from 2011 to June 25, 2021, limited to the English language and excluding animal studies, was conducted. The databases included Ovid MEDLINE and Epub ahead of print, in-process and other nonindexed citations, and daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; Web of Science; and Scopus. Results The initial search yielded 344 articles, from which 19 (5.5%) articles were left on the final source list for this scoping review. Articles were divided into three main groups as follows: studies with the main focus on autism spectrum disorder, attention-deficit/hyperactivity disorder, and internalizing disorders such as anxiety disorders. Most of the studies used either cardio-fitness chest straps with electrocardiogram sensors or wrist-worn biosensors, such as watches by Fitbit. Both allowed passive data collection of the physiological signals. Conclusions Our scoping review found a large heterogeneity of methods and findings in artificial intelligence studies in child psychiatry. Overall, the largest gap identified in this scoping review is the lack of randomized controlled trials, as most studies available were pilot studies and feasibility trials. 

Background: Individuals with major depressive disorder (MDD) and a lifetime history of attempted suicide demonstrate lower antidepressant response rates than those without a prior suicide attempt. Identifying biomarkers of antidepressant response and lifetime history of attempted suicide may help augment pharmacotherapy selection and improve the objectivity of suicide risk assessments. Towards this goal, this study sought to use network science approaches to establish a multi-omics (genomic and metabolomic) signature of antidepressant response and lifetime history of attempted suicide in adults with MDD. Methods: Single nucleotide variants (SNVs) which associated with suicide attempt(s) in the literature were identified and then integrated with a) p180-assayed metabolites collected prior to antidepressant pharmacotherapy and b) a binary measure of antidepressant response at 8 weeks of treatment using penalized regression-based networks in 245 ‘Pharmacogenomics Research Network Antidepressant Medication Study (PGRN-AMPS)’ and 103 ‘Combining Medications to Enhance Depression Outcomes (CO-MED)’ patients with major depressive disorder. This approach enabled characterization and comparison of biological profiles and associated antidepressant treatment outcomes of those with ( N = 46) and without ( N = 302) a self-reported lifetime history of suicide attempt. Results: 351 SNVs were associated with suicide attempt(s) in the literature. Intronic SNVs in the circadian genes CLOCK and ARNTL (encoding the CLOCK:BMAL1 heterodimer) were amongst the top network analysis features to differentiate patients with and without a prior suicide attempt. CLOCK and ARNTL differed in their correlations with plasma phosphatidylcholines, kynurenine, amino acids, and carnitines between groups. CLOCK and ARNTL -associated phosphatidylcholines showed a positive correlation with antidepressant response in individuals without a prior suicide attempt which was not observed in the group with a prior suicide attempt. Conclusion: Results provide evidence for a disturbance between CLOCK:BMAL1 circadian processes and circulating phosphatidylcholines, kynurenine, amino acids, and carnitines in individuals with MDD who have attempted suicide. This disturbance may provide mechanistic insights for differential antidepressant pharmacotherapy outcomes between patients with MDD with versus without a lifetime history of attempted suicide. Future investigations of CLOCK:BMAL1 metabolic regulation in the context of suicide attempts may help move towards biologically-augmented pharmacotherapy selection and stratification of suicide risk for subgroups of patients with MDD and a lifetime history of attempted suicide. 

Age at depressive onset (AAO) corresponds to unique symptomatology and clinical outcomes. Integration of genome-wide association study (GWAS) results with additional “omic” measures to evaluate AAO has not been reported and may reveal novel markers of susceptibility and/or resistance to major depressive disorder (MDD). To address this gap, we integrated genomics with metabolomics using data-driven network analysis to characterize and differentiate MDD based on AAO. This study first performed two GWAS for AAO as a continuous trait in (a) 486 adults from the Pharmacogenomic Research Network-Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS), and (b) 295 adults from the Combining Medications to Enhance Depression Outcomes (CO-MED) study. Variants from top signals were integrated with 153 p180-assayed metabolites to establish multi-omics network characterizations of early (