Faculty Bibliography

Biomarkers that predict symptom trajectories after trauma can facilitate early detection or intervention for posttraumatic stress disorder (PTSD) and may also advance our understanding of its biology. Here, we aimed to identify trajectory-based biomarkers using blood transcriptomes collected in the immediate aftermath of trauma exposure. Participants were recruited from an Emergency Department in the immediate aftermath of trauma exposure and assessed for PTSD symptoms at baseline, 1, 3, 6, and 12 months. Three empirical symptom trajectories (chronic-PTSD, remitting, and resilient) were identified in 377 individuals based on longitudinal symptoms across four data points (1, 3, 6, and 12 months), using latent growth mixture modeling. Blood transcriptomes were examined for association with longitudinal symptom trajectories, followed by expression quantitative trait locus analysis. GRIN3B and AMOTL1 blood mRNA levels were associated with chronic vs. resilient post-trauma symptom trajectories at a transcriptome-wide significant level (N = 153, FDR-corrected p value = 0.0063 and 0.0253, respectively). We identified four genetic variants that regulate mRNA blood expression levels of GRIN3B. Among these, GRIN3B rs10401454 was associated with PTSD in an independent dataset (N = 3521, p = 0.04). Examination of the BrainCloud and GTEx databases revealed that rs10401454 was associated with brain mRNA expression levels of GRIN3B. While further replication and validation studies are needed, our data suggest that GRIN3B, a glutamate ionotropic receptor NMDA type subunit-3B, may be involved in the manifestation of PTSD. In addition, the blood mRNA level of GRIN3B may be a promising early biomarker for the PTSD manifestation and development.

Importance/UNASSIGNED:Major life stressors, such as loss and trauma, increase the risk of depression. It is known that individuals show heterogeneous trajectories of depressive symptoms following major life stressors, including chronic depression, recovery, and resilience. Although common genetic variation has been associated with depression risk, genomic factors that could help discriminate trajectories of risk vs resilience following adversity have not been identified. Objective/UNASSIGNED:To assess the discriminatory accuracy of a deep neural net combining joint information from 21 psychiatric and health-related multiple polygenic scores (PGSs) for discriminating resilience vs other longitudinal symptom trajectories with use of longitudinal, genetically informed data on adults exposed to major life stressors. Design, Setting, and Participants/UNASSIGNED:The Health and Retirement Study is a longitudinal panel cohort study in US citizens older than 50 years, with data being collected once every 2 years between 1992 and 2010. A total of 2071 participants who were of European ancestry with available depressive symptom trajectory information after experiencing an index depressogenic major life stressor were included. Latent growth mixture modeling identified heterogeneous trajectories of depressive symptoms before and after major life stressors, including stable low symptoms (ie, resilience), as well as improving, emergent, and preexisting/chronic symptom patterns. Twenty-one PGSs were examined as factors distinctively associated with these heterogeneous trajectories. Local interpretable model-agnostic explanations were applied to examine PGSs associated with each trajectory. Data were analyzed using the DNN model from June to July 2020. Exposures/UNASSIGNED:Development of depression and resilience were examined in older adults after a major life stressor, such as bereavement, divorce, and job loss, or major health events, such as myocardial infarction and cancer. Main Outcomes and Measures/UNASSIGNED:Discriminatory accuracy of a deep neural net model trained for the multinomial classification of 4 distinct trajectories of depressive symptoms (Center for Epidemiologic Studies-Depression scale) based on 21 PGSs using supervised machine learning. Results/UNASSIGNED:Of the 2071 participants, 1329 were women (64.2%); mean (SD) age was 55.96 (8.52) years. Of these, 1638 (79.1%) were classified as resilient, 160 (7.75) in recovery (improving), 159 (7.7%) with emerging depression, and 114 (5.5%) with preexisting/chronic depression symptoms. Deep neural nets distinguished these 4 trajectories with high discriminatory accuracy (multiclass micro-average area under the curve, 0.88; 95% CI, 0.87-0.89; multiclass macro-average area under the curve, 0.86; 95% CI, 0.85-0.87). Discriminatory accuracy was highest for preexisting/chronic depression (AUC 0.93), followed by emerging depression (AUC 0.88), recovery (AUC 0.87), resilience (AUC 0.75). Conclusions and Relevance/UNASSIGNED:The results of the longitudinal cohort study suggest that multivariate PGS profiles provide information to accurately distinguish between heterogeneous stress-related risk and resilience phenotypes.

BACKGROUND:Multiple symptoms of suicide risk have been assessed based on visual and auditory information, including flattened affect, reduced movement, and slowed speech. Objective quantification of such symptomatology from novel data sources can increase the sensitivity, scalability, and timeliness of suicide risk assessment. OBJECTIVE:We aimed to examine measurements extracted from video interviews using open-source deep learning algorithms to quantify facial, vocal, and movement behaviors in relation to suicide risk severity in recently admitted patients following a suicide attempt. METHODS:We utilized video to quantify facial, vocal, and movement markers associated with mood, emotion, and motor functioning from a structured clinical conversation in 20 patients admitted to a psychiatric hospital following a suicide risk attempt. Measures were calculated using open-source deep learning algorithms for processing facial expressivity, head movement, and vocal characteristics. Derived digital measures of flattened affect, reduced movement, and slowed speech were compared to suicide risk with the Beck Scale for Suicide Ideation controlling for age and sex, using multiple linear regression. RESULTS:=0.32). CONCLUSIONS:Digital measurements of facial affect, movement, and speech prevalence demonstrated strong effect sizes and linear associations with the severity of suicidal ideation.

The necessary requirement of a traumatic event preceding the development of Posttraumatic Stress Disorder, theoretically allows for administering preventive and early interventions in the early aftermath of such events. Machine learning models including biomedical data to forecast PTSD outcome after trauma are highly promising for detection of individuals most in need of such interventions. In the current study, machine learning was applied on biomedical data collected within 48 h post-trauma to forecast individual risk for long-term PTSD, using a multinominal approach including the full spectrum of common PTSD symptom courses within one prognostic model for the first time. N = 417 patients (37.2% females; mean age 46.09 ± 15.88) admitted with (suspected) serious injury to two urban Academic Level-1 Trauma Centers were included. Routinely collected biomedical information (endocrine measures, vital signs, pharmacotherapy, demographics, injury and trauma characteristics) upon ED admission and subsequent 48 h was used. Cross-validated multi-nominal classification of longitudinal self-reported symptom severity (IES-R) over 12 months and bimodal classification of clinician-rated PTSD diagnosis (CAPS-IV) at 12 months post-trauma was performed using extreme Gradient Boosting and evaluated on hold-out sets. SHapley Additive exPlanations (SHAP) values were used to explain the derived models in human-interpretable form. Good prediction of longitudinal PTSD symptom trajectories (multiclass AUC = 0.89) and clinician-rated PTSD at 12 months (AUC = 0.89) was achieved. Most relevant prognostic variables to forecast both multinominal and dichotomous PTSD outcomes included acute endocrine and psychophysiological measures and hospital-prescribed pharmacotherapy. Thus, individual risk for long-term PTSD was accurately forecasted from biomedical information routinely collected within 48 h post-trauma. These results facilitate future targeted preventive interventions by enabling future early risk detection and provide further insights into the complex etiology of PTSD.

Digital health technologies are advancing characterization of mental health and functioning using objective, sensitive, and scalable tools for measurement of disease. These efforts directly address well-documented issues with traditional clinical assessments of psychiatric functioning, which can be burdensome, subjective, and insensitive to change. In this article, we highlight novel approaches for digital phenotyping of mental health. Each approach is categorized by the way biomarker data are collected, focusing on passive monitoring, active assessment, individual self-report, and biological measurement. Common challenges faced by each of these approaches are discussed, including pathways to validation, regulatory approval, and integration into patient care and clinical research. Finally, we present our perspective on the promise of such technology, focusing on how integration of independent digital measurement tools into a common technological infrastructure would allow for highly accurate, multimodal machine learning models for unprecedented objective measurement of mental health.

Women are at higher risk for developing posttraumatic stress disorder (PTSD) compared to men, yet little is known about the biological contributors to this sex difference. One possible mechanism is differential immunological and neuroendocrine responses to traumatic stress exposure. In the current prospective study, we aimed to identify whether sex is indirectly associated with the probability of developing nonremitting PTSD through pro-inflammatory markers and whether steroid hormone concentrations influence this effect. Female (n = 179) and male (n = 197) trauma survivors were recruited from an emergency department and completed clinical assessment within 24 h and blood samples within ∼three hours of trauma exposure. Pro-inflammatory cytokines (IL-6, IL-1

Introduction/UNASSIGNED:Motor abnormalities have been shown to be a distinct component of schizophrenia symptomatology. However, objective and scalable methods for assessment of motor functioning in schizophrenia are lacking. Advancements in machine learning-based digital tools have allowed for automated and remote "digital phenotyping" of disease symptomatology. Here, we assess the performance of a computer vision-based assessment of motor functioning as a characteristic of schizophrenia using video data collected remotely through smartphones. Methods/UNASSIGNED:Eighteen patients with schizophrenia and 9 healthy controls were asked to remotely participate in smartphone-based assessments daily for 14 days. Video recorded from the smartphone front-facing camera during these assessments was used to quantify the Euclidean distance of head movement between frames through a pretrained computer vision model. The ability of head movement measurements to distinguish between patients and healthy controls as well as their relationship to schizophrenia symptom severity as measured through traditional clinical scores was assessed. Results/UNASSIGNED:= 0.04), primarily with negative symptoms of schizophrenia. Conclusions/UNASSIGNED:Remote, smartphone-based assessments were able to capture meaningful visual behavior for computer vision-based objective measurement of head movement. The measurements of head movement acquired were able to accurately classify schizophrenia diagnosis and quantify symptom severity in patients with schizophrenia.

Background/UNASSIGNED:Alterations in multiple domains of cognition have been observed in individuals who have experienced a traumatic stressor. These domains may provide important insights in identifying underlying neurobiological dysfunction driving an individual's clinical response to trauma. However, such assessments are burdensome, costly, and time-consuming. To overcome barriers, efforts have emerged to measure multiple domains of cognitive functioning through the application of machine learning (ML) models to passive data sources. Methods/UNASSIGNED:We utilized automated computer vision and voice analysis methods to extract facial, movement, and speech characteristics from semi-structured clinical interviews in 81 trauma survivors who additionally completed a cognitive assessment battery. A ML-based regression framework was used to identify variance in visual and auditory measures that relate to multiple cognitive domains. Results/UNASSIGNED:= 0.63), consistent with the high test-retest reliability of traditional cognitive assessments. Face, voice, speech content, and movement have all significantly contributed to explaining the variance in predicting functioning in all cognitive domains. Conclusions/UNASSIGNED:The results demonstrate the feasibility of automated measurement of reliable proxies of cognitive functioning through low-burden passive patient evaluations. This makes it easier to monitor cognitive functions and to intervene earlier and at a lower threshold without requiring a time-consuming neurocognitive assessment by, for instance, a licensed psychologist with specialized training in neuropsychology.