Dimensional clinical phenotyping using post-mortem brain donor medical records: post-mortem RDoC profiling is associated with Alzheimer's disease neuropathology.

Introduction: Transdiagnostic dimensional phenotypes are essential to investigate the relationship between continuous symptom dimensions and pathological changes. This is a fundamental challenge to post-mortem work, as assessments of phenotypic concepts need to rely on existing records. Methods: We adapted well-validated methodologies to compute National Institute of Mental Health Research Domain Criteria (RDoC) scores using natural language processing (NLP) from electronic health records (EHRs) obtained from post-mortem brain donors and tested whether cognitive domain scores were associated with Alzheimer's disease neuropathological measures. Results: Our results confirm an association of EHR-derived cognitive scores with neuropathological findings. Notably, higher neuropathological load, particularly neuritic plaques, was associated with higher cognitive burden scores in the frontal (ß = 0.38, P = 0.0004), parietal (ß = 0.35, P = 0.0008), temporal (ß = 0.37, P = 0.0004) and occipital (ß = 0.37, P = 0.0003) lobes. Discussion: This proof-of-concept study supports the validity of NLP-based methodologies to obtain quantitative measures of RDoC clinical domains from post-mortem EHR. The associations may accelerate post-mortem brain research beyond classical case-control designs.

Dimensional clinical phenotyping using post-mortem brain donor medical records: Association with neuropathology.

INTRODUCTION: Transdiagnostic dimensional phenotypes are essential to investigate the relationship between continuous symptom dimensions and pathological changes. This is a fundamental challenge to postmortem work, as assessment of newly developed phenotypic concepts needs to rely on existing records. METHODS: We adapted well-validated methodologies to compute NIMH research domain criteria (RDoC) scores using natural language processing (NLP) from electronic health records (EHRs) obtained from post-mortem brain donors and tested whether RDoC cognitive domain scores were associated with hallmark Alzheimer's disease (AD) neuropathological measures. RESULTS: Our results confirm an association of EHR-derived cognitive scores with hallmark neuropathological findings. Notably, higher neuropathological load, particularly neuritic plaques, was associated with higher cognitive burden scores in the frontal (ß=0.38, p=0.0004), parietal (ß=0.35, p=0.0008), temporal (ß=0.37, p=0. 0004) and occipital (ß=0.37, p=0.0003) lobes. DISCUSSION: This proof of concept study supports the validity of NLP-based methodologies to obtain quantitative measures of RDoC clinical domains from postmortem EHR.

Impact of the COVID-19 Pandemic on the Employment and Educational Outcomes of Individuals in a First-Episode Psychosis Clinic.

OBJECTIVE: A central objective of early psychosis therapy is to restore social functioning (e.g., through employment and education). Employment and educational outcomes during the COVID-19 pandemic were examined in a well-defined cohort of patients receiving care in an early psychosis clinic. METHODS: Data were extracted from the electronic health records of 128 patients receiving care at McLean Hospital's first-episode psychosis (FEP) clinic between January 1 and September 21 in 2019 and 2020. Using a generalized linear model with a Gaussian distribution and robust standard errors, the authors compared the average changes in the weekly employment and education proportions before and after COVID-19 lockdowns with the same changes in 2019. RESULTS: Employment losses among patients with FEP were greater than among the general population and persisted through the end of follow-up. In 2020, average employment after a stay-at-home order was instituted was 33% lower than before the order compared with the change in employment during the same period in 2019. The effect was stronger among men and those who identified as non-White, were age <21 years, or did not have a college education. Although educational engagement recovered in the fall of 2020, it still remained below the 2019 levels. CONCLUSIONS: Employment disruptions were major and persistent among the FEP population, which might affect short- and long-term outcomes. Innovative approaches are needed to help patients transition to remote employment, file unemployment claims, and use online hiring platforms to ameliorate the indirect effects of the COVID-19 pandemic.