Defining Major Depressive Disorder Cohorts Using the EHR: Multiple Phenotypes Based on ICD-9 Codes and Medication Orders.

BACKGROUND: Major Depressive Disorder (MDD) is one of the most common mental illnesses and a leading cause of disability worldwide. Electronic Health Records (EHR) allow researchers to conduct unprecedented large-scale observational studies investigating MDD, its disease development and its interaction with other health outcomes. While there exist methods to classify patients as clear cases or controls, given specific data requirements, there are presently no simple, generalizable, and validated methods to classify an entire patient population into varying groups of depression likelihood and severity. METHODS: We have tested a simple, pragmatic electronic phenotype algorithm that classifies patients into one of five mutually exclusive, ordinal groups, varying in depression phenotype. Using data from an integrated health system on 278,026 patients from a 10-year study period we have tested the convergent validity of these constructs using measures of external validation, including patterns of psychiatric prescriptions, symptom severity, indicators of suicidality, comorbidity, mortality, health care utilization, and polygenic risk scores for MDD. RESULTS: We found consistent patterns of increasing morbidity and/or adverse outcomes across the five groups, providing evidence for convergent validity. LIMITATIONS: The study population is from a single rural integrated health system which is predominantly white, possibly limiting its generalizability. CONCLUSION: Our study provides initial evidence that a simple algorithm, generalizable to most EHR data sets, provides categories with meaningful face and convergent validity that can be used for stratification of an entire patient population.

Factors Affecting Electroconvulsive Therapy Ictal Outcomes: Duration and Postictal Suppression.

Electroconvulsive therapy (ECT) is an effective and rapid treatment for severe depression, however predictors of therapeutic outcomes remain insufficiently understood. Ictal duration and postictal suppression are two outcomes that may be correlated with patient response, yet patient and treatment variables which may influence these outcomes have not been thoroughly explored. We collected ECT stimulus metrics, EEG parameters, patient demographics, primary diagnosis, and anesthesia type for retrospective ECTs. Univariate and multivariate mixed-effects linear regression models were used to identify variables associated with ictal duration and postictal suppression index. For both outcomes, multivariate models which included all variables resulted in the best fit, reflecting the complex influences of a variety of factors on the ictal response. These results are an important step forward in elucidating patterns in retrospective ECT clinical data which may lead to new clinical knowledge of modifiable factors to optimize ECT treatment outcomes.

Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance.

Toxoplasma gondii chronic infection in rodent secondary hosts has been reported to lead to a loss of innate, hard-wired fear toward cats, its primary host. However the generality of this response across T. gondii strains and the underlying mechanism for this pathogen-mediated behavioral change remain unknown. To begin exploring these questions, we evaluated the effects of infection with two previously uninvestigated isolates from the three major North American clonal lineages of T. gondii, Type III and an attenuated strain of Type I. Using an hour-long open field activity assay optimized for this purpose, we measured mouse aversion toward predator and non-predator urines. We show that loss of innate aversion of cat urine is a general trait caused by infection with any of the three major clonal lineages of parasite. Surprisingly, we found that infection with the attenuated Type I parasite results in sustained loss of aversion at times post infection when neither parasite nor ongoing brain inflammation were detectable. This suggests that T. gondii-mediated interruption of mouse innate aversion toward cat urine may occur during early acute infection in a permanent manner, not requiring persistence of parasite cysts or continuing brain inflammation.