Obstacles, Opportunities, and Ethical Considerations for Genomic Investigations of Individuals Continuously Hospitalized with Treatment-resistant Schizophrenia

Abstract

Background and hypothesis: The overarching objective when studying schizophrenia is the development of generalizable knowledge that improves patient health and/or increases our comprehension of their illness. To fully achieve this objective, investigations need to reflect the full range of individual variation found within this heterogeneous population. But individuals committed to state psychiatric institutions have been routinely excluded from research because of concerns that they may not be able to understand or provide adequately informed consent. While reasonable, we believe this approach has enabled policies that support implicit bias, contribute to health care disparities, and limit our knowledge of disease mechanisms and treatment.

Study design: This article provides brief reviews of (1) ethical considerations when recruiting individuals with severely treatment-resistant psychotic symptoms for research, (2) the impact their condition has on decision-making capacity, and finally (3) we provide a first-hand narrative of our experience conducting a genomic study of involuntarily hospitalized individuals and the opportunities/obstacles we encountered.

Study results: Evidence from published literature shows that cognitive impairment, rather than severity of psychopathology, is the greatest threat to decisional capacity. Ethical safeguards and practical considerations have been developed, including (1) institutional/local research committee review and approval, (2) confidentiality, (3) informed consent, (4) assessment of capacity, and (5) community engagement. Our experience demonstrates that carefully selected involuntarily committed individuals can be included in research.

Conclusions: With ethical safeguards, these individuals deserve the opportunity to volunteer for research regarding the mental illness that has profoundly shaped their lives-to do otherwise is discriminatory.

Keywords: continuously hospitalized-TRS; copy number variants; decision-making capacity; extreme phenotype sampling; rare variants; schizophrenia; schizophrenia research ethics; treatment-resistant psychosis.