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Lessons Learned from Deep Phenotyping Patients with Rare Psychiatric Disorders

By Catherine A Brownstein and Joseph Gonzalez-Heydrich

Given the potential sensitivities associated with describing (i.e., phenotyping) patients with potentially stigmatizing psychiatric diagnoses, it is important to acknowledge and respect the wishes of the various parties involved.

The phenotypic description and depiction of a patient in the literature, although deidentified, may still be of great impact to a family.

By way of example, a novel genetic variant was identified as a likely explanation for the clinical presentation of a patient in a large cohort of individuals with neurodevelopmental and/or psychiatric phenotypes, a finding of great medical interest. The research team elected to further study this candidate and collected samples for functional evaluation of the gene variant and preparation of a case report.

Because the patient had a complicated phenotype, several physicians from various specialties were involved in the patient’s care. The paper draft was circulated amongst the collaborating clinicians and researchers and ultimately shared with the patient’s family by one of their involved caregivers. This is typically not a requirement of such studies, as the informed consent process includes the subjects’ understanding and consent for dissemination of deidentified results in the scientific literature. But as a general practice, families are informed about manuscripts in process, and in this case the family had requested to be kept abreast of ongoing developments.

Increasingly, families are interested in being more involved in the research process, so this is a situation of increasing frequency. Likewise, clinicians and researchers increasingly see patients and families as respected partners in research.

There are a number of benefits to including the perspectives of patients in research studies, such as more relevant research questions, lower participant attrition, and improved translation of research findings into practice.  Engaging patients in research also increases accountability, transparency, legitimacy, credibility, and provides assurance that the work is being done in the public interest.

But navigating relationships with patients as partners can be complex.  When patients and families disagree with researchers’ and clinicians’ expert opinions and characterizations of their condition, it can lead to upset and result in the severing of a productive relationship.  This is particularly true when addressing psychiatric diagnoses in juveniles, which can be viewed as stigmatizing.

In this case, as the family reviewed the manuscript, they noted the use of a psychiatric diagnostic term that did not match their view of the child. Although it was always the authors’ intent to describe the child accurately, yet in ways that were respectful to the family’s wishes, this particular concern was not communicated back to the writing team prior to submission, review, and acceptance of the manuscript. Subsequently, the paper was immediately withdrawn from publication and revised to the family’s comfort level without compromising the scientific integrity of the content.

In this regard, the research team and family ultimately collaborated to develop a mutually agreeable presentation that retained its scientific accuracy and medical utility, while also respecting the wishes and partnership of the research participants. Unfortunately, however, although the issue was ultimately addressed, the situation resulted in an understandable loss of trust in the research process.

It is worth emphasizing that in the setting of case report publication, participants and families can identify personal information, even when fully deidentified to the rest of the world. This case highlights the importance of open and early communication amongst clinicians, researchers, and families, such that all involved are aware of any concerns and sensitivities, and any disagreements are overcome in a way that is acceptable to all involved.

Ethical deep phenotyping of psychiatric disorders when patients are partners means that all parties need to have comfort with the phenotypic description before publication.  While the medical field deserves accurate descriptions, respect for the patients and their families is also of utmost importance. Great care should be taken to acknowledge the preferences of participants to prevent inadvertent offenses that result can in the loss of research opportunities, and more importantly, the loss of trust.


Catherine A Brownstein is Scientific Director at the Manton Center for Orphan Disease Research; an Assistant Professor of Pediatrics at Harvard Medical School; a Research Associate in Genetics and Genomics at Boston Children’s Hospital; and the Assistant Director of the Molecular Genomics Core Facility at Harvard Medical School.

Joseph Gonzalez-Heydrich is a Senior Attending Psychiatrist in the Department of Psychiatry at Boston Children’s Hospital and an Associate Professor of Psychiatry at Harvard Medical School.


This post is part of our Ethical, Legal, and Social Implications of Deep Phenotyping symposium. All contributions to the symposium are available here.

The Petrie-Flom Center Staff

The Petrie-Flom Center staff often posts updates, announcements, and guests posts on behalf of others.

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