Returning Individual Research Results from Digital Phenotyping in Psychiatry.

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants' locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant's real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas.

Adolescent OCD Patient and Caregiver Perspectives on Identity, Authenticity, and Normalcy in Potential Deep Brain Stimulation Treatment.

The ongoing debate within neuroethics concerning the degree to which neuromodulation such as deep brain stimulation (DBS) changes the personality, identity, and agency (PIA) of patients has paid relatively little attention to the perspectives of prospective patients. Even less attention has been given to pediatric populations. To understand patients' views about identity changes due to DBS in obsessive-compulsive disorder (OCD), the authors conducted and analyzed semistructured interviews with adolescent patients with OCD and their parents/caregivers. Patients were asked about projected impacts to PIA generally due to DBS. All patient respondents and half of caregivers reported that DBS would impact patient self-identity in significant ways. For example, many patients expressed how DBS could positively impact identity by allowing them to explore their identities free from OCD. Others voiced concerns that DBS-related resolution of OCD might negatively impact patient agency and authenticity. Half of patients expressed that DBS may positively facilitate social access through relieving symptoms, while half indicated that DBS could increase social stigma. These views give insights into how to approach decision-making and informed consent if DBS for OCD becomes available for adolescents. They also offer insights into adolescent experiences of disability identity and "normalcy" in the context of OCD.

Deep Brain Stimulation for Pediatric Dystonia: Clinicians' Perspectives on the Most Pressing Ethical Challenges.

INTRODUCTION: Pediatric deep brain stimulation (pDBS) is commonly used to manage treatment-resistant primary dystonias with favorable results and more frequently used for secondary dystonia to improve quality of life. There has been little systematic empirical neuroethics research to identify ethical challenges and potential solutions to ensure responsible use of DBS in pediatric populations. METHODS: Clinicians (n = 29) who care for minors with treatment-resistant dystonia were interviewed for their perspectives on the most pressing ethical issues in pDBS. RESULTS: Using thematic content analysis to explore salient themes, clinicians identified four pressing concerns: (1) uncertainty about risks and benefits of pDBS (22/29; 72%) that poses a challenge to informed decision-making; (2) ethically navigating decision-making roles (15/29; 52%), including how best to integrate perspectives from diverse stakeholders (patient, caregiver, clinician) and how to manage surrogate decisions on behalf of pediatric patients with limited capacity to make autonomous decisions; (3) information scarcity effects on informed consent and decision quality (15/29; 52%) in the context of patient and caregivers' expectations for treatment; and (4) narrow regulatory status and access (7/29; 24%) such as the lack of FDA-approved indications that contribute to decision-making uncertainty and liability and potentially limit access to DBS among patients who may benefit from it. CONCLUSION: These results suggest that clinicians are primarily concerned about ethical limitations of making difficult decisions in the absence of informational, regulatory, and financial supports. We discuss two solutions already underway, including supported decision-making to address uncertainty and further data sharing to enhance clinical knowledge and discovery.

Clinical and Psychosocial Factors Considered When Deciding Whether to Offer Deep Brain Stimulation for Childhood Dystonia.

INTRODUCTION: Childhood dystonia is often nonresponsive to medications, and refractory cases are increasingly being treated with deep brain stimulation (DBS). However, many have noted that there is little consensus about when DBS should be offered, and there has been little examination of clinicians' decision-making process when determining whether to offer DBS for childhood dystonia. OBJECTIVES: This study aimed to identify and examine the factors considered by pediatric movement disorder specialists before offering DBS. MATERIALS AND METHODS: Semistructured interviews (N = 29) with pediatric dystonia clinicians were conducted, transcribed, and coded. Using thematic content analysis, nine central themes were identified when clinicians were asked about key factors, clinical factors, and psychosocial factors considered before offering pediatric DBS. RESULTS: Clinicians identified nine main factors. Five of these were classified primarily as clinical factors: early intervention and younger age (raised by 86% of respondents), disease progression and symptom severity (83%), etiology and genetic status (79%), clinicians' perceived risks and benefits of DBS for the patient (79%), and exhaustion of other treatment options (55%). The remaining four were classified primarily as psychosocial factors: social and family support (raised by 97% of respondents), patient and caregiver expectations about outcomes and understanding of DBS treatment (90%), impact of dystonia on quality of life (69%), and financial resources and access to care (31%). CONCLUSIONS: Candidacy determinations, in this context, are complicated by an interrelation of clinical and psychosocial factors that contribute to the decision. There is potential for bias when considering family support and quality of life. Uncertainty of outcomes related to the etiology of dystonia makes candidacy judgments challenging. More systematic examination of the characteristics and criteria used to identify pediatric patients with dystonia who can significantly benefit from DBS is necessary to develop clear guidelines and promote the well-being of these children.

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

Psychiatric polygenic risk scores: Child and adolescent psychiatrists' knowledge, attitudes, and experiences.

Psychiatric polygenic risk scores (PRS) have potential utility in psychiatric care and prevention, but there are concerns about their implementation. We surveyed 960 US-based practicing child and adolescent psychiatrists' (CAP) about their experiences, perspectives, and potential uses of psychiatric PRS. While 23% of CAP reported that they had never heard of PRS, 10 % of respondents have had a patient/family bring PRS to them and 4% have generated PRS for patients. Though 25% stated they would request PRS if a patient/caregiver asked, 35% indicated that nothing would prompt them to request PRS. Most respondents (54%) believed psychiatric PRS are currently at least slightly useful and 87% believed they will be so in 5 years. More than 70% indicated they would take action in response to a child with a top fifth percentile psychiatric PRS but no diagnosis: 48% would increase monitoring of symptoms, 42% would evaluate for current symptoms, and 4% would prescribe medications. Yet, most respondents were concerned that high-PRS results could lead to overtreatment and negatively impact patients' emotional well-being. Findings indicate emerging use of psychiatric PRS within child and adolescent psychiatry in the US. It is critical to examine the ethical and clinical challenges that PRS may generate and begin efforts to promote their informed and responsible use.

Return of results in a global survey of psychiatric genetics researchers: practices, attitudes, and knowledge.

PURPOSE: Patient-participants in psychiatric genetics research may be at an increased risk for negative psychosocial impacts related to the return of genetic research results. Examining psychiatric genetics researchers' return of results practices and perspectives can aid the development of empirically informed and ethically sound guidelines. METHODS: A survey of 407 psychiatric genetics researchers from 39 countries was conducted to examine current return of results practices, attitudes, and knowledge. RESULTS: Most respondents (61%) reported that their studies generated medically relevant genomic findings. Although 24% have returned results to individual participants, 52% of those involved in decisions about return of results plan to return or continue to return results. Respondents supported offering "medically actionable" results related to psychiatric disorders (82%), and the majority agreed non-medically actionable risks for Huntington (71%) and Alzheimer disease (64%) should be offered. About half (49%) of respondents supported offering reliable polygenic risk scores for psychiatric conditions. Despite plans to return, only 14% of researchers agreed there are adequate guidelines for returning results, and 59% rated their knowledge about how to manage the process for returning results as poor. CONCLUSION: Psychiatric genetics researchers support returning a wide range of results to patient-participants, but they lack adequate knowledge and guidelines.

Psychiatric genomics researchers' perspectives on best practices for returning results to individual participants.

PURPOSE: Large-scale array-based and sequencing studies have advanced our understanding of the genetic architecture of psychiatric disorders, but also increased the potential to generate an exponentially larger amount of clinically relevant findings. As genomic testing becomes more widespread in psychiatry research, urgency grows to establish best practices for offering return of results (RoR) to individuals at risk or diagnosed with a psychiatric disorder. METHODS: We interviewed an international sample (n = 39) of psychiatric genetics researchers to examine conceptualizations of "best practices" for RoR to individual research participants. RESULTS: While the vast majority of researchers do not offer RoR, most believed medically actionable findings (85%) and clinically valid but non-medically actionable findings (54%) should be offered. Researchers identified three main areas for improvement: interfacing with individual participants; interdisciplinary training, guidance, and integration; and quality planning and resource allocation for returning results. CONCLUSION: There are significant gaps between researchers' visions for "best" versus "actual" RoR practices. While researchers call for participant-centered practices, including consent practices that consider any special needs of participants with psychiatric disorders, return of individually meaningful results, and effective follow-up and provisions for treatment, the current reality is that consent and RoR practices lack standardized and evidence-based norms.

Pediatric Deep Brain Stimulation for Dystonia: Current State and Ethical Considerations.

Dystonia is a movement disorder that can have a debilitating impact on motor functions and quality of life. There are 250,000 cases in the United States, most with childhood onset. Due to the limited effectiveness and side effects of available treatments, pediatric deep brain stimulation (pDBS) has emerged as an intervention for refractory dystonia. However, there is limited clinical and neuroethics research in this area of clinical practice. This paper examines whether it is ethically justified to offer pDBS to children with refractory dystonia. Given the favorable risk-benefit profile, it is concluded that offering pDBS is ethically justified for certain etiologies of dystonia, but it is less clear for others. In addition, various ethical and policy concerns are discussed, which need to be addressed to optimize the practice of offering pDBS for dystonia. Strategies are proposed to help address these concerns as pDBS continues to expand.

Preventing discrimination based on psychiatric risk biomarkers.

Recent studies have identified genomic and nongenomic psychiatric risk biomarkers (PRBs; e.g., genomic variants, blood analytes, gray matter volume). PRBs may soon become a powerful tool for improving psychiatric care and prevention. PRB research and its translation to clinical care, however, may prove to be a double-edged sword. Mental health stigma and discrimination are already widespread, and data caution that biological explanations of psychiatric disorders can exacerbate these stigmatizing attitudes, increasing the desire for social distance and heightening the perceived dangerousness of the patient. As a reaction to the Human Genome Project and historical concerns about eugenics, the international community mobilized to establish legislation to prevent genomic discrimination. But in most countries, these laws are limited to few contexts (e.g., employment, health insurance), and very few countries protect against discrimination based on nongenomic risk biomarkers. Like genomic PRBs, nongenomic PRBs provide information regarding risk for stigmatized psychiatric disorders and have similar-and in some cases greater-predictive value. Numerous large-scale neuroscience and neurogenomics projects are advancing the identification and translation of PRBs. The prospect of PRB-based stigma however, threatens to undermine the potential benefits of this research. Unbridaled by nonexistent or limited PRB anti-discrimination protections, the threat of PRB-based stigma and discrimination may lead many to forego PRB testing, even if shown to have clinical utility. To maximize the clinical and social benefits of PRB-based technologies, educational campaigns should address mental health and PRB stigma, and lawmakers should carefully consider expanding legislation that prohibits PRB-based discrimination.

Psychiatric genetics researchers' views on offering return of results to individual participants.

In the middle of growing consensus that genomics researchers should offer to return clinically valid, medically relevant, and medically actionable findings identified in the course of research, psychiatric genetics researchers face new challenges. As they uncover the genetic architecture of psychiatric disorders through genome-wide association studies and integrate whole genome and whole exome sequencing to their research, there is a pressing need for examining these researchers' views regarding the return of results (RoR) and the unique challenges for offering RoR from psychiatric genetics research. Based on qualitative interviews with 39 psychiatric genetics researchers from different countries operating at the forefront of their field, we provide an insider's view of researchers' practices regarding RoR and the most contentious issues in psychiatry researchers' decision-making around RoR, including what are the strongest ethical, scientific, and practical arguments for and against offering RoR from this research. Notably, findings suggest that psychiatric genetics researchers (85%) overwhelmingly favor offering RoR of at least some findings, but only 22% of researchers are returning results. Researchers identified a number of scientific and practical concerns about RoR, and about how to return results in a responsible way to patients diagnosed with a severe psychiatric disorder. Furthermore, findings help highlight areas for further discussion and resolution of conflicts in the practice of RoR in psychiatric genetics research. As the pace of discovery in psychiatric genetics continues to surge, resolution of these uncertainties gains greater urgency to avoid ethical pitfalls and to maximize the positive impact of RoR.

International Society of Psychiatric Genetics Ethics Committee: Issues facing us.

Psychiatric genetics research is improving our understanding of the biological underpinnings of neurodiversity and mental illness. Using psychiatric genetics in ways that maximize benefits and minimize harms to individuals and society depends largely on how the ethical, legal, and social implications (ELSI) of psychiatric genetics are managed. The International Society of Psychiatric Genetics (ISPG) is the largest international organization dedicated to psychiatric genetics. Given its history, membership, and international reach, we believe the ISPG is well-equipped to contribute to the resolution of these ELSI challenges. As such, we recently created the ISPG Ethics Committee, an interdisciplinary group comprised of psychiatric genetics researchers, clinical geneticists, genetic counselors, mental health professionals, patients, patient advocates, bioethicists, and lawyers. This article highlights key ELSI challenges identified by the ISPG Ethics Committee to be of paramount importance for the ethical translation of psychiatric research into society in three contexts: research settings, clinical settings, and legal proceedings. For each of these arenas, we identify and discuss pressing psychiatric genetics ELSI dilemmas that merit attention and require action. The goal is to increase awareness about psychiatric genetics ELSI issues and encourage dialogue and action among stakeholders.

Looking for Trouble: Preventive Genomic Sequencing in the General Population and the Role of Patient Choice.

Advances in genomics have led to calls for developing population-based preventive genomic sequencing (PGS) programs with the goal of identifying genetic health risks in adults without known risk factors. One critical issue for minimizing the harms and maximizing the benefits of PGS is determining the kind and degree of control individuals should have over the generation, use, and handling of their genomic information. In this article we examine whether PGS programs should offer individuals the opportunity to selectively opt out of the sequencing or analysis of specific genomic conditions (the menu approach) or whether PGS should be implemented using an all-or-nothing panel approach. We conclude that any responsible scale-up of PGS will require a menu approach that may seem impractical to some, but that draws its justification from a rich mix of normative, legal, and practical considerations.