GENETIC DUTIES.

Most of our genetic information does not change, yet the results of our genetic tests might. Labs reclassify genetic variants in response to advances in genetic science. As a result, a person who took a test in 2010 could take the same test with the same lab in 2020 and get a different result. However, no legal duty requires labs or physicians to inform patients when a lab reclassifies a variant, even if the reclassification communicates clinically actionable information. This Article considers the need for such duties and their potential challenges. In so doing, it offers much-needed guidance to physicians and labs, who may face liability, and to courts, which will hear these cases.

LEGAL AND ETHICAL IMPLICATIONS OF CRISPR APPLICATIONS IN PSYCHIATRY.

Gene-environment interactions play a key role in how psychiatric disorders manifest and develop. Psychiatric genetics researchers are making progress in identifying genomic correlates of many disorders. And recently, the field of genetics has given rise to a technology that many claim will revolutionize the biological sciences and propel the field into a transformative phase: the powerful gene-editing tool known as CRISPR-Cas9. This Article illustrates which psychiatric conditions are likely to make an attractive target for CRISPR as the technology evolves and CRISPR therapies becomes a viable tool to manage or prevent disorders in a clinical setting. We examine the potential scientific and clinical challenges of applying CRISPR in the mental health context, along with the regulatory, ethical, and legal issues that might arise as a consequence of these applications.

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.

Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression.

BACKGROUND: Preliminary evidence suggests intravenous ketamine has rapid effects on suicidal cognition, making it an attractive candidate for depressed patients at imminent risk of suicide. In the first randomized controlled trial of ketamine using an anesthetic control condition, we tested ketamine's acute effects on explicit suicidal cognition and a performance-based index of implicit suicidal cognition (Implicit Association Test; IAT) previously linked to suicidal behavior. METHOD: Symptomatic patients with treatment-resistant unipolar major depression (inadequate response to ≥3 antidepressants) were assessed using a composite index of explicit suicidal ideation (Beck Scale for Suicidal Ideation, Montgomery-Asberg Rating Scale suicide item, Quick Inventory of Depressive Symptoms suicide item) and the IAT to assess suicidality implicitly. Measures were taken at baseline and 24 hr following a single subanesthetic dose of ketamine (n = 36) or midazolam (n = 21), a psychoactive placebo agent selected for its similar, rapid anesthetic effects. Twenty four hours postinfusion, explicit suicidal cognition was significantly reduced in the ketamine but not the midazolam group. RESULTS: Fifty three percent of ketamine-treated patients scored zero on all three explicit suicide measures at 24 hr, compared with 24% of the midazolam group (χ(2) = 4.6; P = .03). Implicit associations between self- and escape-related words were reduced following ketamine (P = .01; d = .58) but not midazolam (P = .68; d = .09). Ketamine-specific decreases in explicit suicidal cognition were largest in patients with elevated suicidal cognition at baseline, and were mediated by decreases in nonsuicide-related depressive symptoms. CONCLUSIONS: Intravenous ketamine produces rapid reductions in suicidal cognition over and above active placebo. Further study is warranted to test ketamine's antisuicidal effects in higher-risk samples.