GENETICS

Legal and Ethical implications of CRISPR Applications in Psychiatry

Alexandra L. Foulkes, Takahiro Soda, Martilias Farrell, Paola Giusti-Rodríguez, and Gabriel Lázaro-Muñoz, Legal and Ethical and LEGAL and Ethical Implications of CRISPR Applications in Psychiatry 97 C.L. Rev. 1359 (2019).

Abstract: 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 attractive targets for CRISPR as the technology evolves and CRISPR therapies become viable tools 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.

Nature, Nurture, and Capital Punishment: How Evidence of a Genetic–Environment Interaction, Future Dangerousness, and Deliberation Affect Sentencing Decisions

Natalie Gordon & Edie Greene, Nature, nurture, and capital punishment: How evidence of a genetic–environment interaction, future dangerousness, and deliberation affect sentencing decisions, 36 Sci. L. 65 (2018).

Abstract: Research has shown that the low‐activity MAOA genotype in conjunction with a history of childhood maltreatment increases the likelihood of violent behaviors. This genetic–environment (G × E) interaction has been introduced as mitigation during the sentencing phase of capital trials, yet there is scant data on its effectiveness. This study addressed that issue. In a factorial design that varied mitigating evidence offered by the defense [environmental (i.e., childhood maltreatment), genetic, G × E, or none] and the likelihood of the defendant’s future dangerousness (low or high), 600 mock jurors read sentencing phase evidence in a capital murder trial, rendered individual verdicts, and half deliberated as members of a jury to decide a sentence of death or life imprisonment. The G × E evidence had little mitigating effect on sentencing preferences: participants who received the G × E evidence were no less likely to sentence the defendant to death than those who received evidence of childhood maltreatment or a control group that received neither genetic nor maltreatment evidence. Participants with evidence of a G × E interaction were more likely to sentence the defendant to death when there was a high risk of future dangerousness than when there was a low risk. Sentencing preferences were more lenient after deliberation than before. We discuss limitations and future directions.

Genome-Wide Association Study of Dimensional Psychopathology Using Electronic Health Records

Abstract: Genetic studies of neuropsychiatric disease strongly suggest an overlap in liability. There are growing efforts to characterize these diseases dimensionally rather than categorically, but the extent to which such dimensional models correspond to biology is unknown.

We applied a newly developed natural language processing method to extract five symptom dimensions based on the National Institute of Mental Health Research Domain Criteria definitions from narrative hospital discharge notes in a large biobank. We conducted a genome-wide association study to examine whether common variants were associated with each of these dimensions as quantitative traits.

Among 4687 individuals, loci in three of five domains exceeded a genome-wide threshold for statistical significance. These included a locus spanning the neocortical development genes RFPL3 and RFPL3S for arousal (p = 2.29 × 10-8) and one spanning the FPR3 gene for cognition (p = 3.22 × 10-8).

Natural language processing identifies dimensional phenotypes that may facilitate the discovery of common genetic variation that is relevant to psychopathology. Read the full article.

Behavioral Genetics in Criminal and Civil Courts

Abstract: Although emerging findings in psychiatric and behavioral genetics create hope for improved prevention, diagnosis, and treatment of disorders, the introduction of such data as evidence in criminal and civil proceedings raises a host of ethical, legal, and social issues. Should behavioral and psychiatric genetic data be admissible in judicial proceedings? If so, what are the various means for obtaining such evidence, and for what purposes should its admission be sought and permitted? How could, and should, such evidence affect judicial outcomes in criminal and civil proceedings? And what are the potential implications of using behavioral and psychiatric genetic evidence for individuals and communities, and for societal values of equality and justice? This article provides an overview of the historical and current developments in behavioral genetics. We then explore the extent to which behavioral genetic evidence has—and should—affect determinations of criminal responsibility and sentencing, as well as the possible ramifications of introducing such evidence in civil courts, with a focus on tort litigation and child custody disputes. We also consider two ways in which behavioral genetic evidence may come to court in the future—through genetic theft or the subpoena of a litigant’s biospecimen data that was previously obtained for clinical or research purposes—and the concerns that these possibilities raise. Finally, we highlight the need for caution and for approaches to prevent the misuse of behavioral genetic evidence in courts. Read the full article.

“Genetic Influences on Measures of the Environment: A Systematic Review” by Kenneth S. Kendler and Jessica H. Baker, Psychological Medicine (2007)

Abstract: Traditional models of psychiatric epidemiology often assume that the relationship between individuals and their environment is unidirectional, from environment to person. Accumulating evidence from developmental and genetic studies has made this perspective increasingly untenable. Literature search using Medline, PsycINFO, article references and contact with experts to identify all papers examining the heritability of measures of environments of relevance to psychiatry/psychology.

We identified 55 independent studies organized into seven categories: general and specific stressful life events (SLEs), parenting as reported by child, parenting reported by parent, family environment, social support, peer interactions, and marital quality. Thirty-five environmental measures in these categories were examined by at least two studies and produced weighted heritability estimates ranging from 7% to 39%, with most falling between 15% and 35%. The weighted heritability for all environmental measures in all studies was 27%. The weighted heritability for environmental measures by rating method was: self-report 29%, informant report 26%, and direct rater or videotape observation (typically examining 10 min of behavior) 14%.

Genetic influences on measures of the environment are pervasive in extent and modest to moderate in impact. These findings largely reflect ‘actual behavior’ rather than ‘only perceptions’. Etiologic models for psychiatric illness need to account for the non-trivial influences of genetic factors on environmental experiences. Request access to the full article.