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Ethical Issues in Psychiatric Genetics. Paul S. Appelbaum, M.D. Dollard Professor of Psychiatry, Medicine and Law Director, Division of Psychiatry, Law and Ethics Department of Psychiatry College of Physicians and Surgeons Columbia University. Key Aspects of Psychiatric Genetics - 1.

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ethical issues in psychiatric genetics

Ethical Issues in Psychiatric Genetics

Paul S. Appelbaum, M.D.

Dollard Professor of Psychiatry, Medicine and Law

Director, Division of Psychiatry, Law and Ethics

Department of Psychiatry

College of Physicians and Surgeons

Columbia University

key aspects of psychiatric genetics 1

Key Aspects of Psychiatric Genetics - 1

Most disorders studied have shown some degree of hereditability, indicating a genetic contribution to causation


bipolar disorder has a hereditability of 0.8

i.e., 80% of the variance in transmission is attributable to genetic factors

(Cowan, et al., 2002)

key aspects of psychiatric genetics 2

Key Aspects of Psychiatric Genetics – 2

No psychiatric disorder is entirely determined by genetic factors

Even monozygotic twins show only 50% concordance for schizophrenia, indicating a substantial non-genetic contribution.

key aspects of psychiatric genetics 3
Key Aspects of Psychiatric Genetics – 3
  • Most disorders are likely to be influenced by multiple genes, each contributing only a small portion of the variance
  • Such disorders represent “complex traits,” with multiple molecular paths to a disordered phenotype
gene environment interactions 1
Gene – Environment Interactions - 1
  • Genes linked to disorders may have their effect by heightening sensitivity to environmental occurrences
  • Thus, a genetic loading may be necessary but not sufficient to induce a psychiatric disorder

(Rutter & Silberg, 2002)

gene environment interactions 2
Gene – Environment Interactions - 2
  • Example comes from study of serotonin transporter in Dunedin sample of 847 26-year-olds
  • Two alleles for promoter region: long and short
  • Subjects with at least one short allele were significantly more likely to become depressed, but only in combination with stressful life events
gene environment interactions 3
Gene – Environment Interactions – 3
  • Short allele also predicted suicidal ideation and attempts after stress
  • Only in subjects with short allele was childhood maltreatment predictive of adult depression

(Caspi, et al. 2003)

limits to current knowledge
Limits to Current Knowledge
  • Characteristics of genetics of psychiatric disorders have made identification of disorder-inducing genes difficult
  • Findings regarding loci linked to disorders are usually unreplicated (e.g., bipolar disorder in Amish study)
  • Few genes directly tied to disorders (exceptions include: 5-HTT & ApoE)
implications for ethical issues
Implications for Ethical Issues
  • Most concerns based on anticipated knowledge in the future
  • Nature of psychiatric genetics may mitigate some issues
  • Nonetheless useful to consider where concerns may arise, even if answers aren’t always clear
ethical issues in genetic testing
Ethical Issues in Genetic Testing
  • As tests for genes associated with psychiatric disorders become available, a variety of issues will arise
prenatal testing
Prenatal Testing
  • Should parents be allowed/encouraged to test fetuses to decide on abortion?

- Current practices would appear to permit this, even if risk is very low—fetal or preimplantation

- But systematic removal of alleles will reduce positive effects of carrier state for the population as a whole

- Example may be increased creativity apparently associated with mood disorders

would prenatal testing be used
Would Prenatal Testing Be Used?
  • Survey of 48 family members of people with schizophrenia, 64 clinicians, 162 researchers
  • Asked to assume that only a small percentage of people with the identified gene would develop the disorder
  • 56.2% of family members would opt for prenatal testing, and 56.3% of clinicians and 25.3% of researchers would recommend it

(DeLisi &Bertisch, 2006)

testing of children
Testing of Children
  • Should parents be allowed to test children for predisposition to adult-onset disorders?

- Nuffield Report suggests answer is no, unless intervention is possible

- But would “avoiding stress” be enough of an intervention to warrant testing for 5-HTT alleles?

- And what would negative impact be of “protecting” vulnerable children?

testing of adoptees
Testing of Adoptees
  • Should adopting parents be allowed to test potential adoptees?

- Rates of psychopathology elevated in adoptive children

- Risk of creating group of “genetically tainted” unadoptables must be balanced against adoptive parents’ “right to know”

would testing of adoptees be requested
Would Testing of Adoptees Be Requested?
  • Previously cited survey of clinicians and researchers
  • 100% of clinicians and 52% of researchers believe that adoption agencies should reveal a history of schizophrenia in a parent
  • 50% of clinicians and 18.4% of researchers believe that adoption agencies should reveal a history of schizophrenia in a cousin

(DeLisi and Bertisch, 2006)

testing of adults 1
Testing of Adults - 1
  • Should testing be encouraged, allowed, or restricted?

- Answer may depend on possibility of intervention, but also to desire to avoid reproduction

- Perhaps market will provide the answer

* Only 10% of people whose parents have Huntington’s disease are ever tested (Nuffield Report, 1998)

* Suggests widespread fear of negative impact of knowledge

testing of adults 2
Testing of Adults - 2
  • Should direct marketing of genetic tests to consumers be permitted?

- Positive results may be misinterpreted without genetic counseling

- But such tests are already being aggressively promoted, e.g., for genes related to breast cancer, hypercholesterolemia, Gaucher’s disease, etc.

- How well will patients be able to use this information?

patients ability to assimilate genetic testing information
Patients’ Ability to Assimilate Genetic Testing Information
  • Study of 108 women who were at elevated risk for breast cancer
  • Tested for BRCA at university cancer program and received genetic counseling
  • Subjects entered program with vastly excessive estimates of their risk
  • After counseling, the estimates dropped, but still significantly overestimated risk (av. 19%)

(Gurmankin et al., 2005)

premarital testing
Premarital Testing
  • Are there times when premarital testing would be appropriate?

- Tay-Sachs registry may be model here

  • How would availability of genetic data impact decisions?
    • DeLisi and Bertisch study showed 37.5% of family members said they would forgo marriage and having children if they tested positive for schizophrenia
pharmacogenomics and the problem of collateral information
Pharmacogenomics and the Problem of Collateral Information
  • Genetic testing increasingly used to assess drug metabolism, likelihood of response, and susceptibility to side effects
    • E.g., serotonin transporter and SSRIs
  • But pharmacogenomic testing can also reveal propensity to illness, as with serotonin transporter
  • Not limited to psychiatry, e.g., acetylation and environmentally induced cancers
genetic testing and insurance 1
Genetic Testing and Insurance - 1
  • Should insurers (health, life, disability) be able to use genetic test results?

- Allowing decisions on this basis may create a class of uninsurables

- But advocates argue that accurate estimation of risk is the only fair basis for all underwriting – avoids “moral hazard”

- Compulsory testing by insurers has even been suggested (Raithatha & Smith, 2004)

- But in UK insurers agreed to moratorium until 2011

genetic testing and insurance 2
Genetic Testing andInsurance - 2
  • Insurance discrimination already occurs without genetic testing
  • Survey of genetic disease support group members showed:

- 25% refused life insurance

- 22% refused health insurance

- 13% turned down for a job

  • Could testing help some of these people obtain insurance? (Lapham, et al., 1996)
genetic testing and employment
Genetic Testing and Employment
  • ADA in U.S. would appear to bar pre-employment testing
  • By 2003, 29 states had statutes prohibiting discrimination on basis of genetic information

(Clayton, 2003)

  • Hong Kong: exclusion of children of schizophrenics from uniformed services ruled illegal (Wong & Lieh-Mak, 2001)
genetic testing and duty to warn 1
Genetic Testing and Duty to Warn - 1
  • Should physicians be required to warn if testing of patient indicates family members may be at risk?

- Safer v. Pack (NJ) – duty to warn in familial polyposis

- Pate v. Threlkel (FL) – duty to warn in medullary cancer of the thyroid—OK to warn pt.

  • No case yet based on genetic testing per se, though Minn. case raises issue of failure to test
genetic testing and duty to warn 2
Genetic Testingand Duty to Warn - 2
  • Existence of duty probably will depend on
    • Likelihood that others are at risk
    • Severity of consequences
    • Effective interventions
  • Not clear if disclosure to patient will suffice
  • Will existence of duty deter people from being tested?
ethical issues in genetic research 1
Ethical Issues in Genetic Research - 1
  • Should results of tests be revealed to subjects?

- Unless effect on risk is substantial and intervention possible, consensus is that they should not

  • Should results be revealed to family members?

- Again, generally not

- This applies especially to data on paternity

ethical issues in genetic research 2
Ethical Issues in Genetic Research - 2
  • Are family members research subjects if data are collected about them?

- OPRR response to MCV case suggests answer

is “yes”

  • But benefits are few and impediments to research substantial
  • If they are subjects, informed consent should be waived (Parker, 2002)
genetics and criminal justice 1
Genetics and Criminal Justice - 1
  • Does identification of genetic predisposition to criminal behavior call for alteration of our approaches to adjudication of responsibility?

- Discovery of MAOA variant that predisposes to violence makes this a live issue (Brunner, et al., 1993; Caspi, et al., 2002)

- But it would be odd to reduce punishment for those most likely to reoffend

genetics and criminal justice 2
Genetics and Criminal Justice - 2
  • We are unlikely to see major changes based on “genetic defenses”
  • Persons with criminal predispositions will be expected to work harder to control their impulses
ethical issues in psychiatric genetics summary 1
Ethical Issues in Psychiatric Genetics - Summary - 1
  • Status of psychiatric disorders as complex traits will limit ethical problems

- Predictive power of any single allele will be small

- Environmental influences will play major role in outcome

ethical issues in psychiatric genetics summary 2
Ethical Issues in Psychiatric Genetics - Summary - 2
  • But as multiple genes are identified that contribute larger amounts of variance, ethical dilemmas will increase
  • Although solutions are likely to be highly fact-sensitive, it would pay us to begin thinking through these issues

Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA: Abnormal behavior associated with a point mutation in the structured gene for monoamine oxidase A. Science 262:578-580, 1993.

Caspi A, et al.: Role of genotype in the cycle of violence in maltreated children. Science 297:851-854, 2002.

Clayton EW: Ethical, legal, and social implications of genomic medicine. N Engl J Med 349:562-9, 2003.

Cowan WM, Kopnisky KL, Hyman SE: The Human Genome Project and its impact on psychiatry. Annu Rev Neurosci 25:1-50, 2002.


Deftos LJ: The evolving duty to disclose the presence of genetic disease to relatives. Acad Med 73:962-8, 1998.

DeLisi L, Bertisch H: A preliminary comparison of the hopes of researchers, clinicians, and families for the future ethical use of genetic findings on schizophrenia. Am J Med Gen 141B:110-115, 2006.

Gurmankin AD, Domchek S, Stopfer J, et al.: Patients’ resistance to risk information in genetic counseling for BRCA 1/2. Arch Intern Med 165:523-529, 2005.

Lapham EV, Kezma C, Weiss JO: Genetic discrimination: perspectives of consumers. Science 274:621-624, 1996.


Nuffield Council on Bioethics: Mental Disorders and Genetics. The Ethical Context. September 1998.

Parker LS: Ethical issues in bipolar disorders pedigree research: privacy concerns, informed consent, and grounds for waiver. Bipolar Disord 4:1-16, 2002.

Pate v. Threlkel, 661 So.2d 278 (Fla. 1995)

Plomin R, McGuffin P: Psychopathologyin the postgenomic era. Annu Rev Psychol 54:205-28, 2003.


Raithatha N, Smith RD: Disclosure of genetic tests for health insurance: is it ethical not to? Lancet 363:395-6, 2004.

Rutter M, Silberg J: Gene-environment interplay in relation to emotional and behavioral disturbance. Annu Rev Psychol 53:463-590, 2002.

Safer v. Pack, 677 A.2d 1188 (N.J. App. 1996).


Wong JG, Lieh-Mak F: Genetic discrimination and mental illness: a case report. J Med Ethics 27:393-397, 2001.