The Generative Brain

Schwartz M et al. Genetic Testing in Prion Disease: Psychological Consequences of the Decisions to Know or Not to Know (Front Genet 2019, PMID 31616476, PMC6764331)

A short exploratory study, published as a Brief Research Report in Frontiers in Genetics in September 2019, from the APHP Department of Genetics at Pitie-Salpetriere in Paris together with the French national CJD reference unit and the Paris Brain Institute. It looks back at the 30 people at risk of a genetic prion disease who consulted the department about presymptomatic PRNP testing between 2004 and 2017, and in 2017 asked them about anxiety, depression and how they lived with the decision to test or not. Twenty of the 30 chose testing. Of those reached in 2017, high anxiety was common in untested relatives and in people who had learned they did not carry the family variant, and the authors conclude that living in such a family is a burden whatever the decision or result. They argue that counselling should also reach non-carriers and people who choose not to test, and that more support is needed at the time a relative is first diagnosed. Later counselling reviews, the 2026 Israeli testing framework and a 2026 UK psychological intervention preprint cite it. This entry stays at aggregate level and records nothing about any individual. Information only, not medical or genetic counselling advice.

Key facts

  • Nine authors: Mathias Schwartz (first author), Marie Lise Babonneau, Christilla Boucher, Elodie Schaerer and Alexandra Durr (corresponding author) of the APHP Department of Genetics at Pitie-Salpetriere; Jean-Philippe Brandel and Stephane Haik of the national CJD reference unit and the Paris Brain Institute (ICM); Jean Louis Laplanche of the Lariboisiere Hospital biochemistry department; and psychologist Marcela Gargiulo of Universite Paris Descartes and the Institute of Myology
  • Published in Front Genet volume 10, article 895, doi 10.3389/fgene.2019.00895, received 26 March 2019, accepted 23 August 2019, e-published 20 September 2019, open access under CC BY 4.0
  • Over 2004 to 2017, 30 asymptomatic at-risk people consulted the department about PRNP testing, against about 950 people at risk of Huntington disease seen over the same period; 20 (67 percent) went ahead with testing, giving 8 carriers and 12 non-carriers, and 10 did not test
  • All 30 were contacted by phone in 2017 and 19 took part (3 of 8 carriers, 10 of 12 non-carriers and 6 of 10 untested), mostly by telephone interview, using the Beck Depression Inventory, the Spielberger state and trait anxiety scales and a semistructured interview
  • Significant anxiety (state anxiety score above 35) was found in 5 of 6 untested participants and 7 of 10 non-carriers, against 1 of 3 carriers; depression scores above threshold were seen in 3 of 6 untested and 4 of 9 non-carriers who completed the scale, and anxiety did not track time since the last consultation
  • The testing protocol was modelled on the Huntington disease process: a multidisciplinary team (geneticist, psychologist, genetic counsellor, social worker, nurses), a first consultation with geneticist and psychologist, at least one psychological session, written consent as French law requires, Sanger sequencing of the whole PRNP coding region on two independent blood samples, and results given at a dedicated consultation about one month later, with follow-up offered
  • Reasons given in aggregate for not testing included how to tell children about a bad result, doubt about coping with it and the lack of any treatment; some said they would test if a preventive treatment trial gave a reason to, and some had set testing aside unless reproductive routes failed
  • Several participants sought testing to inform reproductive choices, and preimplantation or prenatal diagnosis was seen by some as an important option; the paper cites the 2014 Uflacker F198S report for PGD being possible in genetic prion disease
  • The national file of prion disease patients was used to check that no tested carrier had been reported as symptomatic, and the discussion quotes penetrance estimates from the Minikel 2016 and 2019 population work, describing P102L, D178N and E200K as near fully penetrant and V210I and V180I as low penetrance
  • The authors list the limits themselves: a very small sample, low response among carriers, a single time point with no baseline or before and after scores, mostly telephone interviews, and results that are exploratory and not generalisable; no ethics committee approval was needed for a survey under French law, written consent was obtained, and no conflicts were declared
  • No funder or grant is listed in the Europe PMC record, which counts 13 citing records on 17 October 2026, among them the 2022 Goldman and Vallabh counselling review, the 2026 Israeli practice framework for testing asymptomatic relatives and the 2026 Lancet Neurology review of genetic causes and modifiers
  • A June 2026 medRxiv preprint from the UK National Prion Clinic group (Brien, Collinge, Mead and others) on a brief group Acceptance and Commitment Therapy programme for people at genetic risk cites it; that preprint is not peer reviewed

Timeline

  1. 2004First consultations in the period covered by the study at the APHP genetics department.
  2. 2017Survey and interviews with people who had consulted from 2004 to 2017.
  3. 2019Manuscript received by Frontiers in Genetics.
  4. 2019Manuscript accepted.
  5. 2019Published online as Front Genet 10:895 under CC BY.
  6. 2022Cited by the Goldman and Vallabh genetic counselling review and the Appleby review of genetic aspects of prion disease.
  7. 2026Cited by the Israeli practice framework for testing asymptomatic relatives and by the UK ACT intervention preprint.
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