Further Evidence That Cannabis Moderates Familial Correlation of Psychosis-Related Experiences

PLoS One. 2015 Sep 18;10(9):e0137625. doi: 10.1371/journal.pone.0137625. eCollection 2015.


Background: Familial correlations underlie heritability estimates of psychosis. If gene-environment interactions are important, familial correlation will vary as a function of environmental exposure.

Methods: Associations between sibling and parental schizotypy (n = 669 pairs, n = 1222 observations), and between sibling schizotypy and patient CAPE psychosis (n = 978 pairs, n = 1723 observations) were examined as a function of sibling cannabis use. This design is based on the prediction that in unaffected siblings who are not exposed, vulnerability for psychosis will remain latent, whereas in case of exposure, latent psychosis vulnerability may become expressed, at the level of schizotypal symptoms, causing the phenotypic correlation between relatives to become "visible" under the influence of cannabis.

Results: Siblings exposed to recent cannabis use resembled their patient-relative more closely in terms of positive schizotypy (urinalysis(+):B = 0.30, P<.001; urinalysis(-):B = 0.10, p<0.001; p-interaction = 0.0135). Similarly, the familial correlation in positive schizotypy between parent and sibling was significantly greater in siblings recently exposed to cannabis (urinalysis(+):B = 0.78, P<.001; urinalysis(-):B = 0.43, p<0.001; p interaction = 0.0017). Results were comparable when using lifetime cannabis frequency of use as exposure instead of recent use. Parental schizotypy did not predict cannabis use in the healthy sibling, nor in the patient. Similarly, parental cannabis use was not associated with level of schizotypy in the sibling, nor with psychotic symptoms in the patient, making gene-environment correlation unlikely.

Conclusion: Familial correlation of psychosis-related experiences varies considerably as a function of exposure to cannabis, confirming the importance of gene-cannabis interaction in shifts of expression of psychosis-related experiences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cannabis* / chemistry
  • Family
  • Female
  • Gene-Environment Interaction
  • Humans
  • Male
  • Marijuana Smoking / epidemiology*
  • Marijuana Smoking / genetics
  • Middle Aged
  • Pedigree
  • Phenotype
  • Psychotic Disorders / epidemiology*
  • Psychotic Disorders / genetics
  • Siblings
  • Young Adult

Grant support

The infrastructure for the GROUP study is funded by the Geestkracht program of the Dutch Health Research Council (ZON-MW, grant number 10-000-1002) and matching funds from participating unversities and mental health care organizations (Site Amsterdam: Academic Psychiatric Centre AMC, Ingeest, Arkin, Dijk en Duin, Rivierduinen, Erasmus MC, GGZ Noord Holland Noord; Site Utrecht: University Medical Centre Utrecht, Altrecht, Symfora, Meerkanten, Riagg Amersfoort, Delta; Site Groningen: University Medical Center Groningen, Lentis, GGZ Friesland,GGZ Drenthe, Dimence, Mediant, GGZ De Grote Rivieren and Parnassia psycho-medical centre; Site Maastricht: Maastricht University Medical Center, GGZ Eindhoven, GGZ Midden-Brabant, GGZ Oost-Brabant, GGZ Noord- Midden Limburg, Mondriaan Zorggroep, Prins Clauscentrum Sittard, RIAGG Roermond, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem). The analyses were supported by unrestricted grants from Jansen-Cilag, Eli Lilly and Company, Astra-Zeneca and Lundbeck. The research leading to these results has received funding from the European Community's Seventh Framework Program under grant agreement No. HEALTH-F2-2009-241909 (Project EU-GEI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.