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Age at onset of psychotic disorder: cannabis, BDNF Val66Met, and sex-specific models of gene-environment interaction.

Abstract

Discovering modifiable predictors for age at onset may help to identify predictors of transition to psychotic disorder in the "at-risk mental state." Inconsistent effects of sex, BDNF Val66Met (rs6265), and cannabis use on age of onset were previously reported. BDNF Val66Met and cannabis use before illness onset were retrospectively assessed in a sample of 585 patients with schizophrenia and their association with age at onset was evaluated. Cannabis use was significantly associated with earlier age at onset of psychotic disorder (AOP; average difference 2.7 years, P < 0.001), showing dose-response effects with higher frequency and earlier age at first use. There was a weak association between BDNF Val66Met genotype and AOP (difference 1.2 years; P = 0.050). No evidence was found for BDNF × cannabis interaction (interaction χ(2) (1) = 0.65, P = 0.420). However, a significant BDNF × cannabis × sex interaction was found (interaction χ(2) (1) = 4.99, P = 0.026). In female patients, cannabis use was associated with earlier AOP in BDNF Met-carriers (difference 7 years), but not in Val/Val-genotypes. In male patients, cannabis use was associated with earlier AOP irrespective of BDNF Val66Met genotype (difference 1.3 years). BDNF Val66Met genotype in the absence of cannabis use did not influence AOP, neither in female or male patients with psychotic disorder. Complex interactions between cannabis and BDNF may shape age at onset in female individuals at risk of psychotic disorder. No compelling evidence was found that BDNF genotype is associated with age at onset of psychotic disorder in the absence of cannabis use.

Authors+Show Affiliations

University Psychiatric Centre Catholic University Leuven, Kortenberg, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21305693

Citation

Decoster, Jeroen, et al. "Age at Onset of Psychotic Disorder: Cannabis, BDNF Val66Met, and Sex-specific Models of Gene-environment Interaction." American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, vol. 156B, no. 3, 2011, pp. 363-9.
Decoster J, van Os J, Kenis G, et al. Age at onset of psychotic disorder: cannabis, BDNF Val66Met, and sex-specific models of gene-environment interaction. Am J Med Genet B Neuropsychiatr Genet. 2011;156B(3):363-9.
Decoster, J., van Os, J., Kenis, G., Henquet, C., Peuskens, J., De Hert, M., & van Winkel, R. (2011). Age at onset of psychotic disorder: cannabis, BDNF Val66Met, and sex-specific models of gene-environment interaction. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, 156B(3), pp. 363-9. doi:10.1002/ajmg.b.31174.
Decoster J, et al. Age at Onset of Psychotic Disorder: Cannabis, BDNF Val66Met, and Sex-specific Models of Gene-environment Interaction. Am J Med Genet B Neuropsychiatr Genet. 2011;156B(3):363-9. PubMed PMID: 21305693.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age at onset of psychotic disorder: cannabis, BDNF Val66Met, and sex-specific models of gene-environment interaction. AU - Decoster,Jeroen, AU - van Os,Jim, AU - Kenis,Gunter, AU - Henquet,Cecile, AU - Peuskens,Joseph, AU - De Hert,Marc, AU - van Winkel,Ruud, Y1 - 2011/02/08/ PY - 2010/06/09/received PY - 2011/12/30/accepted PY - 2011/2/10/entrez PY - 2011/2/10/pubmed PY - 2011/7/13/medline SP - 363 EP - 9 JF - American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics JO - Am. J. Med. Genet. B Neuropsychiatr. Genet. VL - 156B IS - 3 N2 - Discovering modifiable predictors for age at onset may help to identify predictors of transition to psychotic disorder in the "at-risk mental state." Inconsistent effects of sex, BDNF Val66Met (rs6265), and cannabis use on age of onset were previously reported. BDNF Val66Met and cannabis use before illness onset were retrospectively assessed in a sample of 585 patients with schizophrenia and their association with age at onset was evaluated. Cannabis use was significantly associated with earlier age at onset of psychotic disorder (AOP; average difference 2.7 years, P < 0.001), showing dose-response effects with higher frequency and earlier age at first use. There was a weak association between BDNF Val66Met genotype and AOP (difference 1.2 years; P = 0.050). No evidence was found for BDNF × cannabis interaction (interaction χ(2) (1) = 0.65, P = 0.420). However, a significant BDNF × cannabis × sex interaction was found (interaction χ(2) (1) = 4.99, P = 0.026). In female patients, cannabis use was associated with earlier AOP in BDNF Met-carriers (difference 7 years), but not in Val/Val-genotypes. In male patients, cannabis use was associated with earlier AOP irrespective of BDNF Val66Met genotype (difference 1.3 years). BDNF Val66Met genotype in the absence of cannabis use did not influence AOP, neither in female or male patients with psychotic disorder. Complex interactions between cannabis and BDNF may shape age at onset in female individuals at risk of psychotic disorder. No compelling evidence was found that BDNF genotype is associated with age at onset of psychotic disorder in the absence of cannabis use. SN - 1552-485X UR - https://www.unboundmedicine.com/medline/citation/21305693/Age_at_onset_of_psychotic_disorder:_cannabis_BDNF_Val66Met_and_sex_specific_models_of_gene_environment_interaction_ L2 - https://doi.org/10.1002/ajmg.b.31174 DB - PRIME DP - Unbound Medicine ER -