C. Henquet

Age at Onset of Psychotic Disorder: Cannabis, BDNF Val66Met, and Sex-Specific Models of Gene—Environment Interaction

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 χ2(1) = 0.65, P = 0.420). However, a significant BDNF × cannabis × sex interaction was found (interaction χ2(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.

Do cannabis and urbanicity co-participate in causing psychosis? Evidence from a 10-year follow-up cohort study

BACKGROUND Cannabis use is considered a component cause of psychotic illness, interacting with genetic and other environmental risk factors. Little is known, however, about these putative interactions. The present study investigated whether an urban environment plays a role in moderating the effects of adolescent cannabis use on psychosis risk. METHOD Prospective data (n=1923, aged 14-24 years at baseline) from the longitudinal population-based German Early Developmental Stages of Psychopathology cohort study were analysed. Urbanicity was assessed at baseline and defined as living in the city of Munich (1562 persons per km2; 4061 individuals per square mile) or in the rural surroundings (213 persons per km2; 553 individuals per square mile). Cannabis use and psychotic symptoms were assessed three times over a 10-year follow-up period using the Munich version of the Composite International Diagnostic Interview. RESULTS Analyses revealed a significant interaction between cannabis and urbanicity [10.9% adjusted difference in risk, 95% confidence interval (CI) 3.2-18.6, p=0.005]. The effect of cannabis use on follow-up incident psychotic symptoms was much stronger in individuals who grew up in an urban environment (adjusted risk difference 6.8%, 95% CI 1.0-12.5, p=0.021) compared with individuals from rural surroundings (adjusted risk difference -4.1%, 95% CI -9.8 to 1.6, p=0.159). The statistical interaction was compatible with substantial underlying biological synergism. CONCLUSIONS Exposure to environmental influences associated with urban upbringing may increase vulnerability to the psychotomimetic effects of cannabis use later in life.

Epidermolysis bullosa simplex with mottled pigmentation: Clinical aspects and confirmation of the P24L mutation in the KRT5 gene in further patients

Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a rare dermatologic disorder of autosomal dominant inheritance with intraepidermal blistering after minor trauma, reticular hyperpigmentation unrelated to the blistering, nail dystrophy, and mild palmoplantar keratosis. Keratin 5 and keratin 14 are known to be essential for the basal keratinocyte cytoskeleton and are defective in several forms of epidermolysis bullosa simplex. Recently, a 71C-->T transition in the keratin 5 gene (KRT5) causing a P24L substitution was identified in some patients with EBS-MP. We present a family with three affected members and a sporadic patient with EBS-MP. They exemplify clinically mild expression with intrafamilial variability and the possibility of improvement with time. In all of them, mutation analysis of the KRT5 gene showed the P24L mutation. So far, other mutations in the same or in other genes have not been reported in patients with EBS-MP.

Is psychotic disorder associated with increased levels of craving for cannabis? An Experience Sampling study

Although cannabis use among individuals with psychotic disorder is considerable, little is known about patterns of use and factors contributing to continuation of use. Therefore, we investigated craving in relation to cannabis use in patients with psychotic disorder and healthy controls.

DO CANNABIS AND URBANICITY INTERACT IN CAUSING PSYCHOSIS

This journal suppl. entitled: Abstracts for the 12th International Congress on Schizophrenia Research (ICOSR)

S06-01 Exploring the causal relationship between cannabis and schizophrenia: what is the role of genes and environment?

Frequent use of cannabis has been associated with poor outcome in patients with psychosis or schizophrenia, and research has become more and more interested in the question whether cannabis may actually cause psychosis or schizophrenia. Since only a minority of cannabis users eventually develops psychosis or schizophrenia, cannabis is suggested to be a component cause, potentially interacting with environmental as well as genetic factors. However, little is known about this putative interaction. Recent research in our group has therefore focused on differential sensitivity to cannabis and its psychosis-inducing effects. Experimental and observational work for instance showed that a functional polymorphism within the COMT gene moderates the acute effects of cannabis on psychosis outcome. In this presentation new evidence from epidemiological work is presented, showing gene-environment interactions within the cannabis-psychosis association. These results point to a moderating role for both age of onset of cannabis use and childhood trauma. Also a certain haplotype within the COMT gene was found to increase the risk of developing schizophrenia after adolescent cannabis use. Complex gene-environment interactions as well as interactions between cannabis and other environmental risk factors seem to underlie the cannabis-psychosis relationship. Possible biological mechanisms such as sensitization processes that may underlie these interactions will be discussed.