The effect of childhood maltreatment and cannabis use on adult psychotic symptoms is modified by the COMT Val¹58Met polymorphism.

BACKGROUND: Cannabis use and childhood maltreatment are independent risk factors for the development of psychotic symptoms. These factors have been found to interact in some but not all studies. One of the reasons may be that childhood maltreatment and cannabis primarily induce psychotic symptoms in genetically susceptible individuals. In this context, an extensively studied psychosis vulnerability gene is catechol-methyl-transferase (COMT). Therefore, we aimed to examine whether the COMT Val(158)Met polymorphism (rs4680) moderates the interaction between childhood maltreatment and cannabis use on psychotic symptoms in the general population. METHOD: The discovery sample consisted of 918 individuals from a cross-sectional study. For replication we used an independent sample of 339 individuals from the general population. RESULTS: A significant three-way interaction was found between childhood maltreatment, cannabis use, and the COMT genotype (rs4680) in the discovery sample (P=0.006). Val-homozygous individuals displayed increased psychotic experiences after exposure to both cannabis use and childhood maltreatment compared to Met-heterozygous and Met-homozygous individuals. Supportive evidence was found in the replication sample with similar effect and direction even though the results did not reach statistical significance (P=0.25). CONCLUSIONS: These findings suggest that a functional polymorphism in the COMT gene may moderate the interaction between childhood maltreatment and cannabis use on psychotic experiences in the general population. In conclusion, the COMT Val(158)Met polymorphism may constitute a genetic risk factor for psychotic symptoms in the context of combined exposure to childhood maltreatment and cannabis use.

Advanced paternal age and vulnerability to psychotic-like experiences in the offspring.

OBJECTIVE: To investigate whether advanced paternal age is associated with increased psychotic-like experiences (PLEs) and increased sensitivity to Cannabis in the offspring. METHODS: A cross-sectional population-based study in 1684 participants aged 18 to 25. RESULTS: We found no association of paternal age with PLEs. Only the positive dimension subscale was associated to paternal age, but that could be largely contributed to outliers. Also no increased sensitivity to Cannabis smoking was apparent. CONCLUSION: In the general population, we did not find robust support for an association between paternal age and vulnerability to PLEs in 18-25year old offspring.

Cannabis with high cannabidiol content is associated with fewer psychotic experiences.

OBJECTIVE: Cannabis is associated with psychotic outcomes in numerous studies, an effect that is commonly attributed to Δ (9)-tetrahydrocannabinol (Δ 9-THC). An increasing number of authors identify cannabidiol, another component of the cannabis plant, as an antipsychotic agent. The objective of the current study is to investigate the role of cannabidiol content in the association between cannabis use and psychiatric symptoms in a large non-clinical population of cannabis users. METHODS: In a web-based cross-sectional study we obtained detailed information about cannabis use and subclinical psychiatric experiences using the Community Assessment of Psychic Experiences (CAPE). Different types of cannabis (i.e. marijuana, hashish etc.) have distinctive proportions of Δ 9-THC and cannabidiol. Since average concentrations of Δ 9-THC and cannabidiol in the most popular types of cannabis sold on the Dutch market are annually measured, we were able to estimate exposure to Δ 9-THC and cannabidiol. RESULTS: We included 1877 subjects (mean age 23, SD 6.0) who used the same type of cannabis in the majority of the occasions (in >60% of occasions). We found a significant inverse relationship (F(1,1877): 14.577, p<0.001) between cannabidiol content and self-reported positive symptoms, but not with negative symptoms or depression. The estimated effect size of cannabidiol content was small. CONCLUSION: Although the observed effects are subtle, using high cannabidiol content cannabis was associated with significantly lower degrees of psychotic symptoms providing further support for the antipsychotic potential of cannabidiol.

Role of viruses in Kenyan children presenting with acute encephalopathy in a malaria-endemic area.

In malaria-endemic areas, it is difficult to differentiate between cerebral malaria (CM), bacterial meningitis, and viral encephalitis. We examined the cerebrospinal fluid of 49 children who fulfilled the World Health Organization's (WHO) definition of CM and in 47 encephalopathic children, without malaria, looking for viruses with polymerase chain reaction. In the children with CM, four (9%) had evidence of Herpes simplex virus 1 in the cerebrospinal fluid, whereas in the encephalopathy group without malaria, six (12%) were positive. A significant proportion of children who fulfil the WHO clinical definition of CM may have viral encephalitis.