Cannabis Use and Endocannabinoid Receptor Genes: A Pilot Study on Their Interaction on Brain Activity in First-Episode Psychosis (original) (raw)
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Cannabis and Psychosis: A Systematic Review of Genetic Studies
Current Psychiatry Reviews, 2013
Though the basic pathophysiology of psychosis is largely unknown, there is reliable evidence that genes contribute to its aetiology. Epidemiologic studies suggested that chronic use of cannabis is a risk factor for the development of psychosis. Recent researches have focused on the identification of genetic variants that moderate the effect of cannabis on psychosis occurrence.
Psychiatry Research: Neuroimaging, 2015
Cannabinoid receptor 1 (CNR1) gene polymorphisms have been associated with central and peripheral effects of cannabis and schizophrenia pathophysiology. Here, we have tested whether three CNR1 variants (rs1049353, rs1535255 and rs2023239) are associated with changes in brain volumes, body mass index (BMI) or psychopathological scores in a 3-year longitudinal study of 65 first-episode psychosis patients. The rs1049353 at-risk allele was significantly associated with a greater reduction of caudate volume, and the rs2023239 T/C polymorphism showed a significant decrease in thalamic volume after the 3-year period. For those who were not cannabis users, the rs1535255 and rs2023239 polymorphisms had effects in lateral ventricle (LV), and LV and white matter, respectively. The rs2023239 variant also was associated with significant improvements in positive and negative symptoms of schizophrenia. There was no significant effect of any of the variants on changes in BMI over the 3-year study. Finally, an interaction between all three polymorphisms was found involving evolution of positive symptoms. These findings suggest that the cannabinoid pathway is associated with schizophrenia evolution over time. However, further studies using larger cohorts are needed to confirm these results. If confirmed, the present findings could lead in subsequent investigations for identification of novel drug targets for improved treatment of patients suffering from schizophrenia.
Gene-Environment Interactions Underlying the Effect of Cannabis in First Episode Psychosis
Current Pharmaceutical Design, 2012
Cannabis use may be considered as an additional risk factor in a diathesis-stress model of schizophrenia where the risk of developing the illness would be higher in genetic vulnerable people. In this regard, much of the research on cannabis and psychosis is currently focusing on gene-environment interactions. The present review will focus on the interaction between genes and cannabis exposure in the development of psychotic symptoms and schizophrenia and the biological mechanisms of cannabis. Cannabis use has been shown to act together with other environmental factors such as childhood trauma or urbanicity producing synergistic dopamine sensitization effects. Studies on gene-environment interaction have mainly included genetic variants involved in the regulation of the dopaminergic system. The most promising genetic variants in this field are COMT, CNR1, BDNF, AKT1 and NRG1. Additionally, the interaction with other environmental factors and possible gene-gene interactions are considered in the etiological model.
Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis
Schizophrenia bulletin, 2015
Both cannabis use and the dopamine receptor (DRD2) gene have been associated with schizophrenia, psychosis-like experiences, and cognition. However, there are no published data investigating whether genetically determined variation in DRD2 dopaminergic signaling might play a role in individual susceptibility to cannabis-associated psychosis. We genotyped (1) a case-control study of 272 patients with their first episode of psychosis and 234 controls, and also from (2) a sample of 252 healthy subjects, for functional variation in DRD2, rs1076560. Data on history of cannabis use were collected on all the studied subjects by administering the Cannabis Experience Questionnaire. In the healthy subjects' sample, we also collected data on schizotypy and cognitive performance using the Schizotypal Personality Questionnaire and the N-back working memory task. In the case-control study, we found a significant interaction between the rs1076560 DRD2 genotype and cannabis use in influencing t...
The Cannabis Pathway to Non-Affective Psychosis may Reflect Less Neurobiological Vulnerability
Frontiers in psychiatry, 2014
There is a high prevalence of cannabis use reported in non-affective psychosis. Early prospective longitudinal studies conclude that cannabis use is a risk factor for psychosis, and neurochemical studies on cannabis have suggested potential mechanisms for this effect. Recent advances in the field of neuroscience and genetics may have important implications for our understanding of this relationship. Importantly, we need to better understand the vulnerability × cannabis interaction to shed light on the mediators of cannabis as a risk factor for psychosis. Thus, the present study reviews recent literature on several variables relevant for understanding the relationship between cannabis and psychosis, including age of onset, cognition, brain functioning, family history, genetics, and neurological soft signs (NSS) in non-affective psychosis. Compared with non-using non-affective psychosis, the present review shows that there seem to be fewer stable cognitive deficits in patients with ca...
American Journal of Medical Genetics Part B-neuropsychiatric Genetics, 2008
Functional alterations of components of the endogenous cannabinoid system, in particular of the cannabinoid receptor 1 protein (CB1), are hypothetical contributors to many of the symptoms seen in schizophrenia. Variants within the cannabinoid receptor 1 gene (CNR1) have been shown to be directly associated with the hebephrenic form of schizophrenia in a Japanese population. This finding, however, has yet to be replicated. In the present study we sought to study the same (AAT)n-repeat microsatellite of the CNR1 gene which showed association to hebephrenic schizophrenia in Japan, and to investigate whether this microsatellite showed association to a hebephrenic type of schizophrenia in a family-based association study in a population of the Central Valley of Costa Rica. The Lifetime Dimensions of Psychosis Scale and a best estimate consensus process were utilized to identify subjects with schizophrenia who had an elevated lifetime dimensional score for negative and disorganized symptoms, which we used as a proxy for “hebephrenia.” Using the Family Based Association Test we found association of these hebephrenic subjects and the (AAT)n-repeat marker of the CNR1 (multi-allelic P = 0.0368). Our hypothesis that an association with the (AAT)n-repeat marker of CNR1 would not be found with the more general type of schizophrenia was also confirmed. Schizophrenic subjects with prominent lifetime scores for disorganization and negative symptoms (dimension for hebephrenia) are associated with the CNR1 gene and present a type of symptomatology that resembles chronic cannabinoid-induced psychosis. The current finding points to the possibility of different genetic and pathophysiologic mechanisms underlying different types of schizophrenia. © 2008 Wiley-Liss, Inc.
Background Diagnostic categories within the psychosis spectrum are widely used in clinical practice, however psychosis may occur on a continuum. Therefore, we explored whether the continuous distribution of psychotic symptoms across categories is a function of genetic as well as environmental risk factors, such as polygenic risk scores (PRSs) and cannabis use. Methods As part of the EU-GEI study, we genotyped first episode psychosis patients (FEP) and population controls, for whom transdiagnostic dimensions of psychotic symptoms or experiences were generated using item response bi-factor modelling. Linear regression was used, separately in patients and controls, to test the associations between these dimensions and schizophrenia (SZ) PRSs, as well as the combined effect of SZ-PRS and cannabis use on the positive symptom/experience dimensions. Results SZ-PRS was associated with negative (B=0.18; 95%CI 0.03 to 0.34) and positive (B=0.19; 95%CI 0.03 to 0.36) symptom dimensions in 617 F...
functioning in different domains [median reaction time (p = 0.03), episodic memory (p = 0.04), visuoconstructive praxs (p = 0.03) than their non-heavy user counterparts]. Confounding effects of alcohol and tobacco were taken into account. Age and gender were not statistically different between the two groups (p = 0.70 and p = 0.16, respectively). Our study supports the clinical, neuropsychological and neurological specificity associated with the heavy use of cannabis before the onset of schizophrenia. Patients with heavy cannabis use before the onset of schizophrenia may exhibit later neurodevelopmental impairment than those who do not report such use. Schizophrenia associated with heavy cannabis use could represent a specific phenotype.