Confirmation that the AKT1 (rs2494732) Genotype Influences the Risk of Psychosis in Cannabis Users

Forti, Marta Di; Iyegbe, Conrad; Sallis, Hannah M; Kolliakou, Anna; Falcone, M. Aurora; Paparelli, Alessandra; Sirianni, Miriam; Cascia, Caterina La; Stilo, Simona A.; Marques, Tiago Reis; Handley, Rowena; Mondelli, Valeria; Dazzan, Paola; Pariante, Carmine M.; David, Anthony S.; Morgan, Craig; Powell, John; Murray, Robin M.

doi:10.1016/j.biopsych.2012.06.020

Cited by 209 publications

(170 citation statements)

References 34 publications

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“…In particular, as we and others have shown, carriers of the C allele of AKT1 rs2494732, which is involved in dopamine signalling, have an increased risk of psychosis onset after cannabis use (van Winkel et al 2011;Di Forti et al 2012.…”

Section: Introductionmentioning

confidence: 65%

Differences in cannabis-related experiences between patients with a first episode of psychosis and controls

et al. 2015

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Background. Many studies have reported that cannabis use increases the risk of a first episode of psychosis (FEP). However, only a few studies have investigated the nature of cannabis-related experiences in FEP patients, and none has examined whether these experiences are similar in FEP and general populations. The aim of this study was to explore differences in self-reported cannabis experiences between FEP and non-psychotic populations.Method. A total of 252 subjects, who met International Classification of Diseases (ICD)-10 criteria for FEP, and 217 controls who reported cannabis use were selected from the Genetics and Psychosis (GAP) study. The Medical Research Council Social Schedule and the Cannabis Experience Questionnaire were used to collect sociodemographic data and cannabis use information, respectively.Results. Both 'bad' and 'enjoyable' experiences were more commonly reported by FEP subjects than controls. Principal components factor analysis identified four components which explained 62.3% of the variance. Linear regression analysis on the whole sample showed that the type of cannabis used and beliefs about the effect of cannabis on health all contributed to determining the intensity and frequency of experiences. Linear regression analysis on FEP subjects showed that the duration of cannabis use and amount of money spent on cannabis were strongly related to the intensity and frequency of enjoyable experiences in this population.Conclusions. These results suggest a higher sensitivity to cannabis effects among people who have suffered their first psychotic episode; this hypersensitivity results in them reporting both more 'bad' and 'enjoyable' experiences. The greater enjoyment experienced may provide an explanation of why FEP patients are more likely to use cannabis and to continue to use it despite experiencing an exacerbation of their psychotic symptoms.

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Section: Introductionmentioning

confidence: 65%

Differences in cannabis-related experiences between patients with a first episode of psychosis and controls

et al. 2015

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“…Furthermore, convergent findings suggest that CNR1 signaling may be abnormal in patients with this brain disorder, even if the functional specificity of these anomalies is unclear (Dalton et al, 2011). Moreover, CNR1 has been inconsistently associated with diagnoses of schizophrenia (Chavarría-Siles et al, 2008;Seifert et al, 2007), and genetic variability and cannabis use appear to interact in conferring risk for psychosis (Caspi et al, 2005;van Winkel et al, 2011b, Di Forti et al, 2012. Interestingly, CNR1 signaling has been implicated in dopamine signaling (Bloomfield et al, 2014), which is centrally linked with schizophrenia (Weinberger et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…All participants were asked about their use of illicit drugs and those who reported cannabis use were interviewed using the Cannabis Experience Questionnaire (CEQ; Di Forti et al, 2012). This questionnaire allows the detailed assessment of lifetime patterns of cannabis and stimulants use, including age at first use, frequency and duration of use, CNR1 gene, cannabis use and working memory M Colizzi et al and the specific type of cannabis used.…”

Section: Cannabis Usementioning

confidence: 99%

Functional Genetic Variation of the Cannabinoid Receptor 1 and Cannabis Use Interact on Prefrontal Connectivity and Related Working Memory Behavior

Colizzi

Fazio

Ferranti

et al. 2014

Neuropsychopharmacol

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Cannabinoid signaling is involved in different brain functions and it is mediated by the cannabinoid receptor 1 (CNR1), which is encoded by the CNR1 gene. Previous evidence suggests an association between cognition and cannabis use. The logical interaction between genetically determined cannabinoid signaling and cannabis use has not been determined. Therefore, we investigated whether CNR1 variation predicts CNR1 prefrontal mRNA expression in postmortem prefrontal human tissue. Then, we studied whether functional variation in CNR1 and cannabis exposure interact in modulating prefrontal function and related behavior during working memory processing. Thus, 208 healthy subjects (113 males) were genotyped for the relevant functional SNP and were evaluated for cannabis use by the Cannabis Experience Questionnaire. All individuals performed the 2-back working memory task during functional magnetic resonance imaging. CNR1 rs1406977 was associated with prefrontal mRNA and individuals carrying a G allele had reduced CNR1 prefrontal mRNA levels compared with AA subjects. Moreover, functional connectivity MRI demonstrated that G carriers who were also cannabis users had greater functional connectivity in the left ventrolateral prefrontal cortex and reduced working memory behavioral accuracy during the 2-back task compared with the other groups. Overall, our results indicate that the deleterious effects of cannabis use are more evident on a specific genetic background related to its receptor expression.

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“…Data were derived from the Genetics and Psychosis (GAP) study Mondelli et al, 2009;Aas et al, 2011;Di Forti et al, 2012;O'Connor et al, 2012), a case-control study of first-episode psychosis, conducted in consenting patients aged 18-65 years admitted to the South London and Maudsley Mental Health NHS Foundation Trust (SLaM). The study was approved by the local research ethics committee.…”

Section: Samplementioning

confidence: 99%

Cannabis users have higher premorbid IQ than other patients with first onset psychosis

Ferraro

Russo

O’Connor

et al. 2013

Schizophrenia Research

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a b s t r a c t a r t i c l e i n f oBackground: A number of studies have reported that patients with psychosis who use cannabis have better cognitive performance than those who do not. This is surprising as cannabis can impair cognition in healthy subjects. An obvious question is whether the better current performance of psychotic patients who have used cannabis is a reflection of their having a higher premorbid IQ than those psychotic patients who haven't used cannabis. Aim: In a sample of patients at their first episode of psychosis, we tested the hypothesis that patients who smoked cannabis would have a higher premorbid IQ than patients who did not. Methodology: 279 participants (119 patients and 160 healthy controls) were assessed in order to obtain current and premorbid IQ measures and detailed information on cannabis use. We examined the association between cannabis use and both premorbid and current IQ in patients and controls. Results: Patients who had ever smoked cannabis had significantly higher current (p b .001) and premorbid IQ (p = .004) compared to patients who had never used cannabis. This difference was not found among controls. Conclusions: These findings suggest that the better cognitive performance of patients with their first episode of psychosis who have used cannabis compared with those who haven't is due to the better premorbid IQ of the former.

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Confirmation that the AKT1 (rs2494732) Genotype Influences the Risk of Psychosis in Cannabis Users

Cited by 209 publications

References 34 publications

Differences in cannabis-related experiences between patients with a first episode of psychosis and controls

Differences in cannabis-related experiences between patients with a first episode of psychosis and controls

Functional Genetic Variation of the Cannabinoid Receptor 1 and Cannabis Use Interact on Prefrontal Connectivity and Related Working Memory Behavior

Cannabis users have higher premorbid IQ than other patients with first onset psychosis

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