scholarly journals CNR2 GENE AND CANNABIS USE INTERPLAY MODULATES MANIPULATIVE ABILITIES IN FIRST-EPISODE OF PSYCHOSIS

2021 ◽  
Author(s):  
Maitane Oscoz Irurozqui ◽  
Maria Guardiola-Ripoll ◽  
Carmen Almodóvar-Payá ◽  
Amalia Guerrero-Pedraza ◽  
Edith Pomarol-Clotet ◽  
...  

1. Objectives: While endocannabinoid system seems to be involved in processes underlying psychosis, research about Cannabinoid Receptor 2 gene (CNR2) is scarce and inconclusive. Some few reports indicate that CNR2 plays a role in psychiatric conditions, including depression or drug addiction (Onaivi et al., 2009). We aimed to evaluate the role of CNR2 and its interplay with cannabis on cognition and clinical symptoms in patients with a first-episode of psychosis (FEP). 2. Materials and Methods: the sample comprised 50 Caucasian individuals with a FEP (mean age(sd)=26.14(6.55) years, 76% males, 58% cannabis users). There were no differences in age, sex, premorbid IQ and antipsychotic dose between cannabis users (CU) and non-users (CNU). Neuropsychological (premorbid IQ - TAP-E, current IQ - WAIS, memory - WMS, executive function - BADS) and clinical (psychotic symptoms - PANSS, general functioning - GAF) scales were administered. Genetic variability was assessed by genotyping one Single Nucleotide Polymorphism (SNP) in CNR2 gene (rs2501431) (qPCR, TaqMan). 3. Results and conclusions: genotypic frequencies did not differ between cannabis users and non-users. CNR2 was not associated with PANSS scores.; however, it showed a differential effect on the performance IQ (measured by the matrix reasoning test - WAIS), conditional to the cannabis use (beta=0.73, p=0.02),. In particular, cannabis non-users with the AA genotype (23.53%) showed higher scores (mean(sd)=10.25 (1.87)) than those with at least one copy of the G allele (76.47%, mean(sd)=6.05(0.99); while cannabis users showed scores in the opposite direction (AA (42.31%): 8.21(1.09) and GG/GA (57.69%): 10.28(0.92)). Our results align with previous studies reporting the association of the CNR2 gene with psychiatric diseases (Ishiguro et al. 2007; Onaivi et al., 2008) adding evidence on the interplay of this gene with cannabis use on cognitive outcomes in first-episode psychosis. However, evidence is still scant, and further investigation in larger samples is needed.

2020 ◽  
Author(s):  
Maitane Oscoz Irurozqui ◽  
◽  
Maria Guardiola-Ripoll ◽  
Carmen Almodóvar-Payà ◽  
Salavador Sarró ◽  
...  

Objectives. To evaluate the association of cannabis use, genes of the endocannabinoid system and their interaction on clinical symptoms and cognitive performance in patients with a first-episode of pyschosis. Background. The role of both cannabis use and individual genetic background has been shown in the risk for psychosis. However, the influence of cannabis and variability at endocannabinoid genes on the psychosis outcome still remains inconclusive. Materials and Methods. The sample comprised 43 Caucasian individuals with a first-episode of psychosis (mean age(sd)=25.80(6.39) years, 76.7% males, 51.2% cannabis users).There were no differences in age and sex between cannabis users and non-users. Genetic variability was assessed by genotyping one Single Nucleotide Polymorphism (SNP) in each gene (CNR1-rs1049353 and CNR2-rs2501431). Clinical (PANSS, GAF) and neuropsychological (WAIS, WMS, BADS) scales were administered. Results and conclusions. Genotypic frequencies did not differ between cannabis users and non-users. Cannabis use was associated with better manipulative abilities (IQ-M-WAIS, p=0.029) and better executive function (BADS, p=0.036). CNR1-T allele carriers presented higher disorganized and negative syndrome scores (p=0.001 and p=0.044, respectively). The interaction models evidenced a combined effect of CNR1 and cannabis use on the negative syndrome-PANSS (p=0.037). These results suggest the role of cannabis use and genetic background on cognitive and psychopathological outcomes in first-episode psychosis. However, evidence is still scant, and further investigation in larger samples is needed.


2013 ◽  
Vol 44 (1) ◽  
pp. 117-126 ◽  
Author(s):  
L. Clausen ◽  
C. R. Hjorthøj ◽  
A. Thorup ◽  
P. Jeppesen ◽  
L. Petersen ◽  
...  

BackgroundSeveral studies indicate that cannabis use among patients with psychotic disorders is associated with worse outcome, but only a few studies have controlled for baseline condition and medication.MethodAt 5-year follow-up, interviews were carried out with 314 first-episode psychosis patients included in the OPUS trial. The patients included were in the age range of 18 to 45 years old and 59% were male. Cannabis use was extracted from the Schedule for Clinical Assessment in Neuropsychiatry. At follow-up, the patients were divided into different groups according to the variable cannabis use: abstainers, stoppers, starters and continuers. Psychotic, negative and disorganized dimensions (ranging from zero to five) were calculated for each of the four groups based on the Schedule for the Assessment of Positive and Negative Symptoms in Schizophrenia.ResultsCannabis users were younger (24.6 years v. 27.4 years, p < 0.001) and had a lower level of education. At the 5-year follow-up, users of cannabis had higher scores on the psychotic dimension [difference 0.97, 95% confidence interval (CI) 0.41–1.53, p = 0.001] and lower levels of the Global Assessment of Functioning (difference 8.26, 95% CI 2.13–14.39, p = 0.01). Those who stopped using cannabis between entry and 5-year follow-up had a significantly lower level of psychotic symptoms at 5-year follow-up even after controlling for baseline level of psychotic symptoms and for insufficient antipsychotic medication (adjusted difference in psychotic dimension –1.04, 95% CI –1.77 to –0.31, p = 0.006).ConclusionsContinuous cannabis use was associated with higher levels of psychotic symptoms after 5 years, and this association was only partly explained by insufficient antipsychotic medication.


2013 ◽  
Vol 44 (3) ◽  
pp. 499-506 ◽  
Author(s):  
J. M. Stone ◽  
H. L. Fisher ◽  
B. Major ◽  
B. Chisholm ◽  
J. Woolley ◽  
...  

BackgroundCannabis use has been reported to be associated with an earlier onset of symptoms in patients with first-episode psychosis, and a worse outcome in those who continue to take cannabis. In general, studies have concentrated on symptoms of psychosis rather than mania. In this study, using a longitudinal design in a large naturalistic cohort of patients with first-episode psychosis, we investigated the relationship between cannabis use, age of presentation to services, daily functioning, and positive, negative and manic symptoms.MethodClinical data on 502 patients with first-episode psychosis were collected using the MiData audit database from seven London-based Early Intervention in psychosis teams. Individuals were assessed at two time points – at entry to the service and after 1 year. On each occasion, the Positive and Negative Syndrome Scale, Young Mania Rating Scale and Global Assessment of Functioning Scale disability subscale were rated. At both time points, the use of cannabis and other drugs of abuse in the 6 months preceding each assessment was recorded.ResultsLevel of cannabis use was associated with a younger age at presentation, and manic symptoms and conceptual disorganization, but not with delusions, hallucinations, negative symptoms or daily functioning. Cannabis users who reduced or stopped their use following contact with services had the greatest improvement in symptoms at 1 year compared with continued users and non-users. Continued users remained more symptomatic than non-users at follow-up.ConclusionsEffective interventions for reducing cannabis use may yield significant health benefits for patients with first-episode psychosis.


2013 ◽  
Vol 202 (5) ◽  
pp. 381-382 ◽  
Author(s):  
Celia J. A. Morgan ◽  
Emma Page ◽  
Carola Schaefer ◽  
Katharine Chatten ◽  
Amod Manocha ◽  
...  

SummaryAnandamide is a ligand of the endocannabinoid system. Animals show a depletion following repeated Δ9-tetrahydrocannabinol (THC) administration but the effect of cannabis use on central nervous system levels of endocannabinoids has not been previously examined in humans. Cerebrospinal fluid (CSF) levels of the endocannabinoids anandamide, 2-arachidonoylglycerol (2-AG) and related lipids were tested in 33 volunteers (20 cannabis users). Lower levels of CSF anandamide and higher levels of 2-AG in serum were observed in frequent compared with infrequent cannabis users. Levels of CSF anandamide were negatively correlated with persisting psychotic symptoms when drug-free. Higher levels of anandamide are associated with a lower risk of psychotic symptoms following cannabis use.


2019 ◽  
Author(s):  
Diego Quattrone ◽  
Ulrich Reininghaus ◽  
Alex L. Richards ◽  
Giada Tripoli ◽  
Laura Ferraro ◽  
...  

AbstractBackgroundDiagnostic 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.MethodsAs 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.ResultsSZ-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 FEP, and with all the psychotic experience dimensions in 979 controls. The putative effect of SZ-PRS on either symptom or experience dimensions was of a small magnitude. Cannabis use was additionally associated with the positive dimensions both in FEP (B=0.31; 95%CI 0.11 to 0.52) and in controls (B=0.26; 95%CI 0.06 to 0.46), independently from SZ-PRS.ConclusionsWe report two validators to the latent dimensional structure of psychosis. SZ risk variants and cannabis use independently map onto specific dimensions, contributing to variation across the psychosis continuum. Findings support the hypothesis that psychotic experiences have similar biological substrates as clinical disorders.


2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Teresa Sánchez-Gutiérrez ◽  
Belén Fernandez-Castilla ◽  
Sara Barbeito ◽  
Ana González-Pinto ◽  
Juan Antonio Becerra-García ◽  
...  

Abstract Background. The implications of cannabis use in the onset of early psychosis and the severity of psychotic symptoms have resulted in a proliferation of studies on this issue. However, few have examined the effects of cannabis use on the cognitive symptoms of psychosis (i.e., neurocognitive functioning) in patients with first-episode psychosis (FEP). This systematic review and meta-analysis aim to assess the neurocognitive functioning of cannabis users (CU) and nonusers (NU) with FEP. Methods. Of the 110 studies identified through the systematic review of 6 databases, 7 met the inclusion criteria, resulting in 14 independent samples and 78 effect sizes. The total sample included 304 CU with FEP and 369 NU with FEP. The moderator variables were age at first use, duration of use, percentage of males, and age. Results. Effect sizes were not significantly different from zero in any neurocognitive domain when users and NU were compared. Part of the variability in effect sizes was explained by the inclusion of the following moderator variables: (1) frequency of cannabis use (β = 0.013, F = 7.56, p = 0.017); (2) first-generation antipsychotics (β = 0.019, F = 34.46, p ≤ 0.001); and (3) country where the study was carried out (β = 0.266, t = 2.06, p = 0.043). Conclusions. This meta-analysis indicates that cannabis use is not generally associated with neurocognitive functioning in patients with FEP. However, it highlights the deleterious effect of low doses of cannabis in some patients. It also stresses the importance of the type of antipsychotic prescription and cannabis dose as moderator variables in the neurocognitive functioning of CU with FEP.


2021 ◽  
Vol 53 ◽  
pp. S125-S126
Author(s):  
M. Oscoz Irurozqui ◽  
C. Almodóvar-Payá ◽  
M. Guardiola-Ripoll ◽  
A. Guerrero-Pedraza ◽  
A. Aquino ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diego Quattrone ◽  
Ulrich Reininghaus ◽  
Alex L. Richards ◽  
Giada Tripoli ◽  
Laura Ferraro ◽  
...  

AbstractDiagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.


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