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Genetic Predisposition vs Individual-Specific Processes in the Association Between Psychotic-like Experiences and Cannabis Use.

ABSTRACT: Importance:Previous research indicates that cannabis use is associated with psychotic-like experiences (PLEs). However, it is unclear whether this association results from predispositional (ie, shared genetic) factors or individual-specific factors (eg, causal processes, such as cannabis use leading to PLEs). Objectives:To estimate genetic and environmental correlations between cannabis use and PLEs, and to examine PLEs in twin and nontwin sibling pairs discordant for exposure to cannabis use to disentangle predispositional from individual-specific effects. Design, Setting, and Participants:In this cross-sectional analysis, diagnostic interviews and self-reported data were collected from 2 separate population-based samples of twin and nontwin sibling pairs. Data from the Human Connectome Project were collected between August 10, 2012, and September 29, 2015, and data from the Australian Twin Registry Cohort 3 (ATR3) were collected between August 1, 2005, and August 31, 2010. Data were analyzed between August 17, 2017, and July 6, 2018. The study included data from 1188 Human Connectome Project participants and 3486 ATR3 participants, totaling 4674 participants. Main Outcomes and Measures:Three cannabis-involvement variables were examined: frequent use (ie, ?100 times), a DSM-IV lifetime cannabis use disorder diagnosis, and current cannabis use. Genetic and environmental correlations between cannabis involvement and PLEs were estimated. Generalized linear mixed models examined PLE differences in twin and nontwin sibling pairs discordant for cannabis use. Results:Among the 4674 participants, the mean (SD) age was 30.5 (3.2) years, and 2923 (62.5%) were female. Data on race/ethnicity were not included as a covariate owing to lack of variability within the ATR3 sample; among the 1188 participants in the Human Connectome Project, 875 (73.7%) were white. Psychotic-like experiences were associated with frequent cannabis use (??=?0.11; 95% CI, 0.08-0.14), cannabis use disorder (??=?0.13; 95% CI, 0.09-0.16), and current cannabis use (??=?0.07; 95% CI, 0.04-0.10) even after adjustment for covariates. Correlated genetic factors explained between 69.2% and 84.1% of this observed association. Within discordant pairs of twins/siblings (Npairs, 308-324), Psychotic-like experiences were more common in cannabis-exposed individuals compared with their relative who used cannabis to a lesser degree (????.23, P?

SUBMITTER: Karcher NR

PROVIDER: S-EPMC6400636 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Genetic Predisposition vs Individual-Specific Processes in the Association Between Psychotic-like Experiences and Cannabis Use.

Karcher Nicole R NR Barch Deanna M DM Demers Catherine H CH Baranger David A A DAA Heath Andrew C AC Lynskey Michael T MT Agrawal Arpana A

JAMA psychiatry 20190101 1

<h4>Importance</h4>Previous research indicates that cannabis use is associated with psychotic-like experiences (PLEs). However, it is unclear whether this association results from predispositional (ie, shared genetic) factors or individual-specific factors (eg, causal processes, such as cannabis use leading to PLEs).<h4>Objectives</h4>To estimate genetic and environmental correlations between cannabis use and PLEs, and to examine PLEs in twin and nontwin sibling pairs discordant for exposure to ...[more]

PMID: 30347017

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Project description:ImportanceThere is concern about potentially causal effects of tobacco use on psychosis, but epidemiological studies have been less robust in attempts to minimize effects of confounding than studies of cannabis use have been.ObjectivesTo examine the association of patterns of cigarette and cannabis use with preceding and subsequent psychotic experiences, and to compare effects of confounding across these patterns.Design, setting, and participantsThis cohort study used data from the Avon Longitudinal Study of Parents and Children, which initially consisted of 14 062 children. Data were collected periodically from September 6, 1990, with collection ongoing, and analyzed from August 8, 2016, through June 14, 2017. Cigarette and cannabis use data were summarized using longitudinal latent class analysis to identify longitudinal classes of substance use. Associations between classes and psychotic experiences at age 18 years were assessed.ExposuresDepending on the analysis model, exposures were longitudinal classes of substance use or psychotic experiences at age 12 years.Main outcomes and measuresLogistic regression was used to examine the associations between substance use longitudinal classes and subsequent onset of psychotic experiences.ResultsLongitudinal classes were derived using 5300 participants (56.1% female) who had at least 3 measures of cigarette and cannabis use from ages 14 to 19 years. Prior to adjusting for a range of potential confounders, there was strong evdience that early-onset cigarette-only use (4.3%), early-onset cannabis use (3.2%), and late-onset cannabis use (11.9%) (but not later-onset cigarette-only use [14.8%]) latent classes were associated with increased psychotic experiences compared with nonusers (65.9%) (omnibus P < .001). After adjusting for confounders, the association for early-onset cigarette-only use attenuated substantially (unadjusted odds ratio [OR], 3.03; 95% CI, 1.13-8.14; adjusted OR, 1.78; 95% CI, 0.54-5.88), whereas those for early-onset cannabis use (adjusted OR, 3.70; 95% CI, 1.66-8.25) and late-onset cannabis use (adjusted OR, 2.97; 95% CI, 1.63-5.40) remained consistent.Conclusions and relevanceIn this study, our findings indicate that while individuals who use cannabis or cigarettes during adolescence have an increased risk of subsequent psychotic experiences, epidemiological evidence is substantively more robust for cannabis use than it is for tobacco use.

Project description:ImportancePrior neuroimaging studies have suggested that alterations in brain structure may be a consequence of cannabis use. Siblings discordant for cannabis use offer an opportunity to use cross-sectional data to disentangle such causal hypotheses from shared effects of genetics and familial environment on brain structure and cannabis use.ObjectivesTo determine whether cannabis use is associated with differences in brain structure in a large sample of twins/siblings and to examine sibling pairs discordant for cannabis use to separate potential causal and predispositional factors linking lifetime cannabis exposure to volumetric alterations.Design, setting, and participantsCross-sectional diagnostic interview, behavioral, and neuroimaging data were collected from community sampling and established family registries from August 2012 to September 2014. This study included data from 483 participants (22-35 years old) enrolled in the ongoing Human Connectome Project, with 262 participants reporting cannabis exposure (ie, ever used cannabis in their lifetime).Main outcomes and measuresCannabis exposure was measured with the Semi-Structured Assessment for the Genetics of Alcoholism. Whole-brain, hippocampus, amygdala, ventral striatum, and orbitofrontal cortex volumes were related to lifetime cannabis use (ever used, age at onset, and frequency of use) using linear regressions. Genetic (ρg) and environmental (ρe) correlations between cannabis use and brain volumes were estimated. Linear mixed models were used to examine volume differences in sex-matched concordant unexposed (n = 71 pairs), exposed (n = 81 pairs), or exposure discordant (n = 89 pairs) sibling pairs.ResultsAmong 483 study participants, cannabis exposure was related to smaller left amygdala (approximately 2.3%; P = .007) and right ventral striatum (approximately 3.5%; P < .005) volumes. These volumetric differences were within the range of normal variation. The association between left amygdala volume and cannabis use was largely owing to shared genetic factors (ρg = -0.43; P = .004), while the origin of the association with right ventral striatum volumes was unclear. Importantly, brain volumes did not differ between sex-matched siblings discordant for use (fixed effect = -7.43; t = -0.93, P = .35). Both the exposed and unexposed siblings in pairs discordant for cannabis exposure showed reduced amygdala volumes relative to members of concordant unexposed pairs (fixed effect = 12.56; t = 2.97; P = .003).Conclusions and relevanceIn this study, differences in amygdala volume in cannabis users were attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences. Causal influences, in isolation or in conjunction with predispositional factors, may exist for other brain regions (eg, ventral striatum) or at more severe levels of cannabis involvement and deserve further study.

Project description:BackgroundYoung Australians (16-25 years) have the highest rates of past-month cannabis use in the world. Cannabis use increases the risk of alcohol and other drug disorders and depressive disorders, and has a robust dose-response association with psychotic experiences (PEs) and disorders. PEs are subthreshold positive psychotic symptoms, including delusions and hallucinations, which increase the risk of substance use, depressive or anxiety disorders, and psychotic disorders. Access to effective web-based early interventions targeting both cannabis use and PEs could reduce such risk in young people.ObjectiveThe objective of this study is to determine the efficacy and cost-effectiveness of the Keep it Real web-based program compared to an information-only control website among young cannabis users (16-25 years) with PEs.MethodsParticipants are recruited online, and consenting individuals meeting inclusion criteria (aged 16-25 years, who have used cannabis in the past month and experienced PEs in the past 3 months) are automatically randomized to either the Keep it Real web-based program (n=249) or an information-only control website (n=249). Both websites are self-guided (fully automated). The baseline and follow-up assessments at 3, 6, 9, and 12 months are self-completed online. Primary outcome measures are weekly cannabis use, PEs, and the relative cost-effectiveness for quality-adjusted life years. Secondary outcomes include other substance use and related problems, PE-related distress, cannabis intoxication experiences, severity of cannabis dependence, depression/anxiety symptoms, suicidality, and mental well-being and functioning.ResultsRecruitment commenced in February 2019, and the results are expected to be submitted for publication in mid-2021.ConclusionsThis study protocol describes a large randomized controlled trial of a new web-based program for young cannabis users experiencing PEs. If effective, the accessibility and scalability of Keep it Real could help reduce growing public health concerns about the significant social, economic, and health impacts of cannabis use.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12618001107213; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374800.International registered report identifier (irrid)DERR1-10.2196/15803.

Project description:ObjectiveThe authors sought to determine the association of cannabis indicators with self-reported psychotic disorders in the U.S. general population.MethodsParticipants were from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2001-2002; N=43,093) and NESARC-III (2012-2013; N=36,309). Logistic regression was used to estimate standardized prevalences of past-year self-reported psychotic disorders within each survey and to evaluate the association of past-year self-reported psychotic disorders with indicators of nonmedical cannabis use (any use; frequent use [at least three times/week], daily/near-daily use, and DSM-IV cannabis use disorder) compared with those with no past-year nonmedical cannabis use. Whether the strength of associations differed between surveys was indicated by difference-in-difference tests (between-survey contrasts) and ratios of odds ratios between surveys.ResultsSelf-reported psychotic disorders were significantly more prevalent among participants with any nonmedical cannabis use than those without (2001-2002: 1.65% compared with 0.27%; 2012-2013: 1.89% compared with 0.68%). In 2001-2002, self-reported psychotic disorders were unrelated to either frequent use or daily/near-daily use. However, in 2012 - 2013, compared with nonusers, self-reported psychotic disorders were more common among participants with frequent use and those with daily/near-daily nonmedical cannabis use (2012-2013: 2.79% and 2.52%, respectively, compared with 0.68% among nonusers). Self-reported psychotic disorders were significantly more prevalent among participants with cannabis use disorder than nonusers in both surveys (2001-2002: 2.55% compared with 0.27%; 2012 - 2013: 3.38% compared with 0.68%). The strength of these associations did not change over time.ConclusionsData from the U.S. general population, especially more recent data, suggest associations between self-reported psychotic disorder and frequent nonmedical cannabis use and cannabis use disorder. Clinicians and policy makers should consider these relationships when monitoring patients and formulating programs.

Project description:IMPORTANCE:The onset of psychosis is usually preceded by psychotic experiences (PE). Little is known about the etiology of PE and whether the degree of genetic and environmental influences varies across different levels of severity. A recognized challenge is to identify individuals at high risk of developing psychotic disorders prior to disease onset. OBJECTIVES:To investigate the degree of genetic and environmental influences on specific PE, assessed dimensionally, in adolescents in the community and in those who have many, frequent experiences (defined using quantitative cutoffs). We also assessed the degree of overlap in etiological influences between specific PE. DESIGN, SETTING, AND PARTICIPANTS:Structural equation model-fitting, including univariate and bivariate twin models, liability threshold models, DeFries-Fulker extremes analysis, and the Cherny method, was used to analyze a representative community sample of 5059 adolescent twin pairs (mean [SD] age, 16.31 [0.68] years) from England and Wales. MAIN OUTCOMES AND MEASURES:Psychotic experiences assessed as quantitative traits (self-rated paranoia, hallucinations, cognitive disorganization, grandiosity, and anhedonia, as well as parent-rated negative symptoms). RESULTS:Genetic influences were apparent for all PE (15%-59%), with modest shared environment for hallucinations and negative symptoms (17%-24%) and significant nonshared environment (49%-64%) for the self-rated scales and 17% for parent-rated negative symptoms. Three empirical approaches converged to suggest that the etiology in extreme-scoring groups (most extreme scoring: 5%, 10%, and 15%) did not differ significantly from that of the whole distribution. There was no linear change in heritability across the distribution of PE, with the exception of a modest increase in heritability for increasing severity of parent-rated negative symptoms. Of the PE that showed covariation, this appeared to be due to shared genetic influences (bivariate heritabilities, 0.54-0.71). CONCLUSIONS AND RELEVANCE:These findings are consistent with the concept of a psychosis continuum, suggesting that the same genetic and environmental factors influence both extreme, frequent PE and milder, less frequent manifestations in adolescents. Individual PE in adolescence, assessed quantitatively, have lower heritability estimates and higher estimates of nonshared environment than those for the liability to schizophrenia. Heritability varies by type of PE, being highest for paranoia and parent-rated negative symptoms and lowest for hallucinations.

Project description:ImportanceUrbanicity is a well-established risk factor for clinical (eg, schizophrenia) and subclinical (eg, hearing voices and paranoia) expressions of psychosis. To our knowledge, no studies have examined the association of air pollution with adolescent psychotic experiences, despite air pollution being a major environmental problem in cities.ObjectivesTo examine the association between exposure to air pollution and adolescent psychotic experiences and test whether exposure mediates the association between urban residency and adolescent psychotic experiences.Design, setting, and participantsThe Environmental-Risk Longitudinal Twin Study is a population-based cohort study of 2232 children born during the period from January 1, 1994, through December 4, 1995, in England and Wales and followed up from birth through 18 years of age. The cohort represents the geographic and socioeconomic composition of UK households. Of the original cohort, 2066 (92.6%) participated in assessments at 18 years of age, of whom 2063 (99.9%) provided data on psychotic experiences. Generation of the pollution data was completed on October 4, 2017, and data were analyzed from May 4 to November 21, 2018.ExposuresHigh-resolution annualized estimates of exposure to 4 air pollutants-nitrogen dioxide (NO2), nitrogen oxides (NOx), and particulate matter with aerodynamic diameters of less than 2.5 (PM2.5) and less than 10 μm (PM10)-were modeled for 2012 and linked to the home addresses of the sample plus 2 commonly visited locations when the participants were 18 years old.Main outcomes and measuresAt 18 years of age, participants were privately interviewed regarding adolescent psychotic experiences. Urbanicity was estimated using 2011 census data.ResultsAmong the 2063 participants who provided data on psychotic experiences, sex was evenly distributed (52.5% female). Six hundred twenty-three participants (30.2%) had at least 1 psychotic experience from 12 to 18 years of age. Psychotic experiences were significantly more common among adolescents with the highest (top quartile) level of annual exposure to NO2 (odds ratio [OR], 1.71; 95% CI, 1.28-2.28), NOx (OR, 1.72; 95% CI, 1.30-2.29), and PM2.5 (OR, 1.45; 95% CI, 1.11-1.90). Together NO2 and NOx statistically explained 60% of the association between urbanicity and adolescent psychotic experiences. No evidence of confounding by family socioeconomic status, family psychiatric history, maternal psychosis, childhood psychotic symptoms, adolescent smoking and substance dependence, or neighborhood socioeconomic status, crime, and social conditions occurred.Conclusions and relevanceIn this study, air pollution exposure-particularly NO2 and NOx-was associated with increased odds of adolescent psychotic experiences, which partly explained the association between urban residency and adolescent psychotic experiences. Biological (eg, neuroinflammation) and psychosocial (eg, stress) mechanisms are plausible.

Dataset Information

Genetic Predisposition vs Individual-Specific Processes in the Association Between Psychotic-like Experiences and Cannabis Use.

Publications

Genetic Predisposition vs Individual-Specific Processes in the Association Between Psychotic-like Experiences and Cannabis Use.

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