Dataset Information

Common versus psychopathology-specific risk factors for psychotic experiences and depression during adolescence.

ABSTRACT:

Background

An argument often used to support the view that psychotic experiences (PEs) in general population samples are a valid phenotype for studying the aetiology of schizophrenia is that risk factors for schizophrenia show similar patterns of association with PEs. However, PEs often co-occur with depression, and no study has explicitly tested whether risk factors for schizophrenia are shared between PEs and depression, or are psychopathology specific, while jointly modelling both outcomes.

Method

We used data from 7030 subjects from a birth cohort study. Depression and PEs at age 18 years were assessed using self-report questionnaires and semi-structured interviews. We compared the extent to which risk factors for schizophrenia across sociodemographic, familial, neurodevelopmental, stress-adversity, emotional-behavioural and substance use domains showed different associations with PEs and depression within bivariate models that allowed for their correlation.

Results

Most of the exposures examined were associated, to a similar degree, with an increased risk of both outcomes. However, whereas female sex and family history of depression showed some discrimination as potential risk factors for depression and PEs, with stronger associations in the former, markers of abnormal neurodevelopment showed stronger associations with PEs.

Conclusions

The argument that PEs are valid markers for studying the aetiology of schizophrenia, made simply on the basis that they share risk factors in common, is not well supported. PEs seem to be a weak index of genetic and environmental risk for schizophrenia; however, studies disentangling aetiological pathways to PEs from those impacting upon co-morbid psychopathology might provide important insights into the aetiology of psychotic disorders.

SUBMITTER: Kounali D

PROVIDER: S-EPMC4108252 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

Common versus psychopathology-specific risk factors for psychotic experiences and depression during adolescence.

Kounali D D Zammit S S Wiles N N Sullivan S S Cannon M M Stochl J J Jones P P Mahedy L L Gage S H SH Heron J J Lewis G G

Psychological medicine 20140901 12

<h4>Background</h4>An argument often used to support the view that psychotic experiences (PEs) in general population samples are a valid phenotype for studying the aetiology of schizophrenia is that risk factors for schizophrenia show similar patterns of association with PEs. However, PEs often co-occur with depression, and no study has explicitly tested whether risk factors for schizophrenia are shared between PEs and depression, or are psychopathology specific, while jointly modelling both out ...[more]

PMID: 25055173

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Project description:Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value?=?2.57×10??) and rs9960767 (p-value?=?6.23×10??). Replication in an independent sample of 16-year-olds (N?=?3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed.

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:AimsFew studies have investigated risk factors for psychotic major depression (PMD). We aimed to investigate the biological and psychosocial risk factors associated with PMD compared with other psychotic disorders.MethodsBased on the aetiology and ethnicity in schizophrenia and other psychoses (ÆSOP) study, we used a case-control study to identify and recruit, at baseline and 10-year follow-up, all first episode cases of psychosis, presenting for the first time to specialist mental health services in defined catchment areas in the UK. Population-based controls were recruited from the same areas. Data were collected on: sociodemographics; social isolation; childhood adversity; life events; minor physical anomalies; and neurological soft signs.ResultsLiving alone (aOR = 2.26, CI = 1.21-4.23), basic level qualification (aOR = 2.89, CI = 1.08-7.74), being unemployed (aOR = 2.12, CI = 1.13-3.96), having contact with friends less than monthly (aOR = 4.24, CI = 1.62-11.14), having no close confidants (aOR = 4.71, CI = 2.08-10.68), having experienced childhood adversity (aOR = 2.57, CI = 1.02-6.44), family history of mental illness (aOR = 10.68, CI = 5.06-22.52), family history of psychosis (aOR = 12.85, CI = 5.24-31.51), and having more neurological soft signs (aOR = 1.15, CI = 1.07-1.24) were all associated with a follow-up diagnosis of PMD and schizophrenia. Few variables associated with PMD were also associated with a diagnosis of bipolar disorder. Minor physical anomalies were associated with a follow-up diagnosis of schizophrenia and bipolar disorder, but not PMD.ConclusionsRisk factors associated with PMD appear to overlap with those for schizophrenia, but less so for bipolar disorder. Future work on the differential aetiology of PMD, from other psychoses is needed to find the 'specifier' between PMD and other psychoses. Future research on aetiology in PMD, and perhaps other psychoses, should account for diagnostic change.

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.

Project description:ImportanceBiomarkers that are predictive of outcomes in individuals at risk of psychosis would facilitate individualized prognosis and stratification strategies.ObjectiveTo investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (PEs) in the general population.Design, setting, and participantsThis diagnostic study comprised 2 case-control studies nested within the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the Avon Longitudinal Study of Parents and Children (ALSPAC). EU-GEI is an international multisite prospective study of participants at CHR referred from local mental health services. ALSPAC is a United Kingdom-based general population birth cohort. Included were EU-GEI participants who met CHR criteria at baseline and ALSPAC participants who did not report PEs at age 12 years. Data were analyzed from September 2018 to April 2020.Main outcomes and measuresIn EU-GEI, transition status was assessed by the Comprehensive Assessment of At-Risk Mental States or contact with clinical services. In ALSPAC, PEs at age 18 years were assessed using the Psychosis-Like Symptoms Interview. Proteomic data were obtained from mass spectrometry of baseline plasma samples in EU-GEI and plasma samples at age 12 years in ALSPAC. Support vector machine learning algorithms were used to develop predictive models.ResultsThe EU-GEI subsample (133 participants at CHR (mean [SD] age, 22.6 [4.5] years; 68 [51.1%] male) comprised 49 (36.8%) who developed psychosis and 84 (63.2%) who did not. A model based on baseline clinical and proteomic data demonstrated excellent performance for prediction of transition outcome (area under the receiver operating characteristic curve [AUC], 0.95; positive predictive value [PPV], 75.0%; and negative predictive value [NPV], 98.6%). Functional analysis of differentially expressed proteins implicated the complement and coagulation cascade. A model based on the 10 most predictive proteins accurately predicted transition status in training (AUC, 0.99; PPV, 76.9%; and NPV, 100%) and test (AUC, 0.92; PPV, 81.8%; and NPV, 96.8%) data. The ALSPAC subsample (121 participants from the general population with plasma samples available at age 12 years (61 [50.4%] male) comprised 55 participants (45.5%) with PEs at age 18 years and 61 (50.4%) without PEs at age 18 years. A model using proteomic data at age 12 years predicted PEs at age 18 years, with an AUC of 0.74 (PPV, 67.8%; and NPV, 75.8%).Conclusions and relevanceIn individuals at risk of psychosis, proteomic biomarkers may contribute to individualized prognosis and stratification strategies. These findings implicate early dysregulation of the complement and coagulation cascade in the development of psychosis outcomes.

Project description:ObjectiveResearch implicates environmental risk factors, including correlates of urbanicity, deprivation, and environmental toxins, in psychotic-like experiences (PLEs). The current study examined associations between several types of environmental risk factors and PLEs in school-age children, whether these associations were specific to PLEs or generalized to other psychopathology, and examined possible neural mechanisms for significant associations.MethodThe current study used cross-sectional data from 10,328 children 9-10 years old from the Adolescent Brain Cognitive Development (ABCD) Study. Hierarchical linear models examined associations between PLEs and geocoded environmental risk factors and whether associations generalized to internalizing/externalizing symptoms. Mediation models examined evidence of structural magnetic resonance imaging abnormalities (eg, intracranial volume) potentially mediating associations between PLEs and environmental risk factors.ResultsSpecific types of environmental risk factors, namely, measures of urbanicity (eg, drug offense exposure, less perception of neighborhood safety), deprivation (eg, overall deprivation, poverty rate), and lead exposure risk, were associated with PLEs. These associations showed evidence of stronger associations with PLEs than internalizing/externalizing symptoms (especially overall deprivation, poverty, drug offense exposure, and lead exposure risk). There was evidence that brain volume mediated between 11% and 25% of associations of poverty, perception of neighborhood safety, and lead exposure risk with PLEs.ConclusionAlthough in the context of cross-sectional analyses, this evidence is consistent with neural measures partially mediating the association between PLEs and environmental exposures. This study also replicated and extended recent findings of associations between PLEs and environmental exposures, finding evidence for specific associations with correlates of urbanicity, deprivation, and lead exposure risk.

Dataset Information

Common versus psychopathology-specific risk factors for psychotic experiences and depression during adolescence.

Background

Method

Results

Conclusions

Publications

Common versus psychopathology-specific risk factors for psychotic experiences and depression during adolescence.

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