Dataset Information

Investigating the genetic architecture of general and specific psychopathology in adolescence.

ABSTRACT: Whilst associations between polygenic risk scores (PRSs) for schizophrenia and various phenotypic outcomes have been reported, an understanding of developmental pathways can only be gained by modelling comorbidity across psychopathology. We examine how genetic risk for schizophrenia relates to adolescent psychosis-related and internalizing psychopathology using a latent modelling approach, and compare this to genetic risk for other psychiatric disorders, to gain a more comprehensive understanding of the developmental pathways at this age. PRSs for schizophrenia, major depressive disorder, neuroticism and bipolar disorder were generated for individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Multivariate linear regression was used to examine the relationships of these PRSs with psychopathology factors modelled within (i) a correlated factors structure and (ii) a bifactor structure. The schizophrenia PRS was associated with an increase in factors describing psychotic experiences, negative dimension, depression and anxiety, but, when modelling a general psychopathology factor based on these measures, specific effects above this persisted only for the negative dimension. Similar factor relationships were observed for the neuroticism PRS, with a (weak) specific effect only for anxiety once modelling general psychopathology. Psychopathology during adolescence can be described by a general psychopathology construct that captures common variance as well as by specific constructs capturing remaining non-shared variance. Schizophrenia risk genetic variants identified through genome-wide association studies mainly index negative rather than positive symptom psychopathology during adolescence. This has potentially important implications both for research and risk prediction in high-risk samples.

SUBMITTER: Jones HJ

PROVIDER: S-EPMC6082910 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundDiverse behaviour problems in childhood correlate phenotypically, suggesting a general dimension of psychopathology that has been called the p factor. The shared genetic architecture between childhood psychopathology traits also supports a genetic p. This study systematically investigates the manifestation of this common dimension across self-, parent- and teacher-rated measures in childhood and adolescence.MethodsThe sample included 7,026 twin pairs from the Twins Early Development Study (TEDS). First, we employed multivariate twin models to estimate common genetic and environmental influences on p based on diverse measures of behaviour problems rated by children, parents and teachers at ages 7, 9, 12 and 16 (depressive traits, emotional problems, peer problems, autism traits, hyperactivity, antisocial behaviour, conduct problems and psychopathic tendencies). Second, to assess the stability of genetic and environmental influences on p across time, we conducted longitudinal twin modelling of the first phenotypic principal components of childhood psychopathological measures across each of the four ages. Third, we created a genetic p factor in 7,026 unrelated genotyped individuals based on eight polygenic scores for psychiatric disorders to estimate how a general polygenic predisposition to mostly adult psychiatric disorders relates to childhood p.ResultsBehaviour problems were consistently correlated phenotypically and genetically across ages and raters. The p factor is substantially heritable (50%-60%) and manifests consistently across diverse ages and raters. However, residual variation in the common factor models indicates unique contributions as well. Genetic correlations of p components across childhood and adolescence suggest stability over time (49%-78%). A polygenic general psychopathology factor derived from studies of psychiatric disorders consistently predicted a general phenotypic p factor across development (0.3%-0.9%).ConclusionsDiverse forms of psychopathology generally load on a common p factor, which is highly heritable. There are substantial genetic influences on the stability of p across childhood. Our analyses indicate genetic overlap between general risk for psychiatric disorders in adulthood and p in childhood, even as young as age 7. The p factor has far-reaching implications for genomic research and, eventually, for diagnosis and treatment of behaviour problems.

Project description:BACKGROUND:Recent research indicates that the best-fitting structural model of psychopathology includes a general factor capturing comorbidity (p) and several more specific, orthogonal factors. Little is known about the stability of these factors, although two opposing developmental processes have been proposed: dynamic mutualism suggests that symptom-level interaction and reinforcement may lead to a strengthening of comorbidity (p) over time, whereas p-differentiation suggests a general vulnerability to psychopathology that gives way to increasingly distinct patterns of symptoms over time. In order to test both processes, we examine two forms of developmental stability from ages 2 to 14 years: strength (i.e., consistency in the amount of variance explained by general and specific factors) and phenotypic stability (i.e., homotypic and heterotypic continuity). METHODS:Data are from the NICHD Study of Early Child Care and Youth Development. Psychopathology symptoms were assessed nine times between ages 2 and 14 years (n = 1,253) using the Child Behavior Checklist completed by mothers. Confirmatory bifactor modeling was used to test structural models of psychopathology at each age. Consistency in strength was examined by calculating the Explained Common Variance (ECV) and phenotypic stability was investigated with cross-lagged modeling of the general and specific factors. RESULTS:Bifactor models fit the data well across this developmental period. ECV values were reasonably consistent across development, with the general factor accounting for the majority of shared variance (61%-71%). Evidence of both homotypic and heterotypic continuity emerged, with most heterotypic continuity involving the general factor, as it both predicted and was predicted by specific factors. CONCLUSIONS:A bifactor model effectively captures psychopathological comorbidity from early childhood through adolescence. The longitudinal associations between the general and specific factors provide evidence for both the hypothesized processes (dynamic mutualism and p-differentiation) occurring through development.

Project description:BackgroundInternalising and externalising problems commonly co-occur in childhood. Yet, few developmental models describing the structure of child psychopathology appropriately account for this comorbidity. We evaluate a model of childhood psychopathology that separates the unique and shared contribution of individual psychological symptoms into specific internalising, externalising and general psychopathology factors and assess how these general and specific factors predict long-term outcomes concerning criminal behaviour, academic achievement and affective symptoms in three independent cohorts.MethodsData were drawn from independent birth cohorts (Avon Longitudinal Study of Parents and Children (ALSPAC), N = 11,612; Generation R, N = 7,946; Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN), N = 408). Child psychopathology was assessed between 4 and 8 years using a range of diagnostic and questionnaire-based measures, and multiple informants. First, structural equation models were used to assess the fit of hypothesised models of shared and unique components of psychopathology in all cohorts. Once the model was chosen, linear/logistic regressions were used to investigate whether these factors were associated with important outcomes such as criminal behaviour, academic achievement and well-being from late adolescence/early adulthood.ResultsThe model that included specific factors for internalising/externalising and a general psychopathology factor capturing variance shared between symptoms regardless of their classification fits well for all of the cohorts. As hypothesised, general psychopathology factor scores were predictive of all outcomes of later functioning, while specific internalising factor scores predicted later internalising outcomes. Specific externalising factor scores, capturing variance not shared by any other psychological symptoms, were not predictive of later outcomes.ConclusionsEarly symptoms of psychopathology carry information that is syndrome-specific as well as indicative of general vulnerability and the informant reporting on the child. The 'general psychopathology factor' might be more relevant for long-term outcomes than specific symptoms. These findings emphasise the importance of considering the co-occurrence of common internalising and externalising problems in childhood when considering long-term impact.

Dataset Information

Investigating the genetic architecture of general and specific psychopathology in adolescence.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets