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A population-based study of genetic variation and psychotic experiences in adolescents.

ABSTRACT: Psychotic experiences are not uncommon in general population samples, but no studies have examined to what extent confirmed risk variants for schizophrenia are associated with such experiences. A total of 3483 children in a birth cohort study participated in semistructured interviews for psychotic experiences at ages 12 and 18. We examined whether (1) a composite measure of risk for schizophrenia conferred by common alleles (polygenic score) was associated with psychotic experiences, (2) variants with genome-wide evidence for association with schizophrenia were associated with psychotic experiences, and (3) we could identify genetic variants for psychotic experiences using a genome-wide association (GWA) approach. We found no evidence that a schizophrenia polygenic score, or variants showing genome-wide evidence of association with schizophrenia, were associated with adolescent psychotic experiences within the general population. In fact, individuals who had a higher number of risk alleles for genome-wide hits for schizophrenia showed a decreased risk of psychotic experiences. In the GWA study, no variants showed GWA for psychotic experiences, and there was no evidence that the strongest hits (P < 5 × 10(-5)) were enriched for variants associated with schizophrenia in large consortia. Although polygenic scores are weak tools for prediction of schizophrenia, they show strong evidence of association with this disorder. Our findings, however, lend little support to the hypothesis that psychotic experiences in population-based samples of adolescents share a comparable genetic architecture to schizophrenia, or that utilizing a broader and more common phenotype of psychotic experiences will be an efficient approach to increase understanding of the genetic etiology of schizophrenia.

SUBMITTER: Zammit S

PROVIDER: S-EPMC4193688 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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A population-based study of genetic variation and psychotic experiences in adolescents.

Zammit Stanley S Hamshere Marian M Dwyer Sarah S Georgiva Lyudmila L Timpson Nic N Moskvina Valentina V Richards Alexander A Evans David M DM Lewis Glyn G Jones Peter P Owen Michael J MJ O'Donovan Michael C MC

Schizophrenia bulletin 20131030 6

Psychotic experiences are not uncommon in general population samples, but no studies have examined to what extent confirmed risk variants for schizophrenia are associated with such experiences. A total of 3483 children in a birth cohort study participated in semistructured interviews for psychotic experiences at ages 12 and 18. We examined whether (1) a composite measure of risk for schizophrenia conferred by common alleles (polygenic score) was associated with psychotic experiences, (2) variant ...[more]

PMID: 24174267

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Project description:Purpose: Psychotic experiences in childhood (such as hearing voices or being suspicious) represent an important phenotype for early intervention. However, these experiences can be defined in several ways: self-reported psychotic experiences (SRPE) rely exclusively on the child's report, clinically validated psychotic experiences (CRPE) are based on clinical assessment, and attenuated psychotic symptoms (APS) represents a categorization to do with clinical relevance in relation to severity. Very few studies have investigated how these distinctions impact clinical and other domains. The present study aims to compare SRPE, CRPE, and APS among children and adolescents. Methods: This study is part of the Brazilian High-Risk Cohort Study for Psychiatric Disorders, in which 2,241 individuals aged 6-14 years provided self-ratings of 20 psychotic experiences using the Community Assessment of Psychic Experiences (CAPE). A trained psychologist conducted an interview to validate or reject reported experiences and to rate the presence of APS and affective flattening. In parallel, parents provided information about child mental health to an independent interviewer. We tested the association of mutually exclusive categories of non-validated SRPE (nSRPE), clinically validated PE below the threshold for APS (nCRPE), and APS (nSRPE = 33%, nCRPE = 11%, APS = 6%), with parents' information about the child's positive attributes and levels of psychopathology and psychologist assessment of blunted affect. Results: Most associations were qualitatively similar, and there was a dose-response in the strength of associations across categories, such that APS > nCRPE > nSRPE. Experiences in all three categories were associated with female sex. nSRPE were associated with overall levels of psychopathology, but to a lesser degree than nCRPE and APS. APS and nCRPE were associated with less positive attributes, with APS more so than nCRPE. Only APS was associated with affective flattening. Conclusions: In children and adolescents, SRPE, CRPE, and APS all index liability for psychopathology, but as clinician rated relevance increases, associations get stronger and become evident across more domains.

Project description:Psychotic experiences (PEs) are prevalent in the general population, particularly in adolescents. PEs are associated with various negative outcomes such as psychotic, depressive, anxiety and post-traumatic stress disorders and suicidal behavior. Recent studies in the general population have suggested that what makes PEs relevant is not so much the experiences per se, but their association with non-psychotic comorbidity and other transdiagnostic domains. Thus, there is a need for a better understanding of how PEs exist in a larger psychopathological context in adolescents. In the present study we aimed to explore this, using latent profile analysis (LPA) to identify different patterns in which PEs, psychiatric symptoms and psychological processes co-occur. LPA was conducted using data from an adolescent general population subsample (n = 335) with PEs. We conducted LPA, using measures of PEs, psychiatric symptoms and behaviors (depression, anxiety post-traumatic stress disorder and suicidal behavior) and cognitive and affective processes of entrapment/defeat and emotional regulation as manifest variables. We found that the best fit was obtained with a four-class solution that distinguished primarily between different levels of overall severity: “low symptomatology” (19.1%), “mild-moderate symptomatology” (39.4%), “moderate symptomatology” (33.7%); “high symptomatology” (7.8%). Levels of depression, post-traumatic stress symptoms and defeat/entrapment were most differentiated between classes. The high symptomatology group showed the highest scores in all psychiatric symptoms suicidal ideation, and emotional/cognitive domains, except in cognitive reappraisal. This group also showed the highest usage of emotional suppression. Our results suggest that the assessment of mental health risk in adolescents should be aware that PEs exist in a broad context of other domains of psychopathology and transdiagnostic cognitive and affective processes.

Project description:ImportanceGenetic risk factors are known to play a role in the etiology of psychotic experiences in the general population. Little is known about whether these risk factors interact with environmental risks for psychotic experiences.ObjectiveTo assess etiological heterogeneity and exposure to environmental risks associated with psychotic experiences in adolescence using the twin design.Design, setting, and participantsThis twin study, conducted from December 1, 2014, to August 31, 2020, included a UK-based sample of twin pairs aged 16 years. This investigation evaluated the extent to which the genetic variance underlying psychotic experiences and the magnitude of the heritability of psychotic experiences was moderated by exposure to 5 environmental risk factors (bullying, dependent life events, cannabis use, tobacco use, and low birth weight). Psychotic experiences were assessed by 5 self-reported measures and 1 parent-reported measure. Participants' exposure to environmental risks was assessed at birth and age 12 to 16 years. Structural equation models were used to assess differences in the variance in and heritability of psychotic experiences across these exposures, while controlling for gene-environment correlation effects. Analyses were repeated in an independent Swedish sample. Data analyses were performed from September 1, 2018, to August 31, 2020.Main outcomes and measuresPrimary outcome measures were exposure to environmental factors, as measured by a composite score, and psychotic experiences.ResultsA total of 4855 twin pairs (1926 female same-sex pairs, 1397 male same-sex pairs, and 1532 opposite-sex pairs) were included from the Twins Early Development Study (TEDS), and 6435 twin pairs (2358 female same-sex pairs, 1861 male same-sex pairs, and 2216 opposite-sex pairs) were included from the Child and Adolescent Twin Study in Sweden (CATSS). Mean age of twins from TEDS was 16.5 years. Mean age of twins from CATSS was 18.6 years. More exposure to environmental risk factors was associated with having more psychotic experiences. The relative contribution of genetic influences to psychotic experiences was lower with increasing environmental exposure for paranoia (44%; 95% CI, 33%-53% to 38%; 95% CI, 14%-58%), cognitive disorganization (47%; 95% CI, 38%-51% to 32%; 95% CI, 11%-45%), grandiosity (41%; 95% CI, 29%-52% to 32%; 95% CI, 9%-48%), and anhedonia (49%; 95% CI, 42%-53% to 37%; 95% CI, 15%-54%). This pattern was replicated for the measure of psychotic experiences in the independent Swedish replication sample. The heritability of hallucinations and parent-rated negative symptoms remained relatively constant.Conclusions and relevanceFindings of this twin study suggest that environmental factors play a greater role in the etiology of psychotic experiences than genetic factors. The relative importance of environmental factors is even higher among individuals exposed to environmental risks for psychotic experiences, highlighting the importance of a diathesis-stress or bioecological framework for understanding adolescent psychotic experiences.

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A population-based study of genetic variation and psychotic experiences in adolescents.

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A population-based study of genetic variation and psychotic experiences in adolescents.

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