Parent-rated Negative Symptoms Research Articles

Heritability of Psychotic Experiences in Adolescents and Interaction With Environmental Risk

Genetic 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. To assess etiological heterogeneity and exposure to environmental risks associated with psychotic experiences in adolescence using the twin design. This 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. Primary outcome measures were exposure to environmental factors, as measured by a composite score, and psychotic experiences. A 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. Findings 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.

A twin study exploring the association between childhood emotional and behaviour problems and specific psychotic experiences in a community sample of adolescents.

BackgroundChildhood emotional and behaviour problems are antecedents for later psychopathology. This study investigated genetic and environmental influences shaping the longitudinal association between childhood emotional and behaviour problems and specific PEs.MethodIn a community‐based twin sample, parents reported on emotional and behaviour problems when twins were ages 7 and 12 years. At age 16 years, specific PEs were measured using self‐reports and parent reports. Structural equation model‐fitting was conducted.ResultsChildhood emotional and behaviour problems were significantly associated with paranoia, cognitive disorganisation and parent‐rated negative symptoms in adolescence (mean r = .15–.38), and to a lesser extent with hallucinations, grandiosity and anhedonia (mean r = .04‐.12). Genetic influences on childhood emotional and behaviour problems explained significant proportions of variance in adolescent paranoia (4%), cognitive disorganisation (8%) and parent‐rated negative symptoms (3%). Unique environmental influences on childhood emotional and behaviour problems explained ≤1% of variance in PEs. Common environmental influences were only relevant for the relationship between childhood emotional and behaviour problems and parent‐rated negative symptoms (explaining 28% of variance) and are partly due to correlated rater effects.ConclusionsChildhood emotional and behaviour problems are significantly, if weakly, associated with adolescent PEs. These associations are driven in part by common genetic influences underlying both emotional and behaviour problems and PEs. However, psychotic experiences in adolescence are largely influenced by genetic and environmental factors that are independent of general childhood emotional and behaviour problems, suggesting they are not merely an extension of childhood emotional and behaviour problems.

Shared Etiology of Psychotic Experiences and Depressive Symptoms in Adolescence: A Longitudinal Twin Study.

Psychotic disorders and major depression, both typically adult-onset conditions, often co-occur. At younger ages psychotic experiences and depressive symptoms are often reported in the community. We used a genetically sensitive longitudinal design to investigate the relationship between psychotic experiences and depressive symptoms in adolescence. A representative community sample of twins from England and Wales was employed. Self-rated depressive symptoms, paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and parent-rated negative symptoms were collected when the twins were age 16 (N = 9618) and again on a representative subsample 9 months later (N = 2873). Direction and aetiology of associations were assessed using genetically informative cross-lagged models. Depressive symptoms were moderately correlated with paranoia, hallucinations, and cognitive disorganization. Lower correlations were observed between depression and anhedonia, and depression and parent-rated negative symptoms. Nonsignificant correlations were observed between depression and grandiosity. Largely the same genetic effects influenced depression and paranoia, depression and hallucinations, and depression and cognitive disorganization. Modest overlap in environmental influences also played a role in the associations. Significant bi-directional longitudinal associations were observed between depression and paranoia. Hallucinations and cognitive disorganization during adolescence were found to impact later depression, even after controlling for earlier levels of depression. Our study shows that psychotic experiences and depression, as traits in the community, have a high genetic overlap in mid-adolescence. Future research should test the prediction stemming from our longitudinal results, namely that reducing or ameliorating positive and cognitive psychotic experiences in adolescence would decrease later depressive symptoms.

A longitudinal twin study of the association between childhood autistic traits and psychotic experiences in adolescence.

BackgroundThis twin study investigated whether autistic traits during childhood were associated with adolescent psychotic experiences.MethodsData were collected from a community sample of approximately 5000 twin pairs, which included 32 individuals with diagnosed autism spectrum conditions (ASC). Parents rated autistic traits in the twins at four points between ages 8–16 years. Positive, negative, and cognitive psychotic experiences were assessed at age 16 years using self- and parent-report scales. Longitudinal twin analyses tested the associations between these measures.ResultsAutistic traits correlated weakly or nonsignificantly with positive psychotic experiences (paranoia, hallucinations, and grandiosity), and modestly with cognitive psychotic experiences (cognitive disorganisation). Higher correlations were observed for parent-rated negative symptoms and self-reported anhedonia, although the proportion of variance in both accounted for by autistic traits was low (10 and 31 %, respectively). The majority of the genetic influences on negative symptoms and anhedonia were independent of autistic traits. Additionally, individuals with ASC displayed significantly more negative symptoms, anhedonia, and cognitive disorganisation than controls.ConclusionsAutistic traits do not appear to be strongly associated with psychotic experiences in adolescence; associations were also largely restricted to negative symptoms. Of note, the degree to which the genetic and environmental causes of autistic traits influenced psychotic experiences was limited. These findings thus support a phenotypic and etiological distinction between autistic traits and psychotic experiences.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0037-9) contains supplementary material, which is available to authorized users.

Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents.

Occurrence of psychotic experiences is common amongst adolescents in the general population. Twin studies suggest that a third to a half of variance in adolescent psychotic experiences is explained by genetic influences. Here we test the extent to which common genetic variants account for some of the twin-based heritability. Psychotic experiences were assessed with the Specific Psychotic Experiences Questionnaire in a community sample of 2152 16-year-olds. Self-reported measures of Paranoia, Hallucinations, Cognitive Disorganization, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms were obtained. Estimates of SNP heritability were derived and compared to the twin heritability estimates from the same sample. Three approaches to genome-wide restricted maximum likelihood (GREML) analyses were compared: (1) standard GREML performed on full genome-wide data; (2) GREML stratified by minor allele frequency (MAF); and (3) GREML performed on pruned data. The standard GREML revealed a significant SNP heritability of 20 % for Anhedonia (SE = 0.12; p < 0.046) and an estimate of 19 % for Cognitive Disorganization, which was close to significant (SE = 0.13; p < 0.059). Grandiosity and Paranoia showed modest SNP heritability estimates (17 %; SE = 0.13 and 14 %; SE = 0.13, respectively, both n.s.), and zero estimates were found for Hallucinations and Negative Symptoms. The estimates for Anhedonia, Cognitive Disorganization and Grandiosity accounted for approximately half the previously reported twin heritability. SNP heritability estimates from the MAF-stratified approach were mostly consistent with the standard estimates and offered additional information about the distribution of heritability across the MAF range of the SNPs. In contrast, the estimates derived from the pruned data were for the most part not consistent with the other two approaches. It is likely that the difference seen in the pruned estimates was driven by the loss of tagged causal variants, an issue fundamental to this approach. The current results suggest that common genetic variants play a role in the etiology of some adolescent psychotic experiences, however further research on larger samples is desired and the use of MAF-stratified approach recommended.

Psychotic experiences are linked to cannabis use in adolescents in the community because of common underlying environmental risk factors

Cannabis users are more likely to have psychotic experiences (PEs). The degree to which these associations are driven by genetic or environmental influences in adolescence is unknown. This study estimated the genetic and environmental contributions to the relationship between cannabis use and PEs. Specific PEs were measured in a community-based twin sample (4830 16-year-old pairs) using self-reports and parent-reports. Adolescents reported on ever using cannabis. Multivariate liability threshold structural equation model-fitting was conducted. Cannabis use was significantly correlated with PEs. Modest heritability (37%), common environmental influences (55%) and unique environment (8%) were found for cannabis use. For PEs, modest heritability (27–54%), unique environmental influences (E=12–50%) and little common environmental influences (11–20%), with the exception of parent-rated Negative Symptoms (42%), were reported. Environmental influences explained all of the covariation between cannabis use and paranoia, cognitive disorganization and parent-rated negative symptoms (bivariate common environment=69–100%, bivariate unique environment=28–31%), whilst the relationship between cannabis use and hallucinations indicated familial influences. Cannabis use explains 2–5% of variance in positive, cognitive, and negative PEs. Cannabis use and psychotic experience co-occur due to environmental factors. Focus on specific environments may reveal why adolescent cannabis use and psychotic experiences tend to ‘travel together’.

A shared genetic propensity underlies experiences of bullying victimization in late childhood and self-rated paranoid thinking in adolescence.

Background: Bullying is a risk factor for developing psychotic experiences (PEs). Whether bullying is associated with particular PEs, and the extent to which genes and environments influence the association, are unknown. This study investigated which specific PEs in adolescence are associated with earlier bullying victimization and the genetic and environmental contributions underlying their association. Method: Participants were 4826 twin pairs from a longitudinal community-based twin study in England and Wales who reported on their bullying victimization at the age of 12 years. Measures of specific PEs (self-rated Paranoia, Hallucinations, Cognitive disorganization, Grandiosity, Anhedonia, and parent-rated Negative Symptoms) were recorded at age of 16 years. Results: Childhood bullying victimization was most strongly associated with Paranoia in adolescence (r = .26; P < .01), with weaker associations with Hallucinations, Cognitive Disorganization, parent-rated Negative Symptoms (r = .12–.20; P < .01), Grandiosity (r = .04; P < .05), and Anhedonia (r = .00, n.s.). Bivariate twin model-fitting demonstrated that bullying victimization and Paranoia were both heritable (35% and 52%, respectively) with unique environmental influences (39% and 48%, respectively), and bullying victimization showed common environmental influences (26%). The association between bullying victimization and Paranoia operated almost entirely via genetic influences (bivariate heritability = 93%), with considerable genetic overlap (genetic correlation = .55). Conclusion: In contrast to the assumed role of bullying victimization as an environmental trigger, these data suggest that bullying victimization in late childhood is particularly linked to self-rated Paranoia in adolescence via a shared genetic propensity. Clinically, individuals with a history of bullying victimization are predicted to be particularly susceptible to paranoid symptoms.

Consistent etiology of severe, frequent psychotic experiences and milder, less frequent manifestations: a twin study of specific psychotic experiences in adolescence.

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. 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. 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. Psychotic experiences assessed as quantitative traits (self-rated paranoia, hallucinations, cognitive disorganization, grandiosity, and anhedonia, as well as parent-rated negative symptoms). 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). 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.

Are Genetic Risk Factors for Psychosis Also Associated with Dimension-Specific Psychotic Experiences in Adolescence?

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 = 2.57×10−4) and rs9960767 (p-value = 6.23×10−4). 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.

Characterization of Psychotic Experiences in Adolescence Using the Specific Psychotic Experiences Questionnaire: Findings From a Study of 5000 16-Year-Old Twins

We aimed to characterize multiple psychotic experiences, each assessed on a spectrum of severity (ie, quantitatively), in a general population sample of adolescents. Over five thousand 16-year-old twins and their parents completed the newly devised Specific Psychotic Experiences Questionnaire (SPEQ); a subsample repeated it approximately 9 months later. SPEQ was investigated in terms of factor structure, intersubscale correlations, frequency of endorsement and reported distress, reliability and validity, associations with traits of anxiety, depression and personality, and sex differences. Principal component analysis revealed a 6-component solution: paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and parent-rated negative symptoms. These components formed the basis of 6 subscales. Correlations between different experiences were low to moderate. All SPEQ subscales, except Grandiosity, correlated significantly with traits of anxiety, depression, and neuroticism. Scales showed good internal consistency, test-retest reliability, and convergent validity. Girls endorsed more paranoia, hallucinations, and cognitive disorganization; boys reported more grandiosity and anhedonia and had more parent-rated negative symptoms. As in adults at high risk for psychosis and with psychotic disorders, psychotic experiences in adolescents are characterized by multiple components. The study of psychotic experiences as distinct dimensional quantitative traits is likely to prove an important strategy for future research, and the SPEQ is a self- and parent-report questionnaire battery that embodies this approach.