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

ABSTRACT: 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.

SUBMITTER: Zavos HM

PROVIDER: S-EPMC4988737 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Zavos Helena M S HM Eley Thalia C TC McGuire Philip P Plomin Robert R Cardno Alastair G AG Freeman Daniel D Ronald Angelica A

Schizophrenia bulletin 20160318 5

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 di ...[more]

PMID: 26994398

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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:BackgroundEvidence exists that maternal depression in the perinatal period has an adverse effect on a range of early childhood outcomes and increases the risk of offspring depression during adolescence. However, the association between maternal depression during the perinatal period and offspring psychotic experiences has not been investigated. We aimed to investigate whether there is an association between maternal antenatal or postnatal depression and offspring psychotic experiences at 18 years of age.MethodsThis longitudinal study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort, which recruited 14 541 pregnant women with an estimated delivery date between April 1, 1991, and Dec 31, 1992. Perinatal depression was measured using the Edinburgh Postnatal Depression Scale (EPDS); offspring psychotic experiences at 18 years of age were measured using the Psychosis-Like Symptom Interview. Offspring of mothers with complete data on maternal perinatal depression measures, and complete data on outcome (psychotic experiences) and confounding variables were included in the main analysis. For the main analysis, we used logistic regression to examine the associations between maternal depression (antenatal and postnatal) and offspring psychotic experiences at the age of 18 years. We used biprobit regression to model the association between maternal antenatal depression and the two offspring outcomes (psychotic experiences and depression) at 18 years of age jointly.Findings3067 offspring for whom data were available on maternal perinatal depression and offspring psychotic experiences aged 18 years were included in analyses. Maternal antenatal depressive symptoms were associated with offspring psychotic experiences at 18 years of age, with an unadjusted odds ratio (OR) of 1·38 (95% CI 1·18-1·61, p=0·0001) and after adjustment for confounders, an OR of 1·26 (1·06-1·49, p=0·0074). Maternal antenatal depressive symptoms were associated with both offspring psychotic experiences at the age of 18 years (n=2830, OR for a 5-point increase in EPDS score: 1·32 [95% CI 1·16-1·51], p<0·0001) and offspring depression at 18 years (OR for a 5-point increase in EPDS score: 1·18 [1·03-1·34], p=0·016). From joint modelling, there was no evidence that the association between maternal antenatal depression and offspring psychotic experiences differed in strength compared with offspring depression (p=0·19).InterpretationThe offspring of mothers who experience depression in the perinatal period are more likely to report psychotic experiences at 18 years of age. If the association is found to be causal, it would strengthen the case for identifying and treating maternal depression during and after pregnancy.FundingUK Medical Research Council and the Wellcome Trust.

Project description:BACKGROUND:The direction of the association between inflammation and depressive symptoms remains inconsistent. The objective of this study was to evaluate the temporal relationship between inflammation and depressive symptoms, and to assess the role of genetic factors on this association. METHODS:In this longitudinal cross-lagged twin difference study, we examined 166 (83 pairs) middle-aged male twins recruited from the Vietnam Era Twin Registry, who were assessed at baseline and after 7?years of follow-up. We assayed plasma levels of two inflammatory biomarkers, interleukin-6 (IL-6) and high sensitivity C-reactive protein (CRP) and measured depressive symptoms using the Beck Depression Inventory-II (BDI). To evaluate the direction of the association, we constructed multivariable mixed-effects regression models and calculated standardized beta-coefficients to compare the strength of the within-pair association for both pathways. We then conducted a stratified analysis by zygosity and assessed the associations in monozygotic and dizygotic twin pairs separately. RESULTS:The 166 twins were 95% white and had a mean (SD) age of 54 (3) years at baseline. The cross-lagged analysis showed significant and positive associations from visit 1 IL-6 to visit 2 BDI across all models (beta-coefficients ranging from 0.18 to 0.22). However, the opposite pathway (visit 1 BDI to visit 2 IL-6) was not significant after adjusting for confounding factors. In contrast, visit 1 BDI was significantly associated with visit 2 CRP in all models (beta-coefficients ranging from 0.23 to 0.33), while the opposite pathway (visit 1 CRP to visit 2 BDI) showed no significant association. When stratifying by zygosity, significant associations from IL-6 to depression were only seen in monozygotic twins, but associations from depression to CRP were more robust in dizygotic twins, which implies that genetic factors may play a role in this association. CONCLUSIONS:The association between inflammation and depression may be bidirectional. Elevated IL-6 levels are more likely to be a risk factor of depression rather than a consequence, while the opposite may be true for elevated CRP. The biological underpinnings of these bidirectional pathways need further evaluation.

Dataset Information

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

Publications

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

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