On Psychotic Phenomena and Unruliness: studies on the childhood risk for severe mental illness

Psychiatric disorders in adulthood, including severe mental illnesses, commonly have antecedents in childhood or adolescence. A better understanding of the developmental pathways of psychiatric problems in early childhood might help to achieve a more comprehensive understanding of severe mental illness in adults. The general aim of this thesis was to gain insights into the neurodevelopmental pathways of children at increased risk for severe mental illness. Here we focussed on two prevalent yet impairing psychiatric phenotypes of childhood: psychotic phenomena and disruptive behaviour problems. Each of these constellations of psychiatric symptoms is in its own right predictive of substantially poorer psychosocial functioning in the long term. All studies described in this thesis were conducted in the context of the Generation R Study, a population-based cohort study in Rotterdam, the Netherlands. The findings and interpretations of the individual studies are discussed in the broader context of the existing literature. More specifically, several methodological considerations are discussed pertaining to the neurodevelopmental model of psychosis, the neurodevelopmental model of disruptive behaviour, analytical methods of behavioural heterogeneity, assessment of psychotic experiences in children and the link between cannabis use and psychopathology. We conclude with several recommendations for improved clinical practice and future research

A Prospective Cohort Study on the Intergenerational Transmission of Childhood Adversity and Subsequent Risk of Psychotic Experiences in Adolescence

BACKGROUND AND HYPOTHESIS: Previous studies have shown a robust relationship between childhood adversity and subsequent psychotic symptoms. However, the role of familial risk factors underlying this relationship remains largely unclear. Here, we tested whether offspring childhood adversity and postnatal maternal psychopathology mediated the relationship between maternal childhood adversity and offspring psychotic experiences. STUDY DESIGN: N = 3068 mother-offspring dyads were included. Maternal history of childhood adversity was retrospectively assessed using the Childhood Trauma Questionnaire during pregnancy. Maternal psychopathology was assessed during and after pregnancy. Twenty-four offspring childhood adversities were assessed by maternal interview when the child was 10 years old. Offspring psychotic experiences were examined using self-report at 14 years. Structural equation mediation models were conducted to explore whether maternal postnatal psychopathology and offspring childhood adversities sequentially mediated the relationship between maternal childhood adversity and offspring psychotic experiences. Analyses were adjusted for sociodemographic confounders. STUDY RESULTS: Maternal history of childhood adversity was associated with offspring childhood adversities (β = 0.12, 95% CI: 0.09 to 0.16). Offspring childhood adversity mediated the association of maternal childhood adversity with offspring hallucinations (βindirect effect = 0.008, 95% CI: 0.002 to 0.014, proportion mediated = 16.3%) and delusions (βindirect effect = 0.006, 95% CI: 0.000 to 0.012, proportion mediated = 13.1%). CONCLUSIONS: Intergenerational transmission of childhood adversity can be considered of relevance in the etiology of psychosis vulnerability and can potentially serve as a modifiable risk factor

Risk of Psychosis Among Individuals Who Have Presented to Hospital With Self-harm:A Prospective Nationwide Register Study in Sweden

BACKGROUND AND HYPOTHESIS: Recent research showed that young people who presented to hospital with self-harm in Finland had a significantly elevated risk of later psychosis. We investigated the prospective relationship between hospital presentation for self-harm and risk of psychosis in an unprecedentedly large national Swedish cohort.STUDY DESIGN: We used inpatient and outpatient healthcare registers to identify all individuals born between 1981 and 1993 who were alive and living in Sweden on their 12th birthday and who presented to hospital one or more times with self-harm. We compared them with a matched cohort, followed up for up to 20 years, and compared the cumulative incidence of psychotic disorders. Furthermore, we examined whether the strength of the relationship between hospital presentation for self-harm and later psychosis changed over time by examining for cohort effects.STUDY RESULTS: In total, 28 908 (2.0%) individuals presented to hospital with self-harm without prior psychosis diagnosis during the follow-up. For individuals who presented to hospital with self-harm, the cumulative incidence of diagnosed psychosis was 20.7% at 20 years follow-up (hazard radio = 13.9, 95% CI 13.3-14.6, P-value &lt;5 × 10-308). There was no evidence of a dilution of the effect over time: while the incidence of hospital self-harm presentation increased, this did not result in an attenuation over time of the strength of the relationship between hospital self-harm presentation and subsequent psychosis.CONCLUSIONS: Individuals who present to hospital with self-harm in their teens and 20s represent an important risk group for psychosis prediction and prevention.</p

Childhood Adversity and Incident Psychotic Experiences in Early Adulthood:Cognitive and Psychopathological Mediators

Background and Hypothesis Childhood adversity is often described as a potential cause of incident psychotic experiences, but the underlying mechanisms are not well understood. We aimed to examine the mediating role of cognitive and psychopathological factors in the relation between childhood adversity and incident psychotic experiences in early adulthood.Study Design We analyzed data from the Avon Longitudinal Study of Parents and Children, a large population-based cohort study. Childhood adversity was measured prospectively from birth to age 11 years, mediators (anxiety, depression, external locus of control [LoC], negative symptoms) were assessed at approximately 16 years of age, and incident psychotic experiences were assessed at ages 18 and 24 years. Mediation was examined via the counterfactual g-computation formula.Study Results In total, 7% of participants had incident suspected or definite psychotic experiences in early adulthood. Childhood adversity was related to more incident psychotic experiences (ORadjusted = 1.34, 95% CI = 1.21; 1.49), and this association was partially mediated via all mediators examined (proportion mediated: 19.9%). In separate analyses for each mediator, anxiety, depression, external LoC, and negative symptoms were all found to mediate the link between adversity and incident psychotic experiences. Accounting for potential confounders did not modify our results.Conclusions Our study shows that cognitive biases as well as mood symptomatology may be on the causal pathway between early-life adversity and the development of psychotic experiences. Future studies should determine which mediating factors are most easily modifiable and most likely to reduce the risk of developing psychotic experiences

Childhood Adversity and Incident Psychotic Experiences in Early Adulthood:Cognitive and Psychopathological Mediators

Background and Hypothesis Childhood adversity is often described as a potential cause of incident psychotic experiences, but the underlying mechanisms are not well understood. We aimed to examine the mediating role of cognitive and psychopathological factors in the relation between childhood adversity and incident psychotic experiences in early adulthood.Study Design We analyzed data from the Avon Longitudinal Study of Parents and Children, a large population-based cohort study. Childhood adversity was measured prospectively from birth to age 11 years, mediators (anxiety, depression, external locus of control [LoC], negative symptoms) were assessed at approximately 16 years of age, and incident psychotic experiences were assessed at ages 18 and 24 years. Mediation was examined via the counterfactual g-computation formula.Study Results In total, 7% of participants had incident suspected or definite psychotic experiences in early adulthood. Childhood adversity was related to more incident psychotic experiences (ORadjusted = 1.34, 95% CI = 1.21; 1.49), and this association was partially mediated via all mediators examined (proportion mediated: 19.9%). In separate analyses for each mediator, anxiety, depression, external LoC, and negative symptoms were all found to mediate the link between adversity and incident psychotic experiences. Accounting for potential confounders did not modify our results.Conclusions Our study shows that cognitive biases as well as mood symptomatology may be on the causal pathway between early-life adversity and the development of psychotic experiences. Future studies should determine which mediating factors are most easily modifiable and most likely to reduce the risk of developing psychotic experiences

Executive functioning and neurodevelopmental disorders in early childhood

Background: Executive functioning deficits are common in children with neurodevelopmental disorders. However, prior research mainly focused on clinical populations employing cross-sectional designs, impeding conclusions on temporal neurodevelopmental pathways. Here, we examined the prospective association of executive functioning with subsequent autism spectrum disorder (ASD) traits and attention-deficit/hyperactivity disorder (ADHD) traits. Methods: This study included young children from the Generation R Study, a general population birth cohort. The Brief Rating Inventory of Executive Function-Preschool Version w

Teacher-rated aggression and co-occurring behaviors and emotional problems among schoolchildren in four population-based European cohorts

Aggressive behavior in school is an ongoing concern. The current focus is on specific manifestations such as bullying, but the behavior is broad and heterogenous. Children spend a substantial amount of time in school, but their behaviors in the school setting tend to be less well characterized than at home. Because aggression may index multiple behavioral problems, we used three validated instruments to assess means, correlations and gender differences of teacher-rated aggressive behavior with co-occurring externalizing/internalizing problems and social behavior in 39,936 schoolchildren aged 7-14 from 4 population-based cohorts from Finland, the Netherlands, and the UK. Correlations of aggressive behavior were high with all other externalizing problems (r: 0.47-0.80) and lower with internalizing problems (r: 0.02-0.39). A negative association was observed with prosocial behavior (r: -0.33 to -0.54). Mean levels of aggressive behavior differed significantly by gender. Despite the higher mean levels of aggressive behavior in boys, the correlations were notably similar for boys and girls (e.g., aggressive-hyperactivity correlations: 0.51-0.75 boys, 0.47-0.70 girls) and did not vary greatly with respect to age, instrument or cohort. Thus, teacher-rated aggressive behavior rarely occurs in isolation; boys and girls with problems of aggressive behavior likely require help with other behavioral and emotional problems. Important to note, higher aggressive behavior is not only associated with higher amounts of other externalizing and internalizing problems but also with lower levels of prosocial behavior.Peer reviewe

Neural Profile of Callous Traits in Children: A Population-Based Neuroimaging Study

Background Callous traits during childhood, e.g., lack of remorse and shallow affect, are a key risk marker for antisocial behavior. Although callous traits have been found to be associated with structural and functional brain alterations, evidence to date has been almost exclusively limited to small, high-risk samples of boys. We characterized gray and white matter brain correlates of callous traits in over 2000 children from the general population. Methods Data on mother-re