@article {287, title = {Interaction of schizophrenia polygenic risk and cortisol level on pre-adolescent brain structure}, journal = {Psychoneuroendocrinology}, volume = {101}, year = {2019}, pages = {295 - 303}, abstract = {

The etiology of schizophrenia is multi-factorial with early neurodevelopmental antecedents, likely to result from a complex interaction of genetic and environmental risk. However, few studies have examined how schizophrenia polygenic risk scores (PRS) are moderated by environmental factors in shaping neurodevelopmental brain structure, prior to the onset of psychotic symptoms. Here, we examined whether hair cortisol, a quantitative metric of chronic stress, moderated the association between genetic risk for schizophrenia and pre-adolescent brain structure. This study was embedded within the Generation R Study, involving pre-adolescents of European ancestry assessed regarding schizophrenia PRS, hair cortisol, and brain imaging (n\ =\ 498 structural; n\ =\ 526 diffusion tensor imaging). Linear regression was performed to determine the association between schizophrenia PRS, hair cortisol level, and brain imaging outcomes. Although no single measure exceeded the multiple testing threshold, nominally significant interactions were observed for total ventricle volume (Pinteraction = 0.02) and global white matter microstructure (Pinteraction = 0.01) \– two of the most well replicated brain structural findings in schizophrenia. These findings provide suggestive evidence for the joint effects of schizophrenia liability and cortisol levels on brain correlates in the pediatric general population. Given the widely replicated finding of ventricular enlargement and lower white matter integrity among schizophrenia patients, our findings generate novel hypotheses for future research on gene-environment interactions affecting the neurodevelopmental pathophysiology of schizophrenia.

}, keywords = {Diffusion tensor imaging, Gene-environment, Genetic, Neuroimaging, Psychosis, Stress}, issn = {0306-4530}, doi = {https://doi.org/10.1016/j.psyneuen.2018.12.231}, url = {http://www.sciencedirect.com/science/article/pii/S0306453018308862}, author = {Koen Bolhuis and Henning Tiemeier and Philip R. Jansen and Ryan L. Muetzel and Alexander Neumann and Manon H.J. Hillegers and Erica T.L. van den Akker and Elisabeth F.C. van Rossum and Vincent W.V. Jaddoe and Meike W. Vernooij and Tonya White and Steven A. Kushner} } @article {230, title = {Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3{\textendash}16~years from multiple raters in six cohorts in the EU-ACTION project}, journal = {European Child {\&} Adolescent Psychiatry}, year = {2018}, month = {May}, abstract = {

Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety\–depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child\&$\#$39;s age (ages 3 through 16\ years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5{\%} boys), 20,958 5- to 6-year-olds (49.6{\%} boys), 18,291 7- to 8-year-olds (49.0{\%} boys), 27,218 9- to 10-year-olds (49.4{\%} boys), 18,543 12- to 13-year-olds (48.9{\%} boys) and 10,088 15- to 16-year-olds (46.6{\%} boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety\–depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.

Related interactive tool here.

}, issn = {1435-165X}, doi = {10.1007/s00787-018-1169-1}, url = {https://doi.org/10.1007/s00787-018-1169-1}, author = {Meike Bartels and Anne Hendriks and Matteo Mauri and Eva Krapohl and Alyce Whipp and Koen Bolhuis and Conde, Lucia Colodro and Luningham, Justin and Fung Ip, Hill and Fiona Hagenbeek and Roetman, Peter and Gatej, Raluca and Lamers, Audri and Michel G. Nivard and Jenny van Dongen and Lu, Yi and Christel Middeldorp and van Beijsterveldt, Toos and Vermeiren, Robert and Thomas Hankemeier and Kluft, Cees and Medland, Sarah and Lundstr{\"o}m, Sebastian and Richard J. Rose and Pulkkinen, Lea and Vuoksimaa, Eero and Korhonen, Tellervo and Martin, Nicholas G. and Gitta Lubke and Catrin Finkenauer and Vassilios Fanos and Henning Tiemeier and Lichtenstein, Paul and Robert Plomin and Kaprio, Jaakko and Dorret I. Boomsma} } @article {277, title = {During day and night: Childhood psychotic experiences and objective and subjective sleep problems}, journal = {Schizophrenia Research}, year = {2018}, abstract = {

Background
Psychotic experiences comprise auditory and visual perceptive phenomena, such as hearing or seeing things that are not there, in the absence of a psychotic disorder. Psychotic experiences commonly occur in the general pediatric population. Although the majority of psychotic experiences are transient, they are predictive of future psychotic and non-psychotic disorders. They have been associated with sleep problems, but studies with objective sleep measures are lacking. This study assessed whether psychotic experiences were associated with actigraphic sleep measures, symptoms of dyssomnia, nightmares, or other parasomnias.


Methods
This cross-sectional population-based study comprises 4149 children from the Generation R Study. At age 10 years, psychotic experiences including hallucinatory phenomena were assessed by self-report; dyssomnia and parasomnia symptoms were assessed by mother- and child-report. Additionally, at age 11 years, objective sleep parameters were measured using a tri-axial wrist accelerometer in N = 814 children, who wore the accelerometer for five consecutive school days.

Results
Psychotic experiences were not associated with objective sleep duration, sleep efficiency, arousal, or social jetlag. However, psychotic experiences were associated with self-reported dyssomnia (B = 2.45, 95\%CI: 2.13\–2.77, p \< 0.001) and mother-reported parasomnia, specifically nightmares (ORadjusted = 3.59, 95\%CI 2.66\–4.83, p \< 0.001). Similar results were found when analyses were restricted to hallucinatory phenomena.

Conclusions
Childhood psychotic experiences were not associated with objective sleep measures. In contrast, psychotic experiences were associated with nightmares, which are a known risk indicator of psychopathology in pre-adolescence. More research is needed to shed light on the potential etiologic or diagnostic role of nightmares in the development of psychotic phenomena.

}, keywords = {Actigraphy, General population, Hallucinatory phenomena, Parasomnia, Psychosis, Social jetlag}, issn = {0920-9964}, doi = {https://doi.org/10.1016/j.schres.2018.12.002}, url = {http://www.sciencedirect.com/science/article/pii/S0920996418306911}, author = {M. Elisabeth Koopman-Verhoeff and Koen Bolhuis and Charlotte A.M. Cecil and Desana Kocevska and J.J. Hudziak and Manon H.J. Hillegers and Viara R. Mileva-Seitz and Irwin K. Reiss and Liesbeth Duijts and Frank Verhulst and Maartje P.C.M. Luijk and Henning Tiemeier} } @article {263, title = {Maternal and paternal cannabis use during pregnancy and the risk of psychotic-like experiences in the offspring}, journal = {Schizophrenia Research}, volume = {202}, year = {2018}, pages = {322 - 327}, abstract = {

Cannabis use continues to increase among pregnant women. Gestational cannabis exposure has been associated with various adverse outcomes. However, it remains unclear whether cannabis use during pregnancy increases the risk for offspring psychotic-like experiences. In this prospective cohort, we examined the relationship between parental cannabis use during pregnancy and offspring psychotic-like experiences. Comparisons were made between maternal and paternal cannabis use during pregnancy to investigate causal influences of intra-uterine cannabis exposure during foetal neurodevelopmental. This study was embedded in the Generation R birth cohort and included N = 3692 participants. Maternal cannabis exposure was determined using self-reports and cannabis metabolite levels from urine. Paternal cannabis use during pregnancy was obtained by maternal report. Maternal cannabis use increased the risk of psychotic-like experiences in the offspring (ORadjusted = 1.38, 95\% CI 1.03\–1.85). Estimates were comparable for maternal cannabis use exclusively before pregnancy versus continued cannabis use during pregnancy. Paternal cannabis use was similarly associated with offspring psychotic-like experiences (ORadjusted = 1.44, 95\% CI 1.14\–1.82). We demonstrated that both maternal and paternal cannabis use were associated with more offspring psychotic-like experiences at age ten years. This may suggest that common aetiologies, rather than solely causal intra-uterine mechanisms, underlie the association between parental cannabis use and offspring psychotic-like experiences. These common backgrounds most likely reflect genetic vulnerabilities and shared familial mechanisms, shedding a potential new light on the debated causal path from cannabis use to psychotic-like phenomena. Our findings indicate that diagnostic screening and preventative measures need to be adapted for young people at risk for severe mental illness.

}, keywords = {Child psychiatry, Epidemiology, Gestational exposure, Marijuana, Psychosis, Substance use}, issn = {0920-9964}, doi = {https://doi.org/10.1016/j.schres.2018.06.067}, url = {http://www.sciencedirect.com/science/article/pii/S0920996418304110}, author = {Koen Bolhuis and Steven A. Kushner and Selda Yalniz and Manon H.J. Hillegers and Vincent W.V. Jaddoe and Henning Tiemeier and Hanan El Marroun} } @article {273, title = {Preconception and prenatal cannabis use and the risk of behavioural and emotional problems in the offspring; a multi-informant prospective longitudinal study}, journal = {International Journal of Epidemiology}, year = {2018}, pages = {dyy186}, abstract = {

Background:

Studies of the long-term consequences of maternal cannabis use on child development beyond the neonatal period are sparse. In the current study, we use a multi-information approach to assess the association of prenatal cannabis exposure and child behavioural and emotional functioning. To explore the possible causal nature of the association, we investigated whether maternal tobacco and paternal cannabis use during pregnancy were also associated with child problems.

Methods:

The study population included children of a population-based birth cohort in The Netherlands (n = 5903). Information on parental cannabis use was collected using questionnaires; urine of mothers was analysed for the presence of cannabis metabolites. Child behavioural and emotional problems at approximately 7-10\ years were measured using validated teacher-, child- and mother-reports.

Results:

Our findings show associations of maternal cannabis use during pregnancy with offspring externalising problems (B = 0.53; 95\% CI: 0.29-0.77), but not with internalising problems (B = -0.10; 95\% CI: -0.31-0.11). However, maternal cannabis use before pregnancy was also associated with offspring externalising problems (B = 0.27; 95\% CI: 0.02-0.52). Further, cannabis use by the father was associated with child externalising problems (B = 0.36; 95\% CI: 0.22-0.49) but not internalising problems.

Conclusions:

Prenatal exposure to maternal cannabis use is specifically associated with offspring behavioural problems, but not emotional problems. This association is probably not due to an effect of intrauterine cannabis exposure on fetal development, because both maternal and paternal cannabis exposure during pregnancy were related to offspring externalising problems. Our findings suggest that the association can be explained through residual confounding, most likely through shared genetic vulnerabilities for parental cannabis use and offspring behavioural problems.

}, doi = {10.1093/ije/dyy186}, url = {http://dx.doi.org/10.1093/ije/dyy186}, author = {Hanan El Marroun and Koen Bolhuis and Franken, Ingmar H A and Vincent W.V. Jaddoe and Manon H.J. Hillegers and Benjamin B Lahey and Henning Tiemeier} } @article {282, title = {Psychotic-like experiences in pre-adolescence: what precedes the antecedent symptoms of severe mental illness?}, journal = {Acta Psychiatrica Scandinavica}, volume = {138}, year = {2018}, pages = {15-25}, abstract = {

OBJECTIVE:

Adolescent psychotic-like experiences predict the onset of psychosis, but also predict subsequent non-psychotic disorders. Therefore, it is crucial to better understand the aetiology of psychotic-like experiences. This study examined whether (a) child emotional and behavioural problems at 3 and 6 years, or (b) childhood adversities were associated with psychotic-like experiences at age 10 years.

METHOD:

This prospective study was embedded in the Generation R Study; 3984 children (mean age 10 years) completed a psychotic-like experiences questionnaire. Mothers reported problems of their child at ages 3, 6 and 10 years. Additionally, mothers were interviewed about their child\&$\#$39;s adversities.

RESULTS:

Psychotic-like experiences were endorsed by ~20\% of children and predicted by both emotional and behavioural problems at 3 years (e.g. emotional-reactive problems: ORadjusted = 1.10, 95\% CI: 1.06-1.15, aggressive behaviour: ORadjusted = 1.03, 95\% CI: 1.02-1.05) and 6 years (e.g. anxious/depressed problems: ORadjusted = 1.11, 95\% CI: 1.06-1.15, aggressive behaviour: ORadjusted = 1.04, 95\% CI: 1.04-1.05). Childhood adversities were associated with psychotic-like experiences (\>2 adversities: ORadjusted = 2.24, 95\% CI: 1.72-2.92), which remained significant after adjustment for comorbid psychiatric problems.

CONCLUSION:

This study demonstrated associations between early adversities, childhood emotional and behavioural problems and pre-adolescent psychotic-like experiences, which will improve the understanding of children at increased risk of severe mental illness.

}, keywords = {childhood adversities, development, prospective, Psychosis, psychotic symptoms}, doi = {10.1111/acps.12891}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/acps.12891}, author = {Koen Bolhuis and Koopman-Verhoeff, M. E. and Blanken, L. M. E. and Cibrev, D. and Vincent W.V. Jaddoe and Frank Verhulst and Manon H.J. Hillegers and Steven A. Kushner and Henning Tiemeier} } @article {286, title = {Structural Brain Connectivity in Childhood Disruptive Behavior Problems: A Multidimensional Approach}, journal = {Biological PsychiatryBiological Psychiatry}, year = {2018}, month = {08/2018}, abstract = {

BACKGROUND:

Studies of white matter connectivity in children with disruptive behavior have yielded inconsistent results, possibly owing to the trait\&$\#$39;s heterogeneity, which comprises diverse symptoms like physical aggression, irritability, and delinquency. This study examined associations of global and specific white matter connectivity with childhood disruptive behavior problems, while accounting for their complex multidimensionality.

METHODS:

In a large cross-sectional population-based study of 10-year-old preadolescents (n\ = 2567), we assessed four previously described empirically derived dimensions of disruptive behavior problems using the Child Behavior Checklist: physical aggression, irritability, disobedient behavior, and delinquent behavior. Global and specific white matter microstructure was assessed by diffusion tensor imaging.

RESULTS:

Global fractional anisotropy and mean diffusivity were not associated with broad measures of disruptive behavior, e.g., Child Behavior Checklist externalizing problems scale. Global fractional anisotropy was negatively associated with delinquent behavior (β\ =\ -.123, pfalse discovery rate adjusted\ = .028) and global mean diffusivity was positively associated with delinquent behavior (β\ = .205, pfalse discovery rate adjusted \< 0.001), suggesting reduced white matter microstructure in preadolescents with higher levels of delinquent behavior. Lower white matter microstructure in the inferior longitudinal fasciculus, superior longitudinal fasciculus, cingulum, and uncinate underlie these associations. Global white matter microstructure was not associated with physical aggression, irritability, or disobedient behavior.

CONCLUSIONS:

Delinquent behavior, a severe manifestation of childhood disruptive behavior, was associated with lower white matter microstructure in tracts connecting frontal and temporal lobes. These brain regions are involved in decision making, reward processing, and emotion regulation. This study demonstrated that incorporating the multidimensional nature of childhood disruptive behavior traits shows promise in advancing the search for elucidating neurobiological correlates of disruptive behavior.

}, isbn = {0006-3223}, url = {https://doi.org/10.1016/j.biopsych.2018.07.005}, author = {Koen Bolhuis and Ryan L. Muetzel and Stringaris, Argyris and J.J. Hudziak and Vincent W.V. Jaddoe and Manon H.J. Hillegers and Tonya White and Steven A. Kushner and Henning Tiemeier} } @article {192, title = {Disentangling Heterogeneity of Childhood Disruptive Behavior Problems Into Dimensions and Subgroups}, journal = {American Academy of Child and Adolescent Psychiatry. Journal}, volume = {56}, year = {2017}, pages = {678{\textendash}686}, abstract = {

OBJECTIVE:

Irritable and oppositional behaviors are increasingly considered as distinct dimensions of oppositional defiant disorder. However, few studies have explored this multidimensionality across the broader spectrum of disruptive behavior problems (DBPs). This study examined the presence of dimensions and distinct subgroups of childhood DBPs, and the cross-sectional and longitudinal associations between these dimensions.

METHOD:

Using factor mixture models (FMMs), the presence of dimensions and subgroups of DBPs was assessed in the Generation R Study at ages 6 (n\ = 6,209) and 10 (n\ =\ 4,724) years. Replications were performed in two population-based cohorts (Netherlands Twin Registry, n\ = 4,402, and Swedish Twin Study of Child and Adolescent Development, n\ = 1,089) and a clinical sample (n\ = 1,933). We used cross-lagged modeling in the Generation R Study to assess cross-sectional and longitudinal associations between dimensions. DBPs were assessed using mother-reported responses to the Child Behavior Checklist.

RESULTS:

Empirically obtained dimensions of DBPs were oppositional behavior (age 6 years), disobedient behavior, rule-breaking behavior (age 10 years), physical aggression, and irritability (both ages). FMMs suggested that one-class solutions had the best model fit for all dimensions in all three population-based cohorts. Similar results were obtained in the clinical sample. All three dimensions, including irritability, predicted subsequent physical aggression (range, 0.08-0.16).

CONCLUSION:

This study showed that childhood DBPs should be regarded as a multidimensional phenotype rather than comprising distinct subgroups. Incorporating multidimensionality will improve diagnostic accuracy and refine treatment. Future studies need to address the biological validity of the DBP dimensions observed in this study; herein lies an important opportunity for neuroimaging and genetic measures.

}, doi = {10.1016/j.jaac.2017.05.019}, author = {Koen Bolhuis and Gitta Lubke and van der Ende, Jan and Meike Bartels and van Beijsterveldt, Toos and Paul Lichtenstein and Henrik Larsson and Vincent W.V. Jaddoe and Steven A. Kushner and Frank Verhulst and Dorret I. Boomsma and Henning Tiemeier} }