@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 {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 {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} }