Publications by authors named "Henning Tiemeier"

682 Publications

Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.

Nat Genet 2021 Sep 6;53(9):1311-1321. Epub 2021 Sep 6.

Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.
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http://dx.doi.org/10.1038/s41588-021-00923-xDOI Listing
September 2021

The experience of life events and body composition in middle childhood: a population-based study.

Int J Behav Nutr Phys Act 2021 08 25;18(1):109. Epub 2021 Aug 25.

Department of Psychology, Education, and Child Studies, Erasmus University Rotterdam, Burgemeester Oudlaan 50, 3062 PA, Rotterdam, the Netherlands.

While studies suggest potential influences of childhood adversities on obesity development in adulthood, less is known about the short-term association in children. We examined the association between a wide range of life events experienced in the first ten years of life (including maltreatment and milder adversities) and body composition in 5333 ten-year old Dutch children. In structured interviews, mothers retrospectively reported on their children's experience of 24 events. BMI was calculated, and fat mass index and fat free mass index were determined by dual-x-ray absorptiometry scanning. Linear regressions showed that, unadjusted, a higher number of life events was associated with higher BMI and body composition. However, associations attenuated to non-significance after adjustment for covariates. Similar findings were observed for maltreatment and milder life events. Thus, the number of experienced life events was not associated with body composition in middle childhood. Rather, other factors, like socioeconomic conditions, accounted for the relationship between life events and weight development in children.
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http://dx.doi.org/10.1186/s12966-021-01188-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386051PMC
August 2021

Combined polygenic risk scores of different psychiatric traits predict general and specific psychopathology in childhood.

J Child Psychol Psychiatry 2021 Aug 13. Epub 2021 Aug 13.

Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: Polygenic risk scores (PRSs) operationalize genetic propensity toward a particular mental disorder and hold promise as early predictors of psychopathology, but before a PRS can be used clinically, explanatory power must be increased and the specificity for a psychiatric domain established. To enable early detection, it is crucial to study these psychometric properties in childhood. We examined whether PRSs associate more with general or with specific psychopathology in school-aged children. Additionally, we tested whether psychiatric PRSs can be combined into a multi-PRS score for improved performance.

Methods: We computed 16 PRSs based on GWASs of psychiatric phenotypes, but also neuroticism and cognitive ability, in mostly adult populations. Study participants were 9,247 school-aged children from three population-based cohorts of the DREAM-BIG consortium: ALSPAC (UK), The Generation R Study (Netherlands), and MAVAN (Canada). We associated each PRS with general and specific psychopathology factors, derived from a bifactor model based on self-report and parental, teacher, and observer reports. After fitting each PRS in separate models, we also tested a multi-PRS model, in which all PRSs are entered simultaneously as predictors of the general psychopathology factor.

Results: Seven PRSs were associated with the general psychopathology factor after multiple testing adjustment, two with specific externalizing and five with specific internalizing psychopathology. PRSs predicted general psychopathology independently of each other, with the exception of depression and depressive symptom PRSs. Most PRSs associated with a specific psychopathology domain, were also associated with general child psychopathology.

Conclusions: The results suggest that PRSs based on current GWASs of psychiatric phenotypes tend to be associated with general psychopathology, or both general and specific psychiatric domains, but not with one specific psychopathology domain only. Furthermore, PRSs can be combined to improve predictive ability. PRS users should therefore be conscious of nonspecificity and consider using multiple PRSs simultaneously, when predicting psychiatric disorders.
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http://dx.doi.org/10.1111/jcpp.13501DOI Listing
August 2021

Genetic association study of childhood aggression across raters, instruments, and age.

Transl Psychiatry 2021 07 30;11(1):413. Epub 2021 Jul 30.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGG. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (r) among rater-specific assessment of AGG ranged from r = 0.46 between self- and teacher-assessment to r = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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http://dx.doi.org/10.1038/s41398-021-01480-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324785PMC
July 2021

Thalamic Subregions and Obsessive-Compulsive Symptoms in 2,500 Children From the General Population.

J Am Acad Child Adolesc Psychiatry 2021 Jul 1. Epub 2021 Jul 1.

Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands.

Objective: Pediatric obsessive-compulsive disorder (OCD) and clinically relevant obsessive-compulsive symptoms in the general population are associated with increased thalamic volume. It is unknown whether this enlargement is explained by specific thalamic subregions. The relation between obsessive-compulsive symptoms and volume of thalamic subregions was investigated in a population-based sample of children.

Method: Obsessive-compulsive symptoms were measured in children (9-12 years of age) from the Generation R Study using the Short Obsessive-Compulsive Disorder Screener (SOCS). Thalamic nuclei volumes were extracted from structural 3T magnetic resonance imaging scans using the ThalamicNuclei pipeline and regrouped into anterior, ventral, intralaminar/medial, lateral, and pulvinar subregions. Volumes were compared between children with symptoms above clinical cutoff (probable OCD cases, SOCS ≥ 6, n = 156) and matched children without symptoms (n = 156). Linear regression models were fitted to investigate the association between continuous SOCS score and subregional volume in the whole sample (N = 2500).

Results: Children with probable OCD had larger ventral nuclei compared with children without symptoms (d = 0.25, p = .025, false discovery rate adjusted p = .126). SOCS score showed a negative association with pulvinar volume when accounting for overall thalamic volume (β = -0.057, p = .009, false discovery rate adjusted p = .09). However, these associations did not survive multiple testing correction.

Conclusion: The results suggest that individual nuclei groups contribute in varying degrees to overall thalamic volume in children with probable OCD, although this did not survive multiple comparisons correction. Understanding the role of thalamic nuclei and their associated circuits in pediatric OCD could lead toward treatment strategies targeting these circuits.
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http://dx.doi.org/10.1016/j.jaac.2021.05.024DOI Listing
July 2021

Neonatal DNA methylation and childhood low prosocial behavior: An epigenome-wide association meta-analysis.

Am J Med Genet B Neuropsychiatr Genet 2021 06 25;186(4):228-241. Epub 2021 Jun 25.

Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Low prosocial behavior in childhood has been consistently linked to later psychopathology, with evidence supporting the influence of both genetic and environmental factors on its development. Although neonatal DNA methylation (DNAm) has been found to prospectively associate with a range of psychological traits in childhood, its potential role in prosocial development has yet to be investigated. This study investigated prospective associations between cord blood DNAm at birth and low prosocial behavior within and across four longitudinal birth cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. We examined (a) developmental trajectories of "chronic-low" versus "typical" prosocial behavior across childhood in a case-control design (N = 2,095), and (b) continuous "low prosocial" scores at comparable cross-cohort time-points (N = 2,121). Meta-analyses were performed to examine differentially methylated positions and regions. At the cohort-specific level, three CpGs were found to associate with chronic low prosocial behavior; however, none of these associations was replicated in another cohort. Meta-analysis revealed no epigenome-wide significant CpGs or regions. Overall, we found no evidence for associations between DNAm patterns at birth and low prosocial behavior across childhood. Findings highlight the importance of employing multi-cohort approaches to replicate epigenetic associations and reduce the risk of false positive discoveries.
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http://dx.doi.org/10.1002/ajmg.b.32862DOI Listing
June 2021

The occurrence of internalizing problems and chronic pain symptoms in early childhood: what comes first?

Eur Child Adolesc Psychiatry 2021 Jun 17. Epub 2021 Jun 17.

Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.

Chronic pain and internalizing problems are characterized by concurrent associations but the directionality of this relationship in early childhood remains unclear. This prospective study aimed to investigate the bidirectional effect of chronic pain and internalizing problems and test the persistence of pain over time in a population-based sample of preschoolers. The study was embedded in Generation R, a large population-based cohort. Mothers of 3,996 children assessed their child's experienced pain and internalizing problems at 3 and 6 years. At 3 years, paternal reports were available too. Reports of family functioning, discipline practices and parental psychopathology were also collected. The prevalence of chronic pain was 2.7% (106) and 8.0% (294) at baseline and follow-up, respectively. The presence of internalizing problems at child age 3 years predicted chronic pain at 6 years, for both maternal (OR 1.05, 95% CI 1.02,1.07, p < 0.001) and paternal (OR 1.03, 95%CI 1.00, 1.06, p < 0.05) internalizing problem reports, when adjusted for potential confounding factors. In contrast, chronic pain did not increase the likelihood of internalizing problems. The temporal relationship between chronic pain and internalizing problems appears to follow a largely unidirectional trend in early childhood, with internalizing problems increasing the likelihood of concurrent physical symptoms. Current understanding of the directionality of this relationship, highlights the importance for comprehensive assessment of psychiatric problems contributing to the manifestation of chronic pain.
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http://dx.doi.org/10.1007/s00787-021-01821-7DOI Listing
June 2021

Childhood loneliness as a specific risk factor for adult psychiatric disorders.

Psychol Med 2021 Jun 14:1-9. Epub 2021 Jun 14.

Department of Psychiatry, Vermont Center for Children, Youth and Families, University of Vermont, Burlington, USA.

Background: Loneliness is a major risk factor for both psychological disturbance and poor health outcomes in adults. This study aimed to assess whether childhood loneliness is associated with a long-term disruption in mental health that extends into adulthood.

Methods: This study is based on the longitudinal, community-representative Great Smoky Mountains Study of 1420 participants. Participants were assessed with the structured Child and Adolescent Psychiatric Assessment interview up to eight times in childhood (ages 9-16; 6674 observations; 1993-2000) for childhood loneliness, associated psychiatric comorbidities and childhood adversities. Participants were followed up four times in adulthood (ages 19, 21, 25, and 30; 4556 observations of 1334 participants; 1999-2015) with the structured Young Adult Psychiatric Assessment Interview for psychiatric anxiety, depression, and substance use outcomes.

Results: Both self and parent-reported childhood loneliness were associated with adult self-reported anxiety and depressive outcomes. The associations remained significant when childhood adversities and psychiatric comorbidities were accounted for. There was no evidence for an association of childhood loneliness with adult substance use disorders. More associations were found between childhood loneliness and adult psychiatric symptoms than with adult diagnostic status.

Conclusion: Childhood loneliness is associated with anxiety and depressive disorders in young adults, suggesting that loneliness - even in childhood - might have long-term costs in terms of mental health. This study underscores the importance of intervening early to prevent loneliness and its sequelae over time.
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http://dx.doi.org/10.1017/S0033291721001422DOI Listing
June 2021

Lateralization of Resting-State Networks in Children: Association with Age, Sex, Handedness, Intelligence Quotient, and Behavior.

Brain Connect 2021 Jul 26. Epub 2021 Jul 26.

Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State, Georgia Tech, Emory, Atlanta, Georgia, USA.

Lateralization in brain function has been associated with age and sex in previous work; however, there has been less focus on lateralization of functional networks during development. We aim to examine laterality in typical development; a clearer understanding of how and to what extent functional brain networks are lateralized in typical development may eventually prove to hold predictive information in psychopathology. In this study, we examine the lateralization of resting-state networks assessed with a group-independent component analysis using resting-state functional magnetic resonance imaging from a large cohort consisting of 774 children, ages 6-10 years. This is an extension of our previous work on normal aging in adults, where we now assess whether there are similar patterns in children. Unlike the results from our study of healthy aging in adults, which showed a decrease in laterality with increasing age, in this study we found both decreases and increases in lateralization in multiple networks with development. For example, auditory and sensorimotor regions had greater bilateral connectivity with development, whereas regions including the dorsolateral frontal cortex (Brodmann area left 9 and left 46) showed an increase in left lateralization with development. Our findings support a complex, nonlinear association between laterality and age in school-age children, a time when brain function and structure are developing rapidly. We also found brain networks in which laterality was significantly associated with sex, handedness, and intelligence quotient, but we did not find any significant association with behavioral scores. Impact statement Lateralization in brain function has been associated with age and sex in several previous studies; however, there has been less focus on lateralization of functional networks during development. A clearer understanding of how and to what extent functional brain networks are lateralized in typical development may eventually prove to hold predictive information in psychopathology. In this study, we examine the lateralization of resting-state networks assessed with a group-independent component analysis using resting-state functional magnetic resonance imaging from a large cohort consisting of 774 children, ages 6-10 years.
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http://dx.doi.org/10.1089/brain.2020.0863DOI Listing
July 2021

Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders.

Biol Psychiatry 2021 Mar 23. Epub 2021 Mar 23.

Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois; Department of Psychiatry and Behavioral Sciences, North Shore University Health System, Evanston, Illinois.

Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.

Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH.

Results: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10; rs73033497, p = 8.8 × 10; rs7914279, p = 6.4 × 10), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05).

Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
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http://dx.doi.org/10.1016/j.biopsych.2021.02.972DOI Listing
March 2021

Fetal Growth Trajectories Among Small for Gestational Age Babies and Child Neurodevelopment.

Epidemiology 2021 Sep;32(5):664-671

The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.

Background: Being born small for gestational age (SGA, <10th percentile) is a risk factor for worse neurodevelopmental outcomes. However, this group is a heterogeneous mix of healthy and growth-restricted babies, and not all will experience poor outcomes. We sought to determine whether fetal growth trajectories can distinguish who will have the worst neurodevelopmental outcomes in childhood among babies born SGA.

Methods: The present analysis was conducted in Generation R, a population-based cohort in Rotterdam, the Netherlands (N = 5,487). Using group-based trajectory modeling, we identified fetal growth trajectories for weight among babies born SGA. These were based on standard deviation scores of ultrasound measures from mid-pregnancy and late pregnancy in combination with birth weight. We compared child nonverbal intelligence quotient (IQ) and attention deficit hyperactivity disorder (ADHD) symptoms at age 6 between SGA babies within each growth trajectory to babies born non-SGA.

Results: Among SGA individuals (n = 656), we identified three distinct fetal growth trajectories for weight. Children who were consistently small from mid-pregnancy (n = 64) had the lowest IQ (7 points lower compared to non-SGA babies, 95% confidence interval [CI] = -11.0, -3.5) and slightly more ADHD symptoms. Children from the trajectory that started larger but were smaller at birth showed no differences in outcomes compared to children born non-SGA.

Conclusions: Among SGA children, those who were smaller beginning in mid-pregnancy exhibited the worst neurodevelopmental outcomes at age 6. Fetal growth trajectories may help identify SGA babies who go on to have poor neurodevelopmental outcomes.
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http://dx.doi.org/10.1097/EDE.0000000000001387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338787PMC
September 2021

Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts.

Eur J Epidemiol 2021 May 28. Epub 2021 May 28.

ISGlobal, Barcelona Institute for Global Health, C. Doctor Aiguader 88, 08003, Barcelona, Spain.

The potential etiological role of early acetaminophen exposure on Autism Spectrum Conditions (ASC) and Attention-Deficit/Hyperactivity Disorder (ADHD) is inconclusive. We aimed to study this association in a collaborative study of six European population-based birth/child cohorts. A total of 73,881 mother-child pairs were included in the study. Prenatal and postnatal (up to 18 months) acetaminophen exposure was assessed through maternal questionnaires or interviews. ASC and ADHD symptoms were assessed at 4-12 years of age using validated instruments. Children were classified as having borderline/clinical symptoms using recommended cutoffs for each instrument. Hospital diagnoses were also available in one cohort. Analyses were adjusted for child and maternal characteristics along with indications for acetaminophen use. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. The proportion of children having borderline/clinical symptoms ranged between 0.9 and 12.9% for ASC and between 1.2 and 12.2% for ADHD. Results indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have borderline or clinical ASC (OR = 1.19, 95% CI 1.07-1.33) and ADHD symptoms (OR = 1.21, 95% CI 1.07-1.36) compared to non-exposed children. Boys and girls showed higher odds for ASC and ADHD symptoms after prenatal exposure, though these associations were slightly stronger among boys. Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms. These results replicate previous work and support providing clear information to pregnant women and their partners about potential long-term risks of acetaminophen use.
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http://dx.doi.org/10.1007/s10654-021-00754-4DOI Listing
May 2021

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

PLoS One 2021 29;16(4):e0238667. Epub 2021 Apr 29.

Department of Biological Psychology, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238667PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084195PMC
September 2021

Adverse intergenerational effects of ethnically-divisive social contexts on children's mental health: A prospective cohort study in the Netherlands.

Soc Sci Med 2021 05 20;277:113932. Epub 2021 Apr 20.

Harvard T.H. Chan School of Public Health, Department of Social and Behavioral Sciences, Boston, MA, United States.

Background: Around the world, international migration and growing economic inequality have contributed to heightened perceptions of intergroup threat (i.e., feeling that people outside of one's social group are hostile to their physical or emotional well-being). Exposures related to intergroup threat, like negative intergroup contact, are inherently stressful and may contribute to higher levels of psychological distress in the population. This longitudinal study investigated whether maternal experiences of negative intergroup contact are related to poor mental health outcomes among ethnically diverse children in The Netherlands.

Methods: Data are from 4025 mother-child pairs in the Generation R Study, a multi-ethnic Dutch birth cohort initiated in 2005. Mothers' experiences of negative intergroup contact were assessed during pregnancy. Child mental health was indexed by problem behavior reported by parents and teachers using the Child Behavior Checklist. Linear mixed-effects models tested longitudinal associations of maternal-reported negative intergroup contact with child problem behavior reported by mothers at ages 3, 5, and 9 years, considering a range of potential confounders. Sensitivity analyses examined whether results were replicated using child data from other informants.

Results: In fully adjusted models, higher levels of negative intergroup contact were associated with more problem behavior averaged across childhood for both non-Dutch (standardized B = 0.10, 95% CI = 0.05, 0.14) and Dutch children (standardized B = 0.12, 95% CI = 0.08, 0.15). Sensitivity analyses with data from other informants largely supported primary findings.

Conclusions: Comparable adverse intergenerational effects on mental health were observed among both ethnic minority and majority children whose mothers experienced negative intergroup contact. These findings suggest that ethnically divisive social contexts may confer widespread risks, regardless of a child's ethnic background. To our knowledge, this study is the first to examine exposures related to intergroup threat from an epidemiologic perspective and provides proof of principle that such exposures may be informative for population health.
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http://dx.doi.org/10.1016/j.socscimed.2021.113932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205087PMC
May 2021

Half the body in one model: how obesity impacts the brain.

Authors:
Henning Tiemeier

J Clin Endocrinol Metab 2021 Apr 19. Epub 2021 Apr 19.

Department of Social and Behavioral Science, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

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http://dx.doi.org/10.1210/clinem/dgab247DOI Listing
April 2021

The predictive value of neurobiological measures for recidivism in delinquent male young adults.

J Psychiatry Neurosci 2021 Apr 12;46(2):E271-E280. Epub 2021 Apr 12.

From the Amsterdam University Medical Centers, Department of Child and Adolescent Psychiatry, Amsterdam, Netherlands (Zijlmans, Marhe, Bevaart, van Duin, Luijks, Popma); the Erasmus University Rotterdam, Department of Psychology, Education and Child Studies, Rotterdam, Netherlands (Marhe, Franken); the Harvard T. H. Chan School of Public Health, Department of Social and Behavioral Sciences, Boston, Massachusetts (Tiemeier); the Erasmus University Medical Center, Department of Child and Adolescent Psychiatry, Rotterdam, Netherlands (Tiemeier); and Leiden University, Department of Criminal Law and Criminology, Leiden, Netherlands (Popma).

Background: Neurobiological measures have been associated with delinquent behaviour, but little is known about the predictive power of these measures for criminal recidivism and whether they have incremental value over and above demographic and behavioural measures. This study examined whether selected measures of autonomic functioning, functional neuroimaging and electroencephalography predict overall and serious recidivism in a sample of 127 delinquent young adults.

Methods: We assessed demographics; education and intelligence; previous delinquency and drug use; behavioural traits, including aggression and psychopathy; and neurobiological measures, including heart rate, heart rate variability, functional brain activity during an inhibition task and 2 electroencephalographic measures of error-processing. We tested longitudinal associations with recidivism using Cox proportional hazard models and predictive power using C-indexes.

Results: Past offences, long-term cannabis use and reactive aggression were strongly associated with recidivism, as were resting heart rate and error-processing. In the predictive model, demographics, past delinquency, drug use and behavioural traits had moderate predictive power for overall and for serious recidivism (C-index over 30 months [fraction of pairs in the data, where the higher observed survival time was correctly predicted]: C30 = 0.68 and 0.75, respectively). Neurobiological measures significantly improved predictive power (C30 = 0.72 for overall recidivism and C30 = 0.80 for serious recidivism).

Limitations: Findings cannot be generalized to females, and follow-up was limited to 4 years.

Conclusion: Demographic and behavioural characteristics longitudinally predicted recidivism in delinquent male young adults, and neurobiological measures improved the models. This led to good predictive function, particularly for serious recidivism. Importantly, the most feasible measures (autonomic functioning and electroencephalography) proved to be useful neurobiological predictors.
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http://dx.doi.org/10.1503/jpn.200103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061739PMC
April 2021

The iBerry study: a longitudinal cohort study of adolescents at high risk of psychopathology.

Eur J Epidemiol 2021 Apr 1;36(4):453-464. Epub 2021 Apr 1.

Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

The iBerry study is a population-based cohort study designed to investigate the transition from subclinical symptoms to a psychiatric disorder. Adolescents were selected based on their self-reported emotional and/or behavioral problems assessed by completing the strengths and difficulties questionnaire-youth (SDQ-Y) in their first year of high school. A total of 16,736 SDQ-Y questionnaires completed in the academic years 2014-2015 and 2015-2016 by students in the greater Rotterdam area in the Netherlands were screened. A high-risk group of adolescents was then selected based on the 15% highest-scoring adolescents, and a low-risk group was randomly selected from the 85% lowest-scoring adolescents, with a 2.5:1 ratio between the number of high-risk and low-risk adolescents. These adolescents were invited to come with one parent for a baseline visit consisting of interviews, questionnaires, neuropsychological tests, and biological measurements to assess determinants of psychopathology. A total of 1022 high-risk and low-risk adolescents (mean age at the first visit: 15.0 years) enrolled in the study. The goal of the iBerry study is to follow these adolescents for a 10-year period in order to monitor any changes in their symptoms. Here, we present the study design, response rate, inclusion criteria, and the characteristics of the cohort; in addition, we discuss possible selection effects. We report that the oversampling procedure was successful at selecting a cohort of adolescents with a high rate of psychiatric problems based on comprehensive multi-informant measurements. The future results obtained from the iBerry Study will provide new insights into the way in which the mental health of high-risk adolescents changes as they transition to adulthood. These findings will therefore facilitate the development of strategies designed to optimize mental healthcare and prevent psychopathology.
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http://dx.doi.org/10.1007/s10654-021-00740-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076148PMC
April 2021

Maternal polyunsaturated fatty acids during pregnancy and offspring brain development in childhood.

Am J Clin Nutr 2021 07;114(1):124-133

Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: Emerging evidence suggests an association of maternal PUFA concentrations during pregnancy with child cognitive and neuropsychiatric outcomes such as intelligence and autistic traits. However, little is known about prenatal maternal PUFAs in relation to child brain development, which may underlie these associations.

Objectives: We aimed to investigate the association of maternal PUFA status during pregnancy with child brain morphology, including volumetric and white matter microstructure measures.

Methods: This study was embedded in a prospective population-based study. In total, 1553 mother-child dyads of Dutch origin were included. Maternal plasma glycerophospholipid PUFAs were assessed in midpregnancy. Child brain morphologic outcomes, including total gray and white matter volumes, as well as white matter microstructure quantified by global fractional anisotropy and mean diffusivity, were measured using MRI (including diffusion tensor imaging) at age 9-11 y.

Results: Maternal ω-3 (n-3) long-chain PUFA (LC-PUFA) concentrations during pregnancy had an inverted U-shaped relation with child total gray volume (linear term: β: 16.7; 95% CI: 2.0, 31.5; quadratic term: β: -1.1; 95% CI: -2.1, -0.07) and total white matter volume (linear term: β: 15.7; 95% CI: 3.6, 27.8; quadratic term: β: -1.0; 95% CI: -1.8, -0.16). Maternal gestational ω-6 LC-PUFA concentrations did not predict brain volumetric differences in children, albeit the linolenic acid concentration was inversely associated with child total white matter volume. Maternal PUFA status during pregnancy was not related to child white matter microstructure.

Conclusions: Sufficient maternal ω-3 PUFAs during pregnancy may be related to more optimal child brain development in the long term. In particular, exposure to lower ω-3 PUFA concentrations in fetal life was associated with less brain volume in childhood. Maternal ω-6 LC-PUFAs were not related to child brain morphology.
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http://dx.doi.org/10.1093/ajcn/nqab049DOI Listing
July 2021

The association between genetically determined ABO blood types and major depressive disorder.

Psychiatry Res 2021 05 24;299:113837. Epub 2021 Feb 24.

Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; German Centre for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.

ABO blood types and their corresponding antigens have long been assumed to be related to different human diseases. So far, smaller studies on the relationship between mental disorders and blood types yielded contradicting results. In this study we analyzed the association between ABO blood types and lifetime major depressive disorder (MDD). We performed a pooled analysis with data from 26 cohorts that are part of the MDD working group of the Psychiatric Genomics Consortium (PGC). The dataset included 37,208 individuals of largely European ancestry of which 41.6% were diagnosed with lifetime MDD. ABO blood types were identified using three single nucleotide polymorphisms in the ABO gene: rs505922, rs8176746 and rs8176747. Regression analyses were performed to assess associations between the individual ABO blood types and MDD diagnosis as well as putative interaction effects with sex. The models were adjusted for sex, cohort and the first ten genetic principal components. The percentage of blood type A was slightly lower in cases than controls while blood type O was more prominent in cases. However, these differences were not statistically significant. Our analyses found no evidence of an association between ABO blood types and major depressive disorder.
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http://dx.doi.org/10.1016/j.psychres.2021.113837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071927PMC
May 2021

Housing Boston's Chronically Homeless Unsheltered Population: 14 Years Later.

Med Care 2021 Apr;59(Suppl 2):S170-S174

Department of Medicine, Massachusetts General Hospital, Boston, MA.

Objective: The long-term outcomes of permanent supportive housing for chronically unsheltered individuals, or rough sleepers, are largely unknown. We therefore assessed housing outcomes for a group of unsheltered individuals who were housed directly from the streets after living outside for decades.

Methods: Using an open-cohort design, 73 chronically unsheltered individuals were enrolled and housed in permanent supportive housing directly from the streets of Boston from 2005 to 2019. Through descriptive, regression, and survival analysis, we assessed housing retention, housing stability, and predictors of survival.

Results: Housing retention at ≥1 year was 82% yet fell to 36% at ≥5 years; corresponding Kaplan-Meier estimates for retention were 72% at ≥1, 42.5% at ≥5, and 37.5% at ≥10 years. Nearly half of the cohort (45%) died while housed. The co-occurrence of medical, psychiatric, and substance use disorder, or "trimorbidity," was common. Moves to a new apartment were also common; 38% were moved 45 times to avoid an eviction. Each subsequent housing relocation increased the risk of a tenant returning to homelessness. Three or more housing relocations substantially increased the risk of death.

Conclusions: Long-term outcomes for this permanent supportive housing program for chronically unsheltered individuals showed low housing retention and poor survival. Housing stability for this vulnerable population likely requires more robust and flexible and long-term medical and social supports.
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http://dx.doi.org/10.1097/MLR.0000000000001409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958978PMC
April 2021

Mental Health in Early Childhood and Changes in Cardiometabolic Dysregulation by Preadolescence.

Psychosom Med 2021 04;83(3):256-264

From the Department of Social and Behavioral Sciences (Qureshi, Tiemeier, Kubzansky), Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Psychology, Education and Child Studies (Derks), Erasmus University Rotterdam, Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry/Psychology (Derks) and; The Generation R Study Group, Department of Pediatrics (Jaddoe), Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands; and Department of Epidemiology (Williams, Koenen), Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Objective: Poor mental health in childhood is associated with a greater risk of cardiometabolic disease in adulthood, but less is known about when these associations begin to emerge. This study tests whether poor mental health (indexed by emotional and behavioral problems) in early childhood predicts increases in cardiometabolic dysregulation over 4 years of follow-up.

Methods: Data are from 4327 participants in the Generation R Study. Problem behaviors were reported by mothers using the Child Behavior Checklist at age 6 years. Repeated measurements of six cardiometabolic parameters were collected at ages 6 and 10 years: high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, systolic and diastolic blood pressures, C-reactive protein, and body mass index. Standardized measures were used to create continuous cardiometabolic dysregulation scores at ages 6 and 10 years. Change in dysregulation was defined as the difference in dysregulation scores over time. Cross-sectional and prospective associations were tested using linear regression, sequentially adjusting for relevant confounders. Additional analyses examined whether prospective relationships were robust to adjustment for baseline levels of dysregulation.

Results: There was no association between child problem behaviors and cardiometabolic dysregulation at age 6 years. However, higher levels of problem behaviors predicted increases in cardiometabolic dysregulation (β = 0.12, 95% confidence interval = 0.00-0.23) from ages 6 to 10 years.

Conclusions: Worse child mental health may be associated with increases in cardiometabolic dysregulation by preadolescence. To our knowledge, this is the first study to demonstrate that adverse physiologic effects of psychological distress identified in adult populations may be observed as early as childhood.
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http://dx.doi.org/10.1097/PSY.0000000000000927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016708PMC
April 2021

Schizophrenia polygenic risk is associated with child mental health problems through early childhood adversity: evidence for a gene-environment correlation.

Eur Child Adolesc Psychiatry 2021 Feb 26. Epub 2021 Feb 26.

Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.

Previous studies have shown that schizophrenia polygenic risk predicts a multitude of mental health problems in the general population. Yet it is unclear by which mechanisms these associations arise. Here, we explored a possible gene-environment correlation in the association of schizophrenia polygenic risk with mental health problems via childhood adversity. This study was embedded in the population-based Generation R Study, including N = 1901 participants with genotyping for schizophrenia polygenic risk, maternal reporting of childhood adversity, and Child Behaviour Checklist measurement of mental health problems. Independent replication was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3641). Associations were analysed with Poisson regression and statistical mediation analysis. Higher burden of schizophrenia polygenic risk was associated with greater exposure to childhood adversity (P-value threshold < 0.5: Generation R Study, OR = 1.08, 95%CI 1.02-1.15, P = 0.01; ALSPAC, OR = 1.02, 95%CI 1.01-1.03, P < 0.01). Childhood adversities partly explained the relationship of schizophrenia polygenic risk with emotional, attention, and thought problems (proportion explained, range 5-23%). Direct effects of schizophrenia polygenic risk and adversity on mental health outcomes were also observed. In summary, genetic liability to schizophrenia increased the risk for mental health problems in the general paediatric population through childhood adversity. Although this finding could result from a mediated causal relationship between genotype and mental health, we argue that these observations most likely reflect a gene-environment correlation, i.e. adversities are a marker for the genetic risk that parents transmit to children. These and similar recent findings raise important conceptual questions about preventative interventions aimed at reducing childhood adversities.
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http://dx.doi.org/10.1007/s00787-021-01727-4DOI Listing
February 2021

Aggressive behavior, emotional, and attention problems across childhood and academic attainment at the end of primary school.

Soc Psychiatry Psychiatr Epidemiol 2021 May 22;56(5):837-846. Epub 2021 Feb 22.

Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Purpose: To assess whether aggressive behavior and emotional problems from early childhood onwards are related to academic attainment at the end of primary education, and whether these associations are independent of attention problems.

Methods: Data on 2546 children participating in a longitudinal birth cohort in Rotterdam were analyzed. Aggressive behavior, attention and emotional problems at ages 1½, 3, 5 and 10 years were assessed with the Child Behavior Checklist. Academic attainment at the end of primary school (12 years of age) was measured with the CITO test, a national Dutch academic test score.

Results: Aggressive behavior from age 1½ to 10 years was negatively associated with academic attainment, but these associations attenuated to non-significance when accounting for comorbid attention problems. For emotional problems, first, only problems at 10 years were associated with poorer academic attainment. Yet, when accounting for attention problems, the association reversed: more emotional problems from 1½ to 10 years were associated with a better academic attainment. Attention problems at ages 1½ to 10 years were negatively associated with academic attainment, independent of comorbid emotional problems or aggressive behavior.

Conclusions: Attention problems across childhood are related to a poorer academic attainment, while emotional problems predicted better academic attainment. Moreover, the relationship between aggressive behavior and academic attainment was explained by comorbid attention problems. Future research should determine the mechanisms through which attention problems and emotional problems affect academic attainment, to inform strategies for the promotion of better educational attainment.
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http://dx.doi.org/10.1007/s00127-021-02039-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068650PMC
May 2021

Association of maternal pre-pregnancy low or increased body mass index with adverse pregnancy outcomes.

Sci Rep 2021 Feb 15;11(1):3831. Epub 2021 Feb 15.

Guangdong Institute of Family Planning Science and Technology, 17th Meidong Road, Yuexiu District, 510245, Guangzhou, People's Republic of China.

This study investigated the association between pre-pregnancy body mass index (BMI) and adverse pregnancy outcomes among women participated in the National Free Preconception Health Examination Project in Guangdong Province, China, and explored these associations according to maternal age. Pre-pregnancy BMI was classified into underweight (BMI < 18.5 kg/m), healthy weight (18.5-23.9 kg/m), overweight (24.0-27.9 kg/m), and obesity (≥ 28.0 kg/m) according to Chinese criteria. Outcomes were preterm birth (PTB, delivery before 37 weeks of gestation), large for gestational age (LGA, birthweight above the 90th percentile for gestational age by infants' sex), small for gestational age (SGA, birthweight below the 10th percentile for gestational age by infants' sex), primary caesarean delivery, shoulder dystocia or birth injury, and stillbirth. Adjusted incidence risk ratios (aIRR) were calculated for underweight, overweight and obesity, respectively. Compared with healthy weight, underweight was associated with increased risk of PTB (aIRR 1.06, 95%CI 1.04-1.09) and SGA (1.23, 1.22-1.26) but inversely associated with LGA (0.83, 0.82-0.85), primary caesarean delivery (0.88, 0.87-0.90) and stillbirth (0.73, 0.53-0.99). Overweight was associated with increased risk of LGA (1.17, 1.14-1.19), primary caesarean delivery (1.18, 1.16-1.20) and stillbirth (1.44, 1.03-2.06), but inversely associated with SGA (0.92, 0.90-0.95) and shoulder dystocia or birth injury (0.86, 0.79-0.93). Obesity was associated with increased risk of PTB (1.12, 1.05-1.20), LGA (1.32, 1.27-1.37), primary caesarean delivery (1.45, 1.40-1.50), but inversely associated with SGA (0.92, 0.87-0.97). The aIRRs for underweight, overweight and obesity in relation to these adverse pregnancy outcomes ranged from 0.65 to 1.52 according to maternal age. In Chinese population, maternal pre-pregnancy BMI was significantly associated with the risk of adverse pregnancy outcomes and the risk differs according to maternal age. Further investigation is warranted to determine whether and how counselling and interventions for women with low or increased BMI before pregnancy can reduce the risk of adverse pregnancy outcomes.
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http://dx.doi.org/10.1038/s41598-021-82064-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884680PMC
February 2021

Associations of pre-pregnancy impaired fasting glucose and body mass index among pregnant women without pre-existing diabetes with offspring being large for gestational age and preterm birth: a cohort study in China.

BMJ Open Diabetes Res Care 2021 02;9(1)

Department of Epidemiology, Family Planning Special Hospital of Guangdong, Guangzhou, China.

Introduction: Associations of pre-pregnancy impaired fasting glucose (IFG) and body mass index (BMI) with large for gestational age (LGA) and preterm birth (PTB) have been poorly understood. We aimed to investigate the associations of maternal BMI, separately and together with pre-pregnancy IFG, with LGA and PTB in Chinese population. We also aimed to quantify these associations by maternal age.

Research Design And Methods: This was a retrospective cohort study of women from the National Free Preconception Health Examination Project with singleton birth from 121 counties/districts in 21 cities of Guangdong Province, China, from January 1, 2013 to December 31, 2017. Women were included if they did not have pre-existing chronic diseases (diabetes, hypertension, etc). Participants were divided into eight groups according to their BMI (underweight (BMI <18.5 kg/m), normal weight (18.5-23.9 kg/m), overweight (24.0-27.9 kg/m), and obesity (≥28.0 kg/m)) and pre-pregnancy fasting glucose status (normoglycemia (fasting glucose concentration <6.1 mmol/L) and IFG (6.1-7.0 mmol/L)). Adjusted incidence risk ratios (aIRRs) and 95% CIs of LGA, severe LGA, PTB and early PTB were estimated.

Results: We included 634 030 women. The incidences of LGA, severe LGA, PTB and early PTB for the study population were 7.1%, 2.5%, 5.1% and 1.1%, respectively. Compared with normal weight mothers with normoglycemia, overweight and obese mothers irrespective of IFG had a higher risk of LGA (eg, obesity with IFG aIRR 1.85 (1.60-2.14)) and severe LGA (eg, obesity with IFG 2.19 (1.73-2.79)). The associations of BMI and pre-pregnancy fasting glucose status with LGA were similar found among women of all age groups. Underweight with normoglycemia had 6.0% higher risk of PTB (1.06 (1.03-1.09)) and 8.0% higher risk of early PTB (1.08 (1.02-1.17)), underweight with IFG had 14.0% higher risk of PTB (1.14 (1.02-1.27)), and obese mothers with IFG had 45.0% higher risk of PTB (1.45 (1.18-1.78)). The associations of BMI and pre-pregnancy fasting glucose status with PTB differed by maternal age.

Conclusion: Overweight and obesity regardless of IFG were associated with an increased risk of LGA, and these associations were similarly observed among mothers of all age groups. Underweight regardless of IFG, and obesity with IFG were associated with an increased risk of PTB, but the associations differed by maternal age. Findings from this study may have implications for risk assessment and counselling before pregnancy.
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http://dx.doi.org/10.1136/bmjdrc-2020-001641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878137PMC
February 2021

Peer-reported bullying, rejection and hallucinatory experiences in childhood.

Acta Psychiatr Scand 2021 06 16;143(6):503-512. Epub 2021 Feb 16.

Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.

Objective: Psychotic experiences, such as hallucinations, occur commonly in children and have been related to bullying victimization. However, whether bullying perpetration, peer rejection, or peer acceptance are related to hallucinatory experiences has remained under-examined. We used a novel peer nomination method to examine whether (i) bullying perpetration and (ii) social positions within peer networks were associated with future hallucinatory experiences.

Methods: This prospective study was embedded in the population-based Generation R Study. Bullying perpetration, peer rejection, and peer acceptance were assessed using peer nominations at age 7 years (N = 925). Using a social network analysis, we estimated social positions within peer rejection and acceptance networks. Bullying victimization was assessed using self-reports. Self-reported hallucinatory experiences were assessed at age 10 years. Analyses were adjusted for sociodemographic covariates.

Results: Higher levels of bullying perpetration were prospectively associated with an increased burden of hallucinatory experiences (OR = 1.22, 95% CI 1.05-1.43, p = 0.011). Bullies had a 50% higher, and bully-victims had a 89% higher odds, of endorsing hallucinatory experiences three years later than children who were not involved in bullying (OR = 1.50, 95% CI 1.01-2.24, p = 0.045; OR = 1.89, 95% CI 1.15-3.10, p = 0.012). Unfavorable positions within peer rejection networks, but not peer acceptance networks, were associated with an increased risk for hallucinatory experiences (OR = 1.24, 95% CI 1.07-1.44, p = 0.024).

Conclusion: Using peer reports, we observed that bullies and socially rejected children have a higher likelihood to report hallucinatory experiences in pre-adolescence. Children who are both a bully and a victim of bullying (ie, bully-victims) may be particularly vulnerable for psychotic experiences.
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http://dx.doi.org/10.1111/acps.13282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248258PMC
June 2021

Identifying causative mechanisms linking early-life stress to psycho-cardio-metabolic multi-morbidity: The EarlyCause project.

PLoS One 2021 21;16(1):e0245475. Epub 2021 Jan 21.

Empirica Communication and Technology Research, Bonn, Germany.

Introduction: Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards the shared risk of these diseases and the development of coordinated preventive and therapeutic interventions.

Methods And Analysis: This paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union's Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shapes an individual's physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life-course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245475PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819604PMC
June 2021

Overview of CAPICE-Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe-an EU Marie Skłodowska-Curie International Training Network.

Eur Child Adolesc Psychiatry 2021 Jan 20. Epub 2021 Jan 20.

Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

The Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of individual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention deficit hyperactivity disorder. CAPICE brings together eight birth and childhood cohorts as well as other cohorts from the EArly Genetics and Life course Epidemiology (EAGLE) consortium, including twin cohorts, with unique longitudinal data on environmental exposures and mental health problems, and genetic data on participants. Here we describe the objectives, summarize the methodological approaches and initial results, and present the dissemination strategy of the CAPICE network. Besides identifying genetic and epigenetic variants associated with these phenotypes, analyses have been performed to shed light on the role of genetic factors and the interplay with the environment in influencing the persistence of symptoms across the lifespan. Data harmonization and building an advanced data catalogue are also part of the work plan. Findings will be disseminated to non-academic parties, in close collaboration with the Global Alliance of Mental Illness Advocacy Networks-Europe (GAMIAN-Europe).
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http://dx.doi.org/10.1007/s00787-020-01713-2DOI Listing
January 2021
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