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1.
Biol Psychiatry ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31570195

RESUMO

BACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4). RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99). CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

2.
Environ Int ; 132: 105124, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31479957

RESUMO

BACKGROUND: Animal studies suggest that organophosphate (OP) pesticides exposure affects thyroid function, but evidence in humans remains sparse and inconclusive. Gestational exposure is of particular interest, since thyroid hormone is essential for fetal brain development. OP pesticides are able to cross the placental and blood-brain barrier and may interfere with fetal development processes regulated by thyroid hormone. OBJECTIVE: To investigate the association of gestational OP pesticides exposure during pregnancy with maternal and cord blood thyroid hormone concentrations. METHODS: This study was embedded within Generation R (Rotterdam, the Netherlands), a prospective population-based birth cohort. Mother-child pairs with OP pesticides assessment and maternal (N = 715) or cord blood (N = 482) thyroid hormone measurements were included. OP pesticides exposure was assessed at <18, 18-25, and >25 weeks gestation by measuring six urinary dialkylphosphate (DAP) metabolites. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) were measured in maternal and cord blood. Maternal measures also included total thyroxine (TT4) and TPO antibodies (TPOAbs). To study the association of creatinine-adjusted DAP metabolite concentrations with thyroid function and TPO antibodies, multivariable linear regression models including relevant confounders were used. RESULTS: There was no association of DAP metabolites with maternal TSH, FT4, TT4 or TPOAb concentrations during pregnancy. Similarly, there was no association of DAP metabolites with cord blood TSH or FT4. Results did not change when DAP concentrations were analyzed at individual time points or as mean gestational exposure. CONCLUSION: Gestational OP pesticides exposure, as assessed by repeatedly measured urinary DAP metabolite concentrations in an urban population, was not associated with maternal or cord blood thyroid hormone concentrations. These findings do not support a mediating role for serum thyroid hormone availability in the relation of early life exposure to low levels of OP pesticides with child neurodevelopment. However, disruption of the thyroid system at tissue level cannot be excluded. In addition, this is one of the first studies on this subject and measurement error in DAP metabolites might have resulted in imprecise estimates. Future studies should use more urine samples to increase precision and should investigate specific OP pesticide metabolites.

3.
Hum Mol Genet ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31518406

RESUMO

Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. While the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. While it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition towards loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study (GWAS) meta-analysis of loneliness to 511 280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18 498 individuals with electronic health record data to conduct a PheWAS with. A genetic predisposition towards loneliness was associated with cardiovascular, psychiatric, and metabolic disorders, and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.

4.
Nat Commun ; 10(1): 3346, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431621

RESUMO

Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors of long-term mortality in the circulation of 44,168 individuals (age at baseline 18-109), of whom 5512 died during follow-up. We apply a stepwise (forward-backward) procedure based on meta-analysis results and identify 14 circulating biomarkers independently associating with all-cause mortality. Overall, these associations are similar in men and women and across different age strata. We subsequently show that the prediction accuracy of 5- and 10-year mortality based on a model containing the identified biomarkers and sex (C-statistic = 0.837 and 0.830, respectively) is better than that of a model containing conventional risk factors for mortality (C-statistic = 0.772 and 0.790, respectively). The use of the identified metabolic profile as a predictor of mortality or surrogate endpoint in clinical studies needs further investigation.

5.
Environ Health Perspect ; 127(8): 87005, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31419153

RESUMO

BACKGROUND: Perturbations in fetal growth may have adverse consequences for childhood and later life health. Organophosphate pesticide (OP) exposure has been associated with reduced birth weight at delivery but results are not consistent. We investigated this question by utilizing ultrasound measures of size in utero in combination with measures from delivery. METHODS: Within Generation R, a population-based prospective cohort conducted between 2002 and 2006 in Rotterdam, Netherlands, we measured dialkyl phosphates (DAPs), OP metabolites, in urine samples from early, middle, and late pregnancy and created a subject-specific average to estimate OP exposure ([Formula: see text]). Ultrasound measures of head circumference, femur length, and estimated fetal weight from middle and late pregnancy and delivery measures were converted to standard deviation scores (SDS). Associations with DAP average were examined in linear mixed effects models that included an interaction term between gestational age at measurement and DAP average to investigate whether the relationship differed over time. Windows of vulnerability to exposure were assessed by modeling urinary DAPs from each visit in relation to growth measurements. RESULTS: A 10-fold increase in average DAPs was associated with a [Formula: see text] SDS decrease in fetal length (95% [Formula: see text], [Formula: see text]) and a [Formula: see text] SDS decrease in estimated fetal weight (95% [Formula: see text], [Formula: see text]) at 20 weeks of gestation. These differences corresponded to 5% and 6% decreases relative to the mean. Effect estimates were greatest in magnitude for DAP concentrations measured early in pregnancy. Associations between average DAPs and growth measures at delivery were positive but not significant for head circumference and length and were null for weight. CONCLUSIONS: Maternal urinary DAPs were associated with decreased fetal weight and length measured during mid-pregnancy, but not at delivery. https://doi.org/10.1289/EHP4858.

6.
Child Dev ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31364163

RESUMO

To examine the contributions of maternal and paternal age on offspring externalizing and internalizing problems, this study analyzed problem behaviors at age 10-12 years from four Dutch population-based cohorts (N = 32,892) by a multiple informant design. Bayesian evidence synthesis was used to combine results across cohorts with 50% of the data analyzed for discovery and 50% for confirmation. There was evidence of a robust negative linear relation between parental age and externalizing problems as reported by parents. In teacher-reports, this relation was largely explained by parental socio-economic status. Parental age had limited to no association with internalizing problems. Thus, in this large population-based study, either a beneficial or no effect of advanced parenthood on child problem behavior was observed.

7.
Environ Int ; 131: 105002, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31369979

RESUMO

BACKGROUND: Prenatal exposure to organophosphate (OP) pesticides has been associated with altered neuronal cell development and behavioral changes in animal offspring. However, the few studies investigating the association between prenatal OP pesticide exposure and neurodevelopmental outcomes such as Attention-Deficit Hyperactivity Disorder (ADHD) and autistic traits in children produced mixed findings. OBJECTIVE: The objective of the present study was to examine whether maternal urinary concentrations of OP pesticide metabolites are associated with ADHD and autistic traits in children participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands. METHOD: Maternal concentrations of 6 dialkylphosphates (DAPs) were measured using gas chromatography coupled with tandem mass spectrometry in urine samples collected at <18 weeks, 18-25 weeks, and > 25 weeks of gestation in 784 mother-child pairs. DAP metabolite concentrations were expressed as molar concentrations divided by creatinine levels and log10 transformed. ADHD traits were measured at ages 3, 6, and 10 years using the Child Behavior Checklist (CBCL) (n = 781) and autistic traits were measured at age 6 years using the Social Responsiveness Scale (SRS) (n = 622). First, regression models were fit for the averaged prenatal exposure across pregnancy. Second, we investigated associations for each collection phase separately, and applied a mutually adjusted model in which the effect of prenatal DAP concentrations from each time period on ADHD and autistic traits were jointly estimated. All associations were adjusted for relevant confounders. RESULTS: Median DAP metabolite concentration was 309 nmol/g creatinine at <18 weeks, 316 nmol/g creatinine at 18-25 weeks, and 308 nmol/g creatinine at >25 weeks of gestation. Overall, DAP metabolite concentrations were not associated with ADHD traits. For instance, a log10 increase in averaged total DAP concentrations across gestation was not associated with a lower ADHD score (-0.03 per SD 95 CI: -0.28 to 0.23). Similarly, no associations between maternal DAP concentrations and autistic traits were detected. CONCLUSIONS: In this study of maternal urinary DAP metabolite concentrations during pregnancy, we did not observe associations with ADHD and autistic traits in children. These are important null observations because of the relatively high background DAP concentrations across pregnancy, the relatively large sample size, and the 10-year follow-up of the offspring. Given the measurement error inherent in our OP pesticide exposure biomarkers, future studies using more urine samples are needed to accurately measure OP pesticide exposure over pregnancy in relation to ADHD and autistic traits.

8.
Thyroid ; 29(9): 1316-1326, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31426724

RESUMO

Background: Thyroid hormone is essential for optimal fetal brain development. Evidence suggests that both low and high maternal thyroid hormone availability may have adverse effects on child neurodevelopmental outcomes, but the effect on behavioral problems remains unclear. We studied the association of maternal thyrotropin (TSH) and free thyroxine (fT4) concentrations during the first 18 weeks of pregnancy with child attention-deficit hyperactivity disorder (ADHD). Methods: A total of 7669 mother-child pairs with data on maternal thyroid function and child ADHD were selected from three prospective population-based birth cohorts: INfancia y Medio Ambiente (INMA; N = 1073, Spain), Generation R (N = 3812, The Netherlands), and Avon Longitudinal Study of Parents and Children (ALSPAC; N = 2784, United Kingdom). Exclusion criteria were multiple pregnancy, fertility treatment, usage of medication affecting the thyroid, and pre-existing thyroid disease. We used logistic regression models to study the association of maternal thyroid function with the primary outcome, ADHD, assessed via the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria by parents and/or teachers at a median child age of 4.5 to 7.6 years, and with the secondary outcome, an ADHD symptom score above the 90th percentile. Effect modification by gestational age and sex was tested with interaction terms and stratified analyses. Results: Overall, 233 (3%) children met the criteria for ADHD. When analyzed continuously, neither fT4 nor TSH was associated with a higher risk of ADHD (odds ratio [OR] 1.1, 95% confidence interval [CI 1.0-1.3], p = 0.060 and OR 0.9 [CI 0.9-1.1], p = 0.385, respectively) or with high symptom scores. When investigating effect modification by gestational age, a higher fT4 was associated with symptoms above the 90th percentile but only in the first trimester (for fT4 per 1 SD: OR 1.2 [CI 1.0-1.4], p = 0.027). However, these differential effects by gestational age were not consistent. No significant effect modification by sex was observed. Conclusions: We found no clear evidence of an association between maternal thyroid function and child ADHD.

9.
Sleep ; 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31270542

RESUMO

STUDY OBJECTIVES: Poor sleep may destabilize axonal integrity and deteriorate cerebral white matter. In middle-aged and older adults sleep problems increase alongside structural brain changes, but the temporal relation between these processes is poorly understood. We studied longitudinal associations between sleep and cerebral white matter microstructure. METHODS: 1201 persons (59.3±7.9 years, 55% women) were followed across 5.8 years (3.9-10.8). Total sleep time (TST, hours), sleep efficiency (SE, percentage), sleep onset latency (SOL, minutes), and wake after sleep onset (WASO, minutes) were measured at baseline using a wrist-worn actigraph. White matter microstructure (global and tract-specific fractional anisotropy (FA) and mean diffusivity (MD)) was measured twice with diffusion tensor imaging (DTI). RESULTS: Poor sleep was associated with worse white matter microstructure up to 7 years later but did not predict trajectories of DTI over time. Longer TST was associated with higher global FA (ß=0.06, 95%CI: 0.01,0.12), but not with MD. Persons with higher SE had higher global FA (ß=0.01, 95%CI:0.002,0.01) and lower MD (ß=-0.01, 95%CI:-0.01,-0.0004). Consistently, those with more WASO had lower global FA (ß=-0.003, 95%CI: -0.005,-0.001) and higher MD (ß=0.002, 95%CI:0.0004,0.004). Global findings seemed to be driven by microstructural alterations in the cingulum, anterior forceps of corpus callosum, projection and association tracts. CONCLUSIONS: Middle-aged and older persons with more WASO, lower SE and shorter TST have worse microstructure of cerebral white matter. Microstructural alterations are most pronounced projection and association tracts, in the cingulum, and in the anterior forceps of corpus callosum.

11.
Lancet Diabetes Endocrinol ; 7(8): 629-637, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31262704

RESUMO

BACKGROUND: Adequate thyroid hormone availability during pregnancy is necessary for optimal fetal brain development. During the first 18-20 weeks of gestation, fetal thyroid hormone availability largely depends on the placental transfer of maternal thyroxine. Although various studies have shown that maternal thyroid dysfunction is associated with suboptimal child neurodevelopmental outcomes, the most vulnerable time window remains to be identified. The aim of this study is to examine the association of maternal thyroid function with child brain morphology and to study whether any association depends on the timing of thyroid assessment. METHODS: This prospective cohort study was part of the Generation R Study in Rotterdam, Netherlands, with a prospective population-based birth cohort. Pregnant women living in Rotterdam with an expected delivery date between April 1, 2002, and Jan 1, 2006, were eligible. Other inclusion criteria were maternal serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) measurement in early or mid-pregnancy (≤18 weeks) and available brain MRI data for child at age 10 years. Exclusion criteria were pre-existing thyroid disorder, thyroid disorder treatment, twin pregnancy, in-vitro fertilisation-induced pregnancy, and suboptimal-quality MRI data or major incidental finding on MRI. The main outcome was the association between maternal TSH and FT4 concentrations with brain MRI outcomes of children. Regression analyses accounted for gestational age at blood sampling, maternal age, ethnicity, education level, smoking, thyroid peroxidase antibody positivity, child sex, age at MRI, and total intracranial volume. Effect modification by gestational age at blood sampling was also investigated. FINDINGS: Between Dec 1, 2001, and June 30, 2005, 7069 women were enrolled during early or mid-pregnancy (≤18 weeks of gestation), of whom 5088 were not included because they did not have available data on maternal serum TSH or FT4 concentrations (n=1175), their child did not have brain MRI done (n=3377), or they met exclusion criteria (n=536). Thus, 1981 mother-child pairs were included in the study, with TSH and FT4 concentrations measured during pregnancy at a median of 13·1 weeks of gestation (IQR 12·1-14·5) and offspring brain morphology assessed by MRI at a median age of 9·9 years (9·7-10·2). Maternal TSH had an inverted U-shaped association with offspring total grey matter volume (p=0·007) and with cortical grey matter volume (p=0·022). The association of maternal TSH with child total grey matter volume (pinteraction=0·053) and cortical volume (pinteraction=0·086) differed by the duration of gestation. Analyses stratified for gestational age at blood sampling showed an inverted U-shaped association of maternal TSH with child total grey matter volume and cortical grey matter volume, which was most evident at 8 weeks gestation. After about 14 weeks of gestation, TSH was no longer associated with child brain morphology. Maternal FT4 concentrations were not associated with child total grey matter volume after adjusting for total intracranial volume (p=0·75). INTERPRETATION: Here, we show that both low and high maternal thyroid function are associated with smaller child total grey matter and cortical volume. To the best of our knowledge, this study is the first to show that an association with a neurodevelopmental outcome is most evident when maternal thyroid function is measured early in pregnancy. These novel findings suggest that embryonic brain development is particularly vulnerable to altered maternal thyroid function. FUNDING: Netherlands Organisation for Health Research and Development and the Sophia Children's Hospital Foundation.

12.
Environ Int ; 131: 104927, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31326824

RESUMO

BACKGROUND: The association between air pollution exposure and emotional and behavioural problems in children is unclear. We aimed to assess prenatal and postnatal exposure to several air pollutants and child's depressive and anxiety symptoms, and aggressive symptoms in children of 7-11 years. METHODS: We analysed data of 13182 children from 8 European population-based birth cohorts. Concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter (PM) with diameters of ≤10 µm (PM10), ≤ 2.5 µm (PM2.5), and between 10 and 2.5 µm (PMcoarse), the absorbance of PM2.5 filters (PM2.5abs), and polycyclic aromatic hydrocarbons (PAHs) were estimated at residential addresses of each participant. Depressive and anxiety symptoms and aggressive symptoms were assessed at 7-11 years of age using parent reported tests. Children were classified in borderline/clinical range or clinical range using validated cut offs. Region specific models were adjusted for various socio-economic and lifestyle characteristics and then combined using random effect meta-analysis. Multiple imputation and inverse probability weighting methods were applied to correct for potential attrition bias. RESULTS: A total of 1896 (14.4%) children were classified as having depressive and anxiety symptoms in the borderline/clinical range, and 1778 (13.4%) as having aggressive symptoms in the borderline/clinical range. Overall, 1108 (8.4%) and 870 (6.6%) children were classified as having depressive and anxiety symptoms, and aggressive symptoms in the clinical range, respectively. Prenatal exposure to air pollution was not associated with depressive and anxiety symptoms in the borderline/clinical range (e.g. OR 1.02 [95%CI 0.95 to 1.10] per 10 µg/m3 higher NO2) nor with aggressive symptoms in the borderline/clinical range (e.g. OR 1.04 [95%CI 0.96 to 1.12] per 10 µg/m3 higher NO2). Similar results were observed for the symptoms in the clinical range, and for postnatal exposures to air pollution. CONCLUSIONS: Overall, our results suggest that prenatal and postnatal exposure to air pollution is not associated with depressive and anxiety symptoms or aggressive symptoms in children of 7 to 11 years old.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31240728

RESUMO

BACKGROUND: Sleep problems occur in up to 30% of children and have been associated with adverse developmental outcomes. However, due to a lack of longitudinal neuroimaging studies, the neurobiological changes that may underlie some of these associations have remained unclear. This study explored the association between sleep problems during childhood and white matter (WM) microstructure in preadolescence. METHODS: Children from the population-based birth cohort, the Generation R Study, who had repeatedly assessed sleep problems between 1.5 and 10 years of age and a MRI scan at age 10 (N = 2,449), were included. Mothers reported on their child's sleep problems using the Child Behavior Checklist (CBCL 1.5-5) when children were 1.5, 3, and 6 years of age. At age 2, mothers completed very similar questions. At age 10, both children and their mothers reported on sleep problems. We used whole-brain and tract-specific fractional anisotropy (FA) and mean diffusivity (MD) values obtained through diffusion tensor imaging as measures of WM microstructure. RESULTS: Childhood sleep problems at 1.5, 2, and 6 years of age were associated with less WM microstructural integrity (approximately 0.05 SD lower global FA score per 1-SD sleep problems). In repeated-measures analyses, children with more sleep problems (per 1-SD) at baseline had lower FA values at age 10 in particular in the corticospinal tract (-0.12 SD, 95% CI:-0.20;-0.05), the uncinate fasciculus (-0.12 SD, 95% CI:-0.19;-0.05), and the forceps major (-0.11 SD, 95% CI:-0.18;-0.03), although effect estimates across the tracts did not differ substantially. CONCLUSIONS: Childhood sleep disturbances are associated with less WM microstructural integrity in preadolescence. Our results show that early neurodevelopment may be a period of particular vulnerability to sleep problems. This study cannot demonstrate causality but suggests that preventive interventions addressing sleep problems should be further explored to test whether they impact adverse neurodevelopment.

15.
Nat Commun ; 10(1): 2581, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197173

RESUMO

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.


Assuntos
Metilação de DNA/fisiologia , Diabetes Mellitus Tipo 2/genética , Glucose/metabolismo , Insulina/metabolismo , Obesidade/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Ilhas de CpG/genética , Diabetes Mellitus Tipo 2/metabolismo , Epigênese Genética/fisiologia , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Estudo de Associação Genômica Ampla/métodos , Homeostase/genética , Humanos , Masculino , Redes e Vias Metabólicas/genética , Pessoa de Meia-Idade , Obesidade/metabolismo , Polimorfismo de Nucleotídeo Único/fisiologia , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-31049953

RESUMO

BACKGROUND: Internalising and externalising problems commonly co-occur in childhood. Yet, few developmental models describing the structure of child psychopathology appropriately account for this comorbidity. We evaluate a model of childhood psychopathology that separates the unique and shared contribution of individual psychological symptoms into specific internalising, externalising and general psychopathology factors and assess how these general and specific factors predict long-term outcomes concerning criminal behaviour, academic achievement and affective symptoms in three independent cohorts. METHODS: Data were drawn from independent birth cohorts (Avon Longitudinal Study of Parents and Children (ALSPAC), N = 11,612; Generation R, N = 7,946; Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN), N = 408). Child psychopathology was assessed between 4 and 8 years using a range of diagnostic and questionnaire-based measures, and multiple informants. First, structural equation models were used to assess the fit of hypothesised models of shared and unique components of psychopathology in all cohorts. Once the model was chosen, linear/logistic regressions were used to investigate whether these factors were associated with important outcomes such as criminal behaviour, academic achievement and well-being from late adolescence/early adulthood. RESULTS: The model that included specific factors for internalising/externalising and a general psychopathology factor capturing variance shared between symptoms regardless of their classification fits well for all of the cohorts. As hypothesised, general psychopathology factor scores were predictive of all outcomes of later functioning, while specific internalising factor scores predicted later internalising outcomes. Specific externalising factor scores, capturing variance not shared by any other psychological symptoms, were not predictive of later outcomes. CONCLUSIONS: Early symptoms of psychopathology carry information that is syndrome-specific as well as indicative of general vulnerability and the informant reporting on the child. The 'general psychopathology factor' might be more relevant for long-term outcomes than specific symptoms. These findings emphasise the importance of considering the co-occurrence of common internalising and externalising problems in childhood when considering long-term impact.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31078631

RESUMO

OBJECTIVE: Exposure to interpersonal violence is a known risk factor for psychopathology. However, it is unclear whether there are sensitive periods when exposure is most deleterious. We aimed to determine if there were time-periods when physical or sexual violence exposure was associated with greater child psychopathology. METHOD: This study (N=4,580) was embedded in Generation R, a population-based prospective birth-cohort. Timing of violence exposure, reported through maternal reports (child age=10 years) was categorized by age at first exposure, defined as: very early (0-3 years), early (4-5 years), middle (6-7 years), and late childhood (8+ years). Using Poisson regression, we assessed the association between timing of first exposure and levels of internalizing and externalizing symptoms, using the Child Behavior Checklist at age 10. RESULTS: Violence exposure at any age was associated with higher internalizing (physical violence: RR=1.46, p<0.0001; sexual violence: RR=1.30, p<.0001) and externalizing symptoms (physical violence: RR=1.52, p<0.0001; sexual violence: RR=1.31, p=0.0005). However, the effects of violence were time-dependent: compared to children exposed at older ages, children first exposed during very early childhood had greater externalizing symptoms. Sensitivity analyses suggested that these time-based differences emerged slowly across ages 1.5, 3, 6 and 10, showing a latency between onset of violence exposure and emergence of symptoms, and were unlikely explained by co-occurring adversities. CONCLUSION: Interpersonal violence is harmful to childhood mental health regardless of when it occurs. However, very early childhood may be a particularly sensitive period when exposure results in worse psychopathology outcomes. Results should be replicated in fully prospective designs.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31069583

RESUMO

Developmental patterns of anxiety and depression symptoms in early childhood have previously been related to anxiety and mood disorders in middle childhood. In the current study, trajectories of anxiety and depression symptoms (1.5-10 years) were related to children's broader psychosocial and school-related functioning at 10 years. We included a population-based sample of 7499 children, for whom primary caregivers reported anxiety and depression symptoms on the Child Behavior Checklist, at children's ages of 1.5, 3, 6, and 10. Growth Mixture Modeling identified four distinct, gender-invariant, trajectories of anxiety and depression symptoms: low (82.4%), increasing (7.4%), decreasing (6.0%), and increasing symptoms up to age 6 followed by a decrease to age 10 (preschool-limited, 4.2%). Children with a non-Dutch ethnicity had lower odds to be in the increasing trajectory and higher odds to be in the decreasing and pre-school limited trajectory. Also, low maternal education predicted the decreasing and pre-school limited trajectory. Higher levels of psychopathology during pregnancy for both mothers and fathers predicted the increasing, decreasing, and preschool-limited trajectory, compared to the low trajectory. At age 10, children in the increasing and preschool-limited trajectory had diminished psychosocial outcomes (friendship-quality and self-esteem) and worse school-related outcomes (school performance and school problems). This study adds to current knowledge by demonstrating that developmental patterns of anxiety and depression symptoms in early childhood are related to broader negative outcomes in middle childhood. Child and family factors could guide monitoring of anxiety and depression symptoms in the general population and provide targets for prevention programs.

20.
Am J Psychiatry ; 176(9): 702-710, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31055967

RESUMO

OBJECTIVE: The authors examined associations of exposure to maternal depressive symptoms at different developmental stages from fetal life to preadolescence with child brain development, including volumetrics and white matter microstructure. METHODS: This study was embedded in a longitudinal birth cohort in Rotterdam, the Netherlands. Participants were 3,469 mother-child pairs with data on maternal depressive symptoms and child neuroimaging at age 10. The authors also measured child emotional and behavioral problems at the time of neuroimaging. The association of maternal depressive symptoms with child brain development at each assessment was examined. Maternal depressive symptom trajectories were modeled across fetal life and childhood to determine the association of maternal depressive symptom patterns over time with child brain development. RESULTS: The single-time-point analyses showed that maternal depressive symptoms at child age 2 months were associated with smaller total gray matter volume and lower global fractional anisotropy (FA), whereas maternal depressive symptoms assessed prenatally or in childhood were not. The trajectory analyses suggested in particular that children exposed to persistently high levels of maternal depressive symptoms across the perinatal period had smaller gray and white matter volumes as well as alterations (i.e., lower FA) in white matter microstructure compared with nonexposed children. Furthermore, the gray matter volume differences mediated the association between postnatal maternal depressive symptoms and child attention problems. CONCLUSIONS: Perinatal maternal depressive symptoms were consistently associated with child brain development assessed 10 years later. These results suggest that the postnatal period is a window of vulnerability for adversities such as maternal depressive symptoms.

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