Lower Childhood IQ Research Articles

Prenatal exposure to common plasticizers: a longitudinal study on phthalates, brain volumetric measures, and IQ in youth.

Exposure to phthalates, used as plasticizers and solvents in consumer products, is ubiquitous. Despite growing concerns regarding their neurotoxicity, brain differences associated with gestational exposure to phthalates are understudied. We included 775 mother-child pairs from Generation R, a population-based pediatric neuroimaging study with prenatal recruitment, who had data on maternal gestational phthalate levels and T1-weighted magnetic resonance imaging in children at age 10 years. Maternal urinary concentrations of phthalate metabolites were measured at early, mid-, and late pregnancy. Child IQ was assessed at age 14 years. We investigated the extent to which prenatal exposure to phthalates is associated with brain volumetric measures and whether brain structural measures mediate the association of prenatal phthalate exposure with IQ. We found that higher maternal concentrations of monoethyl phthalate (mEP, averaged across pregnancy) were associated with smaller total gray matter volumes in offspring at age 10 years (β per log10 increase in creatinine adjusted mEP = -10.7, 95%CI: -18.12, -3.28). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (β for mediated path =-0.31, 95%CI: -0.62, 0.01, p = 0.05, proportion mediated = 18%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. Our findings suggest the global impact of prenatal phthalate exposure on brain volumetric measures that extends into adolescence and underlies less optimal cognitive development.

Genetic correlations between suicide attempts and psychiatric and intermediate phenotypes adjusting for mental disorders.

Suicide attempts are a moderately heritable trait, and genetic correlations with psychiatric and related intermediate phenotypes have been reported. However, as several mental disorders as well as major depressive disorder (MDD) are strongly associated with suicide attempts, these genetic correlations could be mediated by psychiatric disorders. Here, we investigated genetic correlations of suicide attempts with psychiatric and related intermediate phenotypes, with and without adjusting for mental disorders. To investigate the genetic correlations, we utilized large-scale genome-wide association study summary statistics for suicide attempts (with and without adjusting for mental disorders), nine psychiatric disorders, and 15 intermediate phenotypes. Without adjusting for mental disorders, suicide attempts had significant positive genetic correlations with risks of attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorder, MDD, anxiety disorders and posttraumatic stress disorder; higher risk tolerance; earlier age at first sexual intercourse, at first birth and at menopause; higher parity; lower childhood IQ, educational attainment and cognitive ability; and lower smoking cessation. After adjusting for mental disorders, suicide attempts had significant positive genetic correlations with the risk of MDD; earlier age at first sexual intercourse, at first birth and at menopause; and lower educational attainment. After adjusting for mental disorders, most of the genetic correlations with psychiatric disorders were decreased, while several genetic correlations with intermediate phenotypes were increased. These findings highlight the importance of considering mental disorders in the analysis of genetic correlations related to suicide attempts and suggest that susceptibility to MDD, reproductive behaviors, and lower educational levels share a genetic basis with suicide attempts after adjusting for mental disorders.

Differential Unmet Needs and Experience of Restorative Dental Care in Trajectories of Dental Caries Experience: A Birth Cohort Study

Dental caries is a chronic and cumulative disease but little has been reported on the continuity of the disease and its treatment through life. Group-based multi-trajectory modeling was used to identify developmental trajectories of untreated carious tooth surfaces (DS), restored tooth surfaces (FS), and teeth extracted due to caries (MT) from ages 9 to 45 years in a New Zealand longitudinal birth cohort, the Dunedin Multidisciplinary Health and Development Study (n = 975). Associations between early-life risk factors and trajectory group membership were examined by specifying the probability of group membership according to a multinomial logit model. Six trajectory groups were identified and labeled: “low caries rate”; “moderate caries rate, maintained”; “moderate caries rate, unmaintained”; “high caries rate, restored”; “high caries rate, tooth loss”; and “high caries rate, untreated caries”. The two moderate-caries-rate groups differed in count of FS. The three high-caries-rate groups differed in the relative proportion of accumulated DS, FS, and MT. Early childhood risk factors associated with less favorable trajectories included higher dmfs scores at age 5, lack of exposure to community water fluoridation during the first 5 years of life, lower childhood IQ, and low childhood socioeconomic status. Parent self-ratings of their own or their child’s oral health as “poor” were associated with less favorable caries experience trajectories. Children who had clinical signs of dental caries together with a parent rating of child’s oral health as poor were more likely to follow a less favorable caries trajectory. Higher deciduous dentition caries experience at age 5 years was associated with less favorable caries trajectories, as were children whose parents gave “poor” ratings of their own or their child’s oral health. These findings highlight the considerable intergenerational continuity in dental caries experience from early childhood to midlife. Subjective measures of child oral health are informative and might aid as predictors of adult caries experience in cases where childhood dental clinical data were not available.

Prenatal exposure to endocrine disrupting chemicals and brain development in adolescents

Background and Aim Despite growing concerns regarding the neurotoxicity of phthalates and bisphenols, brain differences associated with gestational exposure to these chemicals are understudied. We investigated the extent to which prenatal exposures to these endocrine disrupting chemicals are associated with global brain volumetric measures in adolescents and whether brain measures mediate the association of prenatal exposures with child IQ. Methods We included 908 mother-child pairs from Generation R, a population-based birth cohort, with data on maternal gestational phthalate and/or bisphenol concentrations and T1-weighted magnetic resonance imaging in children at age 10 years. Child IQ was assessed at age 14 years. Maternal urinary concentrations of phthalate metabolites and bisphenols were measured at early, mid-, and late pregnancy. We examined the associations of pregnancy-averaged, creatinine-adjusted concentrations of individual phthalate metabolites as well as ∑di-2-ethylhexyl phthalate, phthalic acid, and bisphenol A with and brain volumetric measures using linear regression. We used mediation modelling to identify the proportion mediated by brain measures in the association of prenatal exposures and child IQ. Results Higher maternal concentrations of monoethyl phthalate (mEP) were associated with smaller total gray matter volumes in offspring at age 10 years (β per log10 increase in creatinine adjusted mEP=-10.27, 95%CI:-17.85, -2.69). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (natural indirect effect=-0.27, 95%CI: -0.55,0.00, proportion mediated=20%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. We found no association between maternal prenatal bisphenols and global brain volumetric measures or child IQ. Conclusions Our findings suggest the global impact of prenatal phthalate exposure on the brain that extends into adolescence and underlies impaired general cognition. Keywords: MRI; Pregnancy, phthalates

Investigating genetic overlaps of the genetic factor differentiating schizophrenia from bipolar disorder with cognitive function and hippocampal volume.

Schizophrenia and bipolar disorder display clinical similarities and dissimilarities. We investigated whether the genetic factor differentiating schizophrenia from bipolar disorder is genetically associated with cognitive phenotypes and hippocampal volumes. We revealed genetic overlaps of the genetic differentiating factor with low general cognitive ability, low childhood IQ, low educational attainment and reduced hippocampal volumes. The genetic correlations with low general cognitive ability and reduced hippocampal volumes were associated with risk of schizophrenia, whereas the genetic correlations with high childhood IQ and educational attainment were associated with risks of bipolar disorder. These findings suggest these disorders have disorder-specific genetic factors related to clinical phenotypes.

Prenatal air pollution and childhood IQ: Preliminary evidence of effect modification by folate

ObjectivesAnimal studies suggest that air pollution is neurotoxic to a developing fetus, but evidence in humans is limited. We tested the hypothesis that higher air pollution is associated with lower child IQ and that effects vary by maternal and child characteristics, including prenatal nutrition. MethodsWe used prospective data collected from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study. Outdoor pollutant exposure during pregnancy was predicted at geocoded home addresses using a validated national universal kriging model that combines ground-based monitoring data with an extensive database of land-use covariates. Distance to nearest major roadway was also used as a proxy for traffic-related pollution. Our primary outcome was full-scale IQ measured at age 4–6. In regression models, we adjusted for multiple determinants of child neurodevelopment and assessed interactions between air pollutants and child sex, race, socioeconomic status, reported nutrition, and maternal plasma folate in second trimester. ResultsIn our analytic sample (N = 1005) full-scale IQ averaged 2.5 points (95% CI: 0.1, 4.8) lower per 5 μg/m3 higher prenatal PM10, while no associations with nitrogen dioxide or road proximity were observed. Associations between PM10 and IQ were modified by maternal plasma folate (pinteraction = 0.07). In the lowest folate quartile, IQ decreased 6.8 points (95% CI: 1.4, 12.3) per 5-unit increase in PM10; no associations were observed in higher quartiles. ConclusionsOur findings strengthen evidence that air pollution impairs fetal neurodevelopment and suggest a potentially important role of maternal folate in modifying these effects.

Adolescents Who Self-Harm and Commit Violent Crime: Testing Early-Life Predictors of Dual Harm in a Longitudinal Cohort Study.

Self-harm is associated with violent offending. However, little is known about young people who engage in "dual-harm" behavior. The authors investigated antecedents, clinical features, and life characteristics distinguishing dual-harming adolescents from those who self-harm only. Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative U.K. cohort of 2,232 twins born in 1994 and 1995. Self-harm in adolescence was assessed through interviews at age 18. Violent offending was assessed using a computer questionnaire at age 18 and police records through age 22. Risk factors were assessed between ages 5 and 12. Adolescent mental health, victimization, personality functioning, and use of support services were measured at age 18. Self-harm was associated with violent crime (odds ratio=3.50, 95% CI=2.61-4.70), even after accounting for familial risk factors. Dual harmers had been victims of violence from childhood and exhibited lower childhood self-control and lower childhood IQ than self-only harmers. Dual harmers experienced higher rates of concurrent psychotic symptoms and substance dependence. They also exhibited distinct personality styles characterized by resistance to change and by emotional and interpersonal lability. However, dual harmers were not more likely than self-only harmers to have contact with mental health services. Dual harmers have self-control difficulties and are immersed in violence from a young age. A treatment- rather than punishment-oriented approach is indicated to meet these individuals' needs. Connecting self-harming adolescents with delinquency-reduction programs and transdiagnostic approaches that target self-regulation may reduce harmful behaviors. Preventing childhood maltreatment and implementing strategies to reduce victimization exposure could mitigate risk for both internalized and externalized violence.

WISC-IV Factor Structures of Japanese Children with Borderline, or Deficient Intellectual Abilities: Testing Measurement Invariance Compared to Simulated Norm

Factor analyses of intelligence tests have been conducted with diverse clinical populations. Factor structures of the Wechsler Intelligence Scale for Children-fourth Edition (WISC-IV) in children with borderline intellectual functioning (BIF) and intellectual disability (ID) were compared to the Japanese norm by using a simulated group. Measurement invariance among simulated, borderline and disability groups was tested by multi-group analyses through structural equation modeling for manual-depended four-factor model. Results indicated that the metric invariance model was supported among the three groups. The correlation coefficients between the four index scores suggested that BIF could be partially explained as resulting from inhibiting and restraining effects among broad abilities when responding to each subtest of intelligence tests. This degrading effect might lower IQ in children having certain clinical problems. On the other hand, ID could be partially understood as a brain impairment consisting of unrelated and isolated activation of broad ability areas. It is concluded that there are differences in factor structures and mechanisms of BIF and ID.

Multi-rater developmental trajectories of hyperactivity\u2013impulsivity and inattention symptoms from 1.5 to 17\xa0years: a population-based birth cohort study

The developmental course of hyperactivity–impulsivity and inattention symptoms from infancy to adolescence has not been documented in a population sample. The aim of this study was to describe the developmental course of hyperactivity–impulsivity and inattention symptoms from 1.5 to 17 years using multiple informants, and to identify perinatal risk factors associated with following elevated (high-risk) trajectories. Using a population-based birth cohort (n = 1374), symptom ratings from mothers (1.5–8 years), teachers (6–13 years) and participant self-reports (10–17 years) were combined using group-based multi-trajectory modeling to identify informants’ convergence in identifying high-symptom trajectories of hyperactivity–impulsivity and inattention over time. Perinatal risk factors associated with high-symptom trajectories were identified using stepwise logistic regression. The study found that symptoms of hyperactivity–impulsivity broadly declined from 1.5 to 17 years while symptoms of inattention remained constant. 21.4% of participants followed elevated trajectories of hyperactivity–impulsivity and 20.2% followed elevated trajectories of inattention; 11.6% followed elevated trajectories of both types of symptoms concurrently. Risk factors for high-risk trajectories of hyperactivity–impulsivity were low maternal education, prenatal alcohol exposure, non-intact family, maternal depression, and low child IQ; for high-risk inattention they were prenatal street drug exposure, early motherhood, low maternal education, maternal depression and low child IQ. Risk factors for trajectories of high-risk hyperactivity–impulsivity and inattention concurrently were low maternal education, maternal depression, and low child IQ. The combination of longitudinal assessments from multiple informants (i.e., mother, teacher, participant-reports) provides a new way to characterize hyperactivity–impulsivity and inattention phenotypes over time.

The Association of Maternal Thyroid Autoimmunity During Pregnancy With Child IQ.

Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for gestational thyroid dysfunction. During the first 18 to 20 weeks of pregnancy, high concentrations of human chorionic gonadotropin (hCG) stimulate the thyroid to ensure adequate thyroid hormone availability for the developing fetus. However, TPOAb-positive women have an impaired thyroidal response to hCG stimulation. To study the association of maternal TPOAb positivity during pregnancy with child IQ. This study was embedded in two prospective birth cohorts: Generation R (Rotterdam, the Netherlands) and Avon Longitudinal Study of Parents and Children (ALSPAC; United Kingdom). Mother-child pairs with available data on early pregnancy TPOAb (≤18 weeks of gestation) and offspring IQ were included (n = 3637 for Generation R and n = 2396 for ALSPAC). Child IQ at 5 to 10 years of age. In Generation R, TPOAb positivity was associated with a 2.0 ± 0.9-point lower mean child IQ (P = 0.03). Sensitivity analyses showed negative effect estimates already from TPOAb concentrations considerably lower than currently used manufacturer cutoffs. In ALSPAC, neither TPOAb positivity nor TPOAb concentrations below manufacturer cutoffs were associated with child IQ (TPOAb positivity: 0.7 ± 1.0; P = 0.45). Adjustment for maternal TSH or free T4 concentrations or urinary iodine/creatinine ratio did not change the results. TPOAb positivity during pregnancy was associated with lower child IQ in Generation R but not in ALSPAC. Further studies are needed to elucidate whether differences between the study populations, such as maternal iodine status, could be the underlying cause for these differences.

Clinical associations of maternal thyroid function with foetal brain development: Epidemiological interpretation and overview of available evidence

Thyroid hormone is an important regulator of early brain development, particularly during early stages of gestation during which foetal thyroid hormone availability depends on the maternal transfer of thyroid hormones. There is a wide range of experimental studies showing that low maternal thyroid hormone availability is associated with suboptimal brain development parameters. While few clinical studies have shown that overt maternal hypothyroidism is associated with lower child IQ, the question whether more subclinical changes in maternal thyroid function could also lead to suboptimal foetal brain development. In this review, we put the latter studies in perspective and discuss their interpretation from an epidemiological and clinical perspective. Furthermore, we extend this discussion to also include future perspective and identify important knowledge gaps in the field.

24.3 EIGHTEEN-YEAR COURSE OF COGNITIVE FUNCTIONING IN PSYCHOTIC DISORDERS: FINDINGS FROM THE SUFFOLK COUNTY MENTAL HEALTH LONGITUDINAL STUDY

BackgroundKnowledge about the long-term cognitive course in psychotic disorders is limited. In this 18-year follow-up of participants of the Suffolk County project we report on the longitudinal course of cognitive performance in individuals with schizophrenia spectrum disorders, affective psychoses and other psychoses. We investigate (i) change in functioning in 6 cognitive domains from 2-years to 20-years follow-up after first admission; (ii) 20-year performance and age-related differences in cognitive performance in patients relative to a never psychotic comparison group; and (iii) key predictors of clinically meaningful cognitive decline in patients.MethodsData came from the Suffolk County Mental Health Project, a prospective study of first-admission patients. Cognitive tests were administered 2 years (n = 399; schizophrenia spectrum: 285, affective psychoses: 226, other psychoses: 117) and 20 years (n = 240; 115, 92, and 34, respectively) after first admission, with 195 individuals completing cognitive tests at both time points. A never psychotic comparison group (N=260) was assessed at year 20.ResultsIndividuals with schizophrenia spectrum disorders showed lower cognitive functioning than those with affective and other psychoses. Over time, patients declined in cognitive performance on almost all tests (d = 0.24 (range 0.12- 0.44)) with comparable magnitude across diagnoses. Longer duration of untreated psychosis and low childhood IQ were significantly associated with clinically relevant decline (>0.5SD) in general verbal ability and processing speed, but there were no robust predictors of cognitive decline across tests. Cross-sectional comparisons of patients to controls showed increasing impairments with age for general verbal ability, verbal fluency, and executive functioning.DiscussionOur findings indicate that cognitive functioning in psychotic disorders continues to decline after the illness onset, that this decline is not specific to schizophrenia but present across psychotic disorders, and that, relative to never-psychotic individuals, impairments on some key-cognitive domains worsen with age. These results imply that cognitive treatment should not only include cognitive remediation but also prevention of age-related cognitive stagnation and/or decline.

Suicide attempt predicted by academic performance and childhood IQ: a cohort study of 26 000 children.

Academic performance in youth, measured by grade point average (GPA), predicts suicide attempt, but the mechanisms are not known. It has been suggested that general intelligence might underlie the association. We followed 26 315 Swedish girls and boys in population-representative cohorts, up to maximum 46 years of age, for the first suicide attempt in hospital records. Associations between GPA at age 16, IQ measured in school at age 13 and suicide attempt were investigated in Cox regressions and mediation analyses. There was a clear graded association between lower GPA and subsequent suicide attempt. With control for potential confounders, those in the lowest GPA quartile had a near five-fold risk (HR 4.9, 95% CI 3.7-6.7) compared to those in the highest quartile. In a mediation analysis, the association between GPA and suicide attempt was robust, while the association between IQ and suicide attempt was fully mediated by GPA. Poor academic performance in compulsory school, at age 16, was a robust predictor of suicide attempt past young adulthood and seemed to account for the association between lower childhood IQ and suicide attempt.

Fluoride exposure and reported learning disability diagnosis among Canadian children: Implications for community water fluoridation.

Recent studies have connected increased fluoride exposure with increased risk of neurodevelopmental-related outcomes, such as ADHD (attention deficit hyperactivity disorder) and lower IQ in children. Our primary objective was to examine the association between fluoride exposure and reported diagnosis of a learning disability among a population-based sample of Canadian children aged 3-12 years. We analyzed data from Cycles 2 and 3 of the Canadian Health Measures Survey. Four measures of fluoride exposure were available: 1) urinary fluoride (μmol/L), 2) creatinine-adjusted urinary fluoride (μmol/mmol), 3) specific gravity-adjusted urinary fluoride (μmol/L), and 4) fluoride concentration of tap water (mg/L) (Cycle 3 only). Diagnosis of a learning disability (yes/no) was based on parental- or self-report. Associations were examined using logistic regression (where possible), unadjusted and adjusted for covariates. When Cycles 2 and 3 were examined separately, reported learning disability diagnosis was not significantly associated with any measure of fluoride exposure in unadjusted or adjusted models. When Cycles 2 and 3 were combined, a small but statistically significant effect was observed such that children with higher urinary fluoride had higher odds of having a reported learning disability in the adjusted model (p = 0.03). However, the association was not observed in models that used creatinine-adjusted urinary fluoride and specific gravity-adjusted urinary fluoride, which are believed to be more accurate measures due to their correction for urinary dilution. Overall, there did not appear to be a robust association between fluoride exposure and parental- or self-reported diagnosis of a learning disability among Canadian children.

How Did Lead Exposure Affect the Children of the '70s?

Lead exposure has been linked to lower IQ in children and adolescents, but effects later in life have not been studied on a large scale.Researchers

Early life risk factors for cerebrovascular disease: A systematic review and meta-analysis.

Cerebrovascular disease (CVD) causes subclinical brain vascular lesions detected using neuroimaging and childhood factors may increase later CVD risk. We searched MEDLINE, PsycINFO, and EMBASE, and meta-analyzed all available evidence on childhood (premorbid) IQ, socioeconomic status (SES), education, and subclinical CVD in later life. Overall odds ratios (OR), mean difference or correlation, and 95% confidence intervals (CIs) were calculated using random effects methods. We identified 30 relevant studies (n = 22,890). Lower childhood IQ and lower childhood SES were associated with more white matter hyperintensities (WMH) (IQ: n = 1,512, r = -0.07, 95% CI -0.12 to -0.02, p = 0.007; SES: n = 243, deep WMH r = -0.18, periventricular WMH r = -0.146). Fewer years of education were associated with several CVD markers (n = 15,439, OR = 1.17, 95% CI 1.05 to 1.31, p = 0.003). No studies assessed early life factors combined. Childhood IQ, SES, and education are associated with increased risk of CVD on neuroimaging in later life. Further studies are required to provide further evidence and thereby inform policy.

The interplay of childhood behavior problems and IQ in the development of later schizophrenia and affective psychoses

Schizophrenia and affective psychoses are both associated with impaired social functioning, but the extent to which childhood behavioral impairments are present prior to onset of illness is less well studied. Moreover, the concurrent relationship of childhood behavior problems and premorbid IQ with subsequent psychotic disorder has not been established. We investigated whether childhood behavior problems are associated with increased risk for adult schizophrenia or affective psychosis, independently and in combination with IQ. The study included individuals with schizophrenia (N=47), affective psychoses (N=45) and non-psychotic controls (N=1496) from the New England Family Study. Behavior problems were prospectively assessed from standardized clinician observations at ages 4 and 7. IQ was assessed with the Stanford-Binet at age 4 and the Wechsler Intelligence Scale for Children at age 7. We found externalizing problems at age 4 and externalizing and internalizing problems at age 7 were associated with later schizophrenia, and both internalizing and externalizing problems at ages 4 and 7 were associated with later development of affective psychoses. Lower IQ at ages 4 and 7 was associated with schizophrenia, while lower IQ was associated with affective psychoses at age 7 only. Examined simultaneously, both lower IQ and behavior problems remained associated with risk of schizophrenia, while only behavior problems remained associated with affective psychoses. Behavior problems appear to be a general marker of risk of adult psychotic disorder, while lower childhood IQ is more specific to risk of schizophrenia. Future research should clarify the premorbid evolution of behavior and cognitive problems into adult psychosis.

Correlates of health-related quality of life in children with drug resistant epilepsy.

Health-related quality of life (HRQL) is compromised in children with epilepsy. The current study aimed to identify correlates of HRQL in children with drug resistant epilepsy. Data came from 115 children enrolled in the Impact of Pediatric Epilepsy Surgery on Health-Related Quality of Life Study (PEPSQOL), a multicenter prospective cohort study. Individual, clinical, and family factors were evaluated. HRQL was measured using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), a parent-rated epilepsy-specific instrument, with composite scores ranging from 0 to 100. A series of univariable linear regression analyses were conducted to identify significant associations with HRQL, followed by a multivariable regression analysis. Children had a mean age of 11.85 ± 3.81 years and 65 (56.5%) were male. The mean composite QOLCE score was 60.18 ± 16.69. Child age, sex, age at seizure onset, duration of epilepsy, caregiver age, caregiver education, and income were not significantly associated with HRQL. Univariable regression analyses revealed that a higher number of anti-seizure medications (p = 0.020), lower IQ (p = 0.002), greater seizure frequency (p = 0.048), caregiver unemployment (p = 0.010), higher caregiver depressive and anxiety symptoms (p < 0.001 for both), poorer family adaptation, fewer family resources, and a greater number of family demands (p < 0.001 for all) were associated with lower HRQL. Multivariable regression analysis showed that lower child IQ (β = 0.20, p = 0.004), fewer family resources (β = 0.43, p = 0.012), and caregiver unemployment (β = 6.53, p = 0.018) were associated with diminished HRQL in children. The results emphasize the importance of child cognition and family variables in the HRQL of children with drug-resistant epilepsy. The findings speak to the importance of offering comprehensive care to children and their families to address the nonmedical features that impact on HRQL.

Mediation of Developmental Risk Factors for Psychosis by White Matter Microstructure in Young Adults With Psychotic Experiences

White matter (WM) abnormalities have been identified in schizophrenia at the earliest stages of the disorder. Individuals in the general population with psychotic experiences (PEs) may show similar changes, suggesting dysfunction due to aberrant neurodevelopment. Studying such people is a powerful means of understanding the nature of neurodevelopmental problems without the confound of clinical management and allows other potential risk factors associated with the schizophrenia spectrum to be taken into account. To compare WM microstructure and myelination in young adults with and without PEs identified from a population-based cohort using diffusion and relaxometry magnetic resonance imaging and to quantify potential mediating effects of WM on several known risk factors for psychosis. In this case-control study, participants were drawn from the UK Avon Longitudinal Study of Parents and Children. Psychotic experiences were assessed using a semistructured interview. Magnetic resonance imaging was carried out at age 20 years in 123 participants who had PEs and 124 individuals serving as controls. Participants with PEs were subdivided into those with operationally defined suspected PEs, definite PEs, and psychotic disorder. Diffusion tensor magnetic resonance imaging and relaxometry-derived myelin water fractions were used to measure WM microstructure and myelination, respectively. Differences in quantitative WM indices were assessed using tract-based spatial statistics. A binary model and a continuum-like ordinal model of PEs were tested. Among the 123 participants who had PEs (mean [SE] age, 20.01 [0.004] years), 37 were male and 86 were female. Among the 124 controls (mean [SE] age, 20.11 [0.004] years), 49 were male and 76 were female. Fractional anisotropy in left frontomedial WM was significantly reduced in individuals with PEs (Montreal Neurological Institute [MNI] coordinates, -18, 37, -2; P = .0046). The ordinal model identified a similar but more widespread effect, with a corresponding increase in radial diffusivity (MNI coordinates, -15, 29, 21; P = .0042). Low birth weight (ρ = -0.155; P = .015) and childhood IQ (ρ = -0.188; P = .003) were associated with the presence of PEs. Results of mediation analysis were consistent with the association between birth weight (21.1% mediation effect; P = 6.20 × 10-3) and childhood IQ (7.9% mediation effect; P = .041) and by PEs being mediated by fractional anisotropy changes in these regions. The results of the study imply the presence of abnormal WM microstructure in young adults with PEs. The results are consistent with the hypothesis that neurodevelopmental factors cause alterations in the cellular composition of WM circuits critical to higher cognitive function. Such alterations may first manifest in childhood as reduced IQ and later contribute to PEs in early adulthood.

Blood lead concentration and thyroid function during pregnancy: results from the Yugoslavia Prospective Study of Environmental Lead Exposure.

Background: Although maternal hypothyroidism increases the risk of adverse neonatal and obstetric outcomes as well as lower IQ in children, the environmental determinants of maternal thyroid dysfunction have yet to be fully explored.Objectives: We aimed to examine associations between mid-pregnancy blood lead (BPb) and concomitant measures of thyroid function among participants in the Yugoslavia Prospective Study of Environmental Lead Exposure.Methods: As part of a population-based prospective study of two towns in Kosovo—one with high levels of environmental lead and one with low—women were recruited during the second trimester of pregnancy, at which time blood samples and questionnaire data were collected. We measured concentrations of BPb, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibodies (TPOAb) in archived serum samples.Results: Compared with women from the unexposed town, women from the exposed town had lower mean FT4 (0.91 ± 0.17 vs. 1.03 ± 0.16 ng/dL), higher mean TPOAb (15.45 ± 33.08 vs. 5.12 ± 6.38 IU/mL), and higher mean BPb (20.00 ± 6.99 vs. 5.57 ± 2.01 μg/dL). No differences in TSH levels were found. After adjustment for potential confounders, for each natural log unit increase in BPb, FT4 decreased by 0.074 ng/dL (95% CI: –0.10, –0.046 ng/dL), and the odds ratio for testing positive to TPOAb was 2.41 (95% CI: 1.53, 3.82). We found no association between BPb and TSH.Conclusions: Prolonged lead exposure may contribute to maternal thyroid dysfunction by stimulating autoimmunity to the thyroid gland.Citation: Kahn LG, Liu X, Rajovic B, Popovac D, Oberfield S, Graziano JH, Factor-Litvak P. 2014. Blood lead concentration and thyroid function during pregnancy: results from the Yugoslavia Prospective Study of Environmental Lead Exposure. Environ Health Perspect 122:1134–1140; http://dx.doi.org/10.1289/ehp.1307669