Search

Background Schizophrenia is associated with elevated levels of circulating C-reactive protein (CRP) and other inflammatory markers, but it is unclear whether these associations extend to psychotic symptoms occurring in adolescence in the general population. A symptom-based approach may provide important clues for apparent trans-diagnostic effect of inflammation, which is also associated with depression and other psychiatric disorders. Methods Based on data from 2421 participants from the Avon Longitudinal Study of Parents and Children birth cohort, we examined associations of serum CRP levels assessed around age 16 with ten positive and ten negative symptoms of psychosis assessed using questionnaires around age 17, using both individual symptoms and symptom dimension scores as outcomes. Regression models were adjusted for sex, body mass index, depressive symptoms, substance use, and other potential confounders. Results Most prevalent positive symptoms were paranoid ideation (4.8%), visual (4.3%) and auditory (3.5%) hallucinations. Negative symptoms were more strongly correlated with concurrent depressive symptoms (r=0.51; P, Highlights • We examined psychotic symptoms in adolescents from a population-based birth cohort. • Common positive symptoms were paranoid ideation, visual and auditory hallucinations. • Negative symptoms were correlated with depressive and positive symptoms. • CRP was similarly associated with positive and negative symptom dimension scores. • CRP was specifically associated with auditory hallucinations and anhedonia.

Highlights • We found that school enjoyment at age 13-14 was strongly associated with academic attainment at age 16. • Children experiencing depressive or externalising symptoms at age 10-11 were less likely to enjoy school and feel connected to staff and teachers at age 13-14. • We found evidence that school enjoyment partially mediated the association between earlier depressive and externalising symptoms and academic attainment. This suggests that children's experience of school could be a potentially important modifiable risk factor for low attainment in children with mental health problems., Background Previous research on the relationship between children's depressive and externalising symptoms, experience of school, and academic attainment is inconclusive. The aims of this study were (i) to test bidirectional associations between children's school experience and depressive and externalising symptoms at age 10-11 and 13-14, (ii) to ascertain whether school experience age 13-14 is associated with academic attainment age 16, and (iii) to test whether school experience mediates the relationship between depressive or externalising symptoms and attainment. Methods Data was used from the Avon Longitudinal Study of Parents and Children (n=6,409). A cross-lagged model was used to investigate bidirectional associations between school experience (enjoyment and connectedness) and depression and externalising at age 10-11 and 13-14. The same framework was used to test if school experience aged 13-14 mediated associations of depressive and externalising symptoms with later attainment. Results Depressive and externalising symptoms at 10-11 were negatively associated with school connectedness (depressive: standardised β=-0.06, CI: -0.11, 0.01; externalizing: β=-0.13, CI: -0.17, -0.08), and school enjoyment at 13-14 (depressive β=-0.04, -0.08, 0.03; externalising: β=-0.08, CI: -0.13, -0.03). School enjoyment at 13-14 was positively associated with attainment at 16 (β=0.10, CI: 0.04, 0.15), and partially mediated associations between depressive and externalising symptoms at 10-11 and attainment at 16 (depressive: proportion mediated 2.2%, CI: -1.5, 5.9; externalising: proportion mediated; 4.7%, CI: 0.7, 10.1,). Limitations Results may be subject to residual confounding. Conclusions School enjoyment is a potentially modifiable risk factor that may affect educational attainment of adolescents with depressive or externalising symptoms.

Deficiencies of many nutrients in pregnancy have adverse effects on fetal brain development with consequent impaired cognitive function in childhood. However, it is unclear whether deficiencies of vitamin B12 prenatally are harmful to the developing fetus. We therefore used the Avon Longitudinal Study of Parents and Children to test the hypothesis that cognitive outcomes in childhood are reduced if their mothers consumed a diet low in vitamin B12 during pregnancy. A detailed exposome analysis was used to identify 9 factors independently associated with low vitamin B12 intake. These were taken into account in each of 26 outcome analyses. Results showed that the children of women with the lowest 10% intake of B12 were at increased risk of poor vocabulary at 24 months, reduced ability at combining words at 38 months, poor speech intelligibility at 6 years, poor mathematics comprehension at school years 4 and 6 (ages 8-9 and 10-11 years), and poor results on the national mathematics tests (age 13). There were no such significant adjusted associations for reading or spelling abilities, or for verbal or full-scale IQ (Intelligence Quotient) at 8 or at 15. Thus, we have confirmed that there are adverse effects on the child's development if the pregnant woman has a low intake of vitamin B12, and we have shown that these are specific to certain speech and mathematical abilities.

Highlights • Negative overgeneral memory predicted subsequent adolescent depressive symptoms. • This association was present in the whole sample, not just high-risk adolescents. • This prospective link is novel in samples without increased risk for depression. • Overgeneral memory may be a risk factor for adolescent depressive symptoms. • Overgeneral memory definition and valence are important to consider in future work., Background Overgeneral autobiographical memory (OGM), the tendency to recall fewer specific memories and recall more repeated or extended events, is associated with subsequent adult depression. However, prospective associations are only found in adolescents with additional risk factors for depression (e.g. OGM for negative material is associated with subsequent depression in females and those at familial risk of depression) and not in community samples. It remains unclear whether OGM is associated with subsequent depression in population-based adolescent samples or just in high-risk adolescents. Methods We examined the relationship between OGM for negative cues (age 13) and adolescent depressive symptoms in a population-based cohort - the Avon Longitudinal Study of Parents and Children. Regression models investigated the association of OGM for negative cues with depressive symptoms at age 12.5 years (n = 3,145) and age 16.5 years (n = 2,345). Associations with alternative measures of OGM were also explored. Gender and maternal depression were examined as potential moderators of these relationships. Results OGM for negative cues was associated with both contemporaneous and prospective depressive symptoms. Only OGM for negative cues and total OGM were prospectively associated with depressive symptoms. There was no evidence of moderation by gender or maternal depression. Limitations Depression was reported 6 months earlier than OGM. Conclusions To our knowledge, this is the first study to find a prospective link between OGM for negative material and depression in a population-based cohort. Results highlight memory biases can precede subsequent adolescent depression in the general population, not just high-risk samples.

Background Lead and mercury are freely transferred across the placenta, while cadmium tends to accumulate in the placenta. Each contributes to adverse neurological outcomes for the child. Although prenatal heavy metal exposure has been linked with an array of neurodevelopmental outcomes in childhood, its association with the development of motor skills in children has not been robustly studied. Aims/objective The aim of the present study was to investigate the association between prenatal exposure to lead, cadmium and mercury, measured as maternal blood concentrations during pregnancy, and motor skills, measured as subtests of the Movement Assessment Battery for Children (Movement ABC) at age 7 years in a large sample of mother–child pairs enrolled in a UK observational birth cohort study (Avon Longitudinal Study of Parents and Children, ALSPAC). Methods Whole blood samples from pregnant women enrolled in ALSPAC were analysed for lead, cadmium and mercury. In a complete case analysis (n = 1558), associations between prenatal blood concentrations and child motor skills assessed by Movement ABC subtests of manual dexterity, ball skills and balance at 7 years were examined in adjusted regression models. Associations with probable developmental coordination disorder (DCD) were also investigated. Results The mean prenatal blood levels were: lead 3.66 ± 1.55 μg/dl; cadmium 0.45 ± 0.54 μg/l; mercury 2.23 ± 1.14 μg/l. There was no evidence for any adverse associations of prenatal lead, cadmium or mercury exposure with motor skills measured at age 7 years with Movement ABC subtests in adjusted regression models. Further, there were no associations with probable DCD. Conclusions There was no evidence to support a role of prenatal exposure to heavy metals at these levels on motor skills in the child at age 7 years measured using the Movement ABC. Early identification of symptoms of motor skills impairment is important, however, to enable investigation, assessment and treatment., Highlights • The association of in utero heavy metal exposure with motor skills in children is unclear. • Whole blood samples from pregnant women were analysed for lead, cadmium and mercury. • Motor skills were assessed by manual dexterity, ball skills and balance ability at 7 years. • There was no evidence for a role of prenatal exposure on motor skills in the child. • Early identification of symptoms of motor skills impairment is still important.

Although childhood maltreatment is associated with long-term impairment, some children function well despite this adversity. This study aimed to identify the key protective factors for good educational attainment and positive emotional health in adolescents who experienced maltreatment in early childhood. Data were analyzed from the Avon Longitudinal Study of Parents and Children, a large UK prospective cohort study. The sample was defined by maternally reported exposure to physical or emotional maltreatment by a parent prior to 5 years. 1118 (8.0%) children were emotionally maltreated and 375 (2.7%) were physically maltreated before the age of 5. There were too few cases of sexual abuse to be considered. Positive outcomes were operationalized as achieving 5 or more grade A*-C GCSE exam grades at 16 years and scores above the cohort median on the self-report Warwick-Edinburgh Mental Wellbeing Scale and Bachmann Self-Esteem Scale at 17.5 years. The associations of individual, family and community covariates with successful adaptation to the adversity of maltreatment were investigated using logistic regression. School related factors, including engagement in extracurricular activities, satisfaction with school and not being bullied were the most important in facilitating resilience in educational attainment, self-esteem and wellbeing. Good communication and social skills was the most protective individual trait. There was insufficient evidence to suggest that family factors were associated with resilience to maltreatment. School-based interventions are recommended to promote positive adaptation following parental maltreatment. Future research should evaluate outcomes across the life-course to understand whether the protective influences of school persist into adulthood.

Background: Picky eating behaviour in young children is a common concern for parents. Objective: To investigate early life factors which are associated with a child becoming a picky eater. Design: Singleton children from the Avon Longitudinal Study of Parents and Children were studied prospectively (n = 5758–6608). Parental-completion questionnaires were used to define ‘picky eating’ status at age 3 years, and child and parental feeding behaviours and practices throughout the first 2 years of life. Multinomial logistic regression models with 3 levels of picky eating (not, somewhat and very picky) as the dependant variables tested associations with antecedent variables, from pregnancy, and the first and second year of life, separately, then combining all significant variables in a final model. Results: Feeding difficulties during complementary feeding and late introduction of lumpy foods (after 9 months) were associated with increased likelihood of the child being very picky. A strong predictor was the child being choosy at 15 months, particularly if the mother was worried about this behaviour. Many children (56%) were considered to be choosy at 15 months: 17% went on to be very picky at 3 years if the mother was not worried, compared with 50% if the mother was very worried by the choosiness. The mother providing fresh fruit and eating the same meal as the child were protective against later ‘picky eating’ while feeding ready-prepared food was predictive. Conclusion: Advice and support to parents could help to reduce picky eating behaviour. Parents should be encouraged to introduce lumpy foods by 9 months, to feed fresh foods particularly fruit, and to eat with their children. Parents should be reassured that choosiness is normal and to continue to provide a variety of foods.

Highlights • At symptom level, IL-6 is associated with diurnal variation in mood, concentration difficulties, fatigue and sleep disturbances. • These are so-called somatic/neurovegetative symptoms of depression. • At dimension level, IL-6 is associated with both somatic/neurovegetative and psychological symptom dimensions. • Somatic/neurovegetative symptoms could be useful treatment targets and markers of treatment response in clinical trials of anti-inflammatory treatment for depression., Background Low-grade inflammation is associated with depression, but studies of specific symptoms are relatively scarce. Association between inflammatory markers and specific symptoms may provide insights into potential mechanism of inflammation-related depression. Using longitudinal data, we have tested whether childhood serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels are associated with specific depressive symptoms in early adulthood. Methods In the ALSPAC birth cohort, serum IL-6 and CRP levels were assessed at age 9 years and 19 depressive symptoms were assessed at age 18 years. We used modified Poisson generalised linear regression with robust error variance to estimate the risk ratio (RR) and 95% confidence interval (95% CI) for each depressive symptom. In addition, we used confirmatory factor analysis to create two continuous latent variables representing somatic/neurovegetative and psychological dimension scores. Structural equation modelling was used to test the associations between IL-6 and these dimension scores. Results Based on data from 2731 participants, IL-6 was associated with diurnal mood variation, concentration difficulties, fatigue and sleep disturbances. The adjusted RRs for these symptoms at age 18 years for participants in top, compared with bottom, third of IL-6 at age 9 years were 1.75 (95% CI, 1.13–2.69) for diurnal mood variation, 1.50 (95% CI, 1.11–2.02) for concentration difficulties, 1.31 (95% CI, 1.12–1.54) for fatigue, and 1.24 (95% CI, 1.01–1.52) for sleep disturbances. At dimension level, IL-6 was associated with both somatic/neurovegetative (β = 0.059, SE = 0.024, P = 0.013) and psychological (β = 0.056, SE = 0.023, P = 0.016) scores. Conclusions Inflammation is associated with specific symptoms of depression. Associations with so-called somatic/neurovegetative symptoms of depression such as fatigue, sleep disturbances and diurnal mood variation indicate that these symptoms could be useful treatment targets and markers of treatment response in clinical trials of anti-inflammatory treatment for depression.

The aim of this study was to examine the longitudinal influences of early life social and biological indicators on objectively measured physical activity. All newborns in 2004 in the city of Pelotas, Southern Brazil were enrolled in a birth cohort study. At the age of 6 years, a follow-up visit included objective assessment of overall physical activity (summarized in milli-g, 1 mg = 0.001 g) by tri-axial wrist worn accelerometry. The associations between early life exposures, such as type of delivery, parity, birth weight, preterm delivery, maternal physical activity, socioeconomic position, and overall physical activity were examined. Valid accelerometry data were obtained from 2604 children (78.2% of the eligible individuals). Girls were less active than boys (β = − 8.65 mg; 95% CI − 10.0; − 7.30). Higher socioeconomic position was related to lower activity levels (β = − 9.69 mg. 95% CI − 12.45; − 6.93) and a similar association was found with maternal schooling. No associations were found with birthweight, type of delivery or preterm delivery. This study provides evidence for the role of some social factors in explaining children's physical activity behaviors, and minimizes the influence of some early life biological factors at determining physical activity levels., Highlights • There was no biological role of early life variables on physical activity behaviors. • There was a strong evidence on the role of social factors. • Higher socioeconomic position was associated to lower physical activity levels.

Background To avoid exposure to mercury, government advice on fish consumption during pregnancy includes information on fish species to avoid and to limit, while encouraging consumption of least two portions of fish per week. Some women may, however, chose to avoid fish completely during pregnancy despite potential benefits to the fetus. Objectives Our aims were to evaluate the effects of blood mercury levels in pregnant women on birth outcomes in the UK, and to compare outcomes in those who ate fish with those who did not. Methods Pregnant women were enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Whole blood samples for singleton pregnancies with a live birth were analysed for Hg by inductively coupled plasma dynamic reaction cell mass spectrometry (n = 4044). Fish intake was determined by a food frequency questionnaire during pregnancy. Data collected on the infants included anthropometric variables and gestational age at delivery. Regression models were adjusted for covariates using SPSS v23. Results There were no significant associations of maternal blood Hg level with birthweight, head circumference or crown–heel length in adjusted linear regression models. Similarly, there were no increased odds of low birthweight or preterm delivery in adjusted logistic regression models. When the models were repeated after stratification into fish-eaters and there were no associations except for a negative association with birthweight in non-fish-eaters (unstandardised B coefficient −58.4 (95% confidence interval −113.8, −3.0) g, p = 0.039). Conclusion Moderate mercury levels in pregnancy were not associated with anthropometric variables, or on the odds of low birthweight or preterm birth. Fish consumption may have a protective effect on birthweight. Consumption of fish in line with government guidelines during pregnancy should be encouraged.

Highlights • This is one of the first longitudinal studies of serum CRP & subsequent schizophrenia. • Elevated serum CRP in adolescence is associated with risk of adult schizophrenia. • The CRP-schizophrenia association is consistent with a dose-response relationship., Objective Meta-analyses of cross-sectional studies confirm an increase in circulating inflammatory markers during acute psychosis. Longitudinal studies are scarce but are needed to understand whether elevated inflammatory markers are a cause or consequence of illness. We report a longitudinal study of serum C-reactive protein (CRP) in adolescence and subsequent risk of schizophrenia and related psychoses in adulthood in the Northern Finland Birth Cohort 1986. Method Serum high-sensitivity CRP was measured at age 15/16 years in 6362 participants. ICD-10 diagnoses of schizophrenia and related psychoses were obtained from centralised hospital inpatient and outpatient registers up to age 27 years. Logistic regression calculated odds ratios (ORs) for psychotic outcomes associated with baseline CRP levels analysed as both continuous and categorical variables using American Heart Association criteria. Age, sex, body mass index, maternal education, smoking, and alcohol use were included as potential confounders. Results By age 27 years, 88 cases of non-affective psychosis (1.38%), of which 22 were schizophrenia (0.35%), were identified. Adolescent CRP was associated with subsequent schizophrenia. The adjusted OR for schizophrenia by age 27 years for each standard deviation (SD) increase in CRP levels at age 15/16 years was 1.25 (95% CI, 1.07–1.46), which was consistent with a linear, dose-response relationship (P-value for quadratic term 0.23). Using CRP as a categorical variable, those with high (>3 mg/L) compared with low (

Purpose The timing of breast and pubic hair development in girls are related, but the degree of correlation has not been well characterized. Periodic observations also are complicated by interval censoring. Methods Data used were from the Avon Longitudinal Study of Parents and Children. Mean age at entry into breast and pubic hair development was determined by the use of parametric survival analysis. The bivariate normal cumulative distribution function was evaluated over the region containing the paired event times; the likelihood was maximized with respect to the correlation coefficient ρ. Results Among 3938 participants, estimated mean ages at entry into Tanner stage 2 for breast and pubic hair development were 10.19 and 10.95, respectively. The likelihood was maximized at ρ = 0.503 to 0.506. This value remained relatively constant among subgroups, although some heterogeneity was observed by maternal and child body mass index and birth order. Conclusions The timing of breast and of pubic hair development is moderately correlated and remain so when it is stratified by characteristics associated with puberty.

Background Low birth weight and rapid infant growth in early infancy are associated with increased risk of childhood asthma, but little is known about the role of postinfancy growth in asthmatic children. Objectives We sought to examine the associations of children's growth patterns with asthma, bronchial responsiveness, and lung function until adolescence. Methods Individual growth trajectories from birth until 10 years of age were estimated by using linear spline multilevel models for 9723 children participating in a population-based prospective cohort study. Current asthma at 8, 14, and 17 years of age was based on questionnaires. Lung function and bronchial responsiveness or reversibility were measured during clinic visits at 8 and 15 years of age. Results Rapid weight growth between 0 and 3 months of age was most consistently associated with increased risks of current asthma at the ages of 8 and 17 years, bronchial responsiveness at age 8 years, and bronchial reversibility at age 15 years. Rapid weight growth was associated with lung function values, with the strongest associations for weight gain between 3 and 7 years of age and higher forced vital capacity (FVC) and FEV1 values at age 15 years (0.12 [95% CI, 0.08 to 0.17] and 0.11 [95% CI, 0.07 to 0.15], z score per SD, respectively) and weight growth between 0 and 3 months of age and lower FEV1/FVC ratios at age 8 and 15 years (−0.13 [95% CI, −0.16 to −0.10] and −0.04 [95% CI, −0.07 to −0.01], z score per SD, respectively). Rapid length growth was associated with lower FVC and FVC1 values at age 15 years. Conclusion Faster weight growth in early childhood is associated with asthma and bronchial hyperresponsiveness, and faster weight growth across childhood is associated with higher FVC and FEV1 values.

Background & Aims Adiposity is a key risk factor for NAFLD. Few studies have examined prospective associations of infant and childhood adiposity with subsequent NAFLD risk. We examined associations of weight-for-height trajectories from birth to age 10 with liver outcomes in adolescence, and assessed the extent to which associations are mediated through fat mass at the time of outcome assessment. Methods Individual trajectories of weight and height were estimated for participants in the Avon Longitudinal Study of Parents and Children using random-effects linear-spline models. Associations of birthweight (adjusted for birth length) and weight change (adjusted for length/height change) from 0–3 months, 3 months–1 y, 1–3 y, 3–7 y, and 7–10 y with ultrasound scan (USS) determined liver fat and stiffness, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) at mean age 17.8 y were assessed with linear and logistic regressions. Mediation by concurrent fat mass was assessed with adjustment for fat mass at mean age 17.8 y. Results Birth weight was positively associated with liver stiffness and negatively with ALT and AST. Weight change from birth to 1 y was not associated with outcomes. Weight change from 1–3 y, 3–7 y, and 7–10 y was consistently positively associated with USS and blood-based liver outcomes. Adjusting for fat mass at mean age 17.8 y attenuated associations toward the null, suggesting associations are largely mediated by concurrent body fatness. Conclusions Greater rates of weight-for-height change between 1 y and 10 y are consistently associated with adverse liver outcomes in adolescence. These associations are largely mediated through concurrent fatness.

Objective To determine whether maternal mental health mediates the relationship between eczema or asthma symptoms and mental well-being in children. Study design Analysis of 7250 children from the Avon Longitudinal Study of Parents and Children. Child mental well-being at 8 years was measured by the Strengths and Difficulties Questionnaire. Binary outcomes were high ‘internalizing’ (anxious/depressive) and ‘externalizing’ (oppositional/hyperactive) problems (high was >90th percentile). Child rash and wheeze categories were ‘none’; ‘early onset transient’ (infancy/preschool only); ‘persistent’ (infancy/preschool and at school age); and ‘late onset’ (school age only). Maternal anxiety and depression were reported during pregnancy and when child was 8 years old. Results Persistent wheezing symptoms were associated with high externalizing (OR 1.74, 95% CI, 1.41-2.15) and internalizing (1.67, 1.35-2.06) problems compared with never wheeze. Maternal anxiety and depression, and disrupted child sleep, attenuated these associations. Persistent rash (externalizing: 1.74, 1.40-2.15; internalizing: 1.42, 1.16-1.74) and late onset rash (externalizing: 1.62, 1.17-2.25; internalizing: 1.46, 1.07-1.99) symptoms were associated with poorer mental well-being compared with no rash at any age. Maternal anxiety and depression, particularly when child was aged 8 years rather than during pregnancy, accounted for the association with internalizing symptoms and partly for externalizing symptoms. Sleep disruption did not mediate the association. Conclusions Maternal anxiety and depression may mediate the association between child rash and wheeze and child mental well-being.

Highlights • The secondary sex ratio is declining in many countries. • We evaluated the effect of prenatal exposure to heavy metals. • There were no associations between heavy metals and the secondary sex ratio. • Further work should be done in large cohorts in other countries., The aim of this study was to evaluate the effect of prenatal exposure to lead, cadmium and mercury levels on the secondary sex ratio. Whole blood samples were collected from pregnant women enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) study at a median gestational age of 11 weeks and were analyzed for lead, cadmium and mercury. Regression analysis was used to identify associations between maternal lead, cadmium and mercury levels and the secondary sex ratio with adjustment for confounders. There was no evidence for associations between maternal lead, cadmium or mercury levels and the secondary sex ratio in this sample. It appears unlikely that alterations in the secondary sex ratio are influenced by exposure to heavy metals, but further work should be done in large cohorts in other countries to confirm these findings.

Objective:\ud To determine whether children with attention deficit hyperactivity disorder (ADHD) and mild intellectual disability (ID) are a clinically distinct ADHD subgroup.\ud \ud Study design:\ud This was a cross-sectional study comparing clinical characteristics (ADHD subtypes, total number of symptoms, and rates of common comorbidities) between children with ADHD and mild ID and those with ADHD and IQ test scores >70, and also between children with ADHD and ID and a general population sample of children with ID alone. The sample comprised a clinical sample of children with ADHD with ID (n = 97) and without ID (n = 874) and a general population sample of children with ID and without ADHD (n = 58).\ud \ud Results:\ud After correcting for multiple statistical tests, no differences were found between the 2 ADHD groups on any measure except the presence of conduct disorder (CD) symptoms and diagnoses. Children with ADHD and ID had higher rates of both (OR, 2.38; 95% CI, 1.71-3.32 and OR, 2.69; 95% CI, 1.69-4.28, respectively). Furthermore, children with ADHD and ID had significantly higher rates of oppositional defiant disorder (OR, 5.54; 95% CI, 2.86-10.75) and CD (OR, 13.66; 95% CI, 3.25-57.42) symptoms and a higher incidence of oppositional defiant disorder diagnoses (OR, 30.99; 95% CI, 6.38-150.39) compared with children with ID without ADHD.\ud \ud Conclusion:\ud Children with ADHD and mild ID appear to be clinically typical of children with ADHD except for more conduct problems. This finding has implications for clinicians treating these children in terms of acknowledging the presence and impact of ADHD symptoms above and beyond ID and dealing with a comorbid CD.

Background Maternal stress in early life has been associated with the development of asthma in children, although it is unclear whether there are any critical periods of exposure. The association of asthma with prenatal exposure to maternal stress has not been reported. Objective We tested whether prenatal and postnatal anxiety and/or depression in pregnant women predicted the risk of their offspring developing asthma in childhood. Methods The Avon Longitudinal Study of Parents and Children is a population-based birth cohort recruited during pregnancy. Data were available on maternal anxiety scores and asthma at age 7½ years in 5810 children. Anxiety was assessed at 18 and 32 weeks of gestation by using the validated Crown-Crisp Experiential Index. Asthma was defined at age 7½ years as doctor-diagnosed asthma with current symptoms or treatment in the previous 12 months. Multivariable logistic regression was used to determine the association of prenatal anxiety with asthma (odds ratio; 95% CI). Results Independent of postnatal anxiety and adjusted for a number of likely confounders, there was a higher likelihood of asthma at age 7½ years (odds ratio, 1.64; 95% CI, 1.25-2.17) in children of mothers in the highest compared with lowest quartile of anxiety scores at 32 weeks of gestation, with evidence for a dose-response ( P value for trend Conclusions Maternal anxiety symptoms as an indicator of stress during fetal life may program the development of asthma during childhood.

$\textit{$Background:}$ Animal studies suggest a role of inflammation in the pathophysiology of anxiety, but human studies of inflammatory markers and anxiety disorders are scarce. We report a study of serum C-reactive protein (CRP) and generalised anxiety disorder (GAD) from the general population-based ALSPAC birth cohort. $\textit{Methods:}$ DSM-IV diagnosis of GAD was obtained from 5365 cohort members during face-to-face clinical assessment at age 16 years, of which 3392 also provided data on serum high sensitivity CRP levels. Logistic regression calculated odds ratio (OR) for GAD among individuals in top and middle thirds of CRP distribution compared with the bottom third. Effect of comorbid depression was assessed. Age, sex, body mass, ethnicity, social class, maternal education, maternal age at delivery, and family history of inflammatory conditions were included as potential confounders. $\textit{Results:}$ Forty participants met DSM-IV criteria for GAD (0.74%). CRP levels were higher in GAD cases compared with the rest of the cohort (P = 0.005). After adjusting for potential confounders, participants in the top third of CRP values compared with the bottom third were more likely to have GAD; adjusted OR 5.06 (95% CI, 1.31-19.59). The association between CRP and GAD was consistent with a linear dose-response relationship. The pattern of association between CRP and GAD remained unchanged after excluding cases with co-morbid depression. $\textit{Conclusions:}$ The findings are consistent with a role of inflammation in anxiety disorders. Longitudinal studies of inflammatory markers, subsequent anxiety taking into account current and past psychological stress are required to understand this association further.

Background: IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy.Objective: To investigate the association between filaggrin loss-of-function mutations and peanut allergy.Methods: Case-control study of 71 English, Dutch, and Irish oral food challenge-positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut >= 8 mm and/or peanut-specific IgE >= 15 kUL(-1)) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis.Results: Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge-positive patients (P = 3.0 x 10(-6); odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 x 10(-5); odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis.Conclusion: Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease. (J Allergy Clin Immunol 2011;127:661-7.)