The effects of the exposure to neurotoxic elements on Italian schoolchildren behavior.

Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency's priority list of hazardous substances where arsenic and lead are ranked as first and second respectively.

Trajectories of internalising and externalising symptoms and inflammation in the general child population.

BACKGROUND: Elevations in inflammatory marker levels have been shown to precede internalising and externalising problems in the general child population. One study has found the reverse, that elevations in inflammatory marker levels in childhood follow internalising and externalising problems. However, the authors did not explore the role of the course of these problems in childhood or adjust for a number of potential confounders including psychosocial stressors and prenatal and perinatal exposures. AIMS: To investigate the association in childhood between the growth of internalising and externalising symptoms and levels of inflammatory markers, while accounting for potential confounders. METHODS: Using data from the Avon Longitudinal Study of Parents and Children, we tested the association between the trajectories of internalising (emotional and social) and externalising (hyperactivity and conduct) problems, at ages 4, 6, 8 and 9 years, and levels of C-reactive protein (CRP) and interleukin 6 (IL-6) at age 9 years. We analysed data (n = 4525) using latent growth curve modelling and linear regression. RESULTS: Children who had increasing levels of internalising symptoms over childhood were more likely to have higher levels of CRP and IL-6 at 9 years of age, even after adjustment for confounders. A one-unit increase in the rate of annual change of internalising symptoms was related to an increase of 12% and 8% in the level of CRP and IL-6, respectively. However, there was no evidence for an association between externalising symptoms and either inflammatory marker. CONCLUSIONS: This study is the first step towards identifying a robust pathway, via increases in emotional and social difficulties, to elevated inflammation in healthy children. This association, if causal, suggests that effective interventions for children experiencing chronic emotional and social difficulties could also have physical health benefits.

Association between prolonged separation from parents and allostatic load among children in China.

OBJECTIVE: To capture the association of exposure to prolonged separation from both parents early in life and allostatic load (AL), a measure of biological multi-system dysregulation. METHODS: We used data from 557 7-12-year-old children enrolled in rural area of Chizhou city, Anhui Province, China. We computed an AL score based on eleven biomarkers representing four regulatory systems: immune/inflammatory system (high sensitivity C-reactive protein); metabolic system (body mass index; high density lipoprotein; low density lipoprotein, total cholesterol; triglycerides; fasting glucose; glycated hemoglobin; insulin) and cardiovascular system (systolic and diastolic blood pressure). Child's experiences of parent-child separation were collected a brief online questionnaire by parents of children. RESULTS: More than 1 in 3 of our participants separated with both parents at age 6 or younger and nearly 1 in 10 persistently separated from both parents after birth. The AL score was significantly higher among children separated from both parents during early childhood (3.25 ± 1.98) or persistently since birth (3.48 ± 1.92), compared with those who did not separated from both parents (2.34 ± 1.53, F = 12.992, P<0.001). After adjustment of demographic covariates, body mass index as well as parent frequency of communication and parental warmth, children who separated from both parents in early childhood (ß = 0.84, 95%CI:0.40, 1.28, P < 0.001) or persistently into adolescence (ß = 1.27, 95%CI:0.43, 2.12, P = 0.003) evinced the highest levels of AL. CONCLUSION: This study is the first to show an association between prolonged parent-child separation and physiological wear-and-tear as measured by AL, which provides potential insights into the biological mechanisms underpinning long-term health outcomes in contexts of parent-child separation.

Ghrelin and leptin levels in children with anxiety disorders.

Background Anxiety disorders are common psychiatric disorders in childhood and an important health problem that is associated with the risk of serious mental, educational and economical problems. Researchers have mentioned many different mechanisms in the etiopathology of anxiety disorders. This study aimed to investigate ghrelin and leptin levels in children with anxiety disorders and thus to contribute to the clarification of anxiety in children. Methods Forty-three children aged 6-12 years with a diagnosis of the Anxiety Disorder according to DSM 5 and 21 healthy children age- and gender-matched to the study group were included. All the subjects were assessed with Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) and State-Trait Anxiety Inventory for Children (STAI-C) scale. Blood samples were obtained in the morning and serum ghrelin and leptin levels were measured with enzyme-linked immunosorbent assay (ELISA) kits. Results In the anxiety group the ghrelin levels were higher than the control group (p = 0.037) but there was no significant difference between the leptin levels (p = 0.430). Also, when the girls in the anxiety group and the girls in the control group were compared, ghrelin levels were higher in the anxiety group (p < 0.01). Conclusions These findings suggest that ghrelin may play a significant role in the etiologic mechanisms of anxiety disorders. However, more detailed studies are needed to explain the linkage between anxiety disorders and neuropeptides.

Elevated Gestational IL-13 During Fetal Development Is Associated With Hyperactivity and Inattention in Eight-Year-Old Children.

Maternal immune activation (MIA) during fetal development leads to behavioral and psychological disorders in the offspring. Concomitantly, insufficient supply of polyunsaturated fatty acids (PUFAs) is suspected to contribute to early neuronal maldevelopment due to the immune modulatory capabilities of PUFAs. However, human data are missing considering both of these aspects and their impact on children's behavioral outcomes. In line, this study aimed to elucidate the influence of gestational cytokines and PUFA-containing lipids during late pregnancy on behavioral sequelae in childhood, particularly focusing on an immune activation shaped by a history of maternal atopic diseases instead of a pathogen-mediated immune response. Based on the prospective mother-child cohort LINA we assessed the unstimulated blood cytokine profiles and concentrations of PUFA-containing lipids of 293 mothers at the 34th week of pregnancy. Maternal history of atopic diseases was obtained from questionnaires and behavior in eight-year-old children was assessed by the standardized Strength and Difficulties Questionnaires (SDQ) generating scores for hyperactivity/inattention, emotional symptoms, conduct problems, and peer relationship problems. Elevated IL-13 increased the risk for the child to show behavioral difficulties, in particular, hyperactive/inattentive behavior [adj. OR (95% CI): 2.47 (1.51-4.02), n = 255 vs. 38] at the age of eight years. Although the presence of maternal atopic dermatitis (AD) was associated with increased gestational IL-13 concentrations [adj. MR (95% CI): 1.17 (1.04-1.32)], no effect on children's behavioral difficulties was observed. However, a decrease in the PUFA containing lipid species PC aa C38:6 was not only associated with an increased gestational IL-13 concentration but also mediated the indirect effect of low PC aa C38:6 concentrations on children's abnormal behavior independent of maternal AD. We additionally assessed whether maternal IL-13 and PC aa C38:6 concentrations translate their effect by altering children's cord blood PC aa C38:6 and IL-13. While also the children's cord blood IL-13 was related to children's behavior, no effect of children's PC aa C38:6 was observed. This is the first study demonstrating that elevated gestational IL-13 increases the risk for children to develop behavioral difficulties. Analyses suggest that a reduced supply of gestational PC aa C38:6 contributes to elevated gestational IL-13 leading to behavioral sequelae in the offspring.

Fluctuations in clinical symptoms with changes in serum 25(OH) vitamin D levels in autistic children: Three cases report.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complicated interactions between genetic and environmental factors. Clinical trials, including case reports, case-control studies, and a double-blinded randomized clinical study, have suggested that high-dose vitamin D3 regimens may ameliorate the core symptoms of ASD. Vitamin D3 supplementation was effective in about three-quarters of children with ASD. To further investigate the relationship between vitamin D and ASD symptoms in vitamin D-responsive autistic children, changes in symptoms were assessed in three children with ASD who were given vitamin D3 supplementation followed by a long interruption. The core symptoms of ASD were remarkably improved during the vitamin D3 supplementation period when serum 25-hydroxyvitamin D [25(OH)]D levels reached over 40.0 ng/mL. However, symptoms reappeared after the supplementation was stopped, when serum 25(OH)D levels fell below 30.0 ng/mL but were again improved with re-administration of vitamin D3 after the interruption, when serum 25(OH)D levels exceeded 40.0 ng/mL. Overall, these results showed that the core symptoms of ASD fluctuated in severity with changes in serum 25(OH)D levels in children, indicating that maintaining a responsive 25(OH)D level is important for treating ASD. Maintaining a serum 25(OH)D level between 40.0 and 100.0 ng/ml may be optimal for producing therapeutic effects in vitamin D-responsive individuals with ASD.

Neurodevelopment in 3-4 year old children exposed to maternal hyperglycemia or adiposity in utero.

BACKGROUND: Prenatal exposure to maternal metabolic complications has been linked to offspring neurodevelopmental problems. However, no studies investigating these links have examined the role of maternal prenatal diet. AIMS: To determine if prenatal exposure to maternal adiposity or hyperglycemia is associated with neurodevelopmental problems in 3-4 year old children, and if links persist following adjustment for confounding variables, including prenatal diet. METHOD: 808 mother-child pairs from the Maternal-Infant Research on Environmental Chemicals-Child Development Plus cohort were used to examine associations between pre-pregnancy body mass index (BMI), hyperglycemia and offspring verbal, performance and full-scale IQ scores, as well as internalizing and externalizing problems. Associations were examined before and after adjustment for prenatal diet along with home environment, maternal depression, education and prenatal smoking. Semi-partial correlations were examined post-hoc to assess the impact of each confounder in the adjusted models. RESULTS: In the unadjusted models, BMI and hyperglycemia predicted lower verbal and full-scale IQ. BMI was also linked to externalizing problems. However, associations were not significant after adjustment. In adjusted models, post-hoc analysis revealed that prenatal diet and home environment accounted for significant variance in verbal and full-scale IQ. The home environment and maternal depression accounted for significant variance in externalizing problems. CONCLUSION: In the adjusted models, maternal metabolic complications were not associated with offspring neurodevelopment. Even while adjusting for well-known risk factors for adverse offspring cognition (home environment, maternal depression), we show for the first time that maternal prenatal diet is an important confounder of the links between maternal metabolic complications and offspring cognition.

MECHANISMS IN ENDOCRINOLOGY: Maternal thyroid dysfunction during pregnancy and behavioural and psychiatric disorders of children: a systematic review.

BACKGROUND: Maternal thyroid dysfunction during pregnancy may lead to persistent neurodevelopmental disorders in the offspring appearing in later life. This study aimed to review the available evidence concerning the relationship between maternal thyroid status during pregnancy and offspring behavioural and psychiatric disorders. METHODS: Systematic electronic database searches were conducted using PubMed, Embase, PsycNET, Scopus, Google Scholar and Cochrane library. Studies including gestational thyroid dysfunction as the exposure and offspring behavioural and psychiatric disorders as the outcome were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed and, after thorough screening by two independent reviewers, 13 articles remained eligible for inclusion in this study. RESULTS: Indicators of maternal thyroid dysfunction, including low and high thyroid hormone level and autoimmune thyroiditis, during early pregnancy, were found to be associated with several offspring behavioural and psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), autism, pervasive developmental problems, externalising behaviour, in addition to epilepsy and seizure. The majority of associations were found with low maternal thyroid hormone level. CONCLUSION: Maternal thyroid function during pregnancy, particularly hypothyroidism, is associated with behavioural and psychiatric disorders in children. Further studies are needed with a capacity to adjust for a fuller range of confounding factors.

Low 25(OH)-vitamin D concentrations are associated with emotional and behavioral problems in German children and adolescents.

BACKGROUND: Evidence has accumulated for the association between low vitamin D serum concentrations and mental health disorders in both children and adults. We performed a cross-sectional analysis in a population-based sample of children and adolescents to detect associations between 25(OH)-vitamin D serum [25(OH)D] concentrations and scores of the five Strengths and Difficulties Questionnaire (SDQ) subscales and the total difficulties score in different age groups (age ≥3-<12 years and ≥12-<18 years). METHODS: 9068 participants of the population-based, nation-wide German Health Interview and Examination Survey for Children and Adolescents (KIGGS) with information on mental health status assessed by the SDQ and 25(OH)D levels were included in the analysis. For statistical analysis we used linear regression models stratified by gender based on different adjustment sets. For the younger subsample the analysis was additionally adjusted for the frequency of playing outside. We compared the associations based on parent- and self-ratings of the SDQ for children and adolescents aged ≥12-<18 years. RESULTS: We found inverse associations between 25(OH)D concentrations and the subscales emotional problems, peer relationship problems and the total difficulties score in both genders after adjustment for potential confounders. The strongest associations were observed in the older subsample for parent-ratings in boys and self-ratings in girls. In the younger subsample the associations were less strong and no longer evident after adjustment for potential confounders such as migration background, socioeconomic status and frequency of playing outside. CONCLUSION: Based on the large-scale cross-sectional study in a German population-based sample of children and adolescents we detected inverse associations between 25(OH)D concentrations and both parent- and self-rated SDQ scores of the total difficulties scale and different subscales with the strongest association in the subsample aged ≥12-<18 years for both genders. Migration background and socioeconomic status were detected as relevant confounders. Further studies-particularly in countries with comparatively low mean 25(OH)D concentrations-in childhood and adolescence are warranted. Longitudinal studies are also necessary to infer direction of effects. Finally, RCTs in children and adolescents are required to determine whether Vitamin D is beneficial for mental health.

Maternal thyroid hormone trajectories during pregnancy and child behavioral problems.

There is ample evidence demonstrating the importance of maternal thyroid hormones, assessed at single trimesters in pregnancy, for child cognition. Less is known, however, about the course of maternal thyroid hormone concentrations during pregnancy in relation to child behavioral development. Child sex might be an important moderator, because there are sex differences in externalizing and internalizing behavioral problems. The current study examined the associations between maternal thyroid hormone trajectories versus thyroid assessments at separate trimesters of pregnancy and child behavioral problems, as well as sex differences in these associations. In 442 pregnant mothers, serum levels of TSH and free T4 (fT4) were measured at 12, 24, and 36weeks gestation. Both mothers and fathers reported on their children's behavioral problems, between 23 and 60months of age. Latent growth mixture modeling was used to determine the number of different thyroid hormone trajectories. Three trajectory groups were discerned: 1) highest and non-increasing TSH with lowest fT4 that decreased least of the three trajectories; 2) increasing TSH and decreasing fT4 at intermediate levels; 3) lowest and increasing TSH with highest and decreasing fT4. Children of mothers with the most flattened thyroid hormone trajectories (trajectory 1) showed the most anxiety/depression symptoms. The following trimester-specific associations were found: 1) lower first-trimester fT4 was associated with more child anxiety/depression, 2) higher first-trimester TSH levels were related to more attention problems in boys only. A flattened course of maternal thyroid hormone concentrations during pregnancy was a better predictor of child anxiety/depression than first-trimester fT4 levels.

Perinatal complications, lipid peroxidation, and mental health problems in a large community pediatric sample.

Replicated evidence indicates that perinatal complications are associated with increased markers of oxidative stress and with mental health problems in children. However, there are fewer reports on the impact of perinatal complications in later phases of development. We aimed to investigate the estimated effects of perinatal complications on levels of lipid peroxidation and on psychopathology in children and adolescents. The study is part of the High Risk Cohort Study for Psychiatric Disorders; the population was composed by 554 students, 6-14 years of age. Serum levels of malondialdehyde, a product of lipid peroxidation, were measured by the TBARS method. A household interview with parents and caregivers was conducted and included inquiries about perinatal history, the Child Behavior Checklist (CBCL), and parent's evaluation, using the Mini International Psychiatric Interview (MINI). We created a cumulative risk index, conceptualized as each individual's cumulative exposure to perinatal complications. Results indicate that perinatal complications were associated with higher levels of TBARS. After adjusting for age, gender, socio-economic status, CBCL total problems score, parental psychopathology, and childhood maltreatment, children exposed to 3 or more perinatal complications had an 26.9% (95% CI 9.9%, 46.6%) increase in TBARS levels, relative to the unexposed group. Exploratory mediation analysis indicated that TBARS levels partially mediated the association between perinatal complications and externalizing problems. In conclusion, an adverse intrauterine and/or early life environment, as proxied by the cumulative exposure to perinatal complications, was independently associated with higher levels of lipid peroxidation in children and adolescents.

Bisphenol A, phthalates and lead and learning and behavioral problems in Canadian children 6-11 years of age: CHMS 2007-2009.

Childhood developmental disorders and related problems such as learning disabilities and attention deficit hyperactivity disorder (ADHD) account for a growing burden on the family, education and health care systems. Exposure to environmental chemicals such as bisphenol A (BPA) and phthalates may play a role in the development of child behavioral problems. Using cross-sectional data from Cycle 1 of the Canadian Health Measures Survey (CHMS), we examined the potential association between urinary concentrations of BPA and various phthalate metabolites and child learning and behavioral problems, considering important covariates such as gender, blood lead and environmental tobacco smoke (ETS). The Strengths and Difficulties Questionnaire (SDQ) outcomes of interest were emotional symptoms, hyperactivity/inattention, and a total difficulties score with borderline and abnormal scores grouped together and compared with children with normal scores. Other outcomes studied included any reported learning disability, a subset of learning disabilities reported as ADD/ADHD (attention deficit disorder) and use of psychotropic medications in the past month. Among children ages 6-11 years, the prevalences of any learning disability, ADD, and ADHD were 8.7%, 1.5% and 2.8%, respectively. Estimated prevalences for SDQ hyperactivity/inattention, emotional symptoms and total difficulties scores were 16.9%, 15.0%, and 13.0%, respectively. Child's urinary BPA was associated with taking psychotropic medications (OR 1.59; 95% CI 1.05-2.40). Urinary MBzP concentration was significantly associated with emotional symptoms in girls (OR 1.38 95% CI 1.09-1.75) but not in boys (OR 1.05 95% CI 0.82-1.36).) Blood lead was significantly associated with several of the outcomes examined, with a significant interaction observed between prenatal smoking and blood lead for the total difficulties score (OR=10.57; 95% CI 2.81-39.69 vs. OR=1.98; 95% CI 1.41-2.79 if mother did not smoke during pregnancy). Although limited by the cross-sectional nature of the study which precludes examining causation, the results suggest that although some indicators of child behavior were significantly associated with their urinary BPA and phthalate concentrations, the major chemical associated with adverse behavioral indicators was lead.

Epilepsy and behavioral changes, type 1 diabetes mellitus and a high titer of glutamic acid decarboxylase antibodies.

Autoantibodies to the 65 kDa isoform of glutamate acid decarboxylase (GAD65Ab) are associated with a range of clinical disorders, including type 1 diabetes (T1D) and stiff-person syndrome (SPS). In this article we describe a young girl who was diagnosed with T1D at the end of her first year of life and developed drug-resistant epilepsy 18 months later, followed by behavioral disturbances. She was admitted to our center at the age of 5 yr, at which time high GAD65Ab titers were detected in the patient's serum and cerebrospinal fluid (CSF). The titer remained elevated during 19 months of follow-up. Furthermore, GAD65Ab in both serum and CSF showed epitope binding characteristics similar to those observed for GAD65Ab in SPS patients, and GAD65Ab in the serum reduced GAD65 enzyme activity. Our results suggest an association between high GAD65Ab titers and epilepsy in children with T1D. Careful titration and characterization of GAD65Ab regarding inhibition of enzyme activity and epitope specificity may be helpful in identifying T1D patients at risk for neurological complications.

Testosterone in relation to behavioral problems in pre-pubertal boys with autism spectrum disorders.

Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by impairment in social communication and presence of stereotyped/restricted behaviors. Children with ASD very often demonstrate co-morbid psychiatric problems, problems known to be affected by testosterone in neurotypical populations. However, there are few reports investigating relationships between testosterone and psychiatric conditions in children with ASD. The aim of this study was to determine the relationship between plasmatic levels of testosterone and behavioral/emotional problems in pre-pubertal boys with ASD. The study sample consisted of 31 pre-pubertal boys (ages 3-10) with ASD. Parents completed the Nisonger Child Behavior Rating Form (NCBRF) to assess specific behavioral/emotional problems as observed in the previous 2 months. Plasmatic testosterone levels were determined in boys according to standardized procedures. It was found that there were positive correlations between testosterone levels and the conduct problems subscale (p=0.034, rs=0.382) of NCBRF and also between testosterone levels and the hyperactive subscale (p=0.025, rs=0.402) of NCBRF. Findings in this study are in line with research conducted in the neurotypical population. This is the first large study investigating testosterone and emotional/behavioral problems in ASD and warrants further research in this field in order to clarify the etiopathogenesis of psychiatric co-morbidities and improve their treatment.

Association of Non-High-Density Lipoprotein Cholesterol with Psychosocial Dysfunction in Children and Adolescents with Obesity.

BACKGROUND: Children with obesity have worse psychosocial functioning compared to their non-overweight peers. Adult studies suggest that several metabolic factors may participate in the etiology of depression in obesity. METHODS: We evaluated the association of several metabolic parameters with psychosocial dysfunction in children with obesity, through a retrospective review of electronic medical records in patients ages 6-17. All parents were asked to complete the Pediatric Symptom Checklist (PSC) questionnaire, a validated measurement of psychosocial dysfunction in children. RESULTS: PSC scores were available in 618 patients. Overall, 11.2% of patients had a PSC score ≥28, suggestive of psychosocial dysfunction. Non-high-density lipoprotein (HDL) cholesterol was associated with a higher PSC score (p = 0.02), after adjusting for age, sex, race, socioeconomic status, and BMI z-score. CONCLUSIONS: Consistent with adult studies, in children and adolescents with obesity, non-HDL cholesterol may play a role in the etiology of psychosocial dysfunction. Further studies are warranted.

Longitudinal patterns of cortisol regulation differ in maltreated and nonmaltreated children.

OBJECTIVE: Child maltreatment is associated with dysregulation of stress-mediating systems and an increased risk of mental and physical health problems. Specifically, disruptions in hypothalamic-pituitary-adrenal (HPA) axis regulation have been reported in maltreated children. The current study investigates whether increased cortisol variability is responsible for inconsistent patterns in the literature. METHOD: This study modeled cortisol activity over 20 weeks in 187 maltreated and 154 nonmaltreated children (mean = 8.4 years, SD = 1.8 years) in order to capture week-to-week cortisol patterns. Maltreatment was assessed through coding of Department of Human Services records. Children attended an after-school program 1 day per week for 20 weeks, where saliva was collected at the same time each day and subsequently assayed for cortisol. RESULTS: Multiple-group growth curves indicated that maltreated and non-maltreated children differ in longitudinal cortisol patterns. Maltreated children showed higher variance in the initial cortisol levels and slope over time compared to nonmaltreated children, indicating greater between-person variability in the maltreated group. Maltreated children with higher cortisol at the first assessment showed cortisol suppression over time, indicating potential HPA blunting after chronic high cortisol levels. The severity, timing, and number of subtypes of maltreatment predicted individuals' cortisol variability, and both maltreatment status and greater cortisol variability predicted more behavior problems. CONCLUSION: Interventions for maltreated children may benefit from pre- and post-intervention HPA assessments to determine a component of treatment efficacy. As maltreatment dimensions predicted differential cortisol regulation, assessment of maltreatment experiences is necessary to understand alterations in behavior and HPA regulation post-intervention.

Blood manganese levels in relation to comorbid behavioral and emotional problems in children with attention-deficit/hyperactivity disorder.

Patients with attention-deficit/hyperactivity disorder (ADHD) appear to be more vulnerable to the development of other psychiatric disorders than the general population. The proposed neurotoxic mechanisms of manganese involve striatal dopamine neurotransmission, implicated in the pathophysiology of ADHD. We investigated whether the adverse impact of manganese is particularly pronounced in children with ADHD. Blood manganese concentration and diagnosis of ADHD were assessed in a general population of 890 children, aged 8-11 years. The main outcome measure was the Child Behavior Checklist (CBCL). A significant interaction was found between ADHD status and blood manganese level in predicting CBCL total problems score as well as anxiety/depression, social problems, delinquent behavior, aggressive behavior, internalizing problems, and externalizing problems. The directions of the interactions indicated that blood manganese level was more positively correlated with CBCL scores in ADHD children than in the healthy population. In ADHD children, only the fifth quintile of blood manganese concentration was significantly associated with the CBCL total problems score. ADHD children may be more vulnerable than the general school-age population to the neurotoxic effects of manganese exposure, which lead to an elevated risk of developing comorbid mental conditions.

Preterm born 9-year-olds have elevated IGF-1 and low prolactin, but levels vary with behavioural and eating disorders.

AIM: This study examined the relationship between hypothalamic-associated hormones and behavioural and eating disorders in children with low birthweight. METHODS: We included 100 children (mean age 9.7 years): 39 were born preterm at <32 gestational weeks, 28 were full-term, but small for gestational age, and 33 were full-term controls. Behavioural histories were analysed, together with fasting blood samples of leptin, insulin, insulin-like growth factor-1 (IGF-I), prolactin, glucagon and cortisol. RESULTS: Preterm children had lower prolactin (p = 0.01) and higher IGF-I than controls (p < 0.05, adjusted for confounders), despite being significantly shorter than the predicted target height (p < 0.001). More preterm children displayed behavioural disorders (38% versus 10%, p < 0.001) and eating disorders (26% versus 8%, p < 0.05) than full-term children. These disorders were associated with lower leptin (p < 0.01), insulin (p < 0.05) and IGF-I (p < 0.05), but correlations between these hormones and leptin were similar among the groups. Combined behavioural and eating disorders were only observed in preterm children, who were also the shortest in height. CONCLUSION: Behavioural and eating disorders among preterm children were associated with low leptin, insulin and IGF-1. Low prolactin in all preterm children indicated an increased dopaminergic tonus, which might inhibit body weight incrementation. This raises speculation about IGF-I receptor insensitivity.

Glycine receptor antibodies in a boy with focal epilepsy and episodic behavioral disorder.

A wide range of clinical presentations including neuromuscular disorders and autoimmune encephalopathies is being recognized to be associated with various autoantibodies. Glycine receptor (GlyR) antibodies have so far been found mainly in adult patients with phenotypes comprising progressive encephalomyelitis with rigidity and myoclonus or stiff-person syndrome. We report a four-year-old boy who presented with a two-year-history of drug-resistant focal epilepsy with unusual seizure semiology, temper tantrums, headache, clumsiness, and intermittently impaired speech. While MRI and CSF were normal, screening for autoimmune antibodies revealed GlyR antibodies in serum. Immunomodulatory treatment with steroids resulted in rapid and complete resolution of symptoms. Our observation widens the spectrum of clinical presentations associated with GlyR antibodies and emphasizes the potential relevance of neuronal autoantibodies in epilepsies of unknown cause in children as well as in adults.

Low blood zinc, iron, and other sociodemographic factors associated with behavior problems in preschoolers.

Previous research supports the link among malnutrition, cognitive dysfunction, and behavioral outcomes; however, less research has focused on micronutrient deficiencies. This study investigates whether micronutrient deficiencies, specifically blood zinc and iron levels, will be associated with increased behavior problem scores, including internalizing and externalizing behaviors. 1314 Children (55% boys and 45% girls) from the Jintan Preschool Cohort in China participated in this study. Venous blood samples were collected and analyzed for zinc and iron when the children were 3-5 years old. Behavior problems were measured with the Child Behavior Checklist (CBCL), which was completed by the parents when children were in their last months of preschool (mean age 5.6 years). General linear multivariate modeling was used, with adjustment for important sociodemographic variables. The results indicate that low zinc levels alone (p = 0.024) and combined low zinc and iron levels (p = 0.022) are significantly associated with increased reports of total behavior problems. We did not find an association between low iron and behavior problems. With regards to sociodemographics, living in the suburbs is associated with increased internalizing problems, while higher mother's education and being female were associated with decreased externalizing problems. This study suggests that micronutrient deficiencies and sociodemographic facts are associated with behavior problems in preschoolers.