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PubMed1997

Neurodevelopment in offspring of hairdressers.

The hypothesis that intrauterine exposure to hairdressers' chemicals adversely affects neurodevelopment of the offspring was investigated. Neurodevelopmental characteristics were analysed using a historical cohort study of reproductive disorders among hairdressers in The Netherlands. Because exposure in hair salons to agents toxic to reproductive processes might have changed over time, two specific study periods were examined: from 1986 to 1988 and from 1991 to 1993. Nine thousand hairdressers and 9000 clothing sales clerks (referent group) who were in the reproductive age in the defined study periods were selected by the trade association for service jobs. Frequency matching assured comparability with regard to age. All women were invited by mail to complete a short self-administered questionnaire on their reproductive history, including questions on the ages of their child at the times of the first words, first sentences, and first steps, and the occurrence of seizures during fever. The results showed that in 1986 to 1988 more children of hairdressers started speaking their first words after 15 months and their first sentences after 24 months. For 1991 to 1993 no increased risks of these outcomes were found. Seizures during fever had occurred more often among children of hairdressers in 1986 to 1988, and in 1991 to 1993, especially when women had been working until maternity leave. Although the quality of the data in this explorative study requires careful interpretation, the consistent results seem to indicate adverse effects on neurodevelopment among offspring of hairdressers in the earlier years (1986 to 1988). In the later years the effect seemed to be disappearing. However, these findings should be confirmed in more detailed studies.

Child, Preschool↗
PubMed1997

Synaptic elimination, neurodevelopment, and the mechanism of hallucinated "voices" in schizophrenia.

OBJECTIVE: After peaking during childhood, synaptic density in the human frontal cortex declines by 30%-40% during adolescence because of progressive elimination of synaptic connections. The characteristic age at onset of schizophrenia--late adolescence and early adulthood--suggests that the disorder could arise from irregularities involving this neurodevelopmental process. METHOD: A computer simulation of a speech perception neural network was developed. Connections within the working memory component of the network were eliminated on the basis of a "Darwinian rule" in order to model loss of synapses. As a comparison, neuronal cell death, also postulated as being linked to both neurodevelopment and schizophrenia, was simulated. The authors determined whether these alterations at low levels could enhance perceptual capacity and at high levels produce spontaneous speech percepts that simulate hallucinated speech or "voices." RESULTS: Eliminating up to 65% of working memory connections improved perceptual ability; beyond that point, network performance declined and speech hallucinations emerged. Simulating excitotoxic neuronal loss at low levels also improved network performance, but in excess it did not produce hallucinations. CONCLUSIONS: The model demonstrates perceptual advantages of selective synaptic elimination as well as selective neuronal loss, suggesting a functional explanation for these aspects of neurodevelopment. The model predicts that psychosis arises from a pathological extension of one of these neurodevelopmental trends, namely, synaptic elimination.

Auditory Perception↗
PubMed2006

In utero exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) and neurodevelopment among young Mexican American children.

OBJECTIVE: We investigated the relationship between prenatal exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) and neurodevelopment of Mexican farm-workers' children in California. METHODS: Participants from the Center for the Health Assessment of Mothers and Children of Salinas study, a birth cohort study, included 360 singletons with maternal serum measures of p,p'-DDT, o,p'-DDT, and p,p'-DDE. Psychomotor development and mental development were assessed with the Bayley Scales of Infant Development at 6, 12, and 24 months. RESULTS: We found a approximately 2-point decrease in Psychomotor Developmental Index scores with each 10-fold increase in p,p'-DDT levels at 6 and 12 months (but not 24 months) and p,p'-DDE levels at 6 months only. We found no association with mental development at 6 months but a 2- to 3-point decrease in Mental Developmental Index scores for p,p'-DDT and o,p'-DDT at 12 and 24 months, corresponding to 7- to 10-point decreases across the exposure range. Even when mothers had substantial exposure, breastfeeding was usually associated positively with Bayley scale scores. CONCLUSIONS: Prenatal exposure to DDT, and to a lesser extent DDE, was associated with neurodevelopmental delays during early childhood, although breastfeeding was found to be beneficial even among women with high levels of exposure. Countries considering the use of DDT should weigh its benefit in eradicating malaria against the negative associations found in this first report on DDT and human neurodevelopment.

Birth Weight↗
PubMed2005

[Role of erythropoietin in brain homeostasis, neurodevelopment and neuroprotection].

Erythropoietin is known as a cytokine regulating the erythrocyte production. Based on recent research it became clear that it is secreted not only by the kidney, but by the central nervous system as well, and erythropoietin receptors are present there, too. Animal and human studies found that the expression of erythropoietin and its receptor is changing through neurodevelopment, which has impact on the differentiation of neuronal cells and is essential for normal neurodevelopment. In addition erythropoietin is protective against several mechanisms of neuronal injury: it alleviates the outcome of hypoxia and glutamate toxicity and has antiapoptotic effects. Based on these results the neuroprotective effects of exogenously administered erythropoietin was studied in several clinical studies. The available data indicate that erythropoietin or its analogues may have a role in neuroprotection in clinical settings.

Animals↗
PubMed1994

Effect of perinatally acquired human immunodeficiency virus infection on neurodevelopment in children during the first two years of life.

OBJECTIVE: To determine the timing, extent, and magnitude of neurodevelopmental problems in children with perinatal HIV infection compared to similar uninfected children of HIV-infected women and controls. METHODS: Neurodevelopmental assessments during the first 24 months of life for 21 HIV-infected children born to HIV-infected mothers, 65 seroreverted children born to HIV-infected mothers, and 95 non-HIV-infected children born to non-HIV-infected mothers were analyzed. Neurodevelopment was assessed by using the Bayley Scales of Infant Development beginning at 3 months of age. Kent Scoring Adaptation was also utilized. A two-stage Hierarchical Linear Model was used for analysis of neurodevelopmental scores. RESULTS: In the initial comparison of these three groups, infected children had significantly lower scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) than the other two groups. The HIV-infected children were further classified into HIV-infected without Centers for Disease Control-defined AIDS, those with lymphoid interstitial pneumonitis (LIP) only as their AIDS-defining illness, and children with an AIDS-defining diagnosis other than LIP in the first 24 months. The children with LIP-only AIDS and the infected children without AIDS on average were not significantly different from the seroreverters or the controls on MDI or PDI, while the children with non-LIP AIDS had significantly lower scores after 3 months of age. Analysis of the Kent scores indicated that the decrement in the non-LIP AIDS children was seen in all five functional domains. CONCLUSION: Children with serious HIV symptomatology appear to be at very high risk for serious developmental impairments, HIV-infected children not highly symptomatic have relatively normal neurodevelopment, and uninfected children of HIV-infected mothers do not appear to be adversely affected by the mother's HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Does transient hypothyroxinemia cause abnormal neurodevelopment in premature infants?

THOP is a relatively common condition whose long-term effects remain uncertain. The preponderance of evidence indicates that at the very least THOP is a marker of elevated risk of neurodevelopmental adversity, but whether this association is truly causal and whether thyroxine treatment in the neonatal period can prevent adverse outcome is as yet unknown. Since the number of infants born and surviving at very early gestations continues to increase, the importance of this condition will be magnified in the future. The major difficulty in establishing the causal role of THOP is the tangled time order of events in the early neonatal period. It is therefore unlikely that further observational studies will advance understanding. Energies should be focused on Assessing neurodevelopment objectively in survivors in each of the TRH trials. Developing a new multicenter trial of newborn supplementation with thyroid hormone that is carefully planned to have sufficient power to assess neurodevelopment in treated and untreated infants under a variety of baseline conditions.

Developmental Disabilities↗
PubMed2026

CNNM2 in schizophrenia: multilevel evidence of genetic susceptibility, magnesium homeostasis, neurodevelopment and cognitive dysfunction.

Schizophrenia (SCZ) is a common psychiatric disorder with a complex, genetically and environmentally influenced etiology, but the specific pathogenesis remains unclear. In recent years, the SCZ susceptibility gene CNNM2 (encoding cyclin M2) located at the 10q24.32-33 locus has received widespread attention. The well-validated SCZ risk interval 10q24.32-33 harbors two independent risk variants: rs11191580 in NT5C2 (significantly associated with CNNM2 mRNA and protein levels) and rs7914558 in CNNM2. Results from functional genomic analyses indicate that lower CNNM2 expression is significantly associated with SCZ. Imaging genetics studies have demonstrated that carriers of risk alleles of CNNM2 SNPs exhibit alterations in brain structure. Animal model studies have revealed that Cnnm2 downregulation in mice leads to impairments in sensorimotor gating and cognitive function. As an Mg2+ transporter, CNNM2 primarily maintains systemic Mg2+ homeostasis. According to clinical studies, a proportion of patients with SCZ exhibit reduced Mg2+ concentrations in plasma and cerebrospinal fluid. CNNM2 dysfunction may contribute to the pathology of SCZ by disrupting Mg2+ homeostasis, thereby affecting neurodevelopment and synaptic plasticity. A systematic consolidation of current evidence supporting the involvement of CNNM2 in SCZ pathogenesis provides a direction for further investigation of the pathological mechanisms underlying this disease, and for identification of novel targets for clinical intervention..

Schizophrenia↗
PubMed1999

Impaired learning and memory and altered hippocampal neurodevelopment resulting from interleukin-2 gene deletion.

Interleukin-2 (IL-2), the protypical T cell growth factor and immunoregulatory cytokine produced by lymphocytes, has been implicated as a brain neurotrophic factor and neuromodulator. The consequences of the absence of endogenous IL-2 on brain development and function were unknown. Brain IL-2 receptors are enriched in the hippocampal formation, an area critical for the acquisition and consolidation of spatial learning and memory. Thus, we tested the hypothesis that mice lacking IL-2 would exhibit alterations in hippocampal-dependent learning and neurodevelopment. Compared with C57BL/6-IL-2+/+ wild-type mice, we observed that C57BL/6-IL-2-/- gene knockout mice had markedly impaired spatial learning and memory in the Morris water maze. No significant deficits in parameters of learning and memory performance were found in severe combined immunodeficient (SCID) mice (C57BL/6scid), however, suggesting that the impaired spatial learning and memory exhibited by IL-2 knockout mice is not attributable to generalized immunodeficiency resulting from the absence of endogenous IL-2. Examination of other domains of behavioral performance showed that the IL-2 knockout and wildtype mice did not differ in measures of fearfulness or locomotor activity in an elevated plus maze, or in reflexive startle responses to auditory stimuli--although prepulse inhibition of acoustic startle (PPI) was increased significantly in IL-2 knockout mice. The spatial learning and memory impairment in IL-2 knockout mice was accompanied by reductions in hippocampal infrapyramidal mossy neuronal fiber length, a factor shown previously to correlate positively with spatial learning ability. These findings indicate that, in addition to being a pivotal cytokine in immune regulation, IL-2 may play a role in the development and regulation of brain neurons involved in spatial learning and memory.

Acoustic Stimulation↗
PubMed2000

The effects of bone morphogenetic protein 2 and 4 (BMP2 and BMP4) on gap junctions during neurodevelopment.

Nervous system deficits account for the third largest group of fatal birth defects (after heart and respiratory problems) in North America. Although considerable advance has been made in neuroscience research, the early events involved in neurogenesis remain to be elucidated. More specifically, the effects of signaling molecules on intercellular communication during neurodevelopment have not yet been studied. The development of the central nervous system is regulated, at least in part, by signaling molecules such as bone morphogenetic proteins (BMPs). In this study, we have used the embryonal mouse P19 cell line to examine the effects of BMP2 and BMP4 on gap junctional communication as well as neuronal and astrocytic differentiation. The undifferentiated P19 cells show high levels of the gap junction protein, connexin43 (Cx43), and functional intercellular coupling. However, Cx43 expression and dye coupling decrease as these cells differentiate into neurons and astrocytes. In contrast, cells treated with BMP2 or BMP4 lose their capacity to differentiate into neurons but not astrocytes, while they maintain extensive gap junctional communication. The very few neurons that remain in the BMP-treated cultures are coupled (a characteristic not seen in the control neurons). Together, our data suggest that BMPs may play a critical role in morphogenesis of P19 cells while they affect gap junctions.

Animals↗
PubMed2006

Neurodevelopment of children with single suture craniosynostosis: a review.

INTRODUCTION: Rates of neurocognitive risk range from 35-50% of school-aged children with isolated single suture craniosynostosis (SSC). It has been hypothesized that early surgical intervention to release suture fusion reduces risk for increased intracranial pressure (ICP) and the corresponding risk to neurodevelopment. However, studies assessing children with SSC have been inconsistent in finding an association between neurocognitive development, age of surgery, and ICP. REVIEW: SSC produces notable distortion of the cranial vault and underlying brain mass. Although a linear relationship between skull distortion, ICP, and neurocognitive deficits has generally been assumed, recent studies have postulated an interactive process between the skull and developing brain that results in neuroanatomical changes that are not limited to areas directly beneath the fused suture. The specific neuropsychological deficits identified in children with SSC including problems with attention and planning, processing speed, visual spatial skills, language, reading, and spelling may be related to the anatomic differences that persist after correction of suture fusion. CONCLUSIONS: Available literature on neurocognitive development of children with SSC is suggestive of mild but persistent neuropsychological deficits, which become more significant as cognitive demands increase at school age. Anatomical studies of children without SSC are beginning to identify particular groups of brain structures that if disrupted or malformed, may be associated with specific cognitive deficits. Controlled research investigating the relationship between persistent anatomical changes and neurocognitive functioning of school-aged children with SSC is needed.

Adolescent↗
PubMed2004

Effects of methylmercury on neurodevelopment in Japanese children in relation to the Madeiran study.

OBJECTIVES: A cross-sectional study was carried out to assess the effects of methylmercury exposure on neurodevelopment in Japanese children, in relation to the Madeiran cross-sectional study, and to estimate benchmark dose (BMD) levels using the data of two studies. METHODS: Mercury levels in hair samples obtained from 327 Japanese mothers and their 7-year-old children, and methylmercury levels in the umbilical cord, were determined. Neurodevelopmental examinations, including the brainstem auditory evoked potential (BAEP), were performed on the children. RESULTS: The medians of hair mercury were 1.63 (0.11-6.86) mug/g for mothers and 1.65 (0.35-6.32) mug/g for children, and a significant correlation was seen between the hair mercury levels in mothers and children. The maternal hair mercury was significantly correlated with the methylmercury in the umbilical cords obtained from 49 children. In 210 children whose mothers had not changed their dietary habits since pregnancy, most of the neurodevelopmental variables were not significantly related to hair mercury levels. The BAEP latencies were significantly shorter in the Japanese children than in the 113 Madeiran 7-year-old children, whose mothers had hair mercury of 1.12-54.5 (median 10.9) mug/g. Significant relationships between the maternal hair mercury level and BAEP latencies (peaks III and V, and interpeak I-III) were found only in the merged data of Japanese and Madeiran children. When the lower 95% confidence limit of BMD (BMDL) was calculated, the BMDLs of mercury exposure for BAEP latencies in the merged data were between 6.9 and 10.5 mug/g, and lower than those in the Madeiran children. CONCLUSIONS: It is suggested that Japanese children may ingest similar doses per body weight of methylmercury to their mothers. If maternal hair mercury was used as a proxy for mercury exposure at birth, no significant dose-effect associations with the BAEP latencies were observed in Japanese children with exposure levels below 6.9 mug/g of hair mercury, but only when higher-level exposures from Madeiran children were included. The BMDL was lower for the merged data than for Madeiran children alone.

Adult↗
PubMed2004

Nutrients, neurodevelopment, and mood.

Human neurodevelopment is the result of genetic and environmental interactions. This paper examines the role of prenatal nutrition relative to psychiatric disorders and explores the relationship among nutrients, mood changes, and mood disorders. Epidemiologic studies have found that adults who were born with a normal, yet low birth weight have an increased susceptibility to diseases such as coronary heart disease, diabetes, and stroke in adulthood. Prenatal caloric malnutrition, low birth weight, and prematurity also increase the risk for neurodevelopmental disorders, schizophrenia, affective disorders, and schizoid and antisocial personality disorders. Placebo-controlled studies in medicated patients suggest that add-on treatment with omega-3 fatty acids, particularly eicosapentaenoic acid, may ameliorate symptoms of major depressive disorder. Additional studies are necessary to confirm any benefits for bipolar disorders.

Adult↗
PubMed1994

Preliminary evidence for an association between minor physical anomalies and second trimester neurodevelopment in schizophrenia.

Two types of markers, dermatoglyphics and minor physical anomalies, have been used as indicators of problems with fetal neurodevelopment in schizophrenia. The degree to which these markers overlap is not known. While it is agreed that abnormal dermatoglyphics reflect early second trimester maldevelopment, the timing of the development of minor physical anomalies has not been determined. Forty-six schizophrenic patients received assessments for minor physical anomalies, dermatoglyphics (right-left ridge count asymmetry and total finger ridge count), and information processing. Higher scores for minor physical anomalies were associated with greater dermatoglyphic asymmetry. Patients who had both types of indicators (high minor physical anomalies and dermatoglyphic asymmetry) did not differ on information-processing measures from patients who had neither. On the basis of the timing of dermatoglyphic development (weeks 14-22 of gestation), the association between minor physical anomalies and dermatoglyphic asymmetry suggests that the relatively high rate of minor physical anomalies observed in schizophrenia can be considered to reflect at least second trimester maldevelopment.

Adult↗
PubMed2005

Suboptimal neurodevelopment in very preterm infants is related to fetal cardiovascular compromise in placental insufficiency.

OBJECTIVE: The purpose of this study was to determine the relationship between fetal cardiovascular hemodynamics and neurodevelopmental outcome in infants born before 32 gestational weeks with placental insufficiency. STUDY DESIGN: Seventeen fetuses that underwent Doppler ultrasonography within 24 hours before delivery were included in this prospective cross-sectional study. Placental histology was examined. Multiple inflammatory markers and vascular endothelial growth factor (VEGF) and its receptor were analyzed from umbilical cord serum. Neurodevelopmental outcome was assessed by Griffiths scales at 1 year of corrected age. RESULTS: Infants with suboptimal outcome (n = 7) had higher umbilical artery, ductus venosus, and inferior vena cava pulsatility index values (P < .05) and lower weight-indexed cardiac outputs (P < .05) than infants with normal outcome (n = 10). Placental histology and serum revealed no inflammation. VEGF values were similar among all infants. CONCLUSION: In placental insufficiency with delivery before 32 gestational weeks, suboptimal neurodevelopment was related to decreased fetal weight-indexed cardiac output and increased systemic venous pressure.

Blood Pressure↗
PubMed2006

Voxel based versus region of interest analysis in diffusion tensor imaging of neurodevelopment.

There are two main methods of quantitative analysis in diffusion tensor imaging (DTI) studies: manual region of interest (ROI) and automated voxel based. The purpose of this study is to compare the results of each of these methods applied to the same data set. Linear correlative analysis was performed for mean diffusivity (Trace/3 ADC) and for fractional anisotropy (FA) versus age within 8-12 years (N = 32) and within 21-27 years (N = 28), as well as a group comparison. SPM analysis identified more structures changing with age, partly due to the limited regions measured with ROI analysis. In general, ROI and voxel-based analysis methods produced comparable results for widespread reductions of Trace/3 ADC and increases of FA with age, particularly for group comparison. The discrepancies (i.e., missed regions) were likely related to problems of spatial normalization for SPM analysis, and masking localized changes by averaging all the voxels within a region of interest for ROI analysis. These two analysis methods for DTI offer complementary results, but neither one yields the complete story of neurodevelopment.

Adult↗
PubMed2002

Pediatric neurodevelopment and sports participation. When are children ready to play sports?

A fundamental knowledge of normal child and adolescent development is essential to providing a developmentally appropriate sports experience for the child, and to providing guidance to parents regarding their child's sport participation. This article reviews neurodevelopment, normal child and adolescent development relevant to sport participation, and developmental readiness to participate in sports. Neurodevelopmental maturation is a complex, continuous process. The sense of social comparison is not achieved until after 6 years of age, and the ability to understand the competitive nature of sports is generally not achieved until 9 years of age. By about 12 years of age, most children are mature enough to comprehend the complex tasks of sports and are physically and cognitively ready to participate in competitive sports with appropriate supervision.

Adolescent↗
PubMedDate not supplied

Neurodevelopment after in utero amiodarone exposure.

It is not known whether amiodarone is neurotoxic to the fetus, as it is to adults. We evaluated neurodevelopment of a historical cohort (N = 10) of children exposed transplacentally to amiodarone. Scores on standardized tests of cognitive and language skills were compared (by Wilcoxon signed rank test) between eight toddlers and matched controls. It was not possible to obtain controls for older amiodarone-exposed children (aged 9.7 and 12.0 years), whose test results were compared descriptively with normative data. There was no difference in IQ scores between amiodarone-exposed toddlers and controls. All had favorable temperaments. However, amiodarone-exposed toddlers showed expressive language skills that were relatively poorer than verbal skills, when compared with controls (p = 0.046). One amiodarone-exposed toddler exhibited global developmental delay. The older amiodarone-exposed children had well-developed social competence, favorable global IQ scores, but problems with reading comprehension, written language, and arithmetic. This picture is reminiscent of the Nonverbal Learning Disability Syndrome. There may be neurotoxicity associated with transplacental exposure to amiodarone. Follow-up is warranted, although most mothers were happy with the development of their children.

Adult↗
PubMed2000

Ten-year follow-up of adolescent-onset anorexia nervosa: physical health and neurodevelopment.

To study the development of physical health and some neuromotor functions in anorexia nervosa (AN) 51 individuals (48 females, three males) with a mean AN onset of 14 years, recruited after community screening, were followed prospectively together with 51 age-, sex-, and school-matched individuals without AN (controls). About 10 years after AN onset, all individuals were examined in respect of physical health and neurodevelopment. There were no deaths. Weight and height had normalised, except in three participants with persistent AN. Significantly more participants with AN had a physical complaint/disorder, including hirsutism. This might be a long-term complication in weight restored AN. Dysdiadochokinesis occurred almost exclusively among individuals with former AN in accordance with our previous studies.

Adolescent↗