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At least 127 records · Page 7Linked to original sources
PubMed2003

The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment: the Boston Circulatory Arrest Trial.

OBJECTIVES: Despite the technical advantages of total circulatory arrest for vital organ support during infant heart surgery, many centers have moved away from its use because of the demonstrated effects of circulatory arrest of long duration on neurodevelopmental outcomes. Our goal was to determine the functional form of the association between duration of circulatory arrest and risk of neurodevelopmental dysfunction. METHODS: From 1988 to 1992, in a single-center trial, infants with d-transposition of the great arteries underwent the arterial switch operation after random assignment to circulatory arrest or low-flow bypass. The alpha-stat method was used, and hematocrit on bypass was maintained at 20%. Developmental, neurologic, and speech outcomes were assessed at 8 years of age in 155 of 160 eligible children (97%). Outcomes selected for analysis were Full-Scale, Verbal, and Performance IQ, Reading and Mathematics Composite, time to complete the Grooved Pegboard (dominant hand), and the Mayo Test for Apraxia. RESULTS: Nonparametric regression and piecewise linear models indicated that neurodevelopmental outcomes were generally not adversely affected unless the duration of circulatory arrest exceeded a threshold of 41 minutes (95% 1-sided lower confidence limit of 32 minutes). CONCLUSIONS: We found that the effect of duration of total circulatory arrest on later neurodevelopmental outcomes is nonlinear, with little influence at shorter durations and with steadily worsening outcomes after longer durations of circulatory arrest. Because the effects of duration of circulatory arrest may vary according to diagnosis, age at surgery, and other bypass and perioperative variables, this study cannot ascertain a universally "safe" duration of total circulatory arrest.

Boston↗
PubMed2000

Distinctive patterns of memory function in subgroups of females with Turner syndrome: evidence for imprinted loci on the X-chromosome affecting neurodevelopment.

X-monosomy is a form of Turner syndrome (TS) in which an entire X chromosome is missing. It is usually assumed that neuropsychological deficits in females with TS result from insufficient dosage of gene products from alleles on the sex chromosomes. If so, then parental origin of the single X chromosome should be immaterial. However, if there are imprinted genes on the X chromosome affecting brain development, neuropsychological development will depend on the parental origin of the single X chromosome. We contrasted verbal and visuospatial memory in females with a single paternal X chromosome (45,X(p)) and those with a single maternal X (45,X(m)). Neither group showed any impairment on immediate story recall; if anything, performance was above control levels. Groups did not differ on a measure of delayed recall. However, when delayed recall was considered after adjusting for level of immediate recall, 45,X(m) females showed enhanced verbal forgetting relative to controls over a delay. On the Rey figure, both groups were poor at copying the figure, but, after adjusting scores for initial copy score and strategy, only the 45,X(p) females showed disproportionate forgetting relative to controls. We propose there may be one or more imprinted genes on the X chromosome that affect the development of lateralised brain regions important for memory function.

Adolescent↗
PubMed2004

The synaptic pathology of schizophrenia: is aberrant neurodevelopment and plasticity to blame?

Synaptic pathology is a feature of the brain in schizophrenia, denoted by alterations in the expression of synaptic proteins. In the absence of data indicative of neurodegenerative processes, the neuropathological features of schizophrenia suggest that the major pathogenic process in the disorder is one of aberrant development. Molecular evidence in support of a neurodevelopmental origin of schizophrenia has come from studies examining the expression of key developmental genes. However, as many of these genes are also involved in synaptic plasticity, their altered expression in schizophrenia also suggests that the disorder may be one of aberrant synaptic plasticity. The aim of this review is to explore whether aberrant development and synaptic plasticity may underlie the synaptic pathology of schizophrenia. It does this in two ways. First, studies in schizophrenia of the expression of two synaptic genes important in synaptic remodeling and plasticity are reviewed, changes in which may be indicative of aberrant synaptic plasticity in the disorder. Second, the possible relationship between the expression of genes involved in development and plasticity with that of presynaptic proteins is examined. Such a relationship, in combination with their altered expression in schizophrenia, may indicate whether developmental and plasticity-related processes may contribute to the synaptic pathology of the disorder. A brief discussion on the possible origins of the synaptic pathology of schizophrenia, and possible future studies, concludes the review.

Animals↗
PubMed2005

Neurodevelopment, neuroplasticity, and new genes for schizophrenia.

Schizophrenia is a complex, debilitating neuropsychiatric disorder. Epidemiological, clinical, neuropsychological, and neurophysiological studies have provided substantial evidence that abnormalities in brain development and ongoing neuroplasticity play important roles in the pathogenesis of the disorder. Complementing these clinical studies, a range of cytoarchitectural, morphometric, ultrastructural, immunochemical, and gene expression methods have been applied in investigations of postmortem brain tissues to characterize the cellular and molecular profile of putative developmental and plastic abnormalities in schizophrenia. While findings have been diverse and many are in need of replication, investigations focusing on higher cortical and limbic brain regions are increasingly demonstrating abnormalities in the structural and molecular integrity of the synaptic complex as well as glutamate-related receptors and signal transduction pathways that play critical roles in brain development, synaptogenesis, and synaptic plasticity. Most exciting have been recent associations of schizophrenia with specific genes, such as neuregulin-1, dysbindin-1, and AKT-1, which are vital to synaptic development, neurotransmission, and plasticity.

Humans↗
PubMed1999

Prenatal cocaine exposure reduces glial cell line-derived neurotrophic factor (GDNF) in the striatum and the carotid body of the rat: implications for DA neurodevelopment.

Glial cell line-derived neurotrophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer, and a member of the transforming growth factor-beta superfamily. GDNF has been shown to promote the survival and morphological differentiation of dopamine (DA) neurons and increase their high-affinity dopamine uptake. In order to determine whether the mechanism for our previously observed cocaine-induced DA reductions in brain and carotid body were GDNF-mediated, we exposed Sprague-Dawley rat fetuses to cocaine via maternal subcutaneous injections (30 mg/kg b.i.d., E7-E19). Brains and carotid bodies of fetuses were excised and processed for assessment of GDNF levels using an Enzyme-Linked ImmunoadSorbent Assay (ELISA). ANOVA indicated that cocaine reduced carotid body GDNF by 36% (F((1,5))=28. 11, p<0.05) and striatal GDNF by 41% (F((1,5))=41.77, p<0.01). Although there was no interaction between drug exposure and fetal uterine position, post-hoc pairwise comparisons indicated that reductions in GDNF in the cocaine groups were due to differences at more distal positions (positions 4-8). The magnitude of the reductions in striatal GDNF (but not carotid body GDNF) in both cocaine-exposed and control fetuses followed a cervical (smallest GDNF reductions) to ovarian (greatest GDNF reductions) uterine position gradient. This pattern was similar to that which we observed in prior studies examining DA reductions in brain following prenatal cocaine exposure. The finding that cocaine reduces GDNF levels in striatum and carotid body support the hypothesis that cocaine's ability to reduce striatal and carotid body DA may be indirect through its ability to reduce GDNF. These data along with previous findings support the hypothesis that cocaine's effects on DA neurons are at least partially due to its indirect effects on trophic activity. The possible mechanisms whereby cocaine affects trophic activity are discussed.

Animals↗
PubMed2001

Neurodevelopment of neonates in neonatal intensive care units and growth of surviving infants at age 2 years.

SUMMARY: The presence of development disorders in neonates attended in a Neonatal Intensive Care Unit (NICU) is highly variable; the aim of this study, therefore, was to determine the evolution of somatic and neurosensory development in a group of neonates requiring treatment in the NICU and to analyse the perinatal and developmental aspects of children presenting abnormalities. PATIENTS AND METHODS: A total of 492 neonates (275 premature, 106 with birthweight < or =1500 g), who were treated in the NICU between January 1994 and December 1997, were followed-up until the age of 2 years. Data were obtained concerning birthweight, body length, head circumference, gestational age, normality of weight for gestational age, single/multiple birth, duration of stay in the NICU and the hospital, duration of mechanically assisted respiration and evolutive somatometry, neurological examination and the Brunet-Lezine development test, adjusted for the gestational age of the neonates, at 6, 12, 18 and 24 months. When abnormal results were detected, Early Attention (EA) programmes were applied. RESULTS: Somatometry at birth in relation to gestational age revealed a weekly weight gain of 8.6%, an increase in body length of 1% and in head circumference of 1% (p<0.001). The evolution of somatic development to the age of 2 years showed that neonates with a birthweight < or =1500 g did not reach the values of neonates with a greater birthweight. The prevalence of cerebral palsy among all neonates was 6.8%, 14.6% among those weighing < or =1500 g, 4% among those weighing 1501-2500 g and 5% among those weighing >2500 g. The overall rate of neurosensory injury was 10.5%. These neonates presented less somatic development than those did with no neurologic disorder. To sum up, most of the neonates attended in the NICU during the 1990s presented a normal pattern of development. Nevertheless, they should be the object of special attention during the first years of life, particularly those neonates with a birthweight < or =1500 g and those presenting neurosensory risk.

Birth Weight↗
PubMed1998

White matter injury in the preterm infant: an important determination of abnormal neurodevelopment outcome.

Periventricular white matter injury, specifically cystic periventricular leukomalacia (PVL) and ipsilateral hemorrhage into white matter associated with periventricular-intraventricular hemorrhage (PV-IVH), contribute significantly to neonatal mortality and long-term neurodevelopmental deficits in the premature infant. The first lesion PVL occurs in approximately 3-4% of infants of birth weight (BW) < 1500 grams. It manifests either as a focal or diffuse lesion within white matter. Although the pathogenesis of PVL is complex and likely multifactorial, principle contributors include vascular factors which markedly increase the risk for ischemia during periods of systemic hypotension and the intrinsic vulnerability of the oligodendrocyte to neurotoxic factors such as free radicals or cytokines. Clinical associations with PVL include a history of chorioamnionitis, prolonged rupture of membranes, asphyxia, sepsis, hypocarbia, etc. The vast majority of infants exhibit long-term neurodevelopmental deficits that affect motor, cognitive and visual function. The second lesion, the ipsilateral hemorrhage into white matter lesion associated with PV-IVH, occurs in approximately 10-15% of infants of BW < 1000 grams. The white matter injury appears to be a venous infarction with hemorrhage occurring as a secondary phenomenon. Prevention of this lesion has to include prevention of the associated PV-IVH. In this regard, the antenatal administration of glucocorticoids has been associated with a significant reduction in the sonographic incidence of severe IVH and the associated white matter involvement. The postnatal administration of indomethacin to high risk infants appears to hold the most promise at the current time in preventing this lesion. The neurodevelopmental outcome with extensive white matter injury is universally poor, affecting long-term motor and cognitive deficits; the long-term outcome is more favorable with lesser involvement. A clearer understanding of pathogenesis of both conditions is essential so as to provide targeted preventative strategies.

Cerebral Hemorrhage↗
PubMed2001

Stem cells in neurodevelopment and plasticity.

The processes of stem cell proliferation and differentiation during embryogenesis are governed by transcription factors that regulate the regional differentiation of the central nervous system (CNS). Do neural "stem" cells persisting in the postnatal CNS disobey this sequence of events? The division of neural progenitor cells is promoted by basic Fibroblast Growth Factor Fgf2 or Epidermal Growth Factor Egf. However, while the intraventricular administration of FgF2 during embryogenesis increases the generation of cortical pyramidal neurons, the same treatment in the adult CNS produces interneurons of the olfactory bulb. The competence of neural progenitor cells to respond to Fgf is dictated by nuclear transcription factors that constrain neuronal fates through time. Developmentally regulated transcriptional programs are regulated by cell interactions, as dividing cells check their molecular signature against that of their environment. Thus, cell surface interactions account for competitive phenomena among pools of cells, including the inhibitory effect of neurons on the division of their progenitors, and may also explain the "permissive" effects of non-CNS environments. The challenge remains to understand the genetic programs that control the fate of progenitor cells within the postnatal CNS and their regulation by stress, apoptosis and environmental perturbations. These programs are likely to be similar to gene cascades that control proliferation, differentiation and migration of progenitor cells at earlier stages of development.

Animals↗
PubMed2002

Pubertal neurodevelopment and the emergence of psychotic symptoms.

One of the chief epidemiological hallmarks of schizophrenia is its modal age at onset in early adulthood. Clinical onset is preceded by an adolescent period that is usually characterized by increasing adjustment problems. Recent theorizing about the etiology of schizophrenia has focused on postpubertal brain changes that may be involved in triggering the expression of vulnerability for schizophrenia. In this paper, we further examine the normal neurodevelopmental processes that occur in adolescence and the underlying role of hormonal factors in controlling the expression of genes that govern brain maturation. We then consider how postpubertal hormone changes might serve to trigger the expression of vulnerability genes that code for abnormal brain development.

Adolescent↗
PubMed2000

Behavioral neurodevelopment abnormalities and schizophrenic disorder: a retrospective evaluation with the Childhood Behavior Checklist (CBCL).

This study is a retrospective report of childhood and adolescence neurobehavioral assessment in patients with schizophrenia and their healthy siblings using the Childhood Behavior Checklist (CBCL). The CBCL ratings were obtained from retrospective maternal reports, for five age periods (birth to 3years, 4-7years, 8-11years, 12-15years and 16-18years) in a sample of 32 patients with schizophrenia. The patients showed a variety of childhood and adolescence behavioral problems when compared with their siblings, and the various types of problems differed in the developmental course of the disease. Cluster analysis was conducted on the childhood premorbid behavior ratings for the schizophrenic patients, and two subgroups emerged: a cluster with an initially low level of behavioral abnormalities (B.A. ) that increased over the years, and a cluster with a high level of B.A. that remain relatively stable until early adulthood. The latter group showed more severe current negative symptoms.

Adolescent↗
PubMed2001

Variation of serotonergic gene expression: neurodevelopment and the complexity of response to psychopharmacologic drugs.

Individual differences in drug effects and treatment response are relatively enduring, continuously distributed, as well as substantially heritable, and are therefore likely to result from an interplay of multiple genomic variations with environmental influences. As the etiology and pathogenesis of behavioral and psychiatric disorders is genetically complex, so is the response to drug treatment. Psychopharmacologic drug response depends on the structure and functional expression of gene products, which may be direct drug targets or may indirectly modify the development and synaptic plasticity of neural networks critically involved in drug response. While formation and integration of these neural networks is dependent on the action of manifold proteins, converging lines of evidence indicate that genetically controlled variability in the expression of genes critical to the development and plasticity of distinct neurocircuits influences a wide spectrum of quantitative traits including treatment response. During brain development, neurotransmitter systems (e.g. serotonergic system), which are frequently targeted by psychotropic drugs, control neuronal specification, differentiation, and phenotype maintenance. The formation and maturation of these neurotransmitter systems, in turn, is directed by an intrinsic genetic program. Based on the notion that complex gene-gene and gene environment interactions in the regulation of brain plasticity are presumed to contribute to interindividual differences in drug response, the concept of developmental psychopharmacogenetics is emerging. This review appraises prototypical genomic variation with impact on gene expression and complementary studies of genetic and environmental effects on brain development and synaptic plasticity in the mouse model. Although special emphasis is given to molecular mechanisms of neurodevelopmental genetics, relevant conceptual and methodological issues pertinent to the dissection of the psychopharmacogenetic-neurodevelopmental interface are also considered.

Animals↗
PubMed1997

Schizophrenia: a disorder of neurodevelopment?

For the first time, there is a pathogenic hypothesis of schizophrenia based upon reasonable empirical data. The hypothesis is that schizophrenia is a disorder arising from aberrant brain development. The neurodevelopmental view of schizophrenia is supported by neuropathological, epidemiological and clinical findings. Here, the evidence in favour of the model is summarized, together with a consideration of its weaknesses.

Brain↗