Factors In Neurodevelopment Research Articles

Latent class analysis to characterize neonatal risk for neurodevelopmental differences.

Neonatal risk factors, such as preterm birth and low birth weight, have been robustly linked to neurodevelopmental deficits, yet it is still unclear why some infants born preterm and/or low birth weight experience neurodevelopmental difficulties while others do not. The current study investigated this heterogeneity in neurodevelopmental abilities by examining additional neonatal morbidities as risk factors, utilizing latent class analysis to classify neonates into groups based on similar neonatal risk factors, and including neonates from the full spectrum of gestational age. Neonates who received neonatal care at an academic public hospital during an almost 10-year period (n = 19,951) were included in the latent class analysis, and 21 neonatal indicators of health were used. Neonatal class, sex, and the interaction between neonatal class and sex were used to examine differences in neurodevelopment at 18 months of age in a typically developing population. The best fitting model included five infant classes: healthy, hypoxic, critically ill, minorly ill, and complicated delivery. Scores on the parent-rated neurodevelopmental measure differed by class such that infants in the critically ill, minorly ill, and complicated delivery classes had lower scores. There was no main effect of sex on the neurodevelopmental measure scores, but the interaction between sex and neonatal class was significant for three out of five neurodevelopmental domains. The current study extends the understanding of risk factors in neurodevelopment by including several neonatal medical conditions that are often overlooked and by using a person-centered, as opposed to variable-centered, approach. Future work should continue to examine risk factors, such as maternal health during pregnancy and medical interventions for newborns, in relation to neonatal risks and neurodevelopment by using a person-centered approach.

Plasma oxysterols in drug-free patients with schizophrenia

Evidence from clinical, genetic, and medical studies has shown the neuronal developmental disorder aspect of schizophrenia (SZ). Whereas oxysterols are vital factors in neurodevelopment, it is still unknown whether they are involved in the pathophysiology of SZ. The current study aims to explore the profile of oxysterols in plasma, ratio to total cholesterol (Tchol) and the association with clinical factors in patients with SZ. Forty men diagnosed with SZ and forty healthy controls matched for age and sex were included in the study. The ratios of cholestane-3β,5α,6β-triol, 27-hydroxycholesterol (27-OHC) and Cholestanol to Tchol increased in the schizophrenic group compared to controls. However, levels of 24S-hydroxycholesterol (24-OHC) were not significantly different between patients and controls. For the SZ patients, the plasma 24-OHC levels were positively correlated with the positive and negative syndrome total scores (PANSS) but negatively correlated with the Montreal Cognitive Assessment scores (MOCA). Moreover, the ratio Cholestanol to Tchol was negatively correlated with MOCA scores and positively correlated with PANSS general. The binary logistic regression analysis revealed that the ratio Cholestane-3β,5α,6β-triol/TChol could be considered as an independent risk factor for SZ. On the other hand, the receiver’s operating characteristics analysis corresponding to potential biomarkers on SZ showed Areas Under the Curve (AUCs) of 82.1%; 69.7% and 77.6% for the ratio of Cholestane-3β,5α,6β-triol/TChol, 27-OHC/TChol and Cholestanol/TChol respectively. The relevance of Cholestane-3β,5α,6β-triol, 27-OHC and Cholestanol assays as biomarkers of this disease deserves further investigation.

Oral language of school-aged children born pretermaturely: a population-based analysis from Madeira Island, Portugal

Premature birth and low birth weight are very important factors in neurodevelopment. Current research in this population focuses on children born prematurely, with no underlying complications in the post-natal period, who are likely to develop specific disorders with their language development and consequently with their learning capabilities too. This study aims to analyse the oral language skills of prematurely born children in comparison to their school-aged peers. The children were assessed in the respective schools, 27 preterm children (16 under 32 weeks and 11 with 32 or more weeks of gestation) and 49 term paired by gender, age, and school year. Tests including simple and complex structures for assessing semantics, morphosyntax, and phonology were used, as well as a test of verbal memory. Preterm born children, regardless of their prematurity grade, showed significantly lower results than their peers, and more than a half of them, 52%, presented low scores in all language tests simultaneously, showing an important language deficit. In contrast, in the term born children group only 14% showed low scores simultaneously in all tests. Verbal memory ability proved to be lower than that of their term peers, regardless of the gestational age and birth weight of preterm children. As a result of this analysis we consider that the evaluation of the linguistic development of these children, even in cases of moderate to late prematurity, should be monitored in order to identify earlier the existence of deficits and prevent psychosocial and learning problems.

Brain-Specific Oxysterols and Risk of Schizophrenia in Clinical High-Risk Subjects and Patients With Schizophrenia.

Accumulating evidence from clinical, genetic, and epidemiologic studies suggest that schizophrenia might be a neuronal development disorder. While oxysterols are important factors in neurodevelopment, it is unknown whether oxysterols might be involved in development of schizophrenia. The present study investigated the relationship between tissue-specifically originated oxysterols and risk of schizophrenia. A total of 216 individuals were recruited in this study, including 76 schizophrenia patients, 39 clinical high-risk (CHR) subjects, and 101 healthy controls (HC). We investigated the circulating levels of brain-specific oxysterol 24(S)-hydroxycholesterol (24OHC) and peripheral oxysterol 27-hydroxycholesterol (27OHC) in all participants and analyzed the potential links between the oxysterols and specific clinical symptoms in schizophrenic patients and CHR. Our data showed an elevation of 24OHC in both schizophrenia patients and CHR than that in HC, while a lower level of 27OHC in the schizophrenia group only. The ratio of 24OHC to 27OHC was only increased in the schizophrenic group compared with CHR and HC. For the schizophrenic patients, the circulating 24OHC levels are significantly associated with disease duration, positively correlated with the positive and negative syndrome total scores, while the 27OHC levels were inversely correlated with the positive symptom scores. Together, our data demonstrated the disruption of tissue-specifically originated cholesterol metabolism in schizophrenia and CHR, suggesting the circulating 24OHC or 24OHC/27OHC ratio might not only be a potential indicator for risk for schizophrenia but also be biomarkers for functional abnormalities in neuropathology of schizophrenia.

Can increased resistance to uterine artery flow be a risk factor for adverse neurodevelopmental outcomes in childhood? A prospective cohort study

A prospective cohort study was conducted to determine whether an increased uterine artery pulsatility index (UtA-PI) in the second trimester of pregnancy is a risk factor for neurodevelopmental outcomes in children 2–3 years of age. A group of pregnant women with a UtA-PI below the 90th percentile (P90) and a second group with a UtA-PI ≥ P90 in the second trimester were included in this study. The children of these women were evaluated during their second or third year of life using the Bayley III Screening Test. A total of 858 pregnancies with UtA-PI < P90 and 96 pregnancies with UtA-PI ≥ 90 were studied. The differences between the groups related to UtA-PI ≥ 90 were detected in relation to the variables of the Caucasian ethnicity, hypertension, newborn weight and stay in the intensive care unit after birth. However, adjusted neurodevelopmental outcomes did not differ between the groups: OR 0.53 (95% CI 0.27–1.04%). This study failed to demonstrate that the UtA-PI is a risk factor for adverse neurodevelopment in children.Impact statementWhat is already known on this subject? Early interventions in children at high risk for neurodevelopmental deficiency have proved to be beneficial. The complications associated with gestation and delivery negatively influence neurodevelopment. Several studies have shown that some adverse pregnancy outcomes such as preeclampsia, foetal growth restriction and foetal death can be predicted by increased resistance to flow in the uterine artery in the second trimester. However, there are no studies evaluating the association of the uterine artery with neurodevelopmental results.What do the results of this study add? This study concludes that neurodevelopment is influenced by multiple environmental and intrinsic factors and cannot be predicted by only one variable, such as the uterine artery blood flow. The brain has repair mechanisms to attenuate insults that occur during gestation and delivery.What are the implications of these findings for clinical practice and/or further research? This study was unable to demonstrate that blood flow in the uterine artery is a risk factor for neurodevelopment. Different, larger studies should be conducted by combining other factors with the uterine artery in an algorithm to allow the early identification of children at risk for neurodevelopmental impairment.

The emerging roles for the chromatin structure regulators CTCF and cohesin in neurodevelopment and behavior.

Recent genetic and technological advances have determined a role for chromatin structure in neurodevelopment. In particular, compounding evidence has established roles for CTCF and cohesin, two elements that are central in the establishment of chromatin structure, in proper neurodevelopment and in regulation of behavior. Genetic aberrations in CTCF, and in subunits of the cohesin complex, have been associated with neurodevelopmental disorders in human genetic studies, and subsequent animal studies have established definitive, although sometime opposing roles, for these factors in neurodevelopment and behavior. Considering the centrality of these factors in cellular processes in general, the mechanisms through which dysregulation of CTCF and cohesin leads specifically to neurological phenotypes is intriguing, although poorly understood. The connection between CTCF, cohesin, chromatin structure, and behavior is likely to be one of the next frontiers in our understanding of the development of behavior in general, and neurodevelopmental disorders in particular.

Prenatal exposure to organophosphate pesticides and child neurodevelopment

Background Organophosphate pesticides (OPs) have been widely used in Spain and early exposure has been suggested as a risk factor for neurodevelopment. We aimed to investigate the effects of prenat...

Fibroblast Growth Factors in Neurodevelopment and Psychopathology

In psychiatric disorders, the effect of genetic and environmental factors may converge on molecular pathways and brain circuits related to growth factor functioning. In this review, we describe how disturbances in fibroblast growth factors (FGFs) and their receptors influence behavior by affecting brain development. Recently, several studies reported associations of members of the FGF family with psychiatric disorders. FGFs are key candidates to modulate the impact of environmental factors, such as stress. Mutant mice for FGF receptor 1 show schizophrenia-like behaviors that are related to general loss of neurons and postnatal glia dysfunction. Mice lacking FGF2, a FGFR1 ligand, show similar reductions in brain volume and hyperactivity, as well as increased anxiety behaviors. FGFR2 and FGF17 are involved in the development of frontal brain regions and impairments in cognitive and social behaviors, respectively. Moreover, treatment with FGF2 was beneficial for depressive and cognitive measures in several animal studies and one human study. These findings indicate the importance of the FGF system with respect to developing novel etiology-directed treatments for psychopathology.

Direct and Indirect Effects of Brain Volume, Socioeconomic Status and Family Stress on Child IQ.

A large literature documents the detrimental effects of socioeconomic disparities on intelligence and neuropsychological development. Researchers typically measure environmental factors such as socioeconomic status (SES), using income, parent's occupation and education. However, SES is more complex, and this complexity may influence neuropsychological outcomes. This studyused principal components analysis to reduce 14 SES and 28 family stress indicators into their core dimensions (e.g. community and educational capital, financial resources, marital conflict). Core dimensions were used in path analyses to examine their relationships with parent IQ and cerebral volume (white matter, grey matter and total brain volume), to predict child IQ in a sample of typically developing children. Parent IQ affected child IQ directly and indirectly through community and educational capital, demonstrating how environmental factors interact with familial factors in neuro-development. There were no intervening effects of cerebral white matter, grey matter, or total brain volume. Findings may suggest that improving community resources can foster the intellectual development of children.

The Origin of Mind: Evolution of Brain, Cognition, and General Intelligence

The Origin of Mind: Evolution of Brain, Cognition, and General Intelligence

Role of Olf-1 and Pax-6 Transcription Factors in Neurodevelopment

The Olf-1 transcription factor is expressed in olfactory sensory neurons where it regulates the expression of genes that encode components of the odorant signal transduction cascade and contributes to the terminal phenotype of these sensory neurons. We examined the pattern of expression of Olf-1 protein during mouse embryogenesis and observed Olf-1 expression transiently in a subset of neural precursor cells in the CNS and peripheral nervous system. The expression of Olf-1 protein was enriched in sensory components and coincided with postmitotic cells and the initiation of overt differentiation within the nervous system. The spatial and temporal patterns of Olf-1 expression during development suggest a role in neurogenesis that is common among different neural cell types. In parallel, the expression pattern of Pax-6, a transcription factor that is widely expressed in the developing nervous system, including the visual and olfactory systems, was examined with a C-terminal antibody. In the retina, Pax-6 protein is detected in the lens, the cornea, and the neural and pigmented retinas. In the olfactory epithelium, Pax-6 protein is expressed exclusively in cells of non-neuronal lineage, including sustentacular cells, basal cells, and Bowman's glands. The nonoverlapping, cellular localization patterns of Pax-6 and Olf-1 demarcate distinct cell lineages within the developing olfactory epithelium.