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PubMedDate not supplied

A pilot study of blood lead levels and neurobehavioral function in children living in Chennai, India.

The relationship between blood lead level and neurodevelopment was assessed in a pilot cross-sectional study of 74 4-14-year-old children in Chennai, India. Mean blood lead level was 11.1 microg/dL (2.5-38.3). The Binet-Kamath IQ test and the Wide Range Assessment of Visual Motor Activity (WRAVMA) were administered to 58 children. Teachers completed the Connor's Behavioral Rating Scale. Excluding two outliers, IQ and WRAVMA composite scores were inversely related to blood lead level, with an effect size of approximately 6 points decline for a 10-microg/dL increase in blood lead. Children in the highest and lowest blood lead quartiles had mean IQs of 95.6+/-13.3 and 102.0+/-22.5, respectively. Behavior ratings were not associated with blood lead level. Lead exposure is a significant problem among Indian children, with many having blood lead levels associated with increased neurodevelopmental risk.

Adolescent↗

PubMed2026

Study of NSD2 using a dTAG system reveals its molecular mechanism and oncogenic implications in t(4;14) multiple myeloma.

The histone H3 lysine 36 dimethylation (H3K36me2) methyltransferase NSD2 is deleted in Wolf-Hirschhorn syndrome and is aberrantly expressed in 10% to 15% of patients with multiple myeloma (MM) because of a t(4;14) translocation. Although NSD2 is thought to be a primary driver in MM, the exact molecular mechanisms by which it regulates transcription remain unclear. We applied the degradation tag (dTAG) system to acutely degrade NSD2 and used this, in combination with time-resolved thiol-linked alkylation for the metabolic sequencing of RNA (SLAM-seq), to identify 307 transcriptional targets of NSD2. Reconstitution with either wild-type NSD2 or a catalytically inactive mutant (NSD2Y1179A) showed that NSD2's transcriptional effects are almost exclusively dependent on its SET domain activity. Mechanistically, H3K36me2 deposition by NSD2 antagonizes H3K27me3 levels, and treatment with 2 distinct Polycomb repressive complex 2 inhibitors demonstrated that approximately half of the NSD2 target genes are regulated in an H3K27me3-dependent manner. Cleavage under targets and tagmentation (CUT&Tag) analysis showed that upon NSD2 depletion, there was an increase in H3K27me3 that occurred at genome-wide intergenic regions rather than at the promoters or gene bodies of NSD2 target genes. These data suggest that NSD2, via H3K36me2, antagonizes H3K27me3 deposition likely at distal regulatory elements, including enhancers, creating a chromatin landscape favorable for target gene transcription. Importantly, NSD2 target genes were enriched for key oncogenic pathways, and 24 transcription factors (TFs) implicated in neurodevelopment and acute leukemia, consistent with its role in Wolf-Hirschhorn syndrome and MM. Eight of these TFs are known oncogenic drivers in acute leukemia or MM, highlighting a novel molecular mechanism for NSD2's role in t(4;14) MM.

Histone-Lysine N-Methyltransferase↗

PubMed2004

Neural stem cells express melatonin receptors and neurotrophic factors: colocalization of the MT1 receptor with neuronal and glial markers.

BACKGROUND: In order to optimize the potential benefits of neural stem cell (NSC) transplantation for the treatment of neurodegenerative disorders, it is necessary to understand their biological characteristics. Although neurotrophin transduction strategies are promising, alternative approaches such as the modulation of intrinsic neurotrophin expression by NSCs, could also be beneficial. Therefore, utilizing the C17.2 neural stem cell line, we have examined the expression of selected neurotrophic factors under different in vitro conditions. In view of recent evidence suggesting a role for the pineal hormone melatonin in vertebrate development, it was also of interest to determine whether its G protein-coupled MT1 and MT2 receptors are expressed in NSCs. RESULTS: RT-PCR analysis revealed robust expression of glial cell-line derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in undifferentiated cells maintained for two days in culture. After one week, differentiating cells continued to exhibit high expression of BDNF and NGF, but GDNF expression was lower or absent, depending on the culture conditions utilized. Melatonin MT1 receptor mRNA was detected in NSCs maintained for two days in culture, but the MT2 receptor was not seen. An immature MT1 receptor of about 30 kDa was detected by western blotting in NSCs cultured for two days, whereas a mature receptor of about 40 - 45 kDa was present in cells maintained for longer periods. Immunocytochemical studies demonstrated that the MT1 receptor is expressed in both neural (beta-tubulin III positive) and glial (GFAP positive) progenitor cells. An examination of the effects of melatonin on neurotrophin expression revealed that low physiological concentrations of this hormone caused a significant induction of GDNF mRNA expression in NSCs following treatment for 24 hours. CONCLUSIONS: The phenotypic characteristics of C17.2 cells suggest that they are a heterogeneous population of NSCs including both neural and glial progenitors, as observed under the cell culture conditions used in this study. These NSCs have an intrinsic ability to express neurotrophic factors, with an apparent suppression of GDNF expression after several days in culture. The detection of melatonin receptors in neural stem/progenitor cells suggests involvement of this pleiotropic hormone in mammalian neurodevelopment. Moreover, the ability of melatonin to induce GDNF expression in C17.2 cells supports a functional role for the MT1 receptor expressed in these NSCs. In view of the potency of GDNF in promoting the survival of dopaminergic neurons, these novel findings have implications for the utilization of melatonin in neuroprotective strategies, especially in Parkinson's disease.

Animals↗

PubMed2006

Study protocol: a double blind placebo controlled trial examining the effect of domperidone on the composition of breast milk [NCT00308334].

BACKGROUND: Domperidone, a drug that enhances upper gastric motility, is an anti-dopaminergic medication that also elevates prolactin levels. It has been shown to safely increase the milk supply of lactating women. To date, researchers have analyzed the effects of domperidone on lactating woman with respect to the quantity of their milk production, adverse effects, and drug levels in the breast milk. However, the effect of domperidone on the macronutrient composition of breast milk has not been studied and current guidelines for fortification of human milk for premature infants do not distinguish between those women using or those not using domperidone. The purpose of this study is to evaluate the effect of domperidone (given to lactating mothers of very preterm infants) on the macronutrient composition of breast milk. METHODS/DESIGN: Mothers of infants delivered at less than 31 weeks gestation, who are at least 3 weeks postpartum, and experiencing lactational failure despite non-pharmacological interventions, will be randomized to receive domperidone (10 mg three times daily) or placebo for a 14-day period. Breast milk samples will be obtained the day prior to beginning treatment and on days 4, 7 and 14. The macronutrient (protein, fat, carbohydrate and energy) and macromineral content (calcium, phosphorus and sodium) will be analyzed and compared between the two groups. Additional outcome measures will include milk volumes, serum prolactin levels (measured on days 0, 4, and 10), daily infant weights and breastfeeding rates at 2 weeks post study completion and at discharge. Forty-four participants will be recruited into the study. Analysis will be carried out using the intention to treat approach. DISCUSSION: If domperidone causes significant changes to the nutrient content of breast milk, an alteration in feeding practices for preterm infants may need to be made in order to optimize growth, nutrition and neurodevelopment outcomes.

Journal Article↗

PubMed2026

Genome-wide characterization of the bZIP gene family in Rattus norvegicus and expression profiling analysis during brain development.

BACKGROUND: The brown rat (Rattus norvegicus) serves as a cornerstone model organism in biomedical research, particularly for understanding physiological homeostasis and stress responses. The basic leucine zipper (bZIP) transcription factor family is a pivotal regulatory network involved in growth, organogenesis, and neurodevelopment. Despite its importance, a systematic characterization of the bZIP gene family in rats has remained elusive. RESULTS: In this study, we performed a genome-wide identification of 61 RnbZIP genes, which were categorized into 10 distinct subfamilies based on phylogenetic relationships and chromosomal localization. Structural analysis revealed conserved motif arrangements within subfamilies, while collinearity analysis identified significant gene duplication events-predominantly tandem and segmental duplications-that have driven the evolutionary expansion of the RnbZIP family. Quantitative analysis showed that members within the same subfamily shared 45%-92% sequence similarity (calculated using the BLOSUM62 scoring matrix), and all duplicated gene pairs underwent strong purifying selection (Ka/Ks < 1). Comparative genomics across seven rodent species further underscored the evolutionary conservation and divergence of these factors. Expression profiling across diverse organs and brain developmental stages indicated that RnbZIP genes exhibit high tissue specificity. Notably, 10 candidate genes, including RnbZIP01, RnbZIP02, and RnbZIP08, demonstrated dynamic expression patterns during brain maturation, suggesting their essential roles in neurodevelopmental processes. CONCLUSIONS: Our findings provide a comprehensive structural and evolutionary framework for the RnbZIP gene family, highlighting their potential regulatory functions in rat organogenesis and brain development. This study establishes a valuable resource for further functional characterization of specific bZIP members in mammalian neurological systems.

Animals↗

PubMed2025

PUS7-dependent Ψ reshapes specific synaptic gene exons to facilitate fear extinction memory formation.

RNA modifications serve as dynamic regulators of neural plasticity through their ability to fine-tune transcript stability and splicing. Pseudouridine (Ψ), an evolutionarily conserved RNA modification catalyzed by pseudouridine synthases, plays established roles in neurodevelopment, yet its functional significance in activity-dependent behavioral adaptation remains poorly defined. Here, we investigate Ψ-mediated epitranscriptomic regulation within the infralimbic prefrontal cortex (ILPFC), a brain region requiring precise synaptic remodeling for the clinically relevant form of fear extinction memory. Combining transcriptome-wide pseudouridylation profiling with behavioral analysis in mice, we identified selective Ψ enrichment at exons of synaptic regulatory genes within ILPFC during fear extinction learning. Fear extinction in the ILPFC drives concomitant exonic Ψ deposition and upregulation of synaptogenic transcripts, processes that involve pseudouridine synthase PUS7. Crucially, PUS7 knockdown in the ILPFC selectively impaired fear extinction memory formation without altering baseline fear expression, establishing a causal link between Ψ-dependent RNA processing and activity-dependent synaptic structural remodeling in this microcircuit. Our findings demonstrate that PUS7-mediated Ψ modification spatiotemporally regulates activity-dependent RNA dynamics in the ILPFC, providing the evidence that epitranscriptomic mechanisms precisely coordinate synaptic gene expression within behaviorally defined brain sub-region. This work bridges molecular RNA biology with systems neuroscience, revealing a novel mechanism for activity-dependent regulation of fear extinction in ILPFC.

Animals↗

PubMed1995

Normal asymmetry of the planum temporale in patients with schizophrenia. Three-dimensional cortical morphometry with MRI.

BACKGROUND: Abnormal cerebral anatomical lateralisation has been reported in schizophrenia and may implicate anomalous neurodevelopment in the aetiology of this disease. A popular recent hypothesis has predicted that such disturbances in normal lateralisation should be especially apparent in the morphology of the temporal lobes. METHOD: A temporal cortical region lying in the plane of the Sylvian fissure--known as the planum temporale--exhibits pronounced leftward asymmetry in normal right-handed males. We compared lateralisation of the planum temporale in schizophrenic and control males using MRI surface-rendering morphometry of the supratemporal cortex. RESULTS: Contrary to the lateralisation hypothesis, normal patterns of leftward planum asymmetry were detected in both the schizophrenic and control groups. Schizophrenics and controls also exhibited a predicted symmetry in the bilateral areas of Heschl's gyrus, a supratemporal cortical structure immediately anterior to the planum. CONCLUSION: These data do not support the notion that neurodevelopmental mechanisms of cerebral asymmetry are abnormal in schizophrenia.

Adult↗

PubMed2001

Early-onset Alzheimer's disease in Scotland: environmental and familial factors.

BACKGROUND: Alzheimer's disease (AD) is a common, complex, age-related disorder in which both genetic and environmental factors are important. AIMS: To integrate recent studies on genetic and environmental factors in AD into a multi-factorial disease model. METHOD: Disease models to explain gene-environment interaction in cardiovascular disease are related to observations on AD. RESULTS: Informative, community-based studies on the genetic epidemiology of AD are rare. Putative risk factors from the Scottish studies include increased paternal age in AD men and coal mining as paternal occupation in both AD and vascular dementia. Migration effects suggest that environmental factors in high-incidence AD areas are important during adult life. CONCLUSIONS: The studies summarised do not provide sufficient data to support a single comprehensive disease model of gene-environment interaction in AD. Future studies will require very large (> or = 600) sample sizes, molecular genetic analysis, and environmental data that span neurodevelopment and the period between disease onset and appearance of clinical symptoms.

Age Factors↗

PubMed2002

Adult psychosis, common childhood infections and neurological soft signs in a national birth cohort.

BACKGROUND: Neurological soft signs preceding adult-onset schizophrenia suggest a neurodevelopmental origin and could reflect physical illness in childhood. AIMS: To investigate possible associations of adult-onset psychosis with neurological soft signs and common infectious illnesses in childhood. METHOD: Using data from the UK National Child Development Study, a longitudinal general population sample, odds ratios were calculated for clinical diagnoses of common childhood viral illnesses and later adult psychotic illness, childhood epilepsy and a range of neurological soft signs. RESULTS: The number of illnesses per individual did not relate either to the number of soft signs, or to any particular adult outcome. Schizophrenia, affective psychosis and epilepsy were not associated with common childhood illness but were associated with neurological soft signs and an increased, but small, frequency of previous meningitis and tuberculosis. CONCLUSIONS: Overall the data support the notion of neurological soft signs as markers of disordered neurodevelopment in schizophrenia (but the early neurological abnormalities are not caused by infectious illness) and an association between meningitis or tuberculosis in childhood and a small proportion of cases of epilepsy, affective psychosis and schizophrenia.

Adult↗

PubMed2004

Birth weight and later risk of depression in a national birth cohort.

BACKGROUND: Low birth weight increases the risk of childhood behavioural problems, but it is not clear whether poor foetal growth has a long-term influence on susceptibility to depression. AIMS: To examine the relation between birth weight and risk of psychological distress and depression. METHOD: At age 16 years 5187 participants in the 1970 British Cohort Study completed the 12-item General Health Questionnaire to assess psychological distress. At age 26 years 8292 participants completed the Malaise Inventory to assess depression and provided information about a history of depression. RESULTS: Women whose birth weight was </=3 kg had an increased risk of depression at age 26 years (OR=1.3; 95% CI1.0-1.5) compared with those who weighed >3.5 kg. Birth weight was not associated with a reported history of depression or with risk of psychological distress at age 16 years. In men there were no associations between any measurement and the full range of birth weight but, compared with men of normal birth weight, those born weighing </=2.5 kg were more likely to be psychologically distressed at age 16 years (OR=1.6,95% CI1.1-2.5) and to report a history of depression at age 26 years (OR=1.6,95% CI1.1-2.3). CONCLUSIONS: Impaired neurodevelopment during foetal life may increase susceptibility to depression.

Adolescent↗

PubMed2004

Association between prenatal exposure to analgesics and risk of schizophrenia.

BACKGROUND: Disturbances in the central nervous system originating during foetal life may increase the risk of schizophrenia. AIMS: To illuminate the hypothesis that prenatal exposure to analgesics may affect foetal neurodevelopment, leading to increased risk of schizophrenia in adulthood. METHOD: Using data from the Copenhagen Perinatal Cohort and from the Danish Psychiatric Central Register, we studied the relationship between prenatal exposure to analgesics and the risk of schizophrenia. The effect of prenatal exposure was adjusted for parental history of schizophrenia, second-trimester viral infections, concomitant drug treatment during pregnancy, an index of pregnancy complications, parental social status and parental age. RESULTS: In a risk set of 7999 individuals, 116 cases of schizophrenia were found (1.5%). Prenatal exposure to analgesics in the second trimester was associated with an elevated risk (adjusted odds ratio 4.75, 95% CI1.9-12.0). Independent of the covariates, the effect remained statistically significant. CONCLUSIONS: Independent of a wide range of possible confounders, a significant association between second-trimester exposure to analgesics and increased risk of schizophrenia was observed.

Adult↗

PubMed2005

Musical behavior in a neurogenetic developmental disorder: evidence from Williams Syndrome.

This paper reviews a series of studies performed to assess the musical abilities and behaviors of individuals with Williams syndrome, a neurogenetic developmental disorder, in the hope of eventually being able to link genes, neurodevelopment, and cognition. Two questionnaire studies addressing the role of music in everyday life, and unusual reactions to sound, are described. Additionally, the findings from two empirical behavioral studies and a neuroimaging study are reviewed. The findings show that individuals with Williams syndrome tend to be more engaged in musical activities than others, and I report a possible neuroanatomical correlate of this engagement, with increased activation in the right amygdala to music and to noise. Williams syndrome represents a compelling model of the relationship between genes, brains, and such complex cognitive behaviors as music.

Adolescent↗

PubMed2006

Disrupted-in-schizophrenia-1 (DISC1): a key susceptibility factor for major mental illnesses.

Here we overview Disrupted-in-Schizophrenia-1 (DISC1), a promising lead in studying the pathophysiology of major mental conditions. Genetic association studies reproducibly suggest involvement of DISC1 in both schizophrenia and bipolar disorder in several ethnic groups. Different from several other susceptibility genes for schizophrenia, such as neuregulin-1 and dysbindin, there are two independent pedigrees in which genetic variations of DISC1 directly segregate with major mental conditions. This uniqueness has facilitated neurobiology of DISC1, which may hopefully lead to an important breakthrough in understanding of pathophysiology of major mental conditions. DISC1 is a multifunctional protein that plays a role in neurodevelopment and cell signaling. In autopsied brains from patients with psychosis and substance abuse, change in subcellular distribution of DISC1 is observed. DISC1 interacts with phosphodiesterase (PDE) 4B that degrades cyclic AMP (cAMP), which may be a regulatory molecule for working memory in the prefrontal cortex. Knockdown expression of DISC1 in developing cerebral cortex in mouse brains leads to changes that resemble, at least in part, the pathology found in patients with schizophrenia. These results support involvement of DISC1 in the pathophysiology of major mental conditions, including schizophrenia, in several mechanisms.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1998

Persistent increases in cerebral lactate concentration after birth asphyxia.

In this prospective study proton magnetic resonance spectroscopy (1H MRS) was used to test the hypothesis that lactate can be detected later than 1 mo after birth in the brains of infants who display severe neurodevelopmental impairment 1 y after transient perinatal hypoxia-ischemia. Data were obtained from three groups of infants: 1) eight infants suffering birth asphyxia followed by perinatal encephalopathy and abnormal neurodevelopmental outcome at 1 y of age (defined as major neurologic impairment, Griffiths quotient <85%, and low optimality score); 2) 10 infants with signs of perinatal hypoxia-ischemia but normal neurodevelopmental outcome at 1 y; and 3) six control infants with uneventful perinatal courses and normal neurodevelopment at 1 y. Between one and four examinations (median 1) were performed at median (range) 11 (4-68) wk after birth, and the cerebral concentration ratio of lactate to creatine plus phosphocreatine (Cr) calculated from each spectrum. Lactate was detected later than the 1st mo after birth in seven of eight infants with abnormal neurodevelopmental outcome [maximum detected lactate/Cr was median (range) 0.44 (0.24-0.67)]. No lactate was detected later than the 1st mo after birth in infants with normal neurodevelopmental outcome, nor in five of six control subjects, although a small amount of lactate was detected in one control infant (lactate/Cr=0.04). These results suggest that the pathologic postasphyxial process, indicated by persistent cerebral lactate, may not be confined to the period immediately after injury.

Asphyxia Neonatorum↗

PubMed1998

Lower incidence of necrotizing enterocolitis in infants fed a preterm formula with egg phospholipids.

Necrotizing enterocolitis (NEC) causes approximately 4000 deaths/y and significant morbidity among U.S.-born preterm infants alone. Various combinations of inadequate tissue oxygenation, bacterial overgrowth, and enteral feeding with immaturity may cause the initial damage to intestinal mucosa that culminates in necrosis. Presently, there is not a way to predict the onset of the disease or to prevent its occurrence. As part of risk-benefit assessment, we compared disease in hospitalized preterm infants fed a commercial (control) preterm formula or an experimental formula with egg phospholipids for a randomized, double-masked, clinical study of diet and infant neurodevelopment. Infants fed the experimental formula developed significantly less stage II and III NEC compared with infants fed the control formula (2.9 versus 17.6%, p < 0.05), but had similar rates of bronchopulmonary dysplasia (23.4 versus 23.5%), septicemia (26 versus 31%), and retinopathy of prematurity (38 versus 40%). Compared with the control formula, the experimental formula provided 7-fold more esterified choline, arachidonic acid (AA, 0.4% of total fatty acids), and docosahexaenoic acid (0.13%). Phospholipids are constituents of mucosal membranes and intestinal surfactant, and their components, AA and choline, are substrates for intestinal vasodilatory and cytoprotective eicosanoids (AA) and the vasodilatory neurotransmitter, acetylcholine (choline), respectively. One or more of these components of egg phospholipids may have enhanced one or more immature intestinal functions to lower the incidence of NEC in this study. Regardless of the potential mechanism, a larger randomized trial designed to test the effect of this egg phospholipid-containing formula on NEC seems warranted.

Adult↗

PubMed2000

Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth.

The present study was designed to evaluate the effect of gestational age and intrauterine growth on the long chain polyunsaturated fatty acid (LCP) synthesis from dietary precursors in neonates as reflected by plasma pools. These have been considered conditionally essential nutrients for normal growth, sensory maturation, and neurodevelopment. In vivo elongation/desaturation of deuterated d5-linoleic acid (d5-LA) to form arachidonic acid (AA), and d5-alpha-linolenic acid (d5-LNA) to form docosahexaenoic acid (DHA), was studied in 19 preterm appropriate-for-gestational-age (AGA) infants, 11 AGA term, and 11 intrauterine growth-retarded (IUGR) infants. They received a dose of 50 mg/kg body weight of d5-LA and d5-LNA enterally during the first days of life; d5-labeled derivatized fatty acids were determined in blood samples obtained at 24, 48, and 96 h after dosing. Lipids were extracted and fatty acids analyzed by gas chromatography and negative ion mass spectrometry. Mean concentrations, microg/mL, and d5/d0 for n-3 and n-6 precursor and products were computed at various times and were also integrated over the complete study period. Significantly higher time-integrated concentration of d5-AA and d5-DHA were observed in preterm infants relative to the other two groups. Time-integrated enrichment of DHA relative to LNA was 100-fold lower in preterms, 410-fold lower in term, and 27-fold lower in IUGR infants. Similar significant declines in product to precursor enrichments were noted for the n-6 series. A significant negative correlation of AA and DHA formation based on time-integrated d5/d0 ratios with gestational age was noted; product/ precursor enrichment versus gas chromatography for the n-6 series had an r of -0.5, p = 0.001, and for the n-3 series had an r of -0.6, p = 0.0001. Birth weight or weight adequacy did not add further strength to the relationship. We conclude that LCP formation from deuterated precursors occurs as early as 26 wk gestation, and in fact is more active at earlier gestational ages; growth retardation appears to slow down or diminish LCP formation. No quantitative estimates of LCP synthesis or nutritional sufficiency can be derived from these data.

Embryonic and Fetal Development↗

PubMed2002

Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response.

Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are frequently used to treat maternal depression during pregnancy, however the effect of increased serotonin (5HT) and gamma-amino-butyric acid (GABA) agonists in the fetal human brain remains unknown. 5HT and GABA are active during fetal neurologic growth and play early roles in pain modulation, therefore, if prolonged prenatal exposure alters neurodevelopment this may become evident in altered neonatal pain responses. To examine biologic and behavioral effects of prenatal exposure, neonatal responses to acute pain (phenylketonuria heel lance) in infants with prolonged prenatal exposure were examined. Facial action (Neonatal Facial Coding System) and cardiac autonomic reactivity derived from the relationship between respiratory activity and short term variations of heart rate (HRV) were compared between 22 infants with SSRI exposure (SE) [fluoxetine (n = 7), paroxetine (n = 11), sertraline (n = 4)]; 16 infants exposed to SSRIs and clonazepam (SE+) [paroxetine (n = 14), fluoxetine (n = 2)]; and 23 nonexposed infants during baseline, lance, and recovery periods of a heel lance. Length of maternal SSRI use did not vary significantly between exposure groups-[mean (range)] SE:SE+ 183 (31-281):141 (54-282) d (p > 0.05). Infants exposed to SE and SE+ displayed significantly less facial activity to heel lance than control infants. Mean HR increased with lance, but was significantly lower in SE infants during recovery. Using measures of HRV and the transfer relationship between heart rate and respiration, SSRI infants had a greater return of parasympathetic cardiac modulation in the recovery period, whereas a sustained sympathetic response continued in the control group. Prolonged prenatal SSRI exposure appears to be associated with reduced behavioral pain responses and increased parasympathetic cardiac modulation in recovery following an acute neonatal noxious event. Possible 5HT-mediated pain inhibition, pharmacologic factors and the developmental course remain to be studied.

Animals↗

PubMed2003

Apolipoprotein E genotype predicts 24-month bayley scales infant development score.

Apolipoprotein E (APOE) regulates cholesterol and fatty acid metabolism, and may mediate synaptogenesis during neurodevelopment. To our knowledge, the effects of APOE4 isoforms on infant development have not been studied. This study was nested within a cohort of mother-infant pairs living in and around Mexico City. A multiple linear regression model was constructed using the 24-mo Mental Development Index (MDI) of the Bayley Scale as the primary outcome and infant APOE genotype as the primary risk factor of interest. Regression models stratified on APOE genotype were constructed to explore effect modification. Of 311 subjects, 53 (17%) carried at least one copy of the APOE4 allele. Mean (SD) MDI scores among carriers with at least one copy of APOE4 were 94.1 (14.3) and among E3/E2 carriers were 91.2 (14.0). After adjustment for covariates, APOE4 carrier status was associated with a 4.4 point (95% confidence interval: 0.1-8.7; p = 0.04) higher 24-mo MDI. In the stratified regression models, the negative effects for umbilical cord blood lead level on 24-mo MDI score was approximately 4-fold greater among APOE3/APOE2 carriers than among APOE4 carriers. These results suggest that subjects with the E4 isoform of APOE may have advantages over those with the E2 or E3 isoforms with respect to early life neuronal/brain development.

Apolipoprotein E2↗