Symptoms In Offspring Research Articles

Characterization of Brain Abnormalities in Lactational Neurodevelopmental Poly I:C Rat Model of Schizophrenia and Depression Using Machine-Learning and Quantitative MRI.

A recent neurodevelopmental rat model, utilizing lactational exposure to polyriboinosinic-polyribocytidilic acid (Poly I:C) leads to mimics of behavioral phenotypes resembling schizophrenia-like symptoms in male offspring and depression-like symptoms in female offspring. To identify mechanisms of neuronal abnormalities in lactational Poly I:C offspring using quantitative MRI (qMRI) tools. Prospective. Twenty Poly I:C rats and 20 healthy control rats, age 130 postnatal day. 7 T. Multiflip-angle FLASH protocol for T1 mapping; multi-echo spin-echo T2-mapping protocol; echo planar imaging protocol for diffusion tensor imaging. Nursing dams were injected with the viral mimic Poly I:C or saline (control group). In adulthood, quantitative maps of T1, T2, proton density, and five diffusion metrics were generated for the offsprings. Seven regions of interest (ROIs) were segmented, followed by extracting 10 quantitative features for each ROI. Random forest machine learning (ML) tool was employed to identify MRI markers of disease and classify Poly I:C rats from healthy controls based on quantitative features. Poly I:C rats were identified from controls with an accuracy of 82.5 ± 25.9% for females and 85.0 ± 24.0% for males. Poly I:C females exhibited differences mainly in diffusion-derived parameters in the thalamus and the medial prefrontal cortex (MPFC), while males displayed changes primarily in diffusion-derived parameters in the corpus callosum and MPFC. qMRI shows potential for identifying sex-specific brain abnormalities in the Poly I:C model of neurodevelopmental disorders. NA TECHNICAL EFFICACY: Stage 2.

Mental health outcomes of offspring exposed to parental intimate partner violence in Rwanda

BackgroundChildren who witness parental intimate partner violence (IPV) are more likely to develop mental health issues compared to those who do not witness such violence.ObjectiveThe main objective of this study is to assess the association between parental intimate partner violence and child mental health outcomes.MethodologyThis cross-sectional study involved 548 participants divided into two groups: parents (N = 304) and offspring (N = 244). The participants were recruited from Mageragere Sector in the City of Kigali (urban), as well as Mbazi and Ruhashya sectors in Huye District (rural). To assess the difference about mental difficulties reported by the offspring, a Mann-Whitney U test was employed to compare the responses of parents and their children on mental health outcomes. Additionally, multiple linear regression analysis was conducted to explore the association between parental intimate partner violence (IPV) and the mental health outcomes of their offspring.ResultsThe results highlighted significant levels of mental and emotional challenges in children, as reported by both parents and the children themselves. Depression and youth conduct problems were more prevalent among the children compared to their parents, whereas anxiety and irritability were more commonly reported by parents than by their children. Intimate partner violence showed to be a predictor of irritability and anxiety symptoms in offspring. In terms of irritability, depression, and youth conduct problems they were identified as predictors of anxiety symptoms. Particularly, anxiety and irritability were revealed to predict youth conduct problems.ConclusionThe study indicates that parental intimate partner violence (IPV) has an impact on the mental well-being of their offspring. Furthermore, it was observed that there is not only a correlation between IPV and poor mental health outcomes, but also a connection between different mental conditions, implying that children exposed to IPV are more prone to experiencing a range of mental issues. As a result, intervention programs should place emphasis on addressing the mental disorders of both parents and children.

Prenatal maternal Inflammation, childhood cognition and adolescent depressive symptoms

BackgroundAccumulating evidence indicates that higher prenatal maternal inflammation is associated with increased depression risk in adolescent and adult-aged offspring. Prenatal maternal inflammation (PNMI) may increase the likelihood for offspring to have lower cognitive performance, which, in turn, may heighten risk for depression onset. Therefore, this study explored the potential mediating role of childhood cognitive performance in the relationship between PNMI and adolescent depressive symptoms in offspring. MethodsParticipants included 696 mother-offspring dyads from the Child Health and Development Studies (CHDS) cohort. Biomarkers of maternal inflammation [interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1RA) and soluble TNF receptor-II (sTNF-RII)] were assayed from first (T1) and second trimester (T2) sera. Childhood (ages 9–11) cognitive performance was assessed via standardized Peabody Picture Vocabulary Test (PPVT), a measure of receptive vocabulary correlated with general intelligence. Adolescent (ages 15–17) depressive symptoms were assessed via self-report. ResultsThere were no significant associations between T1 biomarkers and childhood PPVT or adolescent depressive symptoms. Higher T2 IL1-RA was directly associated with lower childhood PPVT (b = -0.21, SE = 0.08, t = -2.55, p = 0.01), but not with adolescent depressive symptoms. T2 IL-6 was not directly associated with childhood PPVT, but higher T2 IL-6 was directly associated at borderline significance with greater depressive symptoms in adolescence (b = 0.05, SE = 0.03, t = 1.96, p = 0.05). Lower childhood PPVT predicted significantly higher adolescent depressive symptoms (b = -0.07, SE = 0.02, t = -2.99, p < 0.01). There was a significant indirect effect of T2 IL-1RA on adolescent depressive symptoms via childhood PPVT (b = 0.03, 95 % CI = 0.002–0.03) indicating a partially mediated effect. No significant associations were found with T2 sTNF-RII nor IL-8. ConclusionsLower childhood cognitive performance, such as that indicated by a lower PPVT score, represents a potential mechanism through which prenatal maternal inflammation contributes to adolescent depression risk in offspring.

Examining timing effects in the intergenerational transmission of anxiety and depressive symptoms: A genetically informed study.

The present study examined genetic, prenatal, and postnatal environmental pathways in the intergenerational transmission of anxiety and depressive symptoms from parents to early adolescents (when these symptoms start to increase), while considering timing effects of exposure to parent anxiety and depressive symptoms postnatally. The sample was from the Early Growth and Development Study, including 561 adopted children (57% male, 55% White, 13% Black/African American, 11% Hispanic/Latine, 20% multiracial, 1% other; 407 provided data in early adolescence) and their birth (BP) and adoptive parents (AP). Using a trait-state-occasion model with eight assessments from child ages 9 months to 11 years, we partitioned trait-like AP anxiety and depressive symptoms from time-specific fluctuations of AP anxiety and depressive symptoms. Offspring anxiety and depressive symptoms were assessed at 11 years (while controlling for similar symptoms at 4.5 years). Results suggested that time-specific fluctuations of AP1 (mostly mothers) anxiety/depressive symptoms in infancy (9 months) were indirectly associated with offspring anxiety/depressive symptoms at 11 years via offspring anxiety/depressive symptoms at 4.5 years; time-specific fluctuations of AP1 anxiety/depressive symptoms at child age 11 years were concurrently associated with offspring anxiety/depressive symptoms at 11 years. AP2 (mostly fathers) anxiety/depressive symptoms were not associated with offspring symptoms. Genetic and prenatal influences measured by BP internalizing problems were not associated with offspring symptoms. Results suggested infancy and early adolescence as developmental periods when children are susceptible to influences of parent anxiety and depressive symptoms. Preventive interventions should consider time-specific fluctuations in parent anxiety and depressive symptoms during these developmental periods. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms

Prenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined. To determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations. This was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023. Levels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy. Self-reported depressive symptoms at adolescent follow-up. A total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75). In this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

Elevated level of prenatal testosterone and vitamin D3 deficiency during pregnancy, in the presence of prenatal maternal stress, and their association with the development of attention deficit hyperactivity disorder (ADHD)-like symptoms in toddlers.

To investigate the hypothesis that the presence of prenatal maternal stress, increased level of prenatal testosterone, and low level of vitamin D3 in pregnancy is associated with the development of ADHD-like symptoms in toddlers (< 2 years old). The study group comprised 53 pregnant women and 53 infants of these pregnancies. The population cohort of 53 pregnant women were recruited at their 35th to 37th week of pregnancy and investigated prospectively. The participants were selected through targeted selection. Maternal experience of stressful life events was assessed by stress standardised questionnaires, prenatal testosterone was determined in the mothers' saliva by using the immune enzymatic (ELISA) method, and maternal plasma D vitamin was measured using the ECLIA method, during pregnancy. When the age of the offspring was 6 months and then less than 2 years, the mothers completed the child behaviour and temperament checklist. A small but statistically significant association was found between the common symptom complex of ADHD and the level of testosterone and vitamin D3, in the presence of prenatal maternal stress. Multiple regression analysis showed that maternal stressful events during pregnancy significantly predicted ADHD behaviours in offspring. The study supported the hypothesis that prenatal maternal stress, increased level of prenatal testosterone, and low level of vitamin D3 during pregnancy increases the risk of development of ADHD-like symptoms in toddlers (< 2 years old). Also, the obtained results support the hypothesis that the influence of prenatal factors causes ADHD-like symptoms in offspring through a programming effect.

Maternal multivitamin supplementation is associated with symptoms in offspring with autism spectrum disorder: A multi-center study in China

BackgroundWe aimed to investigate the relationship between maternal vitamin D and multivitamin supplementation during pregnancy and the risk of autism spectrum disorder (ASD) and symptoms in offspring with ASD. MethodsThis study enrolled 1321 children with ASD and 1200 typically developing (TD) children under 7 years old in China. Maternal vitamin supplements were classified for vitamin D, multivitamin (with or without vitamin D), and none (no use of vitamin D or multivitamin). For children with ASD, symptoms were assessed with the Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS), and neurodevelopmental levels were evaluated with the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). ResultsMaternal vitamin D and multivitamin supplementation during pregnancy were both significantly associated with a decreased risk of ASD in offspring (P = 0.024 and P < 0.001). The ASD children born to mothers with gestational multivitamin supplementation had lower CARS [β = −1.342 (−2.275, −0.409), P = 0.005] and communication warning behavior [β = −6.631 (−9.899, −3.363), P < 0.001] scores and higher personal-social quotient [β = 3.347 (0.190, 6.504), P = 0.038] than children born to mothers without supplementation. Maternal vitamin D supplementation was not associated with symptoms and development quotients in ASD children (P > 0.05). ConclusionsThis study supports a protective association between maternal vitamin D and multivitamin supplementation during pregnancy and the risk of ASD in offspring. Maternal multivitamin supplementation may potentially moderate the symptoms and personal-social ability in ASD children. Further studies are needed on the role of maternal nutrition in the etiology and autistic symptoms and the underlying molecular mechanisms.

Maternal postpartum depression symptoms and early childhood hyperactive/aggressive behavior are independently associated with later attention deficit/hyperactivity symptoms

Attention deficit/hyperactivity behaviors in children are often unnoticed until they reach school age; however, evidence suggests that attention deficit hyperactivity disorder (ADHD) tends to develop at an earlier age. Recent studies also indicate that perinatal maternal mental health is associated with ADHD symptoms in offspring. This study examines the association between maternal postpartum depression, early hyperactive/aggressive behavior, and later ADHD symptoms. This longitudinal cohort study used data from health checkups and surveys. Mothers with a postpartum Edinburgh postnatal depression scale score ⩾ 9 were considered as having postpartum depression symptoms. The presence of early hyperactive/aggressive behavior was determined based on 3-year-old children’s health checkup data. The ADHD rating scale (ADHD-RS) answered by the caregivers of 182 sixth-grade children was used for the analysis. ADHD-RS scores were significantly higher in children with early hyperactive and/or aggressive behavior (p = .002) and for children of mothers who had postpartum depression symptoms (p < .001). Early hyperactive/aggressive behavior did not mediate the predictive association of maternal postpartum depression symptoms with ADHD symptoms in sixth grade. ADHD symptoms in the sixth grade were independently associated with childhood hyperactive/aggressive behavior at age 3 and maternal postpartum depression symptoms.

Intergenerational transmission of tobacco smoking: The role of the child’s behavioral difficulties. Data from the Danish National Birth cohort (DNBC)

AimsThis study explores the role of offspring behavioral difficulties in the intergeneration transmission of tobacco smoking. MethodsThis longitudinal cohort study is based on children born in Denmark in 1996–2003 participating in the Danish National Birth Cohort (DNBC), followed-up until 18years of age. We included mother-child pairs with complete data regarding the exposure (4 trajectories of maternal daily smoking quantity during pregnancy: low, intermediate/stable, intermediate/decreasing and high), outcome (offspring daily smoking status at 18 years) and mediator (offspring symptoms of hyperactivity-inattention at 11 years), that is 24,588 mother-child pairs. ResultsIn our study population, during pregnancy respectively 86.2%, 6.80%, 4.08% and 2.97% mothers belonged to the low, intermediate/stable, intermediate/decreasing and high smoking trajectory groups. After controlling for covariates using propensity scores, the direct effect of maternal smoking in pregnancy on offspring smoking in adolescence was statistically significant, especially when the mother belonged to the intermediate/stable smoking trajectory group (ORIPW = 2.09, 95% CI: 1.70 – 2.61) or to the high smoking trajectory group (ORIPW = 2.08, 95% CI: 1.52 – 3.11) compared to the low smoking trajectory group. None of the indirect effects of maternal smoking in pregnancy were statistically significant, and neither were the proportions mediated. ConclusionMaternal pregnancy smoking seems to have an influence on offspring smoking in early adulthood, which does not appear to be mediated by offspring behavioral difficulties. Women should be strongly encouraged to quit smoking in pregnancy to reduce both short and long-term health risks among their offspring.

The Quality of Mother-Child Feeding Interactions Predicts Psychopathological Symptoms in Offspring and Mothers Seven Years Later: A Longitudinal Study on the General Population.

The increased risk of internalizing and externalizing symptoms in children has been observed in the presence of maternal psychopathology. This study aimed to investigate a potential pathway involving the quality of early interactions between mothers and their children. A sample of 150 mother-child dyads underwent assessment when the children were 3 years old and around the age of 10. Video recordings of feeding exchanges between mothers and children were analyzed to evaluate the quality of mother-child interactions. Maternal psychopathology and child internalizing and externalizing symptoms were measured through self-report and report-form measures completed by mothers. The quality of mother-child feeding interactions at three years of age significantly differentiated (p < 0.001), eight years later, between mothers at high and low psychopathological risk and between children exhibiting clinical and subclinical internalizing symptoms. Clinically relevant child symptoms were notably more prevalent when the mother-child interaction quality at three years of age was maladaptive, particularly in the context of concurrent high maternal psychopathological risk. The study findings underscore the importance of focusing on the early quality of mother-child feeding interactions to identify potential situations of maternal and child clinical risk for the development of psychopathological symptoms and to guide preemptive measures and policies.

1 Applying a dimensional framework to the study of developmental neurotoxicity

Objective:In recent decades, a large body of evidence has linked prenatal exposure to environmental neurotoxins to adverse intellectual, neurodevelopmental, and psychiatric outcomes in offspring. This evidence has clearly highlighted the widespread impact of neurotoxin exposure on the developing brain; however, it is unclear how and why these exposures alter brain development in a way that appears to increase risk for multiple, seemingly disparate outcomes.Participants and Methods:Shifting our focus from describing links between neurotoxin exposure and symptoms of offspring mental/cognitive problems considered categorically, to investigating how neurotoxins adversely affect domains of functioning known to cut across risk for multiple problems in offspring may be critical to answering these questions. This presentation will discuss how combining research in developmental neurotoxicology with novel systems that take dimensional approaches to understanding emotions, cognition, and behaviour (i.e., the NIHM Research Domain Criteria (RDoC)) may provide a fruitful future research direction for the field. The RDoC framework aims to understand neuropsychological outcomes (i.e., mental health, mental illness, IQ) across major domains of human emotion, cognition, behaviour, and social functioning, rather than within distinct diagnostic categories.Results:Using lead exposure as an example, this presentation will outline a framework for how researchers can use this dimensional approach to develop more specific hypotheses that can reveal how and why neurotoxin exposure increases risk for multiple adverse outcomes and elucidate the mechanisms that may underly these links.Conclusions:Additionally, given that adverse development within domains of functioning can be detected prior to the onset of full-blown diagnoses, this research could enable us to develop more precise, targeted prevention and risk reduction campaigns. Adopting a dimensional framework will provide a more complete picture of the overall impact of prenatal exposure to neurotoxins - critical for informing public health policy.

Infant epigenetic aging moderates the link between Black maternal childhood trauma and offspring symptoms of psychopathology.

Although offspring of women exposed to childhood trauma exhibit elevated rates of psychopathology, many children demonstrate resilience to these intergenerational impacts. Among the variety of factors that likely contribute to resilience, epigenetic processes have been suggested to play an important role. The current study used a prospective design to test the novel hypothesis that offspring epigenetic aging - a measure of methylation differences that are associated with infant health outcomes - moderates the relationship between maternal exposure to childhood adversity and offspring symptomatology. Maternal childhood adversity was self-reported during pregnancy via the ACEs survey and the CTQ, which assessed total childhood trauma as well as maltreatment subtypes (i.e., emotional, physical, and sexual abuse). Offspring blood samples were collected at or shortly after birth and assayed on a DNA methylation microarray, and offspring symptomatology was assessed with the CBCL/1.5-5 when offspring were 2-4 years old. Results indicated that maternal childhood trauma, particularly sexual abuse, was predictive of offspring symptoms (ps = 0.003-0.03). However, the associations between maternal sexual abuse and offspring symptomatology were significantly attenuated in offspring with accelerated epigenetic aging. These findings further our understanding of how epigenetic processes may contribute to and attenuate the intergenerational link between stress and psychopathology.

Maternal exposure to sunlight-irradiated graphene oxide induces neurodegeneration-like symptoms in zebrafish offspring through intergenerational translocation and genomic DNA methylation alterations

The physiochemical properties of graphene oxide may be affected by sunlight irradiation. However, the underlying mechanisms that alter the properties and subsequent intergenerational effects are not sufficiently investigate. Epigenetics is an early sensitive marker for the intergenerational effects of nanomaterial exposure due to the epigenetic memory. In this study, we investigate changes in the physicochemical properties and the intergenerational effects of maternal exposure to simulated sunlight-irradiated polyethyleneimine-functionalized graphene oxide (SL-PEI-GO). Results show that the physicochemical properties of polyethyleneimine-functionalized graphene oxide (PEI-GO) can be altered significantly by the oxidation of carbon atoms with unpaired electrons present in the defects and on the edges of PEI-GO by sunlight. First, the positive charges, sharp edges, defects and disordered structures of SL-PEI-GO make it translocate from maternal zebrafish to offspring, thus catalyzing the production of reactive oxygen species and damaging mitochondria directly. In addition, changes in DNA methylation reduce the expression of protocadherin1a, protocadherin19 and cadherin4, thus destroying cell membrane integrity, cell adhesion and Ca2+ binding. The alteration of DNA methylation induced by maternal exposure activates the Ca2+-CaMKK-brsk2a pathway, which catalyzes the phosphorylation of Tau and eventually results in the appearance of neurodegeneration-like symptoms, including the loss of neurons and neurobehavioral disorders. This study demonstrates that maternal exposure to SL-PEI-GO induces clear neurodegeneration-like symptoms in offspring through both the intergenerational translocation of nanomaterials and differential DNA methylation. These findings may provide new insights into the health risks of nanomaterials altered by nature conditions.

Associations between prenatal maternal stress, maternal inflammation during pregnancy, and children’s internalizing and externalizing symptoms throughout childhood

BackgroundMaternal immune activation is a potential mechanism underlying associations between maternal stress during pregnancy and offspring mental health problems. This study examined associations between prenatal maternal stress, maternal inflammation during pregnancy, and children’s internalizing and externalizing symptoms from 3 to 10 years of age, and whether maternal inflammation mediated the associations between prenatal maternal stress and children’s internalizing and externalizing symptoms. MethodsThis study comprised 4,902 mother–child dyads in the Generation R study. Prenatal maternal stress was assessed using self-reported data collected during pregnancy and analyzed as a latent variable consisting of four stress domains. Maternal inflammation during pregnancy was assessed using serum concentrations of C-reactive protein (CRP) measured at a median of 13.5 weeks’ gestation. Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist (CBCL) by maternal report at ages 3 years, 5 years, and 10 years; paternal-reported CBCL data were also available at 3 years and 10 years. ResultsPrenatal maternal stress was associated with maternal-reported internalizing and externalizing symptoms of the child at 3, 5, and 10 years of age, and with paternal-reported internalizing and externalizing symptoms at 3 and 10 years. Prenatal maternal stress was associated with maternal CRP concentrations prior to, but not after, covariate adjustment. Maternal CRP concentrations during pregnancy were associated with paternal-reported internalizing symptoms of offspring at 10 years of age prior to, but not after, covariate adjustment. There was no evidence that CRP concentrations mediated the associations between prenatal maternal stress and children’s internalizing or externalizing symptoms. ConclusionsMaternal stress during pregnancy is associated with higher levels of internalizing and externalizing symptoms in children, but this association is not because of differences in maternal immune activation linked to maternal stress. Replication of these findings in other cohorts is required; examination of other biomarkers or variation in immune activity during pregnancy would also benefit from further exploration.

Sex-related beneficial effects of exercise on cardiac function and rhythm in autistic rats.

Cardiovascular diseases are prevalent in autistic patients. As exercise is useful in the treatment of medical conditions, this study aimed to identify the effect of low-intensity endurance exercise (LIEE) and moderate-intensity endurance exercise (MIEE) on cardiovascular events in autistic rats. Valproic acid (VPA) was administrated once on gestational day 12.5 to pregnant rats to produce autism-like symptoms in offspring. Thirty-day-old offspring were divided into 12 groups: Male-CTL, Male-VPA, Male-CTL + LIEE, Male-CTL + MIEE, Male-VPA + LIEE, Male-VPA + MIEE, Female-CTL, Female-VPA, Female-CTL + LIEE, Female-CTL + MIEE, Female-VPA + LIEE, and Female-VPA + MIEE. LIEE and MIEE were performed 5 days a week for 30 days. Twenty-four hours after the last exercise session, electrocardiogram and hemodynamic and cardiac function indices were recorded. The results indicated that +dp/dt max and contractility index (CI) decreased in the Female-VPA group compared to the Female-CTL group. LIEE increased these parameters in the Female-VPA + LIEE group. However, MIEE normalized CI in the Male-VPA + MIEE compared to the Male-VPA group. Tau increased in the Female-VPA group compared to the Female-CTL group and it decreased in the Female-VPA + MIEE group compared to the Female-VPA group. LIEE and MIEE recovered the reduction of heart rate and the increase in P, R, and T amplitudes in Male-VPA group. LIEE and MIEE increased heart rate variability in the Male-VPA and Female-VPA groups. The findings showed that LIEE and MIEE alleviated cardiac dysfunction and disturbances in heart rhythm in the autistic offspring. Exercise may be recommended as a routine program for autistic patients to prevent and treat the harmful cardiovascular consequences of autism.

Effect of synthetic folic acid surplus on neurological symptoms in offspring

Background. It has long been known about the need for folic acid for the vital activity of both macro-and microorganisms. It is necessary for the processes of methylation, nucleotide synthesis and also the formation of methionine and reducing the toxic effect of homocysteine. The addition of synthetic folic acid to the diet of pregnant women, as well as at the stage of pre-pregnancy preparation, significantly reduces the risks of fetal neural tube defects, heart defects, and possibly other organs and systems of the body. In addition, folic acid can help improve fertility potential. However, there is evidence of adverse effects of folic acid proficite on the health of older adults (hiding B12-deficient status) and the offspring of mothers taking high doses prescribed by medical specialists like a risks of infectious-inflammatory and allergic diseases of the upper respiratory tract in children, eczema, also disorders of psychomotor development and insulin resistance. In 1980, the direct excitatory effect of folic acid on synaptic transmission in the central nervous system was proved. This is due to the molecular structure, it contains L-glutamate.&#x0D; Therefore, the aim of the work was trying to prove the existing correlation data on probable neuropathologies, including a reduced threshold of seizures, a high risk of epilepsy in a model of offspring of Wistar rats with an increased dosage of folate throughout gestation and including at the stage of pre-gravidar preparation.&#x0D; Methods. We have determined the ability to the first convulsive act by introducing a 20% solution of caffeine at the rate of 100 mg/kg of weight intraperitoneally.&#x0D; Results. In the control group, the average clonus time was 1779.6 seconds, in the experimental group with a 1 mg/kg folic acid per diet dosage of 797.3 seconds, and in the second group with a 5 mg/kg folic acid per diet 439.7 seconds (p 0,01).&#x0D; Conclusion. The obtained results of the difference in the convulsive threshold may be due to changes in synaptic density as a result of an excess of synthetic folic acid during the formation of NT and subsequently during the differentiation of nervous tissue in the central nervous system (in particular, in the 3rd trimester with a massive appearance of glutamatergic receptors), which can affect the processes of neurogenesis and the formation of neural networks.

Group I mGluRs positive allosteric modulators improved schizophrenia-related behavioral and molecular deficits in the Poly I:C rat model

RationaleMaternal polyinosinic-polycytidylic acid (Poly I:C) exposure leads to an increase in various proinflammatory cytokines and causes schizophrenia-like symptoms in offspring. In recent years, group I metabotropic glutamate receptors (mGluRs) have emerged as a potential target in the pathophysiology of schizophrenia. ObjectivesThe aim of our study was to investigate the behavioral and molecular changes by using the mGlu1 receptor positive allosteric modulator (PAM) agent RO 67-7476, and the negative allosteric modulator (NAM) agent JNJ 16259685 and the mGlu5 receptor PAM agent VU-29, and NAM agent fenobam in the Poly I:C-induced schizophrenia model in rats. MethodsFemale Wistar albino rats were treated with Poly I:C on day 14 of gestation after mating. On the postnatal day (PND) 34-35, 56-57 and 83-84, behavioral tests were performed in the male offspring. On the PND84, brain tissue was collected and the level of proinflammatory cytokines was determined by ELISA method. ResultsPoly I:C caused impairments in all behavioral tests and increased the levels of proinflammatory cytokines. While PAM agents caused significant improvements in prepulse inhibition (PPI), novel object recognition (NOR), spontaneous alternation and reference memory tests, they brought the levels of proinflammatory cytokines closer to the control group. NAM agents were ineffective on behavioral tests. It was observed that PAM agents significantly improved Poly I:C-induced disruption in behavioral and molecular analyses. ConclusionsThese results suggest that PAM agents, particularly the mGlu5 receptor VU-29, are also promising and could be a potential target in schizophrenia.

Intergenerational and early life associations of the gut microbiome and stress-related symptomatology among Black American mothers and children

Recent evidence suggests that maternal childhood adversity may have an intergenerational impact, with children of adversity-exposed mothers exhibiting elevated symptoms of psychopathology. At the same time, many children demonstrate resilience to these intergenerational effects. Among the variety of factors that likely contribute to resilience, the composition of the gut microbiome may play a role in buffering the negative impacts of trauma and stress. The current prospective cohort study tested the novel hypothesis that offspring gut microbiome composition is a potential moderator in the relationship between maternal exposure to childhood adversity and offspring symptomatology (i.e., internalizing, externalizing, and posttraumatic stress symptoms). Maternal childhood adversity was self-reported during pregnancy via the Childhood Trauma Questionnaire and Adverse Childhood Experiences (ACEs) survey, and offspring symptomatology was assessed with the Child Behavior Checklist/1.5–5 when offspring were 2–4 years old. Offspring fecal samples were collected between these timepoints (i.e., during 6- to 24-month follow-up visits) for microbiome sequencing. Results indicated that maternal ACEs and the relative abundances of Bifidobacterium, Lactobacillus, and Prevotella were associated with offspring symptomatology. However, there was little evidence that microbial abundance moderated the association between maternal adversity and offspring symptoms. Overall, these findings further our understanding of how the gut microbiome associates with psychopathology, and informs future studies aimed at targeting modifiable factors that may buffer the intergenerational effects of childhood adversity.

Causal effects of maternal exposure to PM2.5 during pregnancy on depression symptoms in adolescence: Identifying vulnerable windows and subpopulations in a national cohort study

Few studies have examined the causal relationship between chronic exposure to air pollutants during pregnancy and depression in adolescent offspring. In addition, it has not been investigated whether exposure is most harmful to adolescents in certain populations and at certain stages of pregnancy.A total of 1975 adolescents from 1632 families from the China Family Panel Study, a representative national longitudinal cohort, were included in this study. We used high-resolution satellite retrieval data to assess the PM2.5 exposure of mothers during pregnancy. Specifically, we employed a two-stage instrumental variable model (IV-2SLS) within the counterfactual causal inference framework, and selected and validated appropriate instruments, thereby mitigating potentially biased results arising from bi-direction between dependent and independent variables. This approach allowed us to explore the causal relationship between maternal PM2.5 exposure during pregnancy and adolescent depression symptoms.The endogeneity of air pollution during pregnancy and the need for a causal model were suggested by the results of the model comparisons. Using the IV-2SLS model, we found that maternal exposure to PM2.5 during pregnancy exacerbates depressive symptoms in the offspring during adolescence (β = 0.2, 95% CI: 0.05–0.34). We also found that exposure during the first trimester may cause greater harm. Adolescents with low household income, being male, irregular exercise habits, living in rural areas, and having mothers with poorer mental status may be more vulnerable.The findings suggest that maternal exposure to PM2.5 during pregnancy may have a negative impact on the depression symptoms of offspring in adolescence and that more attention should be paid to vulnerable populations and the window of vulnerability.

Dysregulation of immune and metabolism pathways in maternal immune activation induces an increased risk of autism spectrum disorders

AimsMaternal immune activation (MIA) via infection during pregnancy is known to be an environmental risk factor for neurodevelopmental disorders and the development of autism spectrum disorders (ASD) in the offspring, but it still remains elusive that the molecular relevance between infection-induced abnormal neurodevelopmental events and an increased risk for ASD development. Main methodsFully considering the extremely high genetic heterogeneity of ASD and the universality of risk-gene with minimal effect-sizes, the gene and pathway-based association analysis was performed with the transcriptomic and DNA methylation landscapes of temporal human embryonic brain development and ASD, and the time-course transcriptional profiling of MIA. We conducted the transcriptional profiling of mouse abnormal neurodevelopment two days following induced MIA via LPS injection at E10.5. Key findingsA novel evidence was proved that illustrated altering four immune and metabolism-related risk pathways, including starch and sucrose metabolism, ribosome, protein processing in endoplasmic reticulum, and retrograde endocannabinoid signaling pathway, which were prominent involvement in the process of MIA regulating abnormal fetal brain development to induce an increased risk of ASD. Here, we have observed that almost all key genes within these risk pathways are significantly differentially expressed at embryonic days (E) 10.5–12.5, which is considered to be the optimal coincidence window of mouse embryonic brain development to study the intimate association between MIA and ASD using mouse animal models. SignificanceThere search establishes that MIA causes dysregulation of immune and metabolic pathways, which leads to abnormal embryonic neurodevelopment, thus promoting development of ASD symptoms in offspring.