Autism spectrum disorder is a serious neurodevelopmental disorder whose early onset significantly affects an individual's social interactions and cognitive function. Recent research suggests that modulating the gut microbiota could be a potential intervention strategy for autism spectrum disorder symptoms. 2'-Fucosyllactose has been identified as a regulator of gut microbiota homeostasis, however, its effectiveness in addressing autism spectrum disorder remains unclear. In this study, the effects of daily supplementation of 2'-FL in 3-week-old male offspring mice for 5 weeks were examined. The results showed that 2'-fucosyllactose significantly improved autism spectrum disorder-like behavioral deficits. Furthermore, supplementation with 2'-fucosyllactose restored intestinal barrier integrity and increased relative abundance of beneficial gut bacteria, particularly Akkermansia and Bifidobacterium that are closely related to bile acid metabolism. Notably, 2'-fucosyllactose treatment elevated the content of bile acids and upregulated the expression of bile acid receptors in the brain. Co-housing experiments further confirmed the crucial role of gut microbiota in mediating the beneficial effects of 2'-fucosyllactose. Overall, this study suggests that 2'-fucosyllactose could alleviate maternal immune activation-induced behavioral deficits and neuroinflammation through the regulation of the gut-brain axis, offering potential therapeutic value.

Polycystic ovarian syndrome (PCOS) is a common female endocrinologic condition that affects both the metabolic and reproductive systems and is the most frequent cause of anovulatory infertility. It is also associated with a range of psychiatric outcomes in individuals, including bulimia nervosa, schizophrenia, bipolar disorder, depression, anxiety, and personality disorders. At the same time, evidence suggests that hyperandrogenism, the characteristic trait of PCOS, may impair fetal neurodevelopment. Epidemiological studies have linked maternal PCOS with a variety of behavioral and psychiatric conditions in offspring including autism spectrum disorder and attention deficit hyperactivity disorder. In this review, we explore evidence for potential underlying biological mechanisms that might explain these observed associations, discuss the complex interplay between genetics and various environmental factors across generations, and highlight avenues for future research.

Prenatal viral infections can lead to neurodevelopmental disorders in offspring. However, how viral-induced maternal perturbations impact fetal brain macrophages remains insufficiently clear. Here, we demonstrated that inflammatory decidual natural killer (NK) cells, triggered by viral infection-induced maternal immune activation, drove macrophage activation, neurodevelopmental disorders, and behavioral deficits in offspring. Extracellular granzyme B (GzmB), predominantly released by the maternal CD49a+ tissue-resident NK subset under type I interferon stimulation, crossed the maternal-fetal barrier and promoted interferon-stimulated gene (ISG)-expressing fetal macrophage accumulation and microglial activation. Targeting extracellular GzmB through the systemic administration of the serine protease inhibitor Serpina3n or genetic ablation of Gzmb in maternal NK cells mitigated neuroimmune disorders in the fetal brain. These findings suggest that exposure to a perturbed maternal milieu reprograms decidual NK cell immunity, disrupting fetal neuroimmune homeostasis and increasing offspring susceptibility to neurodevelopmental disorders later in life.

In both humans and rodents, inappropriate feeding times during pregnancy can cause maternal metabolic abnormalities, increasing the risk of neurodevelopmental disorders in both the mother and offspring. Using a rat model, this study investigates whether feeding only during the inactive phase in rats leads to anxiety-like behaviors and abnormal brain development in fetuses through gut microbiota imbalance.

10-week-old female rats in the inactive-phase feeding group (IF group) were first trained for daytime feeding, ensuring that energy intake was statistically insignificant and different from that of the normal diet feeding group (ND group). They were then paired with male rats, and the previous feeding regimen was continued after pregnancy. Anxiety-like behavior was evaluated using the open-field test. Maternal caecal microbiota was analyzed using 16S rRNA sequencing. Enzyme-linked immunosorbent assay (ELISA) measured serum inflammation factors. RT-PCR was employed to assess mRNA levels of integrity genes and inflammatory cytokines in the maternal hippocampi, intestines, fetal brains, and placentae.

There were no statistically significant differences in energy intake or body weight gain between the IF and ND groups. In the open field test, dams in the IF group exhibited anxiety-like behavior, as indicated by fewer entries into and shorter duration in the central zone. Active-phase fasting elevated maternal serum inflammatory cytokine levels and impaired antioxidant capacity. It also increased intestinal permeability and induced gut microbiota dysbiosis, characterized by a decrease in Akkermansia and an increase in Dubosiella. Changes in the expression of intestinal circadian genes and elevated intestinal inflammatory cytokines were observed. Lipopolysaccharide (LPS) translocated into the maternal circulation, activated Toll-like receptor 4 (TLR 4), and passed through the compromised placental barrier into the fetal brain, leading to increased expression of inflammatory cytokines in the fetal brain.

The misalignment between maternal feeding time and the biological clock during pregnancy disrupts the balance of the gut microbiota and peripheral rhythms. The impaired intestinal and placental barriers allow LPS from the gut to infiltrate the maternal hippocampus and fetal brain, increasing inflammation and impacting both maternal and fetal brain health.

Intrauterine inflammation disrupts tryptophan metabolism in both the placenta and the fetal brain, leading to a shift toward neurotoxic metabolites. These findings highlight the critical role of placental function in neurodevelopment and suggest that inflammation-induced metabolic changes may contribute to neurodevelopmental disorders.

The placenta plays a crucial role beyond nutrient transfer, acting as a dynamic endocrine organ that significantly influences maternal physiology and fetal development. It responds rapidly to even slight changes in the in utero environment to promote fetal survival. Disruptions in placental function are increasingly recognized as key contributors to the origins of neurodevelopmental disorders. In this study, we employed advanced technology to induce intrauterine inflammation through ultrasound-guided administration of LPS into gestational sacs. We then evaluated its effects on the gene expression of enzymes involved in TRP metabolism and conducted a comprehensive LC/MS analysis of the metabolome in the placenta and fetal brain of Wistar rats. Our results show that intraamniotic injection of LPS induces a robust inflammatory response leading to significant alterations in TRP metabolism, including downregulation of tryptophan hydroxylase (TPH) in the placenta, resulting in a decrease in serotonin (5-HT) levels. Similarly, in the fetal brain, exposure to LPS led to reduced Tph expression and increased monoamine oxidase expression, suggesting a decrease in 5-HT synthesis and an increase in its degradation. Furthermore, an upregulation of the kynurenine pathway was observed in both the placenta and fetal brain. Moreover, we detected a shift toward neurotoxicity, evidenced by an imbalance between neuroprotective and neurotoxic metabolites, including decreased levels of kynurenic acid and upregulation of kynurenine monooxygenase in the fetal brain. In conclusion, our findings reveal significant alterations in TRP metabolism following intrauterine inflammation, potentially contributing to neurodevelopmental disorders.

Autism Spectrum Disorder (ASD) is caused by genetic, epigenetic, and environmental factors. Mutations in the human FMR1 gene, encoding the Fragile X Messenger Ribonucleoprotein 1 (FMRP), cause the most common monogenic form of ASD, the Fragile X Syndrome (FXS). This study explored the interaction between the FMR1 gene and a viral-like infection as an environmental insult, focusing on the impact on core autistic-like behaviors and the mGluR1/5-mTOR pathway. Pregnant heterozygous Fmr1 mouse females were exposed to maternal immune activation (MIA), by injecting the immunostimulant Poly (I:C) at the embryonic stage 12.5, simulating viral infections. Subsequently, ASD-like behaviors were analyzed in the adult offspring, at 8-10 weeks of age. MIA exposure in wild-type mice led to ASD-like behaviors in the adult offspring. These effects were specifically confined to the intrauterine infection, as immune activation at later stages, namely puberty (Pubertal Immune Activation, PIA) at post-natal day 35 or adulthood (Adult Immune Activation, AIA) at post-natal day 56, did not alter adult behavior. Importantly, combining the Fmr1 mutation with MIA exposure did not intensify core autistic-like behaviors, suggesting an occlusion effect. Mechanistically, MIA provided a strong activation of the mGluR1/5-mTOR pathway, leading to increased LTP and downregulation of FMRP specifically in the hippocampus. Finally, FMRP modulates mTOR activity via TSC2. These findings further strengthen the key role of the mGluR1/5-mTOR pathway in causing ASD-like core symptoms.

Cytokines interact with their receptor complexes to orchestrate diverse processes-from immune responses to behavioral modulation. Interleukin-17A (IL-17A) mediates protective immune responses by binding to IL-17 receptor A (IL-17RA) and IL-17RC subunits. IL-17A also modulates social interaction, yet the role of cytokine receptors in this process and their expression in the brain remains poorly characterized. Here, we mapped the brain-region-specific expression of all major IL-17R subunits and found that in addition to IL-17RA, IL-17RB-but not IL-17RC-plays a role in social behaviors through its expression in the cortex. We further showed that IL-17E, expressed in cortical neurons, enhances social interaction by acting on IL-17RA- and IL-17RB-expressing neurons. These findings highlight an IL-17 circuit within the cortex that modulates social behaviors. Thus, characterizing spatially restricted cytokine receptor expression can be leveraged to elucidate how cytokines function as critical messengers mediating neuroimmune interactions to shape animal behaviors.

Maternal depression promotes maternal inflammation and the risk of neurodevelopmental disorder in offspring, but the role of inflammation on the association between depression and neurodevelopment in offspring has not been extensively studied in humans. This study aims to examine the mediating role of maternal inflammation on the relationship between maternal depression and neurodevelopment in infants. 146 mother-child pairs were identified from Tianjin Maternal and Child Health Education and Service Cohort (Tianjin MCHESC). Maternal depression was investigated by the Center for Epidemiologic Studies Depression Scale and the Edinburgh Postnatal Depression Scale, and depressive trajectories were identified by latent class growth analysis. Inflammatory biomarkers in the three trimesters were assessed with enzyme-linked immunoassay. The Children Neuropsychological and Behavior Scale-Revision 2016 was used to measure neurodevelopment in infants. Principal component analysis was performed to identify inflammatory condition. Stepwise multiple linear regression analysis and mediation analysis were used to identify association among maternal depression, maternal inflammation and neurodevelopment in infants. Offspring in the low and moderate maternal depression groups exhibited higher adaptive behavior development quotient than those in the high maternal depression group. Higher maternal c-reactive protein level and higher inflammatory level in acute-phase of inflammation in the first trimester, and moderate maternal depression were associated with lower adaptive behavior quotients of infants. Inflammatory level in acute-phase of inflammation in the first trimester significantly mediated the association between maternal depression and adaptive behavior development of infants, with explaining 11.85% of the association. Maternal depression could impair adaptive behavior development in infants by inflammation.

Around 80 % of individuals with neurodevelopmental disorders such as schizophrenia and autism spectrum disorders experience disruptions in sleep/circadian rhythms. We explored whether environmental circadian disruption interacts with prenatal infection, a risk factor for neurodevelopmental disorders, to induce sex-specific deficits in mice. A maternal immune activation (MIA) protocol was used by injecting pregnant mice with viral mimic poly IC or saline at E9.5. Juvenile/adolescent male and female offspring (3-7 weeks old) were then subjected to a standard light:dark cycle (12:12LD) or to constant light (LL). Significant interactions between treatment (MIA, control) and lighting (12:12LD, LL) were evident in behaviors related to cognition, anxiety, and sociability. This pattern persisted in our RNA sequencing analysis of the dorsal hippocampus, where poly IC exposure resulted in numerous differentially expressed genes (DEGs) in males, while exposure to both poly IC and LL led to a marked reduction in DEGs. Through WGCNA analysis, many significant gene modules were found to be positively associated with poly IC (vs. saline) and LL (vs. LD) in males (fewer in females). Many of the identified hub-bottleneck genes were homologous to human genes associated with sleep/circadian rhythms and neurodevelopmental disorders as revealed by GWA studies. The MIA- and LL-associated modules were enriched in microglia gene signatures, which was paralleled by trends of effects of each of the factors on microglia morphology. In conclusion, in a mouse model of prenatal infection, circadian disruption induced by LL during adolescence acts as a modulator of the effects of MIA at behavioral, cellular, and molecular levels.

Background: Emerging evidence suggests that the maternal microbiome plays a crucial role in shaping fetal neurodevelopment, immune programming, and metabolic health. Dysbiosis during pregnancy-whether gastrointestinal, oral, or vaginal-can significantly influence pregnancy outcomes and long-term child health. Materials and Methods: The search was performed using databases such as PubMed, Scopus, and Google Scholar including research published from January 2000 to January 2025. The keywords used were "Fetal Programming", " Maternal Immune Activation", "Maternal microbiome", "Microbiota-Gut-Brain Axis", and "Pregnancy Dysbiosis". Results: The maternal microbiome undergoes substantial changes during pregnancy, with alterations in microbial diversity and function linked to conditions such as gestational diabetes, obesity, and preeclampsia. Pregnancy-related dysbiosis has been associated with adverse neurodevelopmental outcomes, including an increased risk of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and cognitive impairments in offspring. Conclusions: Understanding the intricate relationship between maternal microbiota and fetal health is essential for developing targeted interventions. Personalized microbiome-based strategies, including dietary modifications and probiotic supplementation, hold promise in optimizing pregnancy outcomes and promoting health in offspring.

Prenatal exposure to heavy metals poses risks to fetal brain development, yet the joint effects of these metals remain unclear, with inconsistent findings across statistical models. This study investigates the joint effect of prenatal exposure to cadmium (Cd), nickel (Ni), mercury (Hg), and lead (Pb) on infant neurodevelopment using various statistical approaches. The study included 400 mother-infant pairs. Heavy metal levels were measured in maternal urine samples at the 12th week of gestation, and infant neurodevelopment at 40 days was evaluated by the Bayley Scales of Infant and Toddler Development. Generalized Additive Models (GAM), Multivariable Linear Regression (MLR) with restricted cubic spline (RCS), Bayesian Kernel Machine Regression (BKMR), and Weighted Quantile Sum (WQS) regression were applied to explore the associations between heavy metal exposure and neurodevelopmental outcomes. GAM revealed a significant linear relationship for Cd with cognitive scale (p = 0.045) and expressive language (p = 0.043). MLR confirmed that Cd was negatively associated with both cognitive scale (β = -1.47, p = 0.044) and expressive language (β = -0.32, p = 0.019) and RCS presented a non-linear association between Pb and language scale (p = 0.001). BKMR suggested a negative but non-significant association with most outcomes. WQS indicated a significant adverse effect of metal mixture on expressive language (β = -0.26, 95% CI = -0.44, -0.07), identifying Cd and Ni as the primary contributors. Prenatal exposure to heavy metals have detrimental effects on infant neurodevelopment, especially on language development.

Gestation is a vulnerable developmental period, and exposures during that time may have longterm implications. While evaluating the implications of early exposures on children is an important public health concern, as opposed to other chemical exposures, medications are given for a clinical purpose, and any potential injury must be weighed against the benefits of these medications to the mother and child. This review examines neurodevelopmental outcomes in children following two maternal anesthetic exposures: general anesthesia and labor epidural analgesia. Exposure to general anesthetic agents has been found to interfere with neurodevelopment in animal models, and exposures in children, including prenatal exposures are also associated with worse neurodevelopmental outcomes. While these medications are likely to impact neurodevelopment in animals, it remains unclear if prenatal general anesthetic exposure causes the reported differences in children. As a result, since avoidance or delay of necessary surgery in mothers may result in adverse outcomes in mothers and children, necessary surgery in pregnant mothers should proceed without delay. Concerns about the safety of maternal neuraxial labor analgesia ("epidurals") have also emerged due to a reported association with autism spectrum diagnoses in their children. This may be due to familial factors in pregnant women electing for neuraxial labor analgesia rather than the "epidural" itself. In addition, since clinically significant differences in neurodevelopmental scores in children following exposure have not been found, and a mechanism of injury has not yet been identified in preclinical studies, the benefits of neuraxial labor analgesia appear to outweigh the potential risks.

Prenatal virus infection-induced maternal immune activation (MIA) is linked to a greater risk of neurodevelopmental disorders in offspring. Prenatal exposure to poly(I:C) in pregnant mice is a well-established approach to mimic virus infection-induced MIA, leading to neuropsychiatric disorders and aberrant brain development, especially in the medial prefrontal cortex (mPFC). ATPase phospholipid flippase 8A2 (ATP8A2) is the main phospholipid lipase, expressed in the mPFC and is crucial for maintaining cell membrane stability by flipping phosphatidylserine from the outer leaflet to the inner leaflet of the cell membrane. Atp8a2 knockout or mutation causes a series of phenotypes, including impaired neuronal cell survival, neuroinflammation, altered synaptic plasticity, and behavioral abnormalities. These findings suggest that ATP8A2 expression in the mPFC may be impaired in MIA offspring and that the decrease in ATP8A2 expression may be involved in the development of MIA-induced neuropsychiatric disorders in offspring. No reports addressing this issue have been published. Here, after confirming abnormal affective-/social-related behaviors in adulthood and reduced synapse-associated protein expression on the birth day (P0) and the fourth postnatal day (P4) in the mPFC of MIA offspring that were born to dams exposed prenatally to a single dose of poly(I:C) (10 mg/kg, i.p.), decreased ATP8A2 expression was also observed in the mPFC of MIA offspring at P0 and P4.Upregulating ATP8A2 in the mPFC restored synapse-associated protein levels, along with a partial improvement in the behavioral performance of MIA offspring. Upregulation of ATP8A2 also blocked neuronal phosphatidylserine externalization and eliminated the excitation/inhibition (E/I) imbalance in the mPFC of MIA offspring. This study revealed that the low expression of ATP8A2 following MIA exposure may play a role in mediating abnormal brain development and function in offspring. ATP8A2 potentially represents a novel molecule involved in MIA-induced neuropsychiatric disorders in offspring, and may serve as a novel therapeutic target for the intervention of psychiatric disorders.

Autism spectrum disorder is a pervasive and heterogeneous neurodevelopmental condition characterized by social communication difficulties and rigid, repetitive behaviors. Owing to the complex pathogenesis of autism, effective drugs for treating its core features are lacking. Nonpharmacological approaches, including education, social-communication, behavioral and psychological methods, and exercise interventions, play important roles in supporting the needs of autistic individuals. The advantages of exercise intervention, such as its low cost, easy implementation, and high acceptance, have garnered increasing attention. Exercise interventions can effectively improve the core features and co-occurring conditions of autism, but the underlying neurobiological mechanisms are unclear. Abnormal changes in the gut microbiome, neuroinflammation, neurogenesis, and synaptic plasticity may individually or interactively be responsible for atypical brain structure and connectivity, leading to specific autistic experiences and characteristics. Interestingly, exercise can affect these biological processes and reshape brain network connections, which may explain how exercise alleviates core features and co-occurring conditions in autistic individuals. In this review, we describe the definition, diagnostic approach, epidemiology, and current support strategies for autism; highlight the benefits of exercise interventions; and call for individualized programs for different subtypes of autistic individuals. Finally, the possible neurobiological mechanisms by which exercise improves autistic features are comprehensively summarized to inform the development of optimal exercise interventions and specific targets to meet the needs of autistic individuals.

Evidence suggests that prenatal maternal immunological stress is associated with an increased risk of neurological and psychiatric disorders in the developing offspring. Protecting the embryo during this critical period of neurodevelopment, when the brain is especially vulnerable, is therefore crucial. Polyphenols, with their antioxidant and anti-inflammatory properties, offer promising therapeutic approaches. This study demonstrated a series of behavioral changes induced by maternal immune activation (MIA) triggered by an antigenic solution derived from the H1N1 virus. These changes include significant differences in anxiety and risk assessment behaviors, increased immobility in the forced swim test, impairments in memory and object recognition, and social deficits resembling autism. The phenolic compound resveratrol (RSV) was evaluated for its in vitro antioxidant capacity and characterized using infrared spectroscopy. Administering RSV from embryonic day 14 (E14) to embrionyc day 19 (E19) during MIA effectively reduced its harmful effects on the offspring. This was evidenced by a significant restoration of social behaviors, memory, and recognition, as well as anxiolytic and antidepressant effects in the adult offspring. These findings contribute to new therapeutic strategies for preventing psychiatric disorders associated with neurodevelopmental stressors.

Pregnancy is a transformative period marked by profound physical and emotional changes, with far-reaching consequences for both mother and child. Emerging research has illustrated the pivotal role of a mother's diet during pregnancy in influencing the prenatal gut microbiome and subsequently shaping the neurodevelopment of her offspring. The intricate interplay between maternal gut health, nutrition, and neurodevelopmental outcomes has emerged as a captivating field of investigation within developmental science. Acting as a dynamic bridge between mother and fetus, the maternal gut microbiome, directly and indirectly, impacts the offspring's neurodevelopment through diverse pathways. This comprehensive review delves into a spectrum of studies, clarifying putative mechanisms through which maternal nutrition, by modulating the gut microbiota, orchestrates the early stages of brain development. Drawing insights from animal models and human cohorts, this work underscores the profound implications of maternal gut health for neurodevelopmental trajectories and offers a glimpse into the formulation of targeted interventions able to optimize the health of both mother and offspring. The prospect of tailored dietary recommendations for expectant mothers emerges as a promising and accessible intervention to foster the growth of beneficial gut bacteria, potentially leading to enhanced cognitive outcomes and reduced risks of neurodevelopmental disorders.

Infectious and inflammatory processes during pregnancy in women provoke maternal immunity activation (MIA) and increase the risk of neuropsychiatric disorders in children. These disorders can lead to neurodegenerative diseases later in life. To study these effects, we evaluated the morphological and molecular biological changes in the hippocampus and prefrontal cortex of male and female Wistar rats on the 1st day of postnatal ontogenesis after LPS-induced MIA. The level of calprotectin in the blood serum of postpartum rats, the number and morphological properties of microglial cells in the hippocampus, and the expression of proinflammatory, stem, and adaptation markers in fragments of the prefrontal cortex in offspring of both sexes were determined. It was found that LPS-induced MIA had a negative effect on the developing offspring, with an increase in the level of expression of Nfκb and App in the prefrontal cortex of newborns being observed. Sex differences in morphological and molecular biological changes in the brains of newborn Wistar rats were also revealed: the number of microglial cells increased in male rats, while the number of ramified microglial cells decreased in female rats. In addition, only in females, the expression levels of the mRNA markers for stem cells, Sox2 and Sox9, decreased, while the expression level of Hif1α, which has a neuroprotective effect, increased only in males. These data may explain the differences in the incidence of neurodegenerative diseases among elderly patients of different sexes.

Autism spectrum disorder (ASD) is characterized by difficulties in social interaction, communication, and repetitive behavior, typically diagnosed during early childhood and attributed to altered neuronal network connectivity. Several genetic and environmental risk factors contribute to ASD, including pre- or early life immune activation, which can trigger microglial and astroglial reactivity, impacting early neurodevelopment. In ASD, astrocytes show altered glutamate metabolism, directly influencing neuronal network activity, while microglia display impaired synaptic pruning, an essential developmental process for the refinement of neuronal connections. Additionally, reduced myelination in specific cortical and subcortical regions may affect brain connectivity in ASD, with white matter integrity correlating with the severity of the disorder, suggesting an important role for oligodendrocytes and myelin in ASD. This chapter provides an overview of current literature on the role of neuroglia cells in ASD, with a focus on immune activation, glutamate signaling, synaptic pruning, and myelination.

Schizophrenia is a complex mental disorder influenced by genetic and environmental factors, including dietary habits. Oxidative stress and inflammation play a crucial role in the pathophysiology of schizophrenia. Emerging research suggests that diet may affect schizophrenia through different biological mechanisms beyond oxidative stress and inflammation. In particular, epigenetic changes may alter the expression of genes related to neurodevelopment and neurotransmitter systems, while neuroplasticity plays a crucial role in brain adaptation and resilience to psychiatric disorders.

The literature search included the main available databases (Science Direct, PubMed and Google Scholar), considering the English language, and our screening was performed based on several words such as "schizophrenia", "diet", "nutrients", "obesity", "oxidative stress", "inflammation", "antioxidants" and "prenatal nutritional deficiency". The review focused specifically on studies examining the relevance of diet in schizophrenia, as well as prenatal nutritional deficiency, obesity, oxidative stress, and inflammation associated with this disorder.

Following a review of the literature, it was found that nutritional deficiencies, including lack of omega-3 fatty acids, vitamins D, and B, during the prenatal and postnatal periods can have a negative impact on neurodevelopment and increase the risk of schizophrenia. Patients with schizophrenia have imbalances in antioxidant enzymes, such as glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and reduced levels of antioxidants (vitamin E, vitamin C). These biochemical changes lead to an increase in markers of oxidative stress, including malondialdehyde (MDA). In addition, cytokine-mediated inflammation, microglial activation, and intestinal dysbiosis are associated with the onset of schizophrenia and the severity of schizophrenia symptoms. Currently, there is no universally accepted dietary regimen for control. However, various diets and nutritional methods are being researched and applied to alleviate the symptoms of schizophrenia and improve the overall health of patients, including the Mediterranean diet, the ketogenic diet, the gluten-free diet, and the DASH (Dietary Approaches to Stop Hypertension) diet.

A healthy diet, rich in anti-inflammatory nutrients and antioxidants, may help manage schizophrenia by reducing oxidative stress, preventing complications, and improving quality of life. Omega-3 fatty acids, vitamin D, and B vitamins are particularly important for brain development and function. In this review, we aim to analyze the literature on the influence of diet on schizophrenia, focusing on the role of prenatal nutritional deficiencies, obesity, oxidative stress, and inflammation.

Bisphenol AP (BPAP), an environmental endocrine disruptor, may cause neurodevelopmental disorders affecting human health. Studies have shown that BPAP impacts hormone synthesis and metabolism, causes social behavior abnormalities, and induces anxiety-like behavioral impairments in mice. However, evidence for the neurobehavioral effects of BPAP is still lacking. Here, we examined the toxic effects of BPAP on neurodevelopment using a Drosophila model. We assessed the role of BPAP exposure in autism-like behavior and explored the underlying mechanisms. Our findings indicated that BPAP exposure reduced pupation and eclosion rates and delayed growth in Drosophila. Furthermore, BPAP exposure caused autism-like behaviors, characterized by increased grooming times and aberrant social interactions, along with abnormalities in locomotor activity, as well as learning and memory ability. Mechanistically, we found that BPAP decreases the number of neuroblasts (NBs) and mature intermediate neural progenitors (INPs) in the 3rd larval brain, impairing axon guidance in the mushroom body of the adult Drosophila brain. Additionally, our transcriptome analysis revealed that BPAP exposure alters the expression of neurodevelopment-related genes (Nplp3, sand, lush, and orco) and affects the estrogen signaling pathway (Hsp70Ab, Hsp70Bc, Hsp70Ba, and Hsp70Bb). These changes potentially explain the BPAP-induced autism-like behavior in Drosophila.

Autism spectrum disorders (ASD) have a complex pathogenesis thought to include both genetic and extrinsic factors. Among the latter, inflammation of the developing brain has recently gained growing attention. However, how genetic predisposition and inflammation might converge to precipitate autistic behavior remains elusive. Cerebellar structure and function are well known to be affected in autism. We therefore used cerebellar slice cultures to probe whether inflammatory stimulation and (over)expression of the autism susceptibility gene Engrailed-2 interact in shaping differentiation of Purkinje cells, key organizers of cerebellar histogenesis and function. We show that lipopolysaccharide treatment reduces Purkinje cell dendritogenesis and that this effect is enhanced by over-expression of Engrailed-2 in these cells. The effects of lipopolysaccharide can be blocked by inhibiting microglia proliferation and also by blocking tumor necrosis factor alpha receptor signaling, suggesting microglia and tumor necrosis factor alpha are major players in this scenario. These findings identify Purkinje cells as a potential integrator of genetic and environmental signals that lead to an autism-associated morphology.

The maternal immune activation hypothesis has gained attention over the past 2 decades as a potential contributor to the etiology of autism. This hypothesis posits that maternal conditions associated with inflammation during pregnancy may increase the risk of autism in offspring. Autism is highly heritable, and causal environmental contributors to autism largely remain elusive. We review studies on maternal conditions during pregnancy, all associated with some degree of systemic inflammation, namely maternal infections, autoimmunity, and high body mass index. We also review studies of inflammatory markers in biological samples collected from mothers during pregnancy or from neonates and their relationship with autism assessed in children later in life. Recent reports indicate familial clustering of autism, autoimmunity, and infections, as well as genetic correlations between autism and aspects of immune function. Given this literature, there is an apparent risk of confounding of the reported associations between inflammatory exposures and autism by familial genetic factors in both clinical and epidemiological cohort studies. We highlight recent studies that have attempted to address potential confounding to assess evidence of causal effects of inflammation during early life in autism.

Early life stress correlates with a higher prevalence of neurological disorders, including autism, attention-deficit/hyperactivity disorder, schizophrenia, depression, and Parkinson's disease. These conditions, primarily involving abnormal development and damage of the dopaminergic system, pose significant public health challenges. Microglia, as the primary immune cells in the brain, are crucial in regulating neuronal circuit development and survival. From the embryonic stage to adulthood, microglia exhibit stage-specific gene expression profiles, transcriptome characteristics, and functional phenotypes, enhancing the susceptibility to early life stress. However, the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood. This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia, leading to dopaminergic system disorders, along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions. Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support (e.g., insulin-like growth factor-1) and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning. Furthermore, blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission. Furthermore, inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons, inhibiting dopamine synthesis, reuptake, and receptor activity. Enhanced microglial phagocytosis inhibits dopamine axon extension. These long-lasting effects of microglial perturbations may be driven by early life stress-induced epigenetic reprogramming of microglia. Indirectly, early life stress may influence microglial function through various pathways, such as astrocytic activation, the hypothalamic-pituitary-adrenal axis, the gut-brain axis, and maternal immune signaling. Finally, various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed. These strategies include classical antidepressants and antipsychotics, antibiotics and anti-inflammatory agents, and herbal-derived medicine. Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.

Poor prenatal maternal sleep is a pervasive, yet modifiable, health concern affecting maternal and foetal wellbeing. Experimental rodent studies demonstrate that prenatal maternal sleep deprivation affects offspring brain development and leads to adverse outcomes, including increased anxiety-like behaviour. We examined the relation between prenatal maternal sleep quality and neonatal white matter development and subsequent infant negative emotionality.

Participants included 116 mother-infant (53% female) dyads. Prenatal sleep quality was prospectively assessed three times during gestation (16, 29, and 35 gestational weeks) using the Pittsburgh Sleep Quality Index. Neonatal white matter, as indexed by fractional anisotropy (FA), was assessed via diffusion weighted magnetic resonance imaging. Negative emotionality was measured via behavioural observation and maternal report when the infant was 6-months of age.

More prenatal sleep problems across pregnancy were associated with higher neonatal FA in the uncinate fasciculus (left: b = 0.20, p = .004; right: b = 0.15, p = .027). Higher neonatal uncinate FA was linked to infant negative emotionality, and uncinate FA partially mediated the association between prenatal maternal sleep and behavioural observation of infant negative emotionality.

Findings highlight prenatal sleep as an environmental signal that affects the developing neonatal brain and later infant negative emotionality.

National Institutes of Health (R01MH109662, R01HL155744, P50HD103573, K12AR084226, F32 Training fellowships MH125572, HL165844, MH106440, and diversity supplement R01HL155744-01S1).

An increasing amount of evidence suggests that immune responses may affect trophoblast functioning, which in turn may play a role in gestational disorders and fetal development. This systematic review offers the first summary of in vitro studies on the trophoblast response to immunological triggers, in conjunction with a risk of bias analysis. A search in Pubmed and Embase yielded 110 relevant studies. Primary trophoblasts were the most commonly used cell type, but trophoblast subtypes were not always defined. Similarly, the exact natures of trophoblast cell lines were sometimes unclear. Cytokines and Toll-like receptor agonists were often used as interventions, but most studies focused on a select few substances such as tumor necrosis factor-α and lipopolysaccharide. In regard to the outcome parameters, some important trophoblast functions, such as hormone production and barrier formation were underrepresented. Whether or not risk of bias was high varied strongly between types of bias. Risk of selection bias, for example, was usually low. However, none of the included studies mentioned blinding or plate randomization. Only a select few studies mentioned passage numbers, use of vehicle control or conflict of interest. In conclusion, better characterization of trophoblast subtypes and a broader range of studied interventions and outcome parameters would contribute to a more complete understanding of trophoblast responses to immune stimuli. Additionally, researchers are encouraged to replicate experiments and pay close attention when setting up and writing down methodologies, in order to improve the reproducibility and translatability of their work.

Selective vulnerability offers a conceptual framework for understanding neurodegenerative disorders such as Parkinson's disease, where specific neuronal types are selectively affected and adjacent ones are spared. However, the applicability of this framework to neurodevelopmental disorders, particularly those characterized by atypical social behaviors, such as autism spectrum disorder, remains uncertain. Here we show that an embryonic disturbance, known to induce social dysfunction in male mice, preferentially impaired the gene expression crucial for neural functions in parvocellular oxytocin (OT) neurons-a subtype linked to social rewards-while neighboring cell types experienced a lesser impact. Chemogenetic stimulation of OT neurons at the neonatal stage ameliorated social deficits in early adulthood, concurrent with cell-type-specific sustained recovery of pivotal gene expression within parvocellular OT neurons. Collectively, our data shed light on the transcriptomic selective vulnerability within the hypothalamic social behavioral center and provide a potential therapeutic target through specific neonatal neurostimulation.

The recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring.

Based on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring.

Compared with "low IPAI" group, offspring with "high IPAI" have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted β were - 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and - 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among "high IPAI" group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72).

Our results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

Pregnancy represents a window of vulnerability to fetal development. Disruptions in the prenatal environment during this crucial period can increase the risk of the offspring developing diseases over the course of their lifetime. The central nervous system (CNS) has been shown to be particularly susceptible to changes during crucial developmental windows. To date, research focused on disruptions in the development of the CNS has predominantly centred on the brain, revealing a correlation between exposure to prenatal risk factors and the onset of neuropsychiatric disorders. Nevertheless, some studies indicate that the retina, which is part of the CNS, is also vulnerable to in utero alterations during pregnancy. Such changes may affect neuronal, glial and vascular components of the retina, compromising retinal structure and function and possibly impairing visual function.

A search in the PubMed database was performed, and any literature concerning prenatal risk factors (drugs, diabetes, unbalanced diet, infection, glucocorticoids) affecting the offspring retina were included.

This review collects evidence on the cellular, structural and functional changes occurring in the retina triggered by maternal risk factors during pregnancy. We highlight the adverse impact on retinal development and its long-lasting effects, providing a critical analysis of the current knowledge while underlining areas for future research.

Appropriate recognition of the prenatal risk factors that negatively impact the developing retina may provide critical clues for the design of preventive strategies and for early therapeutic intervention that could change retinal pathology in the progeny.

Congenital Zika virus (ZIKV) infection leads to severe newborn abnormalities, but its long-term impact on childhood immunity is not well understood. This study aims to investigate the serum proteomics in children exposed to ZIKV during pregnancy to understand potential immunological consequences during early childhood.

The study included ZIKV-exposed infants (ZEI) at birth (n = 42) and children exposed to ZIKV (ZEC) at two years of age (n = 20) exposed to ZIKV during pregnancy, as well as healthy controls. Serum proteomic analysis was performed on these groups to assess inflammation and immune profiles. Additionally, antibody titres against two common childhood vaccines, DTaP and MMR, were measured in healthy controls (n = 50) and ZEC (n = 92) to evaluate vaccine-induced immunity.

Results showed elevated inflammation in ZEI with birth abnormalities. Among ZEC, despite most having normal clinical outcomes at two years, their serum proteomics indicated a bias towards Th1-mediated immune responses. Notably, ZEC displayed reduced anti-Diphtheria toxin and anti-Clostridium tetani IgG levels against DTaP and MMR vaccines. They also exhibited lower antibody titres particularly against Th2-biased DTaP vaccines, but not Th1-biased MMR vaccines.

In conclusion, the study highlights the long-term immunological consequences of congenital ZIKV exposure. Heightened inflammation was observed in ZEI with abnormalities at birth, while ZEC maintained a chronic Th1-biased immune profile. The impaired response to Th2-biased vaccines raises concerns about lasting effects of ZIKV exposure on immune responses. Consequently, there is a need for continued longitudinal clinical monitoring to identify potential immune-related complications arising from prenatal exposure to ZIKV.

This work was partially funded by the National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Dental and Craniofacial Research (NIDCR).

Autism spectrum disorder (ASD) is a developmental disorder characterized by social deficits and repetitive behavior. Gastrointestinal (GI) problems, such as constipation, diarrhea, and inflammatory bowel disease, commonly occur in patients with ASD. Previously, GI problems of ASD patients were attributed to intestinal inflammation and vertical mother-to-infant microbiome transmission.

To explore whether GI problems in ASD are related to maternal intestinal inflammation and gut microbiota abnormalities.

An ASD rat model was developed using valproic acid (VPA). Enzyme-linked immunosorbent assay and fecal 16S rRNA sequencing were used to test GI changes.

VPA exposure during pregnancy led to pathological maternal intestinal changes, resulting in alterations in maternal gut microbiota. Additionally, the levels of inflammatory factors also increased. Moreover, prenatal exposure to VPA resulted in impaired duodenal motility in the offspring as well as increased levels of inflammatory factors.

GI problems in ASD may be associated with maternal intestinal inflammation and microbiota abnormality. Future research is required to find more evidence on the etiology and treatment of GI problems in ASD.

Accumulating 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.

Participants 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.

There 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.

Lower 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.

Oxidative stress during pregnancy has been a mechanistic pathway implicated in autism development, yet few studies have examined this association directly. Here, we examined the association of prenatal levels of 8-iso-PGF2α, a widely used measure of oxidative stress, and several neurodevelopmental outcomes related to autism in children. Participants included 169 mother-child pairs from the Early Autism Risk Longitudinal Investigation (EARLI), which enrolled mothers who had an autistic child from a previous pregnancy and followed them through a subsequent pregnancy and until that child reached age 3 years. Maternal urine samples were collected during the second trimester of pregnancy and were later measured for levels of isoprostanes. Child neurodevelopmental assessments included the Mullen Scales of Early Learning (MSEL), the Social Responsiveness Scale (SRS), and the Vineland Adaptive Behavior Scale (VABS), and were conducted around 36 months of age. Primary analyses examined associations between interquartile range (IQR) increases in 8-iso-PGF2α levels, and total composite scores from each assessment using quantile regression. In adjusted analyses, we did not observe statistically significant associations, though estimates suggested modestly lower cognitive scores (β for MSEL = -3.68, 95% CI: -10.09, 2.70), and minor increases in autism-related trait scores (β for SRS T score = 1.68, 95% CI: -0.24, 3.60) with increasing 8-iso-PGF2α. These suggestive associations between decreased cognitive scores and increased autism-related traits with increasing prenatal oxidative stress point to the need for continued investigation in larger samples of the role of oxidative stress as a mechanistic pathway in autism and related neurodevelopmental outcomes.

Autism spectrum disorder (ASD), a heterogeneous group of neurodevelopmental disorders, is characterized by social impairment and repetitive and stereotypic behaviors. Because of the lack of approved laboratory diagnostic markers and effective therapeutic medications, it is one of the most challenging diseases. Therefore, it is urgent to explore potential diagnosis markers or therapeutic targets. Insulin-like growth factor 1 (IGF-1) is a neurotrophic growth factor that enhances brain development. IGF-1 levels in body fluids are lower in preschool children with ASD than in typically developing children, which may serve as a potential diagnostic marker. In various ASD models associated with genetic or environmental exposure, IGF-1 treatment can improve core symptoms or pathological changes, including neuronal development, neural cell survival, balance of synaptic excitation and inhibition, neuroimmunology, and oxidative stress status. In March 2023 an IGF-1 derivative was approved as the first drug for treating Rett syndrome, an ASD-related neurodevelopmental disorder, to improve fundamental symptoms such as social communication. Thus, in this review, we present accumulating evidence of altered IGF-1 levels in ASD patients and the possible mechanisms, as well as evidence that IGF-1 treatment improves the pathophysiology in various ASD models. IGF-1 has the potential to be an early diagnosis marker and an effective therapeutic for ASD.

Maternal exposure to inflammation is one of the causes of autism spectrum disorder (ASD). Electrical stimulation of the vagus nerve exerts a neuroprotective effect via its anti-inflammatory action. We thus investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) can enhance social abilities in a mouse model of ASD induced by maternal immune activation (MIA).

ASD mouse model were constructed by intraperitoneal injection of polyinosinic:polycytidylic acid (poly (I:C)). TaVNS with different parameters were tested in ASD mouse model and in C57BL/6 mice, then various behavioral tests and biochemical analyses related to autism were conducted. ASD model mice were injected with an interleukin (IL)-17a antibody into the brain, followed by behavioral testing and biochemical analyses.

TaVNS reduced anxiety, improved social function, decreased the number of microglia, and inhibited M1 polarization of microglia. Additionally, taVNS attenuated the expression of the IL-17a protein in the prefrontal cortex and blood of ASD model mice. To examine the possible involvement of IL-17a in taVNS-induced neuroprotection, we injected an IL-17a antibody into the prefrontal cortex of ASD model mice and found that neutralizing IL-17a decreased the number of microglia and inhibited M1 polarization. Furthermore, neutralizing IL-17a improved social function in autism model mice.

Our study revealed that reduced neuroinflammation is an important mechanism of taVNS-mediated social improvement and neuroprotection against autism. This effect of taVNS could be attributed to the inhibition of the IL-17a pathway.

Autism spectrum disorder (ASD1) is a behaviorally defined syndrome encompassing a markedly heterogeneous patient population. Many ASD subjects fail to respond to the 1st line behavioral and pharmacological interventions, leaving parents to seek out other treatment options. Evidence supports that neuroinflammation plays a role in ASD pathogenesis. However, the underlying mechanisms likely vary for each ASD patient, influenced by genetic, epigenetic, and environmental factors. Although anti-inflammatory treatment measures, mainly based on metabolic changes and oxidative stress, have provided promising results in some ASD subjects, the use of such measures requires the careful selection of ASD subjects based on clinical and laboratory findings. Recent progress in neuroscience and molecular immunology has made it possible to allow re-purposing of currently available anti-inflammatory medications, used for autoimmune and other chronic inflammatory conditions, as treatment options for ASD subjects. On the other hand, emerging anti-inflammatory medications, including biologic and gate-keeper blockers, exert powerful anti-inflammatory effects on specific mediators or signaling pathways. It will require both a keen understanding of the mechanisms of action of such agents and the careful selection of ASD patients suitable for each treatment. This review will attempt to summarize the use of anti-inflammatory agents already used in targeting ASD patients, and then emerging anti-inflammatory measures applicable for ASD subjects based on scientific rationale and clinical trial data, if available. In our experience, some ASD patients were treated under diagnoses of autoimmune/autoinflammatory conditions and/or post-infectious neuroinflammation. However, there are little clinical trial data specifically for ASD subjects. Therefore, these emerging immunomodulating agents for potential use for ASD subjects will be discussed based on preclinical data, case reports, or data generated in patients with other medical conditions. This review will hopefully highlight the expanding scope of immunomodulating agents for treating neuroinflammation in ASD subjects.

The prevalence of autism spectrum disorder (ASD) is still increasing, which means that this neurodevelopmental lifelong pathology requires special scientific attention and efforts focused on developing novel therapeutic approaches. It has become increasingly evident that neuroinflammation and dysregulation of neuro-immune cross-talk are specific hallmarks of ASD, offering the possibility to treat these disorders by factors modulating neuro-immunological interactions. Mesenchymal stem cell-based therapy has already been postulated as one of the therapeutic approaches for ASD; however, less is known about the molecular mechanisms of stem cell influence. One of the possibilities, although still underestimated, is the paracrine purinergic activity of MSCs, by which stem cells ameliorate inflammatory reactions. Modulation of adenosine signaling may help restore neurotransmitter balance, reduce neuroinflammation, and improve overall brain function in individuals with ASD. In our review article, we present a novel insight into purinergic signaling, including but not limited to the adenosinergic pathway and its role in neuroinflammation and neuro-immune cross-talk modulation. We anticipate that by achieving a greater understanding of the purinergic signaling contribution to ASD and related disorders, novel therapeutic strategies may be devised for patients with autism in the near future.

This study employs bibliometric and visual analysis to elucidate global research trends in Autism Spectrum Disorder (ASD) biomarkers, identify critical research focal points, and discuss the potential integration of diverse biomarker modalities for precise ASD assessment.

A comprehensive bibliometric analysis was conducted using data from the Web of Science Core Collection database until December 31, 2022. Visualization tools, including R, VOSviewer, CiteSpace, and gCLUTO, were utilized to examine collaborative networks, co-citation patterns, and keyword associations among countries, institutions, authors, journals, documents, and keywords.

ASD biomarker research emerged in 2004, accumulating a corpus of 4348 documents by December 31, 2022. The United States, with 1574 publications and an H-index of 213, emerged as the most prolific and influential country. The University of California, Davis, contributed significantly with 346 publications and an H-index of 69, making it the leading institution. Concerning journals, the Journal of Autism and Developmental Disorders, Autism Research, and PLOS ONE were the top three publishers of ASD biomarker-related articles among a total of 1140 academic journals. Co-citation and keyword analyses revealed research hotspots in genetics, imaging, oxidative stress, neuroinflammation, gut microbiota, and eye tracking. Emerging topics included "DNA methylation," "eye tracking," "metabolomics," and "resting-state fMRI."

The field of ASD biomarker research is dynamically evolving. Future endeavors should prioritize individual stratification, methodological standardization, the harmonious integration of biomarker modalities, and longitudinal studies to advance the precision of ASD diagnosis and treatment.

Physiological pain serves as a warning of exposure to danger and prompts us to withdraw from noxious stimuli to prevent tissue damage. Pain can also alert us of an infection or organ dysfunction and aids in locating such malfunction. However, there are instances where pain is purely pathological, such as unresolved pain following an inflammation or injury to the nervous system, and this can be debilitating and persistent. We now appreciate that immune cells are integral to both physiological and pathological pain, and that pain, in consequence, is not strictly a neuronal phenomenon. Here, we discuss recent findings on how immune cells in the skin, nerve, dorsal root ganglia, and spinal cord interact with somatosensory neurons to mediate pain. We also discuss how both innate and adaptive immune cells, by releasing various ligands and mediators, contribute to the initiation, modulation, persistence, or resolution of various modalities of pain. Finally, we propose that the neuroimmune axis is an attractive target for pain treatment, but the challenges in objectively quantifying pain preclinically, variable sex differences in pain presentation, as well as adverse outcomes associated with immune system modulation, all need to be considered in the development of immunotherapies against pain.

To investigate the impact of gut microbiota dysbiosis on neurodevelopment in children.

This study included 338 children aged 0-3 years admitted to our hospital from January to December 2022, The children were divided into a normal neurodevelopment group (169 cases) and a poor neurodevelopment group (169 cases). Basic personal information and clinical data were collected through a detailed questionnaire, and the microbial composition in fecal samples was analyzed using 16S rRNA gene sequencing.

Children in the poor neurodevelopment group showed a significant decrease in gut microbiota diversity compared to those in the normal neurodevelopment group (Shannon index, p < 0.05). The abundance of Bifidobacterium and Veillonella genera significantly decreased (p < 0.05), while the abundance of Streptococcus genus increased significantly (p < 0.05).

There is an association between gut microbiota dysbiosis and poor neurodevelopment in children. The increased abundance of Streptococcus genus and decreased abundance of Bifidobacterium and Veillonella genera in the gut microbiota may be potential risk factors for poor neurodevelopment in preterm infants. Future research should further explore the potential beneficial effects of gut microbiota modulation on neurodevelopment in children.

Maternal immune activation during pregnancy is a risk factor for offspring neuropsychiatric disorders. Among the mechanistic pathways by which maternal inflammation can affect fetal brain development and programming, those involving tryptophan (TRP) metabolism have drawn attention because various TRP metabolites have neuroactive properties. This study evaluates the effect of bacterial (lipopolysaccharides/LPS) and viral (polyinosinic:polycytidylic acid/poly I:C) placental infection on TRP metabolism using an ex vivo model. Human placenta explants were exposed to LPS or poly I:C, and the release of TRP metabolites was analyzed together with the expression of related genes and proteins and the functional activity of key enzymes in TRP metabolism. The rate-limiting enzyme in the serotonin pathway, tryptophan hydroxylase, showed reduced expression and functional activity in explants exposed to LPS or poly I:C. Conversely, the rate-limiting enzyme in the kynurenine pathway, indoleamine dioxygenase, exhibited increased activity, gene, and protein expression, suggesting that placental infection mainly promotes TRP metabolism via the kynurenine (KYN) pathway. Furthermore, we observed that treatment with LPS or poly I:C increased activity in the kynurenine monooxygenase branch of the KYN pathway. We conclude that placental infection impairs TRP homeostasis, resulting in decreased production of serotonin and an imbalance in the ratio between quinolinic acid and kynurenic acid. This disrupted homeostasis may eventually expose the fetus to suboptimal/toxic levels of neuroactive molecules and impair fetal brain development.