Per- and polyfluoroalkyl substances (PFASs) are widespread environmental pollutants. There is increasing evidence that PFASs have various adverse health effects, including renal toxicity, metabolic dysfunction, endocrine disruption, and developmental toxicity. PFASs have been found to accumulate in the placenta, and some PFASs can cross the placental barrier and subsequently accumulate in the fetus via the maternal–fetal circulation. An increasing number of studies have shown that early life exposure to PFASs can affect fetal neurodevelopment. This paper reviews the characteristics of indirect exposure to PFASs in early life, the effects on neurodevelopment in offspring, and the possible mechanisms of toxic effects.

Epidemiological studies have shown that prenatal triphenyl phosphate (TPhP) exposure is related to abnormal neurobehavior in children. However, the neurodevelopmental toxicity of TPhP in mammals is limited. To study the neurodevelopmental toxicity of TPhP in mammals and investigate the underlying mechanism, we used a mouse intrauterine TPhP exposure model. We measured the inflammatory factors (IL-6, TNFα) and NFκB levels, and tryptophan metabolism in placentae, detected the fetal brain transcriptome, hippocampal neuron development and neurobehavioral in the male offspring. The results showed that the protein level of IL-6, TNFα and NFκB in the placenta of the TPhP treatment group (1, 5 mg/kg) were significantly increased. Change of the protein level of these pro-inflammatory factors in maternal serum or fetal brain was not observed. Expression of genes along tryptophan-serotonin metabolism pathway were significantly decreased. While, the concentration of 5-HT levels in the placenta or fetal brain were significantly increased. Consistent with the increased 5-HT, the Nissl body was reduced in the hippocampus of treatment group. The expression of serotonergic neuron gene markers including Tph2, Htr1A, Htr2A, Pet1 and Lmx1b in the hippocampus of treatment group was significantly decreased. The neurobehavioral test showed that TPhP decreased center time that represent anxiety-like behavior, and reduced learning and memory in male offspring. Meanwhile, expression of genes along tryptophan-kynurenine metabolism pathway were significantly increased. The result of the transcriptome analysis of fetal brain showed that the differentially expressed genes are mainly involved in the transcription regulation of DNA as a template in the nucleus, and the enriched pathways are mainly signal pathways regulated by axon guidance and neurotrophic factors, dopaminergic and cholinergic synapses, suggest that not only serotonergic neuronal was affected. Overall, this study demonstrates that TPhP has the potential to induce placental inflammatory response in the placenta, disturb placental tryptophan metabolism, compromise the neuronal development and synaptic transmission, and cause abnormal neurobehavior in male offspring.

Early-life stress increases the risk for posttraumatic stress disorder. However, the epigenetic mechanism of early-life stress-induced susceptibility to posttraumatic stress disorder in adulthood remains unclear. Rat pups were exposed to maternal deprivation during postnatal days 1 to 14 for 3 hours daily and treated with the DNA methyltransferase inhibitor zebularine, L-methionine, or vehicle 7 days before contextual fear conditioning, which was used as a second stress and to mimic the reexperiencing symptom of posttraumatic stress disorder in adulthood. Long-term potentiation, dendritic spine density, DNA methyltransferase mRNA, Reelin gene methylation, and Reelin protein expression in the hippocampal CA1 were measured. Maternal deprivation enhanced contextual fear memory in adulthood. Meanwhile, maternal deprivation decreased DNA methyltransferase mRNA and Reelin gene methylation in the hippocampal CA1 on postnatal days 22 and 90. Reelin protein expression was increased in the hippocampal CA1 following contextual fear conditioning in adulthood. Furthermore, compared with rats that experienced maternal deprivation alone, rats also exposed to contextual fear conditioning showed an enhanced induction of hippocampal long-term potentiation and increased dendritic spine density in the hippocampal CA1 following contextual fear conditioning in adulthood. Zebularine pretreatment led to an enhancement of contextual fear memory, hypomethylation of the Reelin gene, and increased Reelin protein expression in adult rats, while L-methionine had the opposite effects. Maternal deprivation can epigenetically program second-hit stress-induced Reelin expression and enhance the susceptibility to contextual fear memory in adulthood. These findings provide a new framework for understanding the cumulative stress hypothesis.

Aims: We aimed to explore whether RELN contributes to the vulnerability and severity of clinical symptoms of schizophrenia (SZ) in a Chinese population. Methods: The following were conducted in an adult Han Chinese population from southern China: case–control association analyses of 30 representative single nucleotide polymorphisms (SNPs) that were screened according to specific programs based on bioinformatics tools and former research and quantitative trait locus analyses with SNPs and psychiatric symptoms evaluated with the positive and negative symptoms scale. Results: A 4-SNP haplotype consisting of rs362814, rs39339, rs540058, and rs661575 was found to be significantly associated with SZ even after Bonferroni correction (χ² = 29.024, p = 6.42E-04, p_Bonf = 0.017), and the T-C-T-C haplotype was a protective factor for SZ (OR = 0.050, 95% CI = 0.004–0.705). Moreover, the 4-SNP haplotype showed a significant association with G16 (active social avoidance) after false discovery rate correction (χ² = 28.620, p = 1.697E-04, p_FDR = 0.025). In addition, P7 (hostility) was related to the haplotype comprising rs2229864, rs2535764, and rs262355 (χ² = 31.424, p = 2.103E-05, p_adjustment = 0.019) in quantitative trait loci analyses. Conclusion: Overall, this study showed several positive associations between RELN and SZ, as well as psychiatric symptoms, which not only supports the proposition that RELN is a susceptibility gene for SZ but also provides information on a genotype-phenotype correlation for SZ in a Chinese population.

Objective: This study examined the prevalence of posttraumatic stress disorder (PTSD) symptoms in college students 1 month after the lockdown of Wuhan to identify possible risk factors for PTSD symptoms in a cross-sectional study.Methods: Out of 10,502 who responded, 9,274 students impacted by the COVID-19 pandemic were included in our study. PTSD symptoms was evaluated by the Impact of Event Scale-revised (IES-R). Anxiety/depression symptoms were evaluated by the Kessler Psychological Distress Scale (K10). Personality traits, coping style, and social support were assessed by the Eysenck Personality Questionnaire-Revised Short Scale for Chinese (EPQ-RSC), the Simplified Coping Style Questionnaire (SCSQ), and the Social Support Rating Scale (SSRS). Logistic regression analysis was utilized to further explore risk factors for PTSD symptoms.Results: More than 1 month after the COVID-19 outbreak, 13.1% of college students developed PTSD symptoms, indicating that COVID-19 associated stressful experiences were connected with PTSD symptoms. After the COVID-19 outbreak, subjects with symptomatologic PTSD symptoms were more likely to experience strained relationships with their family, to have close contact with COVID-19 patients and to drop out of college. The logistic regression model demonstrated the association factors of PTSD symptoms. Neuroticism, psychoticism and an avoidant coping style were associated with increased risk for PTSD symptoms, while an active coping style was protective against PTSD symptoms during this pandemic.Conclusion: The results showed that PTSD symptoms was prevalent in Chinese college students 1 month after the COVID-19 outbreak. Effective psychological support work should be carried out accordingly.