Objective:To investigate the effects of chronic stress during pregnancy on depressive behavior and DNA methylation of insulin-like growth factor-2 ( IGF-2 )/long non-coding RNA ( lncRNA ) H19 in hippocampus of female offspring rats.Methods:A total of 32 SPF female SD rats were divided into model group and control group according to the random number table. The rats in the model group were treated with chronic unpredictable mild stress (CUMS) to establish the depression model, and the rats in the control group were fed normally.On the 7th day of stress stimulation, all female rats mated with male rats. One day before stress stimulation and 1, 7, 14, 21, 28 days after stress stimulation, blood samples were collected from the inner canthus vein of the rats to determine the plasma corticosterone concentration. Eight female pups were randomly selected from each group on postnatal day 28(PND28) and postnatal day 42 (PND42). Plasma corticosterone concentration was measured after angular vein blood collection. At PND42, the depression-like behavior of female pups in the two groups was measured by sucrose preference test, tail suspension test and forced swimming test. The expression of IGF-2/H19 and related transferases in hippocampus of offspring rats was detected by RT-PCR and Western blot. Methyl target technology was used to capture and sequence 19 CpG sites of IGF-2 differentially methylated region(DMR) fragment 2, 8 CpG sites in H19 imprinting control region (ICR) fragment 1 and 15 CpG sites in H19-ICR fragment 2, and calculate the methylation level of each CpG site. SPSS 26.0 was used for statistical analysis of relevant data by repeated measurement ANOVA, t test and non-parametric test. Results:(1) The data of plasma corticosterone content of the two groups of female rats at different times were analyzed by repeated measurement variance.The results showed that the the interaction effect between time and group was not significant ( F=2.997, P=0.066), and the main effect of time was significant ( F=4.44, P=0.010). The main effect of group was significant ( F=41.40, P=0.001). According to the independent effect analysis of factors between groups, on the 14th, 21st, and 28th days of stress, the plasma corticosterone concentration of the model group was higher than that of the control group (all P<0.001). (2) In the sucrose preference test, the total liquid consumption (11.10(10.38, 11.58) mL, 13.55(12.00, 15.77) mL, Z=-3.055, P=0.002), 1% sucrose water consumption ((5.50±1.30) mL, (8.56±2.04) mL, t=-3.582, P=0.003) and 1% sucrose preference percentage ( (51.35±8.69) %, (62.11±8.05) %, t=-2.576, P=0.022) of female pups in the model group were significantly lower than those in the control group. (3) The duration of immobility in tail suspension test ((126.95±39.89) s, (54.30±25.00) s, t=4.375, P=0.001) and forced swimming test ((7.97±6.66) s, (1.85±2.12) s, t=2.478, P=0.037) of female offspring in the model group were longer than those in the control group. (4) The expression of IGF-2 mRNA ((0.46±0.24), (1.00±0.00), t=3.821, P=0.019) and H19 mRNA ((0.60±0.25), (1.00±0.00), t=3.574, P=0.007) in hippocampus of female pups in the model group were lower than those of control group. The relative expression of IGF-2 protein in female offspring of model group was lower than that in control group ((0.77±0.04), (1.00±0.00), t=9.876, P=0.01). The relative expression of CCTC-binding factor (CTCF) mRNA ((1.29±0.12), (1.00±0.00), t=-4.850, P=0.003) and protein ((1.90±0.28), (1.00±0.00), t=-5.513, P=0.005) were higher than those in the control group. (5) The methylation levels of three CpG sites in the IGF-2 DMR region of female offspring in the model group were lower than those in the control group ( t=-3.21, -3.00, -3.34, all P<0.05), located at chr1215831028, chr1215831055 and chr1215831205, respectively. The methylation level of IGF-2 DMR fragment was lower than that of the control group ( t=-3.453, P=0.048). The relative expression levels of DNMT3A mRNA ( t=5.102, P=0.002), DNMT3A ( t=10.213, P<0.001) and DNMT3B ( t=4.169, P=0.014) in female offspring of the model group were lower than those in the control group. Conclusion:Chronic stress during pregnancy causes depression and despair in female offspring mice, and the mechanism may be related to the decrease of methylation level of imprinted gene IGF-2 DMR caused by the decrease of methyltransferase expression.

Antipsychotic medications are commonly used to treat schizophrenia,but they can have negative effects on lipid metabolism,leading to an increased risk of cardiovascular diseases,reduced life expectancy,and difficulties with treatment adherence.The specific mechanisms by which antipsychotics disrupt lipid metabolism are not well understood.Sterol regulatory element-binding proteins(SREBPs)are important transcriptional factors that regulate lipid metabolism.Proprotein convertase subtilisin/kexin type 9(PCSK9),a gene regulated by SREBPs,plays a critical role in controlling levels of low-density lipoprotein cholesterol(LDL-C)and has become a focus of research on lipid-lowering drugs.Recent studies have shown that antipsychotic drugs can affect lipid metabolism through the SREBP/PCSK9 pathway.A deep understanding of the mechanism for this pathway in antipsychotic drug-related metabolic abnormalities will promote the prevention of lipid metabolism disorders in patients with schizophrenia and the development and application of new drugs.

Mitochondria are the main site of energy metabolism within cells,generating a substantial amount of ATP to supply energy to the human body.Research has shown that alterations in mitochondrial structure and function exist in individuals with schizophrenia,suggesting their potential impact on the onset of psychiatric disorders and clinical treatment efficacy.Therefore,understanding the research progress on the genetic mechanisms,pathological processes,image manifestations of schizophrenia and mitochondrial quality control,and summarizing the relevant evidence of mitochondrial-related targets as potential therapeutic targets for schizophrenia,can provide references for further research.

Schizophrenia is a common chronic mental disorder.Cognitive dysfunction is one of its core symptoms,which severely affects the social functioning of patients.Currently,antipsychotic medication treatments have poor efficacy in improving cognitive functions.Recent studies have found that metformin can improve cognitive dysfunction in patients with schizophrenia.However,the mechanism of action remains unclear.This review summarizes the therapeutic effects of metformin on cognitive dysfunction in schizophrenia patients such as improving insulin resistance,repairing neuronal damage,regulating neuroimmunity,and combating oxidative stress,thereby providing new insights for the treatment of cognitive dysfunction in schizophrenia.

Background Pregnancy-related anxiety has a negative impact on the physical and mental health of pregnant women and the normal growth and development of the fetus. Establishing prediction models for pregnancy-related anxiety to screen associated predictive factors may provide important opportunities for prenatal intervention. Objective To establish a prediction model of pregnancy-related anxiety risk of pregnant women. Methods From January to July 2021, a questionnaire survey on pregnancy-related anxiety and predictors was conducted among pregnant women having routine prenatal check-ups provided by an obstetrics clinic of a tertiary grade A hospital in Ningxia. The socio-demographic characteristics of the subjects were collected, and the pregnant women were evaluated by the Life Event Scale (LES), Perceived Social Support Scale (PSSS), Family APGAR Index (APGAR), and Pregnancy-related Anxiety Questionnaire (PAQ). R 4.2.0 software was used to fit all selected variables by least absolute shrinkage and selection operator (LASSO) regression to identify predictors of pregnancy-related anxiety in the second and third trimesters. On the basis of logistic regression analysis, prediction models of pregnancy-related anxiety in the second and third trimesters were constructed, and the model nomogram and receiver operating characteristic curve (ROC) were drawn. The prediction effect of the model was evaluated by area under the curve (AUC). A calibration chart was drawn to evaluate the calibration of the model. Results A total of 1500 questionnaires were distributed, and 1448 valid questionnaires were recovered, with an effective rate of 96.53%. Among the 1448 pregnant women, the overall positive rate of pregnancy-related anxiety was 28.80% (417/1448), and the positive rates in the second and third trimesters were 29.21% (276/935) and 27.49% (141/513), respectively. The predictors entering the the second trimester model were age of marriage, family care, social support, family expectations for the fetus, physical condition during pregnancy, and whether experiencing life stressful events during pregnancy. The predictors entering the the third trimester model were pregnancy intention, physical discomfort, and whether experiencing life stress during pregnancy. A risk prediction model of pregnancy-related anxiety for the second trimester was established: risk of pregnancy-related anxiety=−0.07× marriage age +0.12× family care −0.03× social support −0.65× family expectation of fetal sex +0.42× physical condition during pregnancy +0.47× whether experiencing life stressful events during pregnancy. A risk prediction model of pregnancy-related anxiety for the third trimester was established: risk of pregnancy-related anxiety=−5.69+0.82× pregnancy intention +1.06× physical discomfort +0.94× whether experiencing life stressful events during pregnancy. The ROC curves of the two models were drawn. The AUC of the second trimester model was 0.71, and the AUC of related validation model was 0.68. The AUC of the third trimester model was 0.72, and the AUC of related validation model was 0.66. Conclusion The risk prediction models of pregnancy-related anxiety constructed based on LASSO regression and logistic regression have good prediction ability, and they suggest that pregnant women in the second trimester with short marriage age, high family care, low social support, family expectations for fetal sex, average physical condition, and experiencing life stress during pregnancy, and pregnant women in the third trimester with spontaneous pregnant intention, unintended pregnancy, physical discomfort, and experiencing life stress during pregnancy are high-risk groups for pregnancy-related anxiety.