Immune dysregulation is associated with symptom dimensions and cognitive deficits in schizophrenia: accessible evidence from complete blood count.

BACKGROUND: Schizophrenia (SCZ) is a psychotic disorder with an unknown pathogenesis accompanied by varying degrees of cognitive deficits. Recent studies have shown that immune dysregulation plays an important role in developing symptoms and cognitive deficits in SCZ. This study aimed to determine the complete blood count (CBC), including white blood cells, neutrophils, monocytes, lymphocytes, platelets, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR), in patients with SCZ and explore their correlations with SCZ symptom dimensions and cognitive function. METHODS: Seventy-four patients with SCZ and 57 age- and sex-matched healthy controls with available demographic and clinical information were recruited for this study. Blood samples were collected, and symptom dimensions and cognitive function were evaluated using the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) separately. RESULTS: Our results demonstrate that SCZ patients showed higher monocyte counts, PLR, MLR, and worse performance in the total MCCB than healthy controls. Neutrophil and lymphocyte counts and NLR were positively related to symptom severity and negatively related to depressive symptoms. White blood cell (WBC) count, monocyte count, and MLR were positively correlated with cognitive performance in patients with SCZ. CONCLUSION: In summary, this study suggests that cognitive deficits and symptom severity in patients were associated with dysregulation of immunity. Moreover, we found that WBC could be used as a marker for symptom severity and cognitive deficits in SCZ and that neutrophils are more closely related to the former and monocytes to the latter. We hope that clinicians will pay more attention to dysregulated immunity in patients with SCZ in the future.

The bidirectional association between the disability in activities of daily living and depression: a longitudinal study in Chinese middle-aged and older adults.

AIM: Depression and disability in activities of daily living (ADL) are common in middle-aged and older adults. This study investigated the bidirectional relationship between depression and disability in ADL in Chinese middle-aged and older adults. METHODS: Data from a baseline study of 17,596 participants from the China Health and Retirement Longitudinal Study (CHARLS) and two follow-up visits at 4 and 7 years were included. We designed Study A and Study B to explore the interaction between depression and disability in ADL in middle-aged and older people. RESULTS: Individuals with disability in ADL at baseline had adjusted odds ratios (ORs) of 1.331 (1.118, 1.584) and 1.969 (1.585, 2.448) for developing depression compared with those without disability in ADL at the 4- and 7-year follow-ups, respectively. Individuals with depression at baseline had adjusted ORs of 1.353 (1.127, 1.625) and 1.347 (1.130, 1.604), respectively, for developing disability in ADL 4 and 7 years later. CONCLUSIONS: There was a bidirectional relationship between depression and disability in ADL. Depression increased the risk of disability in ADL, but this risk did not increase with time, whereas the effect of disability in ADL on depression increased with time.

Systems biological assessment of altered cytokine responses to bacteria and fungi reveals impaired immune functionality in schizophrenia.

Evidence suggests that complex interactions between the immune system and brain have important etiological and therapeutic implications in schizophrenia. However, the detailed cellular and molecular basis of immune dysfunction in schizophrenia remains poorly characterized. To better understand the immune changes and molecular pathways, we systemically compared the cytokine responses of peripheral blood mononuclear cells (PBMCs) derived from patients with schizophrenia and controls against bacterial, fungal, and purified microbial ligands, and identified aberrant cytokine response patterns to various pathogens, as well as reduced cytokine production after stimulation with muramyl dipeptide (MDP) in schizophrenia. Subsequently, we performed single-cell RNA sequencing on unstimulated and stimulated PBMCs from patients and controls and revealed widespread suppression of antiviral and inflammatory programs as well as impaired chemokine/cytokine-receptor interaction networks in various immune cell subpopulations of schizophrenic patients after MDP stimulation. Moreover, serum MDP levels were elevated in these patients and correlated with the course of the disease, suggesting increased bacterial translocation along with disease progression. In vitro assays revealed that MDP pretreatment altered the functional response of normal PBMCs to its re-stimulation, which partially recapitulated the impaired immune function in schizophrenia. In conclusion, we delineated the molecular and cellular landscape of impaired immune function in schizophrenia, and proposed a mutual interplay between innate immune impairment, reduced pathogen clearance, increased MDP translocation along schizophrenia development, and blunted innate immune response. These findings provide new insights into the pathogenic mechanisms that drive systemic immune activation, neuroinflammation, and brain abnormalities in schizophrenia.

A comparison of clinical characteristics of psychiatric inpatients in three hospitals from Western China and America.

BACKGROUND: Different countries have differences in social and cultural context and health system, which may affect the clinical characteristics of psychiatric inpatients. This study was the first to compare cross-cultural differences in the clinical characteristics of psychiatric inpatients in three hospitals from Western China and America. METHODS: Overall, 905 and 1318 patients from three hospitals, one in America and two in Western China, respectively, were included. We used a standardised protocol and data collection procedure to record inpatients' sociodemographic and clinical characteristics. RESULTS: Significant differences were found between hospitals from the two countries. Positive symptoms were the main reason for admission in the Chinese hospitals, while reported suicide and self-injury symptoms more frequently led to hospital admission in America. Moreover, there were more inpatients with combined substance abuse in the American hospital (97.6% vs. 1.9%, P < 0.001). The length of stay (LOS) in America was generally shorter than in China (10.5 ± 11.9 vs. 20.7 ± 13.4, P < 0.001). The dosage of antipsychotic drugs used in the American hospital was higher than in China (275.1 ± 306.9 mg vs. 238.3 ± 212.5 mg, P = 0.002). Regression analysis showed that male sex, older age, retirees, being admitted because of physical symptoms, and using higher doses of antipsychotic drugs were significantly associated with longer hospitalisation in the American hospital (P < 0.05). Comparatively, patients who were divorced, experiencing suicidal ideation, admitted involuntarily, admitted because of physical, depression, or anxiety symptoms, and using higher doses of antipsychotic drugs had longer hospitalisation in Chinese hospitals (P < 0.05). CONCLUSION: Significant variations in clinical characteristics of inpatients were found between hospitals from Western China and America. The LOS in Chinese hospitals was significantly longer, but patients used higher doses of antipsychotic drugs in the American hospital. Admission due to physical symptoms and the use of higher dosage drugs were related to longer LOS in both countries.

Genetically Determined Levels of Serum Metabolites and Risk of Neuroticism: A Mendelian Randomization Study.

BACKGROUND: Neuroticism is a strong predictor for a variety of social and behavioral outcomes, but the etiology is still unknown. Our study aims to provide a comprehensive investigation of causal effects of serum metabolome phenotypes on risk of neuroticism using Mendelian randomization (MR) approaches. METHODS: Genetic associations with 486 metabolic traits were utilized as exposures, and data from a large genome-wide association study of neuroticism were selected as outcome. For MR analysis, we used the standard inverse-variance weighted (IVW) method for primary MR analysis and 3 additional MR methods (MR-Egger, weighted median, and MR pleiotropy residual sum and outlier) for sensitivity analyses. RESULTS: Our study identified 31 metabolites that might have causal effects on neuroticism. Of the 31 metabolites, uric acid and paraxanthine showed robustly significant association with neuroticism in all MR methods. Using single nucleotide polymorphisms as instrumental variables, a 1-SD increase in uric acid was associated with approximately 30% lower risk of neuroticism (OR: 0.77; 95% CI: 0.62-0.95; PIVW = 0.0145), whereas a 1-SD increase in paraxanthine was associated with a 7% higher risk of neuroticism (OR: 1.07; 95% CI: 1.01-1.12; PIVW = .0145). DISCUSSION: Our study suggested an increased level of uric acid was associated with lower risk of neuroticism, whereas paraxanthine showed the contrary effect. Our study provided novel insight by combining metabolomics with genomics to help understand the pathogenesis of neuroticism.

Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial.

BACKGROUND: This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment. METHODS: This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18-60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization. RESULTS: A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects. CONCLUSIONS: After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.

Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice.

Accumulating evidence suggests that gut microbiota plays a role in the pathogenesis of schizophrenia via the microbiota-gut-brain axis. This study sought to investigate whether transplantation of fecal microbiota from drug-free patients with schizophrenia into specific pathogen-free mice could cause schizophrenia-like behavioral abnormalities. The results revealed that transplantation of fecal microbiota from schizophrenic patients into antibiotic-treated mice caused behavioral abnormalities such as psychomotor hyperactivity, impaired learning and memory in the recipient animals. These mice also showed elevation of the kynurenine-kynurenic acid pathway of tryptophan degradation in both periphery and brain, as well as increased basal extracellular dopamine in prefrontal cortex and 5-hydroxytryptamine in hippocampus, compared with their counterparts receiving feces from healthy controls. Furthermore, colonic luminal filtrates from the mice transplanted with patients' fecal microbiota increased both kynurenic acid synthesis and kynurenine aminotransferase II activity in cultured hepatocytes and forebrain cortical slices. Sixty species of donor-derived bacteria showed significant difference between the mice colonized with the patients' and the controls' fecal microbiota, highlighting 78 differentially enriched functional modules including tryptophan biosynthesis function. In conclusion, our study suggests that the abnormalities in the composition of gut microbiota contribute to the pathogenesis of schizophrenia partially through the manipulation of tryptophan-kynurenine metabolism.

LncRNA TUG1 acts as a competing endogenous RNA to mediate CTGF expression by sponging miR-133b in myocardial fibrosis after myocardial infarction.

Myocardial fibrosis (MF) is one of the basic causes of many cardiovascular diseases. Noncoding RNAs (ncRNAs), including microRNA (miRNA) and long noncoding RNA (lncRNA), have been reported to play an indispensable role in MF. The current work is focused on investigating the biological role of lncRNA taurine upregulation gene 1 (TUG1) in activating cardiac myofibroblasts as well as the underlying mechanism. The outcome revealed that after myocardial infarction TUG1 expression increased and miR-133b expression decreased in the rat model of MF. The expression level of TUG1 increased following AngII treatment in cardiac myofibroblast. TUG1 knockdown inhibited the Ang-II induced cardiac myofibroblast activation and TUG1 overexpression increased proliferation and collagen generation of cardiac myofibroblasts. Bioinformatic prediction programs predicted that TUG1 had MRE directly combined with miR-133b seed sequence, luciferase activity, and RIP experiments indicated that TUG1, acted as a sponger and interacted with miR-133b in cardiac myofibroblasts. Furthermore, a target of miR-133b was CTGF and CTGF knockdown counteracted the promotion of MF by miR-133b knockdown. Collectively, our study suggested that TUG1 mediates CTGF expression by sponging miR-133b in the activation of cardiac myofibroblasts. The current work reveals a unique role of the TUG1/miR-133b/CTGF axis in MF, thus suggesting its immense therapeutic potential in the treatment of cardiac diseases.

Duration of Viral Shedding of Discharged Patients With Severe COVID-19.

COVID-19 has drawn global intensive attention. We analyzed the duration of viral shedding and the total time from illness onset to discharge in groups. This has important implications for making decisions for isolation of discharged patients and to provide guidance for the duration of hospitalization of patients with severe COVID-19.

Venous thrombosis and arteriosclerosis obliterans of lower extremities in a very severe patient with 2019 novel coronavirus disease: a case report.

The outbreak of 2019 novel coronavirus disease (COVID-19) began since early December 2019, and has been declared as a public health emergency by the World Health Organization. Due to the hypercoagulable state, blood stasis and endothelial injury, severe patients with COVID-19 are at high risk for thrombosis. We report a case of very severe COVID-19 complicated with venous thrombosis and arteriosclerosis obliterans of lower extremities. Risk stratification for deep vein thrombosis and peripheral arterial disease are of vital importance for the prognosis of COVID-19.

Integrative analysis of genome-wide association study and chromosomal enhancer maps identified brain region related pathways associated with ADHD.

Attention deficit/hyperactivity disorder (ADHD) is among the most common childhood onset psychiatric behavioral disorders, and the pathogenesis of ADHD is still unclear. Utilizing the latest genome wide association studies (GWAS) data and enhancer map, we explored the brain region related biological pathways associated with ADHD. The GWAS summary data of ADHD was driven from a published study, involving 20,183 ADHD cases and 35,191 healthy controls. The brain-related enhancer map was collected from ENCODE and Roadmap Epigenomics (ENCODE + Roadmap) including 489,581 enhancers. Firstly, the chromosomal enhancer maps of four brain regions were aligned with the ADHD GWAS summary data in order to obtain enhancer SNPs. Then the significant enhancers SNPs were subjected to the gene set enrichment analysis (GSEA) for identifying ADHD associated gene sets. A total of 866 pathways and 4 brain tissues were analyzed in this study. We detected several candidate genes for ADHD, such as AHI1, ALG2 and DNM1. We also detected several candidate biological pathways associated with ADHD, such as Reactome SEMA4D in semaphorin signaling and Reactome NCAM1 interactions. Our findings may provide a novel insight into the complex genetic mechanism of ADHD.

Standardized Treatment Strategy for Depressive Disorder.

The treatment strategies of depressive disorder include pharmacological treatment, psychotherapy, and physical therapy (electroconvulsive therapy [ECT], transcranial magnetic stimulation [TMS], etc.). The updated CANMAT guidelines recommended the most second-generation antidepressants as first-line treatments for patients with a major depressive disorder (MDD) of moderate or greater severity. Before antidepressant treatment, comprehensive assessment and safety monitoring are necessary. The application of measurement-based care in the diagnosis and treatment of depression would better ensure that enough dosage and response of antidepressant is achieved at each key point, and the final outcome of disease is improved. It is recommended that antidepressant is used with monotherapy in patients with depression. Antidepressants of different types and different mechanisms could be combined to improve the efficacy for patients with treatment-resistant depression (TRD). To prevent the relapse and recurrence of disease, the long-term treatment comprised of acute treatment, consolidation treatment, and maintenance treatment must be considered for all patients.

Macrocytic anemia is associated with the severity of liver impairment in patients with hepatitis B virus-related decompensated cirrhosis: a retrospective cross-sectional study.

BACKGROUND: Macrocytic anemia is common in liver disease. However, its role in hepatitis B virus (HBV)-related decompensated cirrhosis remains unknown. The aim of the present study was to determine the association between macrocytic anemia and the severity of liver impairment in patients with HBV-related decompensated cirrhosis according to the Model for End Stage Liver Disease (MELD) score. METHODS: A total of 463 participants who fulfilled our criteria were enrolled in this cross-sectional study. Patients were classified into three groups according to anemia types, diagnosed based on their mean corpuscular volume level. Multivariate linear regression analyses were used to determine the association between macrocytic anemia and the MELD score for patients with HBV-related decompensated cirrhosis. RESULTS: Patients with macrocytic anemia had evidently higher MELD scores (10.8 ± 6.6) than those with normocytic anemia (8.0 ± 5.5) or microcytic anemia (6.3 ± 5.1). The association remained robust after adjusting for age, gender, smoking, drinking, and total cholesterol (ß = 1.94, CI: 0.81-3.07, P < 0.001). CONCLUSIONS: Macrocytic anemia was found to be associated with the severity of liver impairment and might be a predictor for short-term mortality in patients with HBV-related decompensated cirrhosis.

The relationship between maternal anxiety and cortisol during pregnancy and birth weight of chinese neonates.

BACKGROUND: To determine the relationship between maternal anxiety and cortisol values and birth weight at various stages of pregnancy. METHODS: Two hundred sixteen pregnant Chinese women were assessed for anxiety and depression and had measurement of morning fasting serum cortisol. Women were assessed either in the first (71), second (72) or third (73) trimester. Birth weights of all children were recorded. RESULTS: There were significant negative correlations between anxiety level and birth weight of - 0.507 (p < 0.01) and - 0.275 (p < 0.05) in trimesters 1and 2. In trimester 3 the negative relation between anxiety and birth weight of -.209 failed to reach significance (p = 0.070). There was no relation between depression and birth weight in any trimester (p > 0.5 for all). Maternal cortisol was significantly inversely related to birth weight in trimester 1 (r = - 0.322) and with borderline significance in trimester 2 (r = - 0.229). Anxiety score and maternal cortisol were significantly correlated in each trimester (r = 0.551, 0.650, 0.537). When both anxiety score and maternal cortisol were simultaneously included in multiple regression analyses only anxiety score remained significant. CONCLUSION: Whilst both maternal anxiety score and maternal cortisol are inversely related to birth weight the associations with anxiety score were more robust perhaps indicating the importance of mechanisms other than, or in addition to, maternal cortisol in mediating the effects of anxiety. The findings indicate the importance of measures to reduce maternal anxiety, particularly of a severe degree, at all stages of pregnancy. TRIAL REGISTRATION: The study was approved by the Ethics Committee of the 1st Affiliated Hospital of Xi'an Jiaotong University.

Methylation of glucocorticoid receptor gene promoter modulates morphine dependence and accompanied hypothalamus-pituitary-adrenal axis dysfunction.

Previous studies demonstrated that dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis played an important role in morphine dependence. Nonetheless, the molecular mechanism underlying morphine-induced HPA axis dysfunction and morphine dependence remains unclear. In the current study, 5'-aza-2'-deoxycytidine (5-aza), an inhibitor of DNA methyltransferases (DNMTs), was used to examine the effects of glucocorticoid receptor (GR) promoter 17 methylation on chronic morphine-induced HPA axis dysfunction and behavioral changes in rats and the underlying mechanism. Our results showed that chronic but not acute morphine downregulated the expression of nuclear GR protein and GR exon 17 variant mRNA, and upregulated the methylation of GR 17 exon promoter in the hippocampus of rats. Meanwhile, 5-aza per se had no effect on observed molecular and behavior change. In contrast, pretreatment of 5-aza into rat hippocampus reversed chronic morphine-induced hypermethylation of GR 17 promoter and decrease in GR expression. Moreover, pretreatment of 5-aza attenuated chronic morphine-enhanced HPA axis reactivity and the naloxone-precipitated somatic signs in morphine-dependent rats. Our results suggest that chronic morphine induced hypermethylation of GR 17 promoter, which then downregulated the expression of hippocampal GR, and was thus involved in chronic morphine-induced dysfunction of the HPA axis and the modulation of morphine dependence. Moreover, chronic morphine-induced hypermethylation of GR 17 promoter may be at least partially due to the increase in hippocampal DNMT 1 expression and its binding at GR 17 promoter in the rat hippocampus. © 2016 Wiley Periodicals, Inc.

Meta-analysis of effects of ABCB1 polymorphisms on clopidogrel response among patients with coronary artery disease.

PURPOSE: The substantial variability in the antiplatelet efficacy of clopidogrel has raised major concerns. Molecular epidemiological research suggests that ABCB1 C3435T polymorphism may be associated with clopidogrel response, but results remain controversial. To derive a more precise evaluation of the associations between ABCB1 C3435T polymorphism and the clinical efficacy of clopidogrel, we have conducted a PRISMA-compliant meta-analysis. METHODS: The PubMed and EMBASE databases were searched for eligible studies up to 25 October 2016. The odds ratio (OR), the standard mean difference (SMD) and 95% confidence interval (CI) were applied to assess the strength of the relationship. RESULTS: Overall, 28 related studies involving 23,243 patients were analyzed. No association was found between the ABCB1 polymorphisms and the primary outcome. In the subgroup analysis, the C3435T mutation significantly reduced platelet activity as tested by the LTA assay in the dominant (SMD -0.140, 95% CI -0.272 to -0.009, P = 0.036) and heterozygous (SMD -0.154, 95% CI -0.290 to -0.017, P = 0.027) models, but the result lacked robustness in the sensitivity analysis. A significant association between the C3435T polymorphism and bleeding risk was also observed with low heterogeneity in the dominant (OR 1.805, 95% CI1.124-2.900, P =0.015, I 2 = 0%), homozygous (OR 1.952, 95% CI 1.055-3.611, P = 0.033, I 2 = 13.2%) and heterozygous (OR 1.793, 95% CI 1.091-2.946, P = 0.021, I 2 = 0%) models in Asian patients. CONCLUSIONS: The results of the meta-analysis suggest that ABCB1 C3435T polymorphism may increase the risk of bleeding in Asian patients treated with clopidogrel. The implied relationship needs to be verified in future basic genetic pharmacology studies.

Effect of Hypokalemia on Functional Outcome at 3 Months Post-Stroke Among First-Ever Acute Ischemic Stroke Patients.

BACKGROUND Hypokalemia has been confirmed to be a predictor of adverse cardiovascular and renal outcomes. There is a paucity of studies focusing on the potential connection between the serum K+ level and the outcome after acute ischemic stroke (AIS). This study investigated whether hypokalemia in the acute stroke stage contributes to worse functional outcome in AIS patients. MATERIAL AND METHODS This retrospective cohort study included consecutive patients with first-ever AIS admitted between June 2015 and March 2016. Patients were divided into 2 groups: hypokalemia (K+ <3.5 mmol/L) and normokalemia (3.5 mmol/L ≤K+ ≤5.5 mmol/L). Primary outcome measure was poor outcome at 3 months (modified Rankin scale >2). Univariate and multivariate logistic regression analyses were used to assess the association between hypokalemia and poor outcome. Receiver operating curve (ROC) analysis was performed to determine the optimal cutoff point of serum K+ level for predicting poor outcome. RESULTS The percent of patients with poor outcome at 3 months was higher in the hypokalemic group (62.9%) than in the normokalemic group (45.5%). Hypokalemic patients tended to have lower fasting glucose at admission, lower Glasgow coma scale score, and longer time from symptom onset to treatment compared with normokalemic patients. Hypokalemia was associated with poor outcome at 3 months after adjusting for potential confounders (odds ratio=2.42, 95% confidence interval=1.21-4.86, P=0.013). ROC analysis showed that the optimal threshold for serum K+ level was 3.7 mmol/L. CONCLUSIONS Hypokalemia at the initial admission is associated with poor prognosis at 3 months in first-ever AIS patients.

HINT1 in Neuropsychiatric Diseases: A Potential Neuroplastic Mediator.

Although many studies have investigated the functions of histidine triad nucleotide-binding protein 1 (HINT1), its roles in neurobiological processes remain to be fully elucidated. As a member of the histidine triad (HIT) enzyme superfamily, HINT1 is distributed in almost every organ and has both enzymatic and nonenzymatic activity. Accumulating clinical and preclinical evidence suggests that HINT1 may play an important role as a neuroplastic mediator in neuropsychiatric diseases, such as schizophrenia, inherited peripheral neuropathies, mood disorders, and drug addiction. Though our knowledge of HINT1 is limited, it is believed that further research on the neuropathological functions of HINT1 would eventually benefit patients with neuropsychiatric and even psychosomatic diseases.

Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect.

The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment.

Effects of Maternal Cortisol during Pregnancy on Children's Blood Pressure Responses.

BACKGROUND: It is well established that birth weight has an effect on subsequent blood pressure. Predominantly experimental studies have also reported effects of altered corticosteroid levels on subsequent cardiovascular responses. In the current study, we have examined the effects of both birth weight and maternal cortisol levels in a cohort of mothers and their pre-adolescent children. PROCEDURE: A total of 216 women and their 7- to 9-year-old children comprised the cohort. The women had been assessed for plasma cortisol during the first (n = 71), second (n = 72) and third (n = 73) trimester. Maternal cortisol had been measured on a fasting sample taken between 9 and 11 a.m. The children's blood pressure and heart rate were recorded in the resting state, in response to a 10-min video game stress challenge and during recovery. Resting values, incremental responses to stress and recovery were evaluated. OBSERVATION: Maternal cortisol levels increased with duration of pregnancy. There were inverse correlations between birth weight and all haemodynamic measures. The positive associations between maternal cortisol and children's haemodynamic measures were most evident in the first and second trimesters. Birth weight was inversely related to maternal cortisol. In multiple regression analyses, the effects of maternal cortisol were more consistent than those of birth weight. CONCLUSION: Both birth weight and maternal cortisol are predictive of children's resting and stress-modulated haemodynamic measures. The effects of birth weight may partly mediate the effects of maternal cortisol.