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Abstract Background Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS). Methods The plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC). Results The plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels. Conclusions These results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia.

ObjectiveThis study aims to analyze the lipid metabolism patterns and identify risk factors for dyslipidemia in Wilson’s Disease (WD), offering novel insights into diagnosis and treatment strategies for unexplained dyslipidemia.MethodsData from Wilson’s disease patients hospitalized at the First People’s Hospital of Shanghai from December 2008 to February 2015 were collected. Patients were categorized into normal lipid (46 cases) and dyslipidemia (42 cases) groups based on lipid levels. Group analyzes were conducted using t-tests, chi-square analysis, and rank sum tests. Spearman correlation, multiple linear regression, or Logistic regression were employed to identify relevant influencing factors.Results1. The incidence of abnormal blood lipids in a series of Wilson’s disease patients was 47.73% (25.12 ± 1.29 years old), and the incidence of control healthy group was 27.40%, with proportions of hypercholesterolemia, hypertriglyceridemia, and low-density lipoprotein cholesterol being 14.77, 30.68, and 29.63%, respectively; 2. Significant differences were observed between the dyslipidemia and normal WD groups in AST/ALT ratio, liver parenchymal echo, liver surface, spleen area, and ultrasound total score.3. Low-and high-density lipoprotein cholesterols (LDL-c and HDL-c) showed no significant correlation with these indicators. Triglyceride (TG) exhibited moderately negative correlation with AST/ALT, liver parenchymal echo, spleen area, and ultrasound score. Total cholesterol (TC) displayed low negative correlation with these factors.Conclusion1. Dyslipidemia incidence in Wilson’s disease patients may exceed that of the normal population, especially in adolescents with unexplained abnormal lipid metabolism; 2. Patients with mild to moderate liver damage are predisposed to elevated triglycerides and total cholesterol, reflecting liver damage impact on lipid metabolism; 3. Glucose metabolism is not implicated in WD-related dyslipidemia; 4. No significant correlation was found between abnormal lipid metabolism and blood concentration of trace elements in WD patients.

ObjectivePrevious research indicates associations between cigarette smoking, insulin-like growth factor-1 (IGF1), and sleep disturbances. This study aimed to examine the association between smoking and sleep quality and investigate the moderating role of IGF1.MethodsThis case-control study involved 146 Chinese adult males (53 active smokers and 93 non-smokers) from September 2014 to January 2016. Sleep quality and disturbances were evaluated using the Pittsburgh Sleep Quality Index (PSQI), which includes seven scales. Pearson correlation analysis and logistic regression analysis were utilized to examine the link between IGF1 levels in cerebrospinal fluid (CSF) and PSQI scores. The effect of IGF1 was assessed using the moderation effect and simple slope analysis, with adjustments made for potential confounders.ResultsActive smokers exhibited significantly higher global PSQI scores and lower IGF1 levels in CSF compared to non-smokers. A significant negative correlation was observed between IGF1 and PSQI scores (â = -0.28, P < 0.001), with a stronger association in non-smokers (Pearson r = -0.30) compared to smokers (Pearson r = -0.01). Smoking was associated with higher global PSQI scores (â = 0.282, P < 0.001), and this association was moderated by IGF1 levels in CSF (â = 0.145, P < 0.05), with a stronger effect at high IGF1 levels (Bsimple = 0.402, p < 0.001) compared to low IGF1 levels (Bsimple = 0.112, p = 0.268). Four subgroup analysis revealed similar results for sleep disturbances (Bsimple = 0.628, P < 0.001), with a marginal moderation effect observed on subjective sleep quality (Bsimple = 0.150, P = 0.070). However, independent associations rather than moderating effects were observed between IGF1 and sleep efficiency and daytime disturbance.ConclusionWe provided evidence to demonstrate the moderation effect of IGF1 on the relationship between smoking and sleep in CSF among Chinese adult males.

BackgroundMany studies showed disrupted tryptophan metabolism in patients with affective disorders. The aims of this study were to explore the differences in the metabolites of tryptophan pathway (TP) and the relationships between TP metabolites and clinical symptoms, therapeutic effect in patients with bipolar disorder with acute manic episode (BD-M), depressive episode (BD-D) and major depressive disorder (MDD).MethodsPatients with BD-M (n=52) and BD-D (n=39), MDD (n=48) and healthy controls (HCs, n=49) were enrolled. The serum neuroactive metabolites levels of the TP were measured by liquid chromatography-tandem mass spectrometry. Hamilton Depression Scale-17 item (HAMD-17) and Young Mania Rating Scale (YMRS) were used to evaluate depressive and manic symptoms at baseline and after 8 weeks of antidepressants, mood stabilizers, some also received antipsychotic medication.ResultsThe levels of tryptophan (TRP) and kynurenic acid (KYNA) were significantly lower and the ratios of tryptophan/kynurenine (TRP/KYN), 5-hydroxytryptamine/tryptophan (5-HT/TRP), quinolinic acid/kynurenic acid (QUIN/KYNA) were higher in BD-M, BD-D, MDD vs. HC. The levels of QUIN and the ratios of QUIN/KYNA were higher in BD-M than in BD-D, MDD, and HCs. The 5-hydroxyindoleacetic acid (5-HIAA) levels of patients with MDD were significantly higher than those in BD-M and BD-D. Binary logistic regression analysis showed the lower peripheral KYNA, the higher the QUIN level, and the higher the risk of BD-M; the lower peripheral KYNA and the higher KYN/TRP and 5-HT/TRP, the higher the risk of BD-D; and the lower the peripheral KYNA level and the higher the KYN/TRP and 5-HT/TRP, the higher the risk of MDD. Correlation analysis, showing a significant association between tryptophan metabolites and improvement of clinical symptoms, especially depression symptoms.ConclusionsPatients with affective disorders had abnormal tryptophan metabolism, which involved in 5-HT and kynurenine pathway (KP) sub-pathway. Tryptophan metabolites might be potential biomarkers for affective disorders and some metabolites have been associated with remission of depressive symptoms.

Abstract Objective Schizophrenia is a serious mental disorder with complex clinical manifestations, while its pathophysiological mechanism is not fully understood. Accumulated evidence suggested the alteration in epigenetic pathway was associated with clinical features and brain dysfunctions in schizophrenia. DNA methyltransferases (DNMTs), a key enzyme for DNA methylation, are related to the development of schizophrenia, whereas the current research evidence is not sufficient. The aim of study was to explore the effects of gene polymorphisms of DNMTs on the susceptibility and symptoms of schizophrenia. Methods The study was case–control study that designed and employed the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) as the diagnostic standard. 134 hospitalized patients with schizophrenia in the Third People's Hospital of Zhongshan City from January 2018 to April 2020 (Case group) as well as 64 healthy controls (Control group) from the same region were involved. Single nucleotide polymorphisms (SNPs) of DNMT1 genes (r s2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) were determined with massARRAY. Linkage disequilibrium analysis and haplotype analysis were performed, and genotype and allele frequencies were compared. The Hardy–Weinberg equilibrium was tested by the Chi-square test in SPSS software (version 20.0, SPSS Inc., USA). The severity of clinical symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS). The correlation between DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs2424932, rs1569686, rs6119954 and rs2424908) and clinical features was analyzed. Results There were no significant differences in genotype, allele frequency and haplotype of DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) between the case and healthy control group. There were significant differences in the PANSS total positive symptom scores, P3 (hallucinatory behavior), P6 (suspicious/persecution), G7 (motor retardation), and G15 (preoccupation) in patients with different DNMT1 gene rs 2114724 and rs 2228611 genotypes. The linkage disequilibrium analysis of gene polymorphic loci revealed that rs 2114724–rs 2228611 was complete linkage disequilibrium, and rs 1569686–rs 2424908, rs 2424932–rs 1569696 and rs 2424932–rs 2424908 were strongly linkage disequilibrium. Conclusion The polymorphisms alteration in genetic pathway may be associated with development of specific clinical features in schizophrenia.

Abstract Introduction Cigarette smoking increases both the risk for insulin resistance and amyloid‐β (Aβ) aggregation, and impaired brain insulin/insulin‐like growth factor 1 (IGF1) signaling might increase risk factors for Alzheimer's disease (AD). We aimed to investigate the association among cerebrospinal fluid (CSF) insulin sensitivity/IGF1, glucose/lactate, and Aβ42 and further explore whether insulin sensitivity contributed to the risk for AD in active smokers. Methods In this cross‐sectional study, levels of insulin, IGF1, and lactate/glucose of 75 active smokers and 78 nonsmokers in CSF were measured. Three polymorphisms regulating IGF1 were genotyped. Analysis of variance was used to compare differences of variables between groups. Partial correlation was performed to test the relationship between CSF biomarkers and smoking status. General linear models were applied to test the interaction of the effect of single nucleotide polymorphisms and cigarette smoking on CSF IGF1 levels. Results In the CSF from active smokers, IGF1 and lactate levels were significantly lower (p = .016 and p = .010, respectively), whereas Aβ42 (derived from our earlier research) and insulin levels were significantly higher (p

Abstract Cortical and subcortical structural alteration has been extensively reported in schizophrenia, including the unusual expansion of gray matter volumes (GMVs) of basal ganglia (BG), especially putamen. Previous genome-wide association studies pinpointed kinectin 1 gene (KTN1) as the most significant gene regulating the GMV of putamen. In this study, the role of KTN1 variants in risk and pathogenesis of schizophrenia was explored. A dense set of SNPs (n = 849) covering entire KTN1 was analyzed in three independent European- or African-American samples (n = 6704) and one mixed European and Asian Psychiatric Genomics Consortium sample (n = 56,418 cases vs. 78,818 controls), to identify replicable SNP-schizophrenia associations. The regulatory effects of schizophrenia-associated variants on the KTN1 mRNA expression in 16 cortical or subcortical regions in two European cohorts (n = 138 and 210, respectively), the total intracranial volume (ICV) in 46 European cohorts (n = 18,713), the GMVs of seven subcortical structures in 50 European cohorts (n = 38,258), and the surface areas (SA) and thickness (TH) of whole cortex and 34 cortical regions in 50 European cohorts (n = 33,992) and eight non-European cohorts (n = 2944) were carefully explored. We found that across entire KTN1, only 26 SNPs within the same block (r2 > 0.85) were associated with schizophrenia across ≥ 2 independent samples (7.5 × 10–5 ≤ p ≤ 0.048). The schizophrenia-risk alleles, which increased significantly risk for schizophrenia in Europeans (q 0.05), and (4) the TH of eight regional cortices potentially (0.006 ≤ p ≤ 0.050; q > 0.05), and consistently decreased (1) the BG GMVs significantly (1.8 × 10–19 ≤ p ≤ 0.050; q

Abstract Attention deficit hyperactivity disorder (ADHD) is associated with reduction of cortical and subcortical gray matter volumes (GMVs). The kinectin 1 gene (KTN1) has recently been reported to significantly regulate GMVs and ADHD risk. In this study, we aimed to identify sex-specific, replicable risk KTN1 alleles for ADHD and to explore their regulatory effects on mRNA expression and cortical and subcortical GMVs. We examined a total of 1020 KTN1 SNPs in one discovery sample (ABCD cohort: 5573 males and 5082 females) and three independent replication European samples (Samples #1 and #2 each with 802/122 and 472/141 male/female offspring with ADHD; and Sample #3 with 14,154/4945 ADHD and 17,948/16,246 healthy males/females) to identify replicable associations within each sex. We examined the regulatory effects of ADHD-risk alleles on the KTN1 mRNA expression in two European brain cohorts (n = 348), total intracranial volume (TIV) in 46 European cohorts (n = 18,713) and the ABCD cohort, as well as the GMVs of seven subcortical structures in 50 European cohorts (n = 38,258) and of 118 cortical and subcortical regions in the ABCD cohort. We found that four KTN1 variants significantly regulated the risk of ADHD with the same direction of effect in males across discovery and replication samples (0.003 ≤ p ≤ 0.041), but none in females. All four ADHD-risk alleles significantly decreased KTN1 mRNA expression in all brain regions examined (1.2 × 10–5 ≤ p ≤ 0.039). The ADHD-risk alleles significantly increased basal ganglia (2.8 × 10–22 ≤ p ≤ 0.040) and hippocampus (p = 0.010) GMVs but reduced amygdala GMV (p = 0.030) and TIV (0.010

Abstract Accumulating evidence suggests that hypothalamic-pituitary-adrenal axis dysfunction might play an important role in the pathophysiology of schizophrenia. The aim of this study was to explore the cortisol response to psychological stress in patients with schizophrenia. In this study, patients with schizophrenia (n = 104) and healthy volunteers (n = 59) were asked to complete psychological stress challenge tasks, which included the Paced Auditory Serial Addition Task and Mirror-Tracing Persistence Task, and pre- and post-task saliva samples were collected to measure cortisol levels. Emotions and psychopathology were assessed by the Positive and Negative Affect Schedule and Positive and Negative Syndrome Scale. The results showed (1) that the cortisol response and negative emotions in patients with schizophrenia differed significantly from those in healthy volunteers, (2) there were significant interactions between the sampling time and diagnosis for saliva cortisol levels, (3) there were significant interactions between the scoring time and diagnosis for the negative affect score of the PANAS, and (4) the changes in salivary cortisol levels and negative affect scores before and after the psychological stress challenge tasks were not correlated with clinical symptoms in patients with schizophrenia. These findings indicated an abnormal cortisol profile in patients with schizophrenia, which might be a biological characteristic of the disease.

BackgroundWe aimed to explore the predictive role of serum BDNF and anxiety-related variables in changes in somatic symptoms post-escitalopram treatment in panic disorder (PD) patients.MethodsNinety PD patients and 99 healthy controls (HCs) were enrolled. PD patients received an 8-week escitalopram treatment. All patients were administered the Panic Disorder Severity Scale–Chinese Version (PDSS-CV) and State-Trait Anxiety Inventory (STAI) to assess panic and anxiety-related symptoms, respectively. Patient Health Questionnaire 15-item scale (PHQ-15) was performed to measure somatic symptoms, and the blood sample was collected to detect serum BDNF levels in all participants. We performed partial correlation analysis and multiple linear regression to explore correlates of PHQ-15 and predictors of PHQ-15 changes post-escitalopram treatment after controlling for age, gender, education levels (set as a dummy variable), the current duration, comorbid AP, and/or GAD.ResultsCompared to HCs, PD patients had lower serum BDNF levels and higher PHQ-15 scores that could be improved post-escitalopram treatment. Lower baseline STAI state (b = −0.07, p = 0.004), and PDSS-CV scores (b = −0.25, p = 0.007), but higher baseline serum BDNF levels (b = 0.35, p = 0.007) contributed to the prediction of PHQ-15 changes post-escitalopram treatment.ConclusionState anxiety, serum BDNF levels, and panic severity could predict changes in somatic symptoms post-escitalopram treatment, our results highlighted that serum BDNF could serve as a biological indicator for improving somatic symptoms in PD patients.

Abstract Previous genome-wide association studies (GWAS) reported that the allele C of rs945270 of the kinectin 1 gene (KTN1) most significantly increased the gray matter volume (GMV) of the putamen and modestly regulated the risk for attention deficit hyperactivity disorder (ADHD). On the other hand, ADHD is known to be associated with a reduction in subcortical and cortical GMVs. Here, we examined the interrelationships of the GMVs, rs945270 alleles, and ADHD symptom scores in the same cohort of children. With data of rs945270 genotypes, GMVs of 118 brain regions, and ADHD symptom scores of 3372 boys and 3129 girls of the Adolescent Brain Cognition Development project, we employed linear regression analyses to examine the pairwise correlations adjusted for the third of the three traits and other relevant covariates, and examine their mediation effects. We found that the major allele C of rs945270 modestly increased risk for ADHD in males only when controlling for the confounding effects of the GMV of any one of the 118 cerebral regions (0.026 ≤ p ≤ 0.059: Top two: left and right putamen). This allele also significantly increased putamen GMV in males alone (left p = 2.8 × 10−5, and right p = 9.4 × 10−5; α = 2.1 × 10−4) and modestly increased other subcortical and cortical GMVs in both sexes (α

ObjectiveOur study aimed to investigate the associations between the serum level of kynurenine pathway (KP) metabolites and P50 auditory gating in non-smoking patients with first-episode schizophrenia (FES).Materials and methodsIn this study, 82 non-smoking patients with FES and 73 healthy controls (HC). P50 auditory gating was measured using a fully functional digital 64-channel EEG system, and the components included S1 amplitude, S2 amplitude, gating ratio (S2/S1), and amplitude difference (S1–S2). Serum levels of kynurenine and kynurenine acid were assessed using a combination of liquid chromatography with tandem mass spectrometry. Psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS).ResultsThe serum kynurenine (251.46 ± 65.93 ng/ml vs. 320.65 ± 65.89 ng/ml, t = –6.38, p < 0.001), and kynurenine acid levels (5.19 ± 2.22 ng/ml vs. 13.26 ± 4.23 ng/ml, t = –14.73, p < 0.001), S1 amplitude [2.88 (1.79, 3.78) μV vs. 3.08 (2.46, 4.56) μV, Z = –2.17, p = 0.030] and S1–S2 [1.60 (0.63, 2.49) μV vs. 1.92 (1.12, 2.93) μV, Z = –2.23, p = 0.026] in patients with FES were significantly lower than those in HC. The serum kynurenine and kynurenine acid levels were negatively associated with S1–S2 (r = –0.32, p = 0.004 and r = –0.42, p < 0.001; respectively) and positively correlated with S2/S1 ratio (r = 0.34, p = 0.002 and r = 0.35, p = 0.002; respectively) in patients.ConclusionOur findings suggested that neuroactive metabolites of the KP might play an important role in sensory gating deficit in first episode patients with schizophrenia. Furthermore, metabolites of the KP may be a new target for the treatment of cognitive impairments in schizophrenia.

Abstract In the brain, AMPA receptors mediate fast excitatory neurotransmission, the dysfunction of which leads to neuropsychiatric disorders. Synaptic function of AMPA receptors is tightly controlled by a protein group called transmembrane AMPAR regulatory proteins (TARPs). TARP γ-8 (also known as CACNG8) preferentially expresses in the hippocampus, cortex and subcortical regions that are critical for emotion generation indicating its association with psychiatric disorders. Here, we identified rs10420324 (T/G), a SNP located in the human CACNG8 gene, regulated reporter gene expression in vitro and TARP γ-8 expression in the human brain. A guanine at the locus (rs10420324G) suppressed transcription likely through modulation of a local G-quadruplex DNA structure. Consistent with these observations, the frequency of rs10420324G was higher in patients with anti-social personality disorder (ASPD) than in controls, indicating that rs10420324G in CACNG8 is more voluntary for ASPD. We then characterized the behavior of TARP γ-8 knockout and heterozygous mice and found that consistent with ASPD patients who often exhibit impulsivity, aggression, risk taking, irresponsibility and callousness, a decreased γ-8 expression in mice displayed similar behaviors. Furthermore, we found that a decrease in TARP γ-8 expression impaired synaptic AMPAR functions in layer 2–3 pyramidal neurons of the prefrontal cortex, a brain region that inhibition leads to aggression, thus explaining, at least partially, the neuronal basis for the behavioral abnormality. Taken together, our study indicates that TARP γ-8 expression level is associated with ASPD, and that the TARP γ-8 knockout mouse is a valuable animal model for studying this psychiatric disease.

ObjectivePrevious studies have implicated intricate interactions between innate immunity and the brain in schizophrenia. Monocytic Toll-like receptor (TLR) 4 signaling, a crucial “sensor” of innate immunity, was reported to be over-activated in link with cognitive impairment in schizophrenia. As TLR4 is predominantly expressed on gliocytes prior to expression in neurons, we hypothesized that higher TLR4 levels may contribute to cognitive deterioration by affecting white matter microstructure.MethodsForty-four patients with stable chronic schizophrenia (SCS) and 59 healthy controls (HCs) were recruited in this study. The monocytic function was detected with lipopolysaccharide (LPS) stimulation to simulate bacterial infection. Basal and LPS- stimulated levels of TLR4, nuclear factor-kappa B (NF-κB), and interleukin (IL)-1β were quantified with flow cytometry. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB) and psychopathological symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). We employed diffusion tensor imaging with a 3-T scanner and evaluated white-matter integrity with fractional anisotropy (FA). Subcortical volume and cortical thickness were also assessed.ResultsThe TLR4/NF-κB/IL-1β signaling pathway was activated in patients with SCS, but responded sluggishly to LPS stimulation when compared with HCs. Furthermore, monocytic TLR4 expressions were inversely correlated with cognitive function and white matter FA, but not with cortical thickness or subcortical gray matter volume in schizophrenia.ConclusionOur findings support altered TLR4 signaling pathway activity in association with deficits in cognition and white matter integrity in schizophrenia.

Abstract Background The aim was to explore the associations between clinical symptoms, demographic variables, social and neurocognitive functioning in euthymic patients with bipolar disorder (BD) stratified by subgroups of DSM-IV BD (type I (BD-I) and type II (BD-II)) and occupational status (employed/unemployed), and to highlight the significance of occupational status when assessing social and neurocognitive functioning in euthymic BD patients. Methods A total of 81 euthymic BD patients were participated in the study. The severity of the depressive and manic/hypomanic symptoms was measured using the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Young Mania Rating Scale (YMRS), respectively. Social functioning and neurocognitive functioning were evaluated by the Functioning Assessment Short Test (FAST) and neurocognitive measures, respectively. Results Employed BD patients displayed greater social functioning (autonomy, occupational functioning, interpersonal relationship domain) and better verbal learning performance and speed of processing than unemployed BD patients. The correlation between neurocognitive functioning and social functioning was stronger in the employed group than in the unemployed group. There were no significant differences in neurocognitive and social functioning between the BD-I and BD-II groups, and the correlation between neurocognitive functioning and social functioning was similar between the BD-I and BD-II groups. Conclusion Employed BD patients may present greater occupational functioning and interpersonal relationships, as well as better verbal learning performance and speed of processing.

Abstract Frontline healthcare nurses devoted themselves to deal with the outbreak of COVID-19, saving many lives. However, they are under incredible unknown psychological pressures with a considerable risk of infection. In this study, a self-administered questionnaire was used to survey 593 frontline nurses in Wuhan City and non-Hubei provinces for psychological responses from March 1 to March 10, 2020. Compared with nurses outside Hubei Province, those working in Wuhan were more likely to feel physically and mentally exhausted. Their probable depression and anxiety were significantly higher than those of nurses outside Hubei province (31.2%, 18.3% vs. 13.8%, 5.9%). Correspondingly, the depressive symptoms were more often reported in the Wuhan group (70.8% vs. 41.4%). Although Wuhan received wishes, concerns, and abundant psychological and material resources from all of the world, the survey-based study found that frontline nurses in Wuhan still had higher depression and anxiety with less social support compared with nurses from non-Hubei provinces. Unexpectedly, only 4.0% of nurses have sought psychological assistance. These findings suggested that the short-term psychological impact of frontline nurses in Wuhan during the COVID-19 outbreak was extremely high compared with nurses outside Hubei Province. This research enlightened the efficient integration of psychological resources, the optimization of the nurse emergency psychological assistance system, and the mental health care of medical staff during the outbreak of epidemics.

The building of cabin hospitals in Wuhan has been proven to be clinically successful in curing mild-symptom COVID-19 patients shortly after the outbreak of COVID-19 in late 2019. At the same time, the psychological effect of patients being treated in cabin hospitals and the features of the psychological status of the whole society remained ambiguous. This study adopted a self-administrated questionnaire to investigate the stress, depression, and anxiety status of patients in cabin hospitals (n = 212) and healthy participants outside of Hubei province (n = 221) in a population level from February 29 to March 01, 2020. The research measured participants’ stress response, depression level, and anxiety level as well as their social support system and their resilience level. Results indicated that in this sudden outbreak of an unknown pandemic, all people (whether or not infected) showed a generally high level of stress, depression, and anxiety, regardless of age, gender, education level, and employment. It also showed that people with a lower level of psychological resilience and social support reported more severe symptoms of depression, anxiety, and stress. Moreover, the research also found a positive effect of cabin hospitals on the psychological recovery of COVID-19 patients. Stress response of patients increased after entering into cabin hospitals, while after 3–4 weeks’ treatment, patients showed a decrease in their depression and anxiety levels. This research advances the understanding of COVID-19 and gives suggestions to optimize the design and the allocation of resources in cabin hospitals and better deal with the unknown pandemics in the future.

Attention deficit hyperactivity disorder (ADHD) occurs more frequently and manifests with greater symptom severity in men than in women. Although studies have implicated basal ganglia dysfunction, the functional connectivity (FC) of the dorsal striatum (DS), particularly in terms of sex differences, has not been fully investigated in ADHD. Here, using resting state fMRI data of a large sample of adults (n = 744; 395 women; 22–36 years) curated from the Human Connectome Project, we performed seed-based correlations for caudate and lentiform nucleus (LN) FC. ADHD symptom severity was quantified with the Achenbach Adult Self-Report ADHD total score as well as inattention and hyperactivity subscores. Imaging data were processed with published routines and evaluated at a corrected threshold. Men showed significantly higher ADHD total score than women. In men, inattention was negatively associated with LN FC with the right superior frontal gyrus. In women, inattention was negatively associated with caudate FC with the right inferior parietal gyrus and positively with LN FC with the left inferior frontal gyrus, and hyperactivity was positively associated with LN FC with a cluster in the dorsal anterior cingulate cortex and supplementary motor area. Sex differences in most of these connectivity patterns were confirmed by slope tests. Further, k-means clustering of FC's identified 3 groups each in men and in women. In men, group 1 showed higher inattention and hyperactivity than both group 2 and 3, and group 2 showed higher inattention than group 3. In women, group 1 showed higher inattention and hyperactivity than group 3 and higher inattention than group 2, and group 2 showed higher hyperactivity than group 3. These findings together suggest sex differences in DS FC as neural markers of ADHD and potentially of ADHD subtypes, with men and women each showing altered FC predominantly in the executive control and ventral attention/saliency networks.

Abstract Background Tubal pregnancy is recognized as one of the most common ectopic pregnancy types. Salpingitis may result in tubal pregnancy by causing fallopian tube occlusion and hydrosalpinx. B cell activation factor (BAFF) is a proinflammatory cytokine that helps regulate both innate and adaptive immune responses. Our previous study firstly showed that BAFF immunostaining appeared on the cellular membrane and in the cytoplasm of tubal epithelial cells, and both BAFF protein and mRNA in human inflamed fallopian tubes had higher expression levels than those in normal fallopian tubes. This study aimed to elucidate the association between the expression of BAFF gene and the inflammation in the human fallopian tube leading to tubal pregnancy. Methods We examined 70 patients undergoing salpingectomy for salpingitis (n = 35) and tubal pregnancy (n = 35). Twenty patients with benign uterine diseases undergoing complete hysterectomy and salpingectomy were recruited into control group. BAFF mRNA and protein in tissue samples were detected by qPCR and Western blotting methods. Furthermore, serum levels of BAFF, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were measured using ELISA kits. Results We found statistically significantly elevated expressions of BAFF mRNA or protein in whole tissue samples, and serum levels of BAFF, TNF-α and IL-6 in whole blood samples from patients with salpingitis and tubal pregnancy, in comparison to the control group. Conclusion Based on the results, high expression of BAFF gene might induce inflammation in the human fallopian tube, suggesting its possible role in the tubal pregnancy process.

Abstract Introduction Our study was designed to examine the relationship between Brain‐Derived Neurotrophic Factor (BDNF) genotypes (rs6265, Val66Met), BDNF plasma levels, and cognitive impairment in Chinese patients with panic disorder (PD). Methods Total 85 patients with PD and 91 healthy controls finally completed all assessments. The severity of panic symptoms and whole anxiety of PD was measured by Panic Disorder Severity Scale–Chinese Version (PDSS‐CV) and Hamilton Anxiety Scale (HAMA‐14). Montreal Cognitive Assessment (MoCA) and some neurocognitive measures were conducted to evaluate the cognitive performance. All participants were detected for the plasma BDNF levels and BDNF Val66Met polymorphism before assessment and treatment. Results No significant differences were found in the BDNF allele frequencies and the BDNF genotype distributions between healthy controls and PD patients. BDNF Met/Met genotype was associated with lower BDNF plasma levels in PD patients, and PD patients with BDNF Met/Met genotype had the lower scores in the attention and speed of processing domains compared to those with Val/Val and Met/Val genotype (p's

BackgroundSelective loss of dopaminergic neurons and diminished putamen gray matter volume (GMV) represents a central feature of Parkinson’s disease (PD). Recent studies have reported specific effects of kinectin 1 gene (KTN1) variants on the putamen GMV.ObjectiveTo examine the relationship of KTN1 variants, KTN1 mRNA expression in the putamen and substantia nigra pars compacta (SNc), putamen GMV, and PD.MethodsWe examined the associations between PD and a total of 1847 imputed KTN1 single nucleotide polymorphisms (SNPs) in one discovery sample [2,000 subjects with PD vs. 1,986 healthy controls (HC)], and confirmed the nominally significant associations (p < 0.05) in two replication samples (900 PD vs. 867 HC, and 940 PD vs. 801 HC, respectively). The regulatory effects of risk variants on the KTN1 mRNA expression in putamen and SNc and the putamen GMV were tested. We also quantified the expression levels of KTN1 mRNA in the putamen and/or SNc for comparison between PD and HC in five independent cohorts.ResultsSix replicable and two non-replicable KTN1-PD associations were identified (0.009 ≤ p ≤ 0.049). The major alleles of five SNPs, including rs12880292, rs8017172, rs17253792, rs945270, and rs4144657, significantly increased risk for PD (0.020 ≤ p ≤ 0.049) and putamen GMVs (19.08 ≤ β ≤ 60.38; 2.82 ≤ Z ≤ 15.03; 5.0 × 10–51 ≤ p ≤ 0.018). The risk alleles of five SNPs, including rs8017172, rs17253792, rs945270, rs4144657, and rs1188184 also significantly increased the KTN1 mRNA expression in the putamen or SNc (0.021 ≤ p ≤ 0.046). The KTN1 mRNA was abundant in the putamen and/or SNc across five independent cohorts and differentially expressed in the SNc between PD and HC in one cohort (p = 0.047).ConclusionThere was a consistent, significant, replicable, and robust positive relationship among the KTN1 variants, PD risk, KTN1 mRNA expression in putamen, and putamen volumes, and a modest relation between PD risk and KTN1 mRNA expression in SNc, suggesting that KTN1 may play a functional role in the development of PD.

ObjectivesMany studies reported structural brain changes in patients with alcohol dependence (PADs). However, no studies identified structural correlates of apathy that might aggravate alcohol misuse. Here, we explored regional differences in cortical thickness in PADs relative to healthy controls (HCs), and examined the potential correlation of regional thickness with the severity of apathy.MethodsMagnetic resonance imaging data were collected from 33 male PADs and 35 male age- and education-matched HCs. We used the FreeSurfer software to investigate group differences in cortical thickness across 148 regions. Apathy was evaluated using the Lille Apathy Rating Scale-Informant (LARS-I). Regression analyses examined the relationship between cortical thickness of regions of interest and apathy score in PADs.ResultsCompared to HCs, PADs showed significant decreases in the cortical thickness of occipito-temporal cortex (OTC), including the left middle occipital gyrus and occipital pole, right superior occipital gyri, and bilateral lingual gyrus; bilateral superior parietal cortex (SPC), including the right intraparietal sulcus; and bilateral inferior parietal cortex (IPC). Furthermore, the cortical thickness of all of the three regions was negatively correlated with the apathy total scores. The cortical thickness of the IPC was also negatively correlated with the action initiation subscore of the LARS-I.ConclusionsThe current results suggest the thickness of bilateral parietal and occipital temporal cortices as neural markers of apathy in PADs. These findings add to the literature by identifying the neural bases of a critical clinical feature of individuals with alcoholism.

Abstract Tardive dyskinesia (TD) is a devastating motor disorder associated with the etiological process of schizophrenia or antipsychotic medication treatments. To examine whether cerebral morphological changes may manifest in TD, we used voxel-based morphometry to analyze high-resolution T1-weighted brain structural magnetic resonance images from 32 schizophrenics with TD (TD group), 31 schizophrenics without TD (non-TD group), and 32 healthy controls (HC group). We also assessed psychopathological symptoms with the Positive and Negative Syndrome Scale (PANSS), and TD severity with the Abnormal Involuntary Movement Scale (AIMS). We compared gray matter volumes (GMVs) among groups, and tested for correlations between GMV changes and psychopathological symptoms or TD severity. The results showed significant differences in GMV in the frontal and temporal cortices, insula and cerebellum among the three groups. Brainstem and inferior frontal and precentral gyri GMVs were significantly larger, whereas cuneus and lingual gyrus GMVs were significantly smaller in the TD group as compared to non-TD group. Further, the cuneus and lingual gyrus GMVs were positively correlated with AIMS scores in the TD group. The current results suggest that TD may be associated with the alterations in GMV that are different from that of schizophrenics without TD. Further studies are needed to confirm and to examine the functional significance of these structural findings.

Abstract Background High-altitude polycythemia (HAPC) is a chronic high-altitude disease that can lead to an increase in the production of red blood cells in the people who live in the plateau, a hypoxia environment, for a long time. The most frequent symptoms of HAPC include headache, dizziness, breathlessness, sleep disorders, and dilation of veins. Although chronic hypoxia is the main cause of HAPC, the fundamental pathophysiologic process and related molecular mechanisms responsible for its development remain largely unclear yet. Aim/methods This study aimed to explore the related hereditary factors of HAPC in the Chinese Han and Tibetan populations. A total of 140 patients (70 Han and 70 Tibetan) with HAPC and 60 healthy control subjects (30 Han and 30 Tibetan) were recruited for a case-control association study. To explore the genetic basis of HAPC, we investigated the association between HAPC and both phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit delta gene (PIK3CD) and collagen type IV α3 chain gene (COL4A3) in Chinese Han and Tibetan populations. Results/conclusion Using the unconditional logistic regression analysis and the false discovery rate (FDR) calculation, we found that eight SNPs in PIK3CD and one SNP in COL4A3 were associated with HAPC in the Tibetan population. However, in the Han population, we did not find any significant association. Our study suggested that polymorphisms in the PIK3CD and COL4A3 were correlated with susceptibility to HAPC in the Tibetan population.

Prodromal Questionnaire (PQ) and Structured Interview for Prodromal Syndromes (SIPS) have been used as a two-stage process for identifying subjects at clinical high risk (CHR) of psychosis. The Prodromal Questionnaire-Brief version (PQ-B) contains 21 items derived from the PQ. The present study aimed to examine the psychometric properties of PQ-B in a Chinese help-seeking outpatient sample and to explore which items can better predict CHR diagnosis by SIPS and future transition to psychosis. In our preliminary epidemiological study, 1461 patients from a pool of 2101 individuals (15-45 years of age) completed the two-stage process. In the present study, 239 (20%) people were randomly selected among the sample who met the initial PQ-B screening criteria but had no positive diagnosis on SIPS, as well as 72 individuals with negative results on both PQ-B and SIPS, 89 prodromal and 105 psychotic subjects, yielding a total of 505 participants. The internal consistency coefficient for the PQ-B was good, with a Cronbach's alpha of 0.897. The concordant validity of PQ-B with SIPS dichotomized diagnosis of prodrome/psychosis versus no psychosis was 0.54. To ensure 80% or a higher sensitivity and a certain specificity, 7 and 24 were respectively set as the cutoff points for the PQ-B total score and distress score for Chinese help-seeking outpatients. A logistic regression model based on six PQ-B items could allow predicting the psychotic diagnosis on SIPS, with an accuracy of 65.8%. Prodromal individuals who scored higher on the 12th item of PQ-B (Do you worry at times that something may be wrong with your mind?) were less likely to convert to psychosis. PQ-B is a useful instrument for screening CHR subjects, but the cutoff score may be higher than that recommended by the author scores for help-seeking individuals in outpatient clinics. Some specific PQ-B items may have significant predictive power on dichotomized SIPS diagnoses and deserve special attention from researchers in future studies.

Several recent studies have supported the hypothesis that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, might be associated with nicotine addiction. Association studies have also suggested that the BDNF gene might play a role in the susceptibility to nicotine dependence but results appear contradictory. The present work was therefore undertaken to examine the association of smoking with the BDNF Val66Met gene polymorphism in Chinese population. The BDNF Val66Met gene polymorphism was examined in 628 healthy male volunteers including 322 smokers and 306 non-smokers. Also, the BDNF serum levels were measured in 136 smokers and 97 nonsmokers. Our results showed no significant association between the BDNF Val66Met polymorphism or serum levels among smokers and non-smokers. Smokers with the Met allele however started smoking significantly earlier than those with the Val/Val genotype (mean age at smoking initiation of 17.4, 17.9 and 21.2 years for Met/Met, Met/Val, and Val/Val, respectively; both p0.05). In addition, there was no main effect of genotype on serum BDNF levels. Our findings suggest that the BDNF Val66Met polymorphism may not be involved in susceptibility to smoking among the Chinese male population, but may influence the age at which smoking is initiated. However, the findings must be interpreted with caution because of the relatively small sample size for an association study. Results should be confirmed in a larger cohort.

Alcohol dependence (AD) is a complex disorder characterized by psychiatric and physiological dependence on alcohol. AD is reflected by regular alcohol drinking, which is highly inheritable. In this study, to identify susceptibility genes associated with alcohol drinking, we performed a genome-wide association study of copy number variants (CNVs) in 2,286 Caucasian subjects with Affymetrix SNP6.0 genotyping array. We replicated our findings in 1,627 Chinese subjects with the same genotyping array. We identified two CNVs, CNV207 (combined p-value 1.91E-03) and CNV1836 (combined p-value 3.05E-03) that were associated with alcohol drinking. CNV207 and CNV1836 are located at the downstream of genes LTBP1 (870 kb) and FGD4 (400 kb), respectively. LTBP1, by interacting TGFB1, may down-regulate enzymes directly participating in alcohol metabolism. FGD4 plays a role in clustering and trafficking GABA(A) receptor and subsequently influence alcohol drinking through activating CDC42. Our results provide suggestive evidence that the newly identified CNV regions and relevant genes may contribute to the genetic mechanism of alcohol dependence.

Several genome-wide association studies (GWASs) reported tens of risk genes for alcohol dependence, but most of them have not been replicated or confirmed by functional studies. The present study used a GWAS to search for novel, functional and replicable risk gene regions for alcohol dependence. Associations of all top-ranked SNPs identified in a discovery sample of 681 African-American (AA) cases with alcohol dependence and 508 AA controls were retested in a primary replication sample of 1,409 European-American (EA) cases and 1,518 EA controls. The replicable associations were then subjected to secondary replication in a sample of 6,438 Australian family subjects. A functional expression quantitative trait locus (eQTL) analysis of these replicable risk SNPs was followed-up in order to explore their cis-acting regulatory effects on gene expression. We found that within a 90 Mb region around PHF3-PTP4A1 locus in AAs, a linkage disequilibrium (LD) block in PHF3-PTP4A1 formed the only peak associated with alcohol dependence at p

Objective: Schizophrenia is often associated with volumetric reductions in cortices and expansions in basal ganglia, particularly the putamen. Recent genome-wide association studies have highlighted the significance of variants in the 3' regulatory region adjacent to the kinectin 1 gene (KTN1) in regulating gray matter volume (GMV) of the putamen. This study aimed to comprehensively investigate the involvement of this region in schizophrenia. Methods: We analyzed 1136 single-nucleotide polymorphisms (SNPs) covering the entire 3' regulatory region in 4 independent dbGaP samples (4604 schizophrenia patients vs. 4884 healthy subjects) and 3 independent Psychiatric Genomics Consortium samples (107 240 cases vs. 210 203 controls) to identify consistent associations. Additionally, we examined the regulatory effects of schiz ophre nia-a ssoci ated alleles on KTN1 mRNA expression in 16 brain areas among 348 subjects, as well as GMVs of 7 subcortical nuclei in 38 258 subjects, and surface areas (SA) and thickness (TH) of the entire cortex and 34 cortical areas in 36 936 subjects. Results: The major alleles (f > 0.5) of 25 variants increased (β > 0) the risk of schizophrenia across 2 to 5 independent samples (8.4 x 10-4 ≤ P ≤ .049). These schiz ophre nia-a ssoci ated alleles significantly elevated (β > 0) GMVs of basal ganglia, including the putamen (6.0 x 10-11 ≤ P ≤ 1.1 x 10-4 ), caudate (8.7 x 10-4 ≤ P ≤ 9.4 x 10-3 ), pallidum (P = 6.0 x 10-4), and nucleus accumbens (P = 2.7 x 10-5). Moreover, they potentially augmented (β > 0) the SA of posterior cingulate and insular cortices, as well as the TH of frontal (pars triangularis and medial orbitofrontal), parietal (superior, precuneus, and inferior), and temporal (transverse) cortices, but potentially reduced (β < 0) the SA of the whole, frontal (medial orbito-frontal), and temporal (pole, superior, middle, and entorhinal) cortices, as well as the TH of rostral middle frontal and superior frontal cortices (8.9 x 10-4 ≤ P ≤ .050). Conclusion: Our findings identify significant and functionally relevant risk alleles in the 3' regulatory region adjacent to KTN1, implicating their crucial roles in the development of schizophrenia. [ABSTRACT FROM AUTHOR]