Discriminative analysis of schizophrenia and major depressive disorder using fNIRS.

BACKGROUND: Research into the shared and distinct brain dysfunctions in patients with schizophrenia (SCZ) and major depressive disorder (MDD) has been increasing. However, few studies have explored the application of functional near-infrared spectroscopy (fNIRS) in investigating brain dysfunction and enhancing diagnostic methodologies in these two conditions. METHODS: A general linear model was used for analysis of brain activation following task-state fNIRS from 131 patients with SCZ, 132 patients with MDD and 130 healthy controls (HCs). Subsequently, seventy-seven time-frequency analysis methods were used to construct new features of fNIRS, followed by the implementation of five machine learning algorithms to develop a differential diagnosis model for the three groups. This model was evaluated by comparing it to both a diagnostic model relying on traditional fNIRS features and assessments made by two psychiatrists. RESULTS: Brain activation analysis revealed significantly lower activation in Broca's area, the dorsolateral prefrontal cortex, and the middle temporal gyrus for both the SCZ and MDD groups compared to HCs. Additionally, the SCZ group exhibited notably lower activation in the superior temporal gyrus and the subcentral gyrus compared to the MDD group. When distinguishing among the three groups using independent validation datasets, the models utilizing new fNIRS features achieved an accuracy of 85.90 % (AUC = 0.95). In contrast, models based on traditional fNIRS features reached an accuracy of 52.56 % (AUC = 0.66). The accuracies of the two psychiatrists were 42.00 % (AUC = 0.60) and 38.00 % (AUC = 0.50), respectively. CONCLUSION: This investigation brings to light the shared and distinct neurobiological abnormalities present in SCZ and MDD, offering potential enhancements for extant diagnostic systems.

Income gap between male and female psychiatric nurses in China: A national survey.

AIM: To investigate gender differences in the actual and expected income among psychiatric nurses in China. BACKGROUND: Although studies have shown that male nurses earn more than female nurses in other countries, there are no published data regarding gender income differences among psychiatric nurses in China. METHODS: We conducted a cross-sectional study involving 41 representative psychiatric hospitals in China. Demographic, income, and job-related data were analyzed using the inverse probability of treatment weighting (IPTW) based on the propensity score. FINDINGS: The sample included 9256 psychiatric nurses, and nearly four-fifths (79.3%) were female. Males earned slightly higher average monthly incomes than female nurses, while initial analysis showed no significant overall gender income difference (p > 0.05). Notably, most participants (92.5%) desired an income increase of at least 10%, with over half (56.2%) expressing significant dissatisfaction with their current income. After adjustment using propensity score combined with IPTW, females in the junior and mid-level groups had significantly lower income than their male counterparts (all p < 0.01), despite having different night shift patterns. However, there were no significant gender differences in actual or expected income among senior-level psychiatric nurses (p > 0.05). CONCLUSION: A majority of psychiatric nurses in China express dissatisfaction with their current incomes and expect higher incomes. Male nurses earned significantly more than female nurses in the junior and mid-level professional groups, potentially due to their differences in night shifts. IMPLICATIONS FOR NURSING POLICY AND HEALTH POLICY: Policymakers and hospital administrators should optimize the income structures of nurses and develop targeted policies to address the gender income gap. Improving nurse income has the potential to enhance motivation and satisfaction within the profession.

MKP1 may be involved in the occurrence of depression by regulating hippocampal autophagy in rats.

BACKGROUND: Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP1) is upregulated in the hippocampus of patients with depression, while pharmacological inhibition of hippocampal MKP1 can mitigate depression-like behaviors in rodents. In addition, MAPK signaling regulates autophagy, and antidepressants were recently shown to target autophagic signaling pathways. We speculated that MKP1 contributes to depression by enhancing hippocampal autophagy through dephosphorylation of the MAPK isoform ERK1/2. METHODS: We established a rat depression model by exposure to chronic unpredictable mild stress (CUMS), and then examined depression-like behaviors in the sucrose preference test (SPT) and forced swimming test (FST) as well as expression changes in hippocampal MKP1, ERK1/2, phosphorylated ERK1/2, and autophagy-related proteins LC3II by Western blotting and immunostaining. These same measurements were repeated in rats exposed to CUMS following hippocampal infusion of a MKP1-targeted shRNA. Finally, the effects of MKP1 expression level on autophagy we examined in rat GMI-R1 microglia. RESULTS: CUMS-exposed rats demonstrated anhedonia in the SPT and helplessness in the FST, two core depression-like behaviors. Expression levels of MKP1 and LC3II were upregulated in the hippocampus of CUMS rats, suggesting enhanced autophagy, while pERK/ERK was downregulated. Knockdown of hippocampal MKP1 mitigated depression-like behaviors, downregulated hippocampal LC3II expression, and upregulated hippocampal pERK/ERK. Similarly, MKP1 knockdown in GMI-R1 cells upregulated pERK/ERK and reduced the number of LC3II autophagosomes, while MKP1 overexpression had the opposite effects. CONCLUSION: Enhanced hippocampal autophagy via MKP1-mediated ERK dephosphorylation may contribute to the development of depression.

Down-regulation of MKP-1 in hippocampus protects against stress-induced depression-like behaviors and neuroinflammation.

Chronic stress is the primary environmental risk factor for major depressive disorder (MDD), and there is compelling evidence that neuroinflammation is the major pathomechanism linking chronic stress to MDD. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a negative regulator of MAPK signaling pathways involved in cellular stress responses, survival, and neuroinflammation. We examined the possible contributions of MKP-1 to stress-induced MDD by comparing depression-like behaviors (anhedonia, motor retardation, behavioral despair), neuroinflammatory marker expression, and MAPK signaling pathways among rats exposed to chronic unpredictable mild stress (CUMS), overexpressing MKP-1 in the hippocampus, and CUMS-exposed rats underexpressing MKP-1 in the hippocampus. Rats exposed to CUMS exhibited MKP-1 overexpression, greater numbers of activated microglia, and enhanced expressions of neuroinflammatory markers (interleukin [IL]-6, [IL]-1ß, tumor necrosis factor [TNF]-ɑ, and decreased phosphorylation levels of ERK and p38 in the hippocampus as well as anhedonia in the sucrose preference test, motor retardation in the open field, and greater immobility (despair) in the forced swimming tests. These signs of neuroinflammation and depression-like behaviors and phosphorylation levels of ERK and p38 were also observed in rats overexpressing MKP-1 without CUMS exposure, while CUMS-induced neuroinflammation, microglial activation, phosphorylation levels of ERK and p38, and depression-like behaviors were significantly reversed by MKP-1 knockdown. Moreover, MKP-1 knockdown promoted the activation of the MAPK isoform ERK, implying that the antidepressant-like effects of MKP-1 knockdown may be mediated by the ERK pathway disinhibition. These findings suggested that hippocampal MKP-1 is an essential regulator of stress-induced neuroinflammation and a promising target for antidepressant development.

Would you choose to be a psychiatrist again? A large-sample nationwide survey of psychiatrists and psychiatry residents in China.

BACKGROUND: The mental health workforce sustainability in China suffers high rates of attrition and the intention to leave. Among current professionals, the intention to choose the same career is an interesting way to gauge their job satisfaction and other factors, and it may affect the career choices of younger generations. We aimed to survey the intention of psychiatrists and psychiatry residents to choose the same career if they could start over and to identify associated factors. METHODS: We conducted an anonymous survey of psychiatrists in 41 tertiary psychiatric hospitals in China. We collected demographic data, work-related information, the sense of professional identity, job satisfaction, and burnout (Maslach Burnout Inventory), and we specifically asked each participant whether they would choose to be a psychiatrist again if they could. RESULTS: Among 3,783 psychiatrists we surveyed, one-quarter responded that they would not choose to be a psychiatrist again if they had a choice, with less than half (47.2%) saying they would. Those who would not choose psychiatry again were more likely to have a negative (relative to positive) professional identity (OR = 7.47, P＜0.001, 95%CI: 4.587-12.164); experience job burnout (OR = 2.945, P＜0.001, 95%CI: 2.356-3.681); be dissatisfied with their job (OR = 2.739, P＜0.001, 95%CI: 2.102-3.569) and excessive regulation (OR = 1.819, P＜0.001, 95%CI: 1.487-2.226); have a heavy workload (OR = 1.749, P＜0.001, 95%CI: 1.423-2.149) or a lower income (OR = 1.748, P＜0.001, 95%CI: 1.415-2.161); be married (relative to single) (OR = 1.604, P = 0.004, 95%CI: 1.165-2.208); be dissatisfied with strained doctor-patient relationship (OR = 1.333, P = 0.005, 95%CI: 1.089-1.632); have more night shifts per month (OR = 1.055, P = 0.021, 95%CI: 1.008-1.104) or work longer hours per week (OR = 1.016, P = 0.001, 95%CI: 1.006-1.025). CONCLUSION: Among psychiatrists in tertiary hospitals in China, those with a heavier workload, poor sense of professional identity, job dissatisfaction, and burnout were less likely to choose psychiatry again. Policymakers and hospital administrators need to take effective measures to improve psychiatrists' sense of professional identity and increase their intention to stay.

LncRNA LZTS1-AS1 induces proliferation, metastasis and inhibits autophagy of pancreatic cancer cells through the miR-532 /TWIST1 signaling pathway.

The 5 year survival rate after diagnosis of pancreatic cancer (PANC) is less than 5%, and it is one of the malignant tumors with the worst prognosis. Identification of novel oncogenes involved in the occurrence of pancreatic cancer is of great significance to improve the overall survival of PANC patients. Our previous study found that miR-532 is a key factor in PANC occurrence and development, and this study further explored its mechanism. We found that the expression of lncRNA LZTS1-AS1 was elevated in PANC tumor tissues and cells, and correlated with poor prognosis. In vitro experiments confirmed that LZTS1-AS1 could promote proliferation, oncogenicity, migration, and invasion of PANC cells, and inhibit apoptosis and autophagy. However, miR-532 had the completely opposite effect, and inhibition of miR-532 counteracted the effect of LZTS1-AS1 on PANC cells. Dual luciferase gene reporter assay and RNA immunoprecipitation assay confirmed the targeting relationship between LZTS1-AS1 and miR-532, and their expression levels were negatively correlated in PANC tissues. Overexpression of TWIST1 could counteract the effect of miR-532 in PANC cells, and the expression levels of both were negatively changed in PANC tissues and cells. Our results suggest that lncRNA LZTS1-AS1 acts as an oncogene to promote the metastasis of PANC and inhibit autophagy, and its mechanism may be to regulate TWIST1 through sponge miR-532. This study provides novel biomarkers and therapeutic targets for PANC.

Gut microbiota-induced microRNA-206-3p increases anxiety-like behaviors by inhibiting expression of Cited2 and STK39.

BACKGROUND: Anxiety disorder is highly prevalent worldwide and represents a chronic and functionally disabling condition, with high levels of psychological stress characterized by cognitive and physiological symptoms. The purpose of this study is to evaluate the clinical significance of gut microbiota regulating microRNA (miR)-206-3p as a biomarker in the anxiety-like behaviors. METHODS: Initially, bioinformatics analysis was performed to predict the related factors for gut microbiota affecting anxiety-like behaviors. Next, the anxiety-like behaviors in mice were measured by multiple experiments. Western blot analysis, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were utilized to measure the levels of 5-hydroxytryptamine (5-HT), brain derived neurotrophic factor (BDNF), and neutrophil expressed (NE) in brain tissues and serum and cAMP responsive element binding protein 1 (CREB) phosphorylation in brain tissues of germ-free (GF) mice. Dual-luciferase reporter gene assay was employed to verify the relationship between miR-206-3p and Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2 (Cited2)/serine/threonine kinase 39 (STK39). Ectopic expression and depletion experiments of miR-206-3p were conducted to determine the expression of miR-206-3p and mRNA and protein levels of Cited2, and STK39 in HT22 cells and brain tissues. Finally, transmission electron microscope (TEM) was used to observe the effects of miR-206-3p on hippocampal mitochondria and synapses. RESULTS: Gut microbiota could elevate miR-206-3p expression in brain tissues to increase the anxiety-like behaviors. GF mice displayed the increased levels of 5-HT, BDNF, and NE in brain tissues and serum and CREB phosphorylation in brain tissues. Cited2/STK39 was identified as the target genes of miR-206-3p. Upregulated miR-206-3p increased anxiety-like behaviors by promoting degeneration of mitochondria and synapses in hippocampus via downregulation of Cited2 and STK39. CONCLUSIONS: In conclusion, the key findings of the current study demonstrate that gut microbiota aggravated anxiety-like behaviors via the miR-206-3p/Cited2/STK39 axis.

A combination of P300 and eye movement data improves the accuracy of auxiliary diagnoses of depression.

BACKGROUND: Exploratory eye movements (EEMs) and P300 are often used to facilitate the clinical diagnosis of depression. However, There were few studies using the combination of EEMs and P300 to build a model for detecting depression and predicting a curative effect. METHODS: Sixty patients were recruited for 2 groups: high frequency repetitive transcranial magnetic stimulation(rTMS) combined with paroxetine group and simple paroxetine group. Clinical efficacy was evaluated by the Hamilton Depression scale-24(HAMD-24), EEMs and P300. The classification model of the auxiliary diagnosis of depression and the prediction model of the two treatments were developed based on a machine learning algorithm. RESULTS: The classification model with the greatest accuracy for patients with depression and healthy controls was 95.24% (AUC = 0.75, recall = 1.00, precision = 0.95, F1-score = 0.97). The root mean square error (RMSE) of the model for predicting the efficacy of high frequency rTMS combined with paroxetine was 3.54 (MAE [mean absolute error] = 2.56, R2 = -0.53). The RMSE of the model for predicting the efficacy of paroxetine was 4.97 (MAE = 4.00, R2 = -0.91). CONCLUSION: Based on the machine learning algorithm, P300 and EEMs data was suitable for modeling to distinguish depression patients and healthy individuals. However, it was not suitable for predicting the efficacy of high frequency rTMS combined with paroxetine or to predict the efficacy of paroxetine.

Enriched environment mitigates depressive behavior by changing the inflammatory activation phenotype of microglia in the hippocampus of depression model rats.

BACKGROUND: Inflammation mediated by microglia has been shown to be involved in the pathogenesis of depression. The enriched environment (EE) can improve depression-like behaviors and reduce inflammatory reactions, but it is unclear whether this is by changing the inflammatory activation phenotype of microglia. METHOD: A depression rat model was established using chronic unpredictable stress (CUS) for four weeks. The rats were then treated with EE or fluoxetine administration during the following three weeks. Behavior tests including sucrose preference, forced swimming and open field were applied to evaluate the depression-like behaviors of rats at the baseline period prior to CUS, the end of fourth week and at the end of the seventh week. Microglial activation and hippocampal neuro-inflammation were detected on postmortem using immunofluorescence, western blotting, and real-time polymerase reaction (PCR). RESULT: The results showed that severe depressive-like behavior was induced by four weeks of CUS. Changes in peripheral blood inflammatory cytokines were detected by ELISA. Immunofluorescent staining showed the IBA-1 of microglia activation marker level significantly increased in affected rats. The hippocampal microglial activation state was determined by measuring the increased levels of iNOS an M1 marker and the decreased levels of CD206, an M2 marker. The activation of NF-κB upregulation of inflammatory cytokines in the hippocampus and factors such as IL-10 were decreased. This study showed that EE and chronic fluoxetine treatment alleviated the depressive-like behavior induced by chronic stress and significantly inhibited microglial activation, activated NF-κB inflammasome and increased pro-inflammatory cytokines. CONCLUSION: EE can alleviate depression-like behavior by modulating the phenotype of microglia, inhibiting pro-inflammatory genes, and promoting anti-inflammatory genes. Furthermore, EE can effectively reduce the phosphorylation and expression levels of NF-κB.

[Effects of 22q11 deficit syndrome on mental symptoms and cognitive function in children and adolescents with schizophrenia].

OBJECTIVE: To investigate the expression of 22 q11 deletion syndrome in children and adolescents with schizophrenia and its effect on mental symptoms and cognitive function. METHODS: Case-control method was used. 134 cases of children and adolescents diagnosed with schizophrenia in hospital from April 2016 to December 2018 were selected as the case group, and the patients in the case group were divided into the two groups including 22 q11 deletion group and the non-deletion group. The control group included 418 healthy children with no history of mental illness or family history. In situ hybridization was used to diagnose 22 q11 microdeletion syndrome, and positive and negative symptom scales and Chinese version of schizophrenia cognitive function battery test were used to score the patients in the case group. RESULTS: The expression of 22 q11 microdeletion was more significant in children and adolescents with schizophrenia(χ~2=33. 52, P<0. 0001). The negative symptoms(P=0. 034), general condition(P=0. 005) and total score(P=0. 001) were significantly increased in the 22 q11 deletion group. The five indicators of attachment test, verbal memory, spatial span, emotional management, continuous operation and total score in the 22 q11 deletion group were significantly lower than those in the non-deletion group(P<0. 05). Among children and adolescents with schizophrenia, there was a significant decrease in the FA value in the 22 q11 deletion group compared with the non-deletion group, mainly distributed in the corpus callosum, the knee and the cingulate tract(P<0. 05), and no increase in the FA value was observed in other brain areas. FA value of corpus callosum somatic white matter in the absence group was positively correlated with visual memory and language fluency. FA value of the knee in corpus callosum was positively correlated with language fluency. FA value of the buckle was positively correlated with spatial width(all P values were less than 0. 05). CONCLUSION: 22 q11 microdeletion is more common in children and adolescents with schizophrenia, which may affect visual memory, language fluency and spatial span by reducing FA values in corpus callosum, knee and cingulate tract.

Associations of serotonin transporter gene promoter polymorphisms and monoamine oxidase A gene polymorphisms with oppositional defiant disorder in a Chinese Han population.

BACKGROUND: Oppositional defiant disorder (ODD) is a behavioral disorder that mainly refers to a recurrent pattern of disobedient, defiant, negativistic and hostile behaviors toward authority figures. Previous studies have showed associations of serotonin transporter (5-HTT) and monoamine oxidase A (MAOA) with behavioral and psychiatric disorders. The purposes of this study were to investigate the potential association of 5-HTT gene promoter polymorphism (5-HTTLPR) and MAOA gene polymorphism with susceptibility to ODD in a Han Chinese school population. METHODS: The 5-HTTLPR gene polymorphism and the MAOA gene polymorphism were genotyped in a case-control study of 257 Han Chinese children (123 ODD and 134 healthy controls). RESULTS: There was significant difference in the allele distribution of 5-HTTLPR (χ2 = 7.849, P = 0.005) between the ODD and control groups. Further, there were significant differences in genotype (χ2 = 5.168, P = 0.023) and allele distributions (χ2 = 10.336, P = 0.001) of the MAOA gene polymorphism that is variable-number tandem repeat (MAOA-uVNTR) between two groups. Moreover, there were significant differences in genotype (χ2 = 4.624, P = 0.032) and allele distributions (χ2 = 9.248, P = 0.002) of MAOA-uVNTR only in the male ODD and healthy groups. CONCLUSIONS: Our results suggest that 5-HTTLPR and MAOA-uVNTR gene variants may contribute to susceptibility to ODD. Further, MAOA-uVNTR gene polymorphism may play a role in susceptibility to ODD only in male children.

Enriched environment combined with fluoxetine ameliorates depression-like behaviors and hippocampal SYP expression in a rat CUS model.

Effects of enriched environment (EE) combined with fluoxetine in a chronic unpredictable stress (CUS) rat model were examined in our study. Thirty male Sprague-Dawley rats were randomly divided into control group, CUS group, CUS+EE group, CUS+fluoxetine group, and CUS+EE+fluoxetine group (n=six per group). Rats in the CUS group were bred under conditions of CUS and separation for 6 weeks; Control group animals were bred in group cages (three rats per cage) under standard laboratory conditions for 6 weeks; Rats in CUS+EE group, CUS+fluoxetine group, and CUS+EE+fluoxetine groups were bred under the conditions of CUS and separation for 6 weeks and had an intervention of EE, an oral gavage of fluoxetine, and an intervention of EE+oral gavage of fluoxetine, respectively, every day for the final 3 weeks. Every rat underwent a behavioral assessment at the beginning of the 1st week, at the end of the 3rd week and at the end of the 6th week. Behavioral assessments included sucrose water consumption, weight measurement, and an open field test (measuring horizontal moving distance, rearing behavior, and defecation). Finally, the level of synaptophysin expressed in the hippocampus was measured with immunohistochemistry. We found that EE, fluoxetine, and EE+fluoxetine all reversed the depression-like behaviors of CUS rats. The effect of EE+fluoxetine appeared to be superior to EE or fluoxetine alone; the expression level of synaptophysin in CA1, CA3, and DG of the hippocampus was decreased in CUS rats, however, exposure to EE, fluoxetine, and EE+fluoxetine all reversed this decrease.

Venlafaxine ameliorates the depression-like behaviors and hippocampal S100B expression in a rat depression model.

BACKGROUND: Accumulating evidence has indicated that S100B may be involved in the pathophysiology of depression. No published study has examined the effect of the antidepressant drug venlafaxine on S100B in animal models of depression. This study investigated S100B expression in the hippocampus and assessed the effect of venlafaxine on S100B mRNA level and protein expression in rats exposed to chronic unpredictable mild stress (CUMS). METHODS: Forty Sprague-Dawley rats were randomly divided into four groups as control, 0, 5 and 10 mg venlafaxine groups. The venlafaxine groups were exposed to CUMS from day 2 to day 43. Venlafaxine 0, 5 and 10 mg/kg were then administered from day 23 to day 43. We performed behavioral assessments with weight change, open-field and sucrose preference, and analyzed S100B protein expression and mRNA level in the hippocampus. RESULTS: The CUMS led to a decrease in body weight, locomotor activity and sucrose consumption, but venlafaxine treatment (10 mg) reversed these CUMS-induced decreases Also, CUMS increased S100B protein expression and mRNA level in the hippocampus, but venlafaxine treatment (10 mg) significantly decreased S100B protein expression and mRNA level, which were significantly lower than the other treatment groups, without significant difference between the 10 mg venlafaxine and the control groups. CONCLUSIONS: Our findings showed that venlafaxine treatment (10 mg) may improve the depression-like behaviors and decrease over-expression of S100B protein and mRNA in the hippocampus in a rat model of depression.

Exploration of the origin of large first hyperpolarizabilities of trisaza-bridged (36) fulleroids.

We investigate theoretically the structures and second-order nonlinear optical (NLO) responses (first hyperpolarizabilities) of 15 trisaza-bridged (36) fulleroids (series-A) and 15 triborane-bridged (36) fulleroids (series-B). 3A has smaller transition energy and smaller ground state dipole moment, resulting in relatively larger static first hyperpolarizability (10647 au). Most trisaza-bridged (36) fulleroids have larger ß values than the corresponding triborane-bridged (36) fulleroids. The f(0) and Δµ remain stable values when substituents R change for series-A except 2A and 5A (for series-B except 5B and 10B) and ß values are proportional to ΔE(-3), which implies that the ß values for series-A and series-B follow the two-level model. Results demonstrate that a proper bridge and lower transition energy ΔE are more favorable to enlarging first hyperpolarizabilities of series-A and series-B. In addition, the frequency-dependent SHG and EOPE are also estimated and discussed. The current work can stimulate experimentalists to synthesize novel NLO materials designed in this work.