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The efficacy of medication and psychotherapy for adolescent depression is controversial, so we conducted a meta-analysis to evaluate the efficacy of combination therapy.We followed the PRISMA checklist in completing the meta-analysis. Relevant literature was searched in PubMed, Web of Science and Embase, Chinese databases CNKI and WanFang Data. We included the literature on the comparison of the fluoxetine plus psychotherapy or cognitive-behavioral therapy (CBT) and each treatment alone for adolescent depression published in 1980-2021. All statistical analyses were performed using Stata software.After careful review, a total of 489 relevant articles were retrieved, and 13 studies were finally included. In comparison with the control group (fluoxetine alone), fluoxetine plus CBT achieved higher response rate (RR=1.12, 95% CI: 1.04, 1.21), lower incidence of adverse Reactions (RR=0.62,95% CI:0.40,0.96), lower proportion of suicide or self-injury (RR=0.94,95% CI:0.74,1.20), and lower one-year recurrence rate (RR=0.27, 95% CI: 0.16, 0.45). Before treatment, there were no significant differences in Hamilton Depression Scale score (HAMD), Children's Depression Rating Scale Revised (CDRS-R) score, and Clinical Global Impression (CGI) Severity score. After treatment, HAMD score (SMD=-1.01, 95% CI:-1.39,-0.63), CDRS-R score (SMD= -0.10,95% CI:-0.26,-0.07), and CGI score (SMD = -0.22, 95% CI: -0.54, -0.10) were significantly lower in the combined treatment group than in the control group.Adolescents simultaneously treated with fluoxetine and CBT had significantly reduced incidence of depressive symptoms, suicide or NSSI, adverse reactions, and one-year recurrence of symptoms, than adolescents treated with fluoxetine alone. This indicates fluoxetine plus CBT may be superior to fluoxetine alone for the clinical treatment of adolescent depression.

The gut-microbiota-brain axis is the most important complex and bidirectional pathway between the gastrointestinal tract and the central nervous system. This study investigated the potential of microbe-induced gut-to-brain signaling to modulate the effect of stress on depressive-like behavior, intestinal barrier, and neuroinflammation. Result showed that fecal microbiota transplantation increased the consumption of sucrose solutions and decreased the immobility time in forced swimming test. This treatment also increased Firmicutes and decreased Bacteroidetes and Desulfobacterota at phylum levels; reduced the loss of villi and epithelial cells; suppressed the inflammatory cell infiltration in the ileum; increased the expression of ZO-1, occludin; protected the mucosal layer function; and suppressed the high levels of inflammasomes (NLRP3, ASC, caspase-1, and IL-1β) in rat brain. In summary, fecal microbiota transplantation improves the depressive-like behavior, alters the gut microbiota imbalance, and alleviates the intestinal tract inflammation, intestinal mucosa disruption, and neuroinflammation in rats induced by chronic unpredictable mild stress.

To date, a systematic characterization of abnormalities in resting-state effective connectivity (rsEC) in obsessive–compulsive disorder (OCD) is lacking. The present study aimed to systematically characterize whole-brain rsEC in OCD patients as compared to healthy controls. Using resting-state fMRI data of 50 unmedicated patients with OCD and 50 healthy participants, we constructed whole-brain rsEC networks using Granger causality analysis followed by univariate and multivariate comparisons between patients and controls. Similar analyses were performed for resting-state functional connectivity (rsFC) networks to examine how rsFC and rsEC differentially capture abnormal brain connectivity in OCD. Univariate comparisons identified 10 rsEC networks that were significantly disrupted in patients, and which were mainly associated with frontal-parietal cortex, basal ganglia, and cerebellum. Conversely, abnormal rsFC networks were widely distributed throughout the whole brain. Multivariate pattern analysis revealed a classification accuracy as high as 80.5% for distinguishing patients from controls using combined whole-brain rsEC and rsFC. The results of the present study suggest disrupted communication of information from frontal-parietal cortex to basal ganglia and cerebellum in OCD patients. Using combined whole-brain rsEC and rsFC, multivariate pattern analysis revealed a classification accuracy as high as 80.5% for distinguishing patients from controls. The alterations observed in OCD patients could aid in identifying treatment mechanisms for OCD.

Objective The aim of this study was to explore the effects of atypical antipsychotics (AaPs) on brain white matter (WM) tracts in healthy individuals with auditory verbal hallucinations (Hi-AVHs). Methods We analyzed neuroimaging, AVH symptoms, and cognitive assessment data obtained from 39 Hi-AVHs who reported being distressed by persistent AVHs and volunteered to receive AaP treatment. We used tract-based spatial statistics (TBSS) and t tests to explore AaP pharmacotherapy effects on AVH symptoms and brain WM alterations in Hi-AVH subjects. Results TBSS and t tests revealed WM alterations after AaP treatment, relative to pretreatment observations. Although AaPs alleviated AVH symptoms, WM alterations in these subjects expanded over 8 months of AaP treatment, encompassing most major WM tracts by the end of the observation period, including the corpus callosum, arcuate fasciculus, cortico-spinal tracts, anterior commissure, and posterior commissure. Conclusions The worsening of AaP-associated WM alterations observed in this study suggest that AaPs may not be a good choice for the treatment of Hi-AVHs despite their ability to alleviate AVHs.

Few advances in schizophrenia research have been translated into clinical practice, despite 60 years of serum biomarkers studies and 50 years of genetic studies. During the last 30 years, neuroimaging studies on schizophrenia have gradually increased, partly due to the beautiful prospect that the pathophysiology of schizophrenia could be explained entirely by the Human Connectome Project (HCP). However, the fallacy of reverse inference has been a critical problem of the HCP. For this reason, there is a dire need for new strategies or research “bridges” to further schizophrenia at the biological level. To understand the importance of research “bridges,” it is vital to examine the strengths and weaknesses of the recent literature. Hence, in this review, our team has summarized the recent literature (1995–2018) about magnetic resonance imaging (MRI) of schizophrenia in terms of regional and global structural and functional alterations. We have also provided a new proposal that may supplement the HCP for studying schizophrenia. As postulated, despite the vast number of MRI studies in schizophrenia, the lack of homogeneity between the studies, along with the relatedness of schizophrenia with other neurological disorders, has hindered the study of schizophrenia. In addition, the reverse inference cannot be used to diagnose schizophrenia, further limiting the clinical impact of findings from medical imaging studies. We believe that multidisciplinary technologies may be used to develop research “bridges” to further investigate schizophrenia at the single neuron or neuron cluster levels. We have postulated about future strategies for overcoming the current limitations and establishing the research “bridges,” with an emphasis on multimodality imaging, molecular imaging, neuron cluster signals, single transmitter biomarkers, and nanotechnology. These research “bridges” may help solve the reverse inference fallacy and improve our understanding of schizophrenia for future studies.

Schizophrenic patients often experience auditory hallucinations (AHs) and visual hallucinations (VHs). However, brain and retinal alterations associated with combined AHs and VHs in schizophrenic patients are unknown. This study aimed o investigate brain and retinal alterations in first episode un-treated schizophrenic patients with combined AHs and VHs (FUSCHAV). FUSCHAV patients (n = 120), divided into four groups according to severity of AH and VH symptoms, were compared to healthy controls (n = 30). Gray matter volume (GMV) and global functional connectivity density (gFCD) were recorded to reflect brain structure and functional alterations. Total retinal thickness was acquired by optical coherence tomography to assess retinal impairment. The majority of FUSCHAV patients (85.8%) demonstrated both GMV reduction and gFCD increases along with retinal thinning compared to healthy controls. The severity of GMV reduction and gFCD increase differed between patient groups, ranked from highest to lowest severity as follows: severe AHs combined with severe VHs (FUSCHSASV, 20 patients), moderate AHs combined with severe VHs (FUSCHMASV, 23 patients), severe AHs combined with moderate VHs (FUSCHSAMV, 28 patients), and moderate AHs combined with moderate VHs (FUSCHMAMV, 26). Retinal impairment was similar among the four FUSCHAV groups. GMV reduction and gFCD increases in the frontal-parietal lobule show an inverted U-shaped pattern among FUSCHAV patients according to AH and VH severity, while retinal impairment remains stable among FUSCHAV groups. These findings indicate a reciprocal deterioration in auditory and visual disturbances among FUSCHAV patients.

This study aimed to investigate alterations in brain function among different subtypes of auditory hallucinations (AH) in drug-naive first episode schizophrenia patients. We recruited 20 patients with drug-naive first episode schizophrenia who had constant commanding and commenting auditory verbal hallucinations (CCCAVH), 15 drug-naive first episode schizophrenia patients who had nonverbal auditory hallucinations (NVAH), and 20 healthy controls to participate in this study. We used global functional connectivity density (gFCD) and one-way analysis of covariance to characterize differences in brain function between the two patient groups. Statistical significance was set at P

Although an increasing number of studies has explored the neural mechanisms of auditory verbal hallucination (AVH) using many modalities, including neuroimaging, neurotransmitters, and electroencephalography, the etiology of AVH remains unclear. In this study, we investigated the neuroimaging characteristics of AVH in patients with bipolar disorder (BD) experiencing depressive episodes with and without AVH. For this study, we recruited 80 patients with BD and depressive status (40 with and 40 without AVH), and 40 healthy individuals. Their global functional connectivity density (gFCD) was screened by functional magnetic resonance imaging. Differences in gFCD among the three groups were tested using voxel-wise one-way analysis of covariance. Patients in both BD groups demonstrated increased gFCD in the central parietal lobe, insular lobe, and middle cingulate cortex, and decreased gFCD in the posterior parietal cortex, lateral prefrontal cortex, and occipital lobe (all bilateral). We defined these alterations as the common aberrant gFCD pattern for BD with and without AVH. Compared with the other two groups, patients in the BD with AVH group demonstrated increased gFCD in the Broca and Wernicke regions, and decreased gFCD in the hippocampus (all bilateral). We defined these alterations as the distinct aberrant gFCD pattern for BD with AVH. To our knowledge, this report is the first to date to describe gFCD alterations in patients with BD with and without AVH. Our findings suggest that disturbances in brain activity and information communication capacity in patients with BD and AVH are located mainly in the left frontoparietal network, control network, and memory circuit. However, these observations were made only in patients with BD during depressive episodes, and without consideration of many factors, such as the treatment mode, symptom relapse, and BD subtype. Hence, the conclusions of this study merely provide clues for further study, and do not fully represent brain alterations in patients with BD and AVH. Further large-sample cohort studies are needed to clarify and expand on these findings.

Structural and functional brain alterations are common in patients with major depressive disorder (MDD). In this review, we assessed the recent literature (1995–2018) on the structural and functional magnetic resonance imaging (MRI) studies of MDD. Despite the growing number of MRI studies on MDD, reverse inference is not possible as MRI scans cannot be used to aid in the diagnosis or treatment planning of patients with MDD. Hence, researchers must develop “bridges” to overcome the reverse inference fallacy in order to build effective tools for MDD diagnostics. From our findings, we proposed that the “bridges” may be built using multidisciplinary technologies, such as artificial intelligence, multimodality imaging, and nanotheranostics, allowing for the further study of MDD at the biological level. In return, the “bridges” will aid in the development of future diagnostics for MDD and other mental disorders.

Due to recent advances in human genomic technologies, there have been explosive interests and extensive research on the genomics of schizophrenia, a severe psychiatric disorder characterized by social cognitive deficits, hallucinations, and delusions. These new technologies, including next-generation sequencing (NGS), genome-wide association studies (GWAS), and the Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) genome editing platform are capable of interrogating and editing the genome directly. In the past few years, these efforts have led to the identification of important loci and genes susceptible to schizophrenia. The findings have increased our understanding of the underlying genetic causes of schizophrenia and aided in the development of new approaches for more effectively diagnosing and treating schizophrenia. Despite the substantial progress, there are several unanswered questions about the genomics of schizophrenia, and there are a number of potential shortcomings in the current literature considering the complexity of the disease and limits of the current technologies. In the present review, we assessed the existing literature on the genomics of schizophrenia, identifying the strengths and study design shortcomings from the following aspects: elucidation of the pathogenesis, early risk prediction and diagnosis, and the treatment of schizophrenia. Moreover, we have proposed solutions to overcome the shortcomings of past studies. Lastly, we have discussed the importance of developing multidisciplinary teams and global research groups in order to improve the lives of schizophrenic patients globally.

Objective. The efficacy of antidepressant drugs combined with psychotherapy is controversial; hence, this meta-analysis was conducted to assess the efficacy of the combination therapy. Methods. Relevant literature was searched in PubMed, Web of Science and Embase, Chinese databases CNKI, and WanFang Data. We included the literature on the comparison of the sertraline combined with cognitive behavioral therapy (CBT) and each treatment alone for adolescent depression published in 2000-2021. Meta-analysis was performed using Stata16.0 software. Results. A total of 421 relevant articles were retrieved, and 14 studies were finally included. In comparison with the control group (sertraline), sertraline combined with CBT achieved higher response rate ( OR = 5.07 , 95% CI: 3.00, 8.58) and lower incidence of adverse reactions ( OR = 0.43 , 95% CI: 0.24, 0.75). Before treatment, there were no significant differences in depression score, anxiety score, and symptom self-rating scale score between the two groups. After treatment, depression score ( SMD = − 2.79 , 95% CI: -3.64, -1.94), anxiety score ( SMD = − 1.22 , 95% CI: -1.96, -0.47), and symptom self-rating scale score ( SMD = − 1.73 , 95% CI: -3.19, -0.27) were significantly lower in the combined treatment group than in the control group. Conclusion. Although the number of comparative trials is small, this study shows that sertraline is effective for adolescent depression, but sertraline combined with CBT is more effective. The latter can significantly reduce the incidence of depressive symptoms, anxiety, and adverse reactions in patients. Therefore, this combination therapy is recommended for the clinical treatment of adolescent depression.

Background Evidence from previous studies has demonstrated that the gut-microbiota-brain axis is vital in regulating of behavior and neuroinflammation in the central nervous system. Considering the putative connection among gut microbiota, neural function, and behavior, the present study investigated the potential signaling of gut microbiota to modulate depression-like behaviors and neuroinflammation. Methods Rats showing depression-like behaviors induced by chronic unpredictable mild stress received fecal microbiota treatment or vehicle for 14 days, and alterations in behavior and neuroinflammation were assessed. ELISA, immunofluorescence staining and Western blot were used to analysis the activation of glial cells and NLRP3 inflammasome. Results Treatment with fecal microbiota transplantation ameliorated depression-like behaviors. 5-Hydroxytryptamine decreased in the chronic unpredictable mild stress rat model but significantly increased after fecal microbiota transplantation. The treatment with fecal microbiota transplantation decreased the production of IL-1β and TNF-α. Moreover, fecal microbiota transplantation administration suppressed the activation of Iba1 positive microglia cells and GFAP positive astrocytes cells and reduced the expression of NLRP3, ASC, Caspase-1, and IL-1β pathway in the prefrontal cortex and hippocampus. Conclusions Fecal microbiota transplantation can improve depression-like behaviors induced by chronic unpredictable mild stress. The anti-depression effects of fecal microbiota transplantation were associated with the suppressed activation of glial cells and NLRP3 inflammasome in the brain.

To date, a systematic characterization of abnormalities in resting-state effective connectivity (rsEC) in obsessive-compulsive disorder (OCD) is lacking. The present study aimed to systematically characterize whole-brain rsEC in OCD patients as compared to healthy controls.Using resting-state fMRI data of 50 unmedicated patients with OCD and 50 healthy participants, we constructed whole-brain rsEC networks using Granger causality analysis followed by univariate and multivariate comparisons between patients and controls. Similar analyses were performed for resting-state functional connectivity (rsFC) networks to examine how rsFC and rsEC differentially capture abnormal brain connectivity in OCD.Univariate comparisons identified 10 rsEC networks that were significantly disrupted in patients, and which were mainly associated with frontal-parietal cortex, basal ganglia, and cerebellum. Conversely, abnormal rsFC networks were widely distributed throughout the whole brain. Multivariate pattern analysis revealed a classification accuracy as high as 80.5% for distinguishing patients from controls using combined whole-brain rsEC and rsFC.The results of the present study suggest disrupted communication of information from frontal-parietal cortex to basal ganglia and cerebellum in OCD patients. Using combined whole-brain rsEC and rsFC, multivariate pattern analysis revealed a classification accuracy as high as 80.5% for distinguishing patients from controls. The alterations observed in OCD patients could aid in identifying treatment mechanisms for OCD.

Objective To explore shared brain structural alterations in patients diagnosed with mental disorders who experience own‐thought auditory verbal hallucinations (OTAVHs). Methods A cohort of 143 first‐diagnosis, nonmedicated patients with OTAVHs was enrolled: 25 with schizophrenia (FUSCH‐OTAVH), 20 with major depression disorder (FUMDD‐OTAVH), 28 with bipolar disorder (FUBD‐OTAVH), 22 patients with posttraumatic stress disorder (FUPTSD‐OTAVH), 21 with anxiety disorder (FUAD‐OTAVH), and 27 with borderline personality disorder (FUBPD‐OTAVH); 25 healthy controls (HCs) participated. The Auditory Hallucinations Rating Scale (AHRS), multiple psychometric scales, voxel‐based morphometry (VBM), tract‐based spatial statistics (TBSS), and multiple regression were used. Results Compared with HCs, patients had increased occipital cortex, dorsal prefrontal cortex (PFC), and striatum gray matter volumes (GMVs), a reduced insular cortex (IC) GMV, and an impaired frontooccipital fasciculus. The following differences were found versus HCs: FUSCH‐OTAVH, reduced PFC and occipital GMVs, increased striatum and thalamus GMVs, impaired arcuate fasciculus, u‐shaped bundle, optic tract, and upper longitudinal fasciculus (LF); FUMDD‐OTAVH, increased posterior frontotemporal junction and hippocampus GMVs; FUMN‐OTAVH, increased posterior frontotemporal junction and parietal cortex GMVs, reduced hippocampus GMV, impaired upper LF; FUPTSD‐OTAVH, increased temporal, hippocampus, and nucleus accumbens GMVs; FUBPD‐OTAVH, increased frontotemporal junction and hippocampus GMVs, impaired upper/lower LF; and FUAD‐OTAVH, increased frontal and temporal cortex, hippocampus GMVs. Conclusions The present findings provide evidence consistent with a bottom‐up and top‐down reciprocal action dysfunction hypothesis of AVHs and with the dopamine hypothesis of AVHs. We observed specific features related to OTAVHs in patients with different mental disorders. The findings, though complex, provide clues for further studies of specific mental disorders., We observed an unified model of shared brain structural alterations in patients with different mental disorders who experience own‐thought auditory verbal hallucinations. These findings support a unified model of own‐thought auditory verbal hallucinations.

Comorbid depressive disorders confound the diagnosis and therapy of schizophrenia. Using a murine model incorporating both MK801 and chronic unpredictable mild stress exposures, we successfully replicated both psychosis and depression. Ex vivo patch clamp recordings and in vivo calcium imaging demonstrated impaired neural activity in the prefrontal cortex (PFC). We then administered triple-drug combinations consisting of two antidepressants (mirtazapine and venlafaxine) plus an antipsychotic (either clozapine or olanzapine), and found improved PFC neuronal activity and performance in behavioral assays. Moreover, the addition of metformin to both psychotropic drug combinations brought further improvements in depressive and schizophrenic-like behaviors and physiological parameters. In summary, our data modeled the neuropathophysiology of schizophrenia with comorbid depression, and may inform drug intervention strategies.

Investigation of auditory verbal hallucinations (AVHs) in schizophrenics is complicated by psychiatric symptoms. Investigating healthy individuals with AVHs (H-AVHs) can obviate such confounding factors. The objective of this study was to explore the effects of antipsychotic treatment on AVHs and gray matter volumes (GMVs) in H-AVH subjects and whether such are effects are influenced by COMT-Val158Met genotype. Magnetic resonance imaging (MRI) and genotyping studies were completed for 42 H-AVH subjects and 42 well-matched healthy controls (HCs). COMT-Met/Met homozygotes (158th codon) were identified as COMT-Met genotype; COMT-Met/Val heterozygotes and COMT-Val/Val homozygotes were identified as COMT-Val genotype. Data were compared across groups (H-AVH vs. HC, and between genotypes) with two-sample t-tests. The H-AVH COMT-Met group showed a stronger response to antipsychotic treatment than the H-AVH COMT-Val group (p COMT-Val158Met genotype and associated with widespread GMV reductions. These findings provide clues for further exploration of treatment targets for AVHs. Treatment associated GMV reductions, however, raise concerns about use of antipsychotics in H-AVH subjects.

Cognitive impairment is one of the core symptoms of schizophrenia. Multiple domains of cognition are affected in patients with schizophrenia, which has a major effect on the functional outcome. Recent studies indicate that SNPs in the gamma-aminobutyric acid type A receptor beta 2 subunit (GABRB2) gene are associated with the risk of schizophrenia, however, the effect of these SNPs on cognitive function in patients with schizophrenia has not been explored. In this study, we first performed a case-control analysis of three SNPs (rs187269 allele A vs. G, rs252944 allele C vs. G, and rs194072 allele A vs. G) in 100 patients and 90 controls, then conducted a meta-analysis and found the SNP rs194072 was associated with schizophrenia (OR = 0.86, P = 0.0119), and survived after Bonferroni correction. The haplotype analysis suggested that the haplotype ACA, comprising the three SNPs (rs187269, rs252944 and rs194072) was also significantly associated with schizophrenia (P = 0.049).Then, we performed an association analysis of three SNPs (rs187269, rs252944 and rs194072) in GABRB2 gene with cognitive performance in patients with first episode schizophrenia. We found that the allele G of rs187269 in the GABRB2 gene was significantly associated with better cognitive flexibility (P = 0.005), a major aspect of executive function, in patients with first episode schizophrenia. The haplotype ACA was significantly associated with cognitive flexibility in patients with schizophrenia (P = 0.023). Our study showed that SNPs in GABRB2 may have a significant effect on cognitive function in patients with schizophrenia, suggesting that modulating GABRB2 may have therapeutic potential to improve cognitive function of patients with schizophrenia.

Fluoride is becoming an ineluctable environmental pollutant and its longterm exposure would cause fluorosis and irreversible brain damage, but the molecular mechanisms remain far from fully understood. In the present study, we firstly evaluated the glycogen synthase kinase 3β (GSK-3β)/β-catenin pathway in the hippocampus of rats exposed to fluoride, given the well-established role of GSK-3β/β-catenin pathway in neuronal death and survival. Our data showed that sustained exposure to 50 mg/L and 100 mg/L NaF in drinking water dose-dependently induced neuronal loss and apoptosis in rat hippocampus. Neurogenesis was also weakened by fluoride administration in the hippocampal dentate gyrus region. Additionally, the synaptic markers, synaptophysin (SYP) and post-synaptic density 95 (PSD95) protein levels, were decreased by 100 mg/L NaF treatment, whereas 50 mg/L NaF only reduced SYP expression, indicating a compromised synaptic function. We further demonstrated that NaF, especially the higher dose, induced GSK-3β activity, with decreased inactive phosphorylated GSK-3β levels and increased GSK-3β, the active form of the kinase. Correspondingly, downstream β-catenin signaling was undermined by NaF treatment as evidenced by the fact that both two doses of NaF decreased nucleus β-catenin status and the higher dose of NaF also reduced cytoplasmic β-catenin protein expression. Taken together, the present study firstly showed the aberrant changes of GSK-3β/β-catenin signaling in the fluoride-exposed brain, highlighting the involvement of GSK-3β/β-catenin signaling in the fluoride-induced neurotoxicity.

Schizophrenia is frequently accompanied by depressive symptoms, but the pathological mechanisms remain to be elucidated. In this study, we used chronic unpredicted mild stress plus MK801 injection to generate a mouse model of schizophrenia with depression, in which in vivo 2-photon calcium imaging and electrophysiological recordings were performed in conjunction with behavioral phenotyping. Compared to mice models with classical depression or to schizophrenia models, the animal models with schizophrenia and depression comorbidity presented worse psychotic and depressive symptoms. These behavioral deficits are associated with impaired neuronal calcium activities in the frontal cortex and thalamic nuclei. Moreover, in sharp contrast to classical models that have a satisfactory response to antipsychotic or antidepressant drugs, this novel schizophrenia with depression model is resilient to combined drug treatment in terms of behavioral and functional recovery. Taken together, these data indicate that schizophrenia with depression likely involves a unique pathophysiology that is different from schizophrenia or depression alone.

Accumulating studies suggest the potential association between epilepsy and vitamin D (VD) in recent years. Vitamin D binding protein (VDBP) is the main VD carrier and can affect the availability of VD and its metabolites. Thus, this study aimed to investigate the association between VDBP polymorphisms and VD level on epilepsy. A total of 220 epilepsy patients and 210 health controls were enrolled and polymorphisms of VDBP (rs4588, rs7041, rs2298849, and rs2282679) genotype were detected using the PCR–ligase detection reaction method. The circulating status of VD metabolites, 25(OH)D and 24,25(OH)2D, was detected by a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and the VD metabolite ratio (VMR), 24,25(OH)2D:25(OH)D, was then calculated. The frequency of rs4588(C>A) and rs2282679(A>C) genotype with AC was significantly lower among the patients relative to the controls [odds ratio, OR = 0.597, 95% confidence interval, CI = 0.401–0.890, p = 0.011 for rs4588(...

Some people with mental illness in China do not receive treatment. We explored how stigma and familial obligation influenced accessibility of social support for patients with depression in China and the potential acceptability of peer support programs. Semi-structured qualitative interviews were conducted with five psychiatrists and 16 patients receiving care for depression from a large psychiatric hospital in Jining, Shandong Province of China. Patients with mental illness reported barriers that prevented them from (a) receiving treatment and (b) relying on informal social support from family members, including stigma, somatization, and community norms. Circumventing these barriers, peer support (i.e., support from others with depression) was viewed by patients as an acceptable means of exchanging information and relying on others for support. Formative research on peer support programs to examine programming and activities may help reduce the burden of unmet mental health care needs in China.

SSRI antidepressant fluoxetine is widely used to treat psychological stress related disorders, however the underlying working mechanisms is not fully understood, as SSRIs can rapidly increase the extracellular serotonin levels but it normally takes weeks to reveal their therapeutic effect in the stress-related psychological disorders. Our previous study demonstrated that purely psychological stress without any physic stimuli induces a biphasic change in the expression of brain-derived neurotrophic factor (BDNF), which immediately decrease and then gradually increase after the stress; and that the latter BDNF increase in response to the psychological stress involves the activation of serotonin system. To investigate the role of BDNF in the fluoxetine treatment for stress-related psychological disorders, we examined the mRNA and protein levels of BDNF in the brain of Sprague-Dawley (SD) rats, which were pretreated with fluoxetine at 10 mg/kg or vehicle solution for 14 days, over 24 hour after an acute psychological stress exposure. In situ hybridization and immunohistochemistry were performed to detect the expression of BDNF at different time points in various brain regions after the psychological stress. We found that fluoxetine treatment completely blocked the BDNF decrease induced by the psychological stress, and also enhanced the gradual increase in the expression of BDNF in most of the brain regions except VTA after the psychological stress. The results suggest that the enhancement in BDNF levels induced by chronic fluoxetine treatment mediates the therapeutic effect against psychological stress.

Tissue plasminogen activator (tPA) is a serine protease involved in cleavage of neurotrophic factors. In addition, tPA and neuroserpin can also directly bind to low density lipoprotein receptor-related protein 1 (LRP1), promoting neurogenesis and neurite outgrowth. Given both the cleavage and non-cleavage actions of the fibrinolytic system are crucial in neurological functions, the present study, for the first time, systematically detected the changes of fibrinolytic system factors in rats exposed to chronic unpredictable mild stress (CUMS) or lipopolysaccharide (LPS) and patients with depression. In general, our data demonstrated that both CUMS and LPS reduced tPA but elevated plasminogen activator inhibitor-1 (PAI-1; SERPINE1) mRNA expression. Intriguingly, decreased expression of neuroserpin and LRP1 was also observed in rats exposed to CUMS or LPS. The down-regulated neuroserpin and LRP1 signaling were confirmed by western blotting and immunoflurence data. Likewise, elevated PAI-1 but a significant reduction of neuroserpin and LRP1 mRNA expression were observed in the peripheral blood mononuclear cells (PBMCs) of patients with first-episode depression, and the mRNA levels of PAI-1, neuroserpin and LRP1 were correlated with the Beck Depression inventory (BDI) scores, further strengthening the clinical significance and involvement of the fibrinolytic system in depression. Collectively, the present study demonstrated the alterations of fibrinolytic system in stressed and inflamed brain and in patients with first-episode depression, firstly showing that not only the cleavage actions, but also the non-cleavage actions of the system may play an essential role in the development of depression. Keywords: tPA, PAI-1, Neuroserpin, LRP1, Depression