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Background: Both major depressive disorder (MDD) and schizophrenia (SCH) are characterized by neurodevelopmental abnormalities; however, transdiagnostic and diagnosis-specific patterns of such abno...

Clinical and preclinical studies suggest that alterations in the peripheral and brain immune system are associated with the pathophysiology of depression, also leading to changes in local glucose metabolism in the brain. Here, the authors identified Yin-Yang 1 (YY1), a transcription factor closely associated with central and peripheral inflammation.Plasma levels of YY1, interleukin (IL) 6, and IL-1β in major depressive disorder (MDD) were collected before and after treatment with vortioxetine, and correlation with clinical and cognitive scores was studied. Chronic unpredictable mild stress was treated with vortioxetine. Micropositron emission tomography (microPET) was used to analyze glucose metabolism and mRNA, and the protein level of the YY1-nuclear factor κB (NF-κB)-IL-1β inflammatory pathway were measured in related brain regions.Plasma levels of YY1 and IL-1β were significantly increased in MDD and decreased after treatment with vortioxetine. Meanwhile, the level of YY1 in plasma was negatively correlated with cognitive functions in patients with MDD and positively correlated with the level of IL-1β in plasma. Compared with the control group, in chronic unpredictable mild stress rats, (microPET) analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum, and medial prefrontal cortex was reversed after treatment. mRNA and protein level of related molecular in YY1-NF-κB-IL-1β inflammatory pathway decreased in the hippocampus and was reversed by vortioxetine.The current study suggests that the YY1-NF-κB-IL-1β inflammatory pathway may play an essential role in both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in emotion regulation and cognition. These findings provide new evidence for the inflammatory mechanisms of depression.

Objective: A few former studies suggested there are partial overlaps in abnormal brain structure and cognitive function between Hypochondriasis (HS) and schizophrenia (SZ). But their differences in brain activity and cognitive function were unclear. Methods: 21 HS patients, 23 SZ patients, and 24 healthy controls (HC) underwent Resting-state functional magnetic resonance imaging (rs-fMRI) with the regional homogeneity analysis (ReHo), subsequently exploring the relationship between ReHo value and cognitive functions. The support vector machines (SVM) were used on effectiveness evaluation of ReHo for differentiating HS from SZ. Results: Compared with HC, HS showed significantly increased ReHo values in right middle temporal gyrus (MTG), left inferior parietal lobe (IPL) and right fusiform gyrus (FG), while SZ showed increased ReHo in left insula, decreased ReHo values in right paracentral lobule. Additionally, HS showed significantly higher ReHo values in FG, MTG and left paracentral lobule but lower in insula than SZ. The higher ReHo values in insula were associated with worse performance in MCCB in HS group. SVM analysis showed a combination of the ReHo values in insula and FG was able to satisfactorily distinguish the HS and SZ patients. Conclusion: our results suggested the altered default mode network (DMN), of which abnormal spontaneous neural activity occurs in multiple brain regions, might play a key role in the pathogenesis of HS, and the resting-state alterations of insula closely related to cognitive dysfunction in HS. Furthermore, the combination of the ReHo in FG and insula was a relatively ideal indicator to distinguish HS from SZ.

A growing number of clinical and preclinical studies suggest that alterations in peripheral and brain immunal system and followed inflammation are associated with the pathophysiology of depression, also leading to the changes in local glucose metabolism in the brain. Here, we identified Yin-yang 1 (YY1), a transcription factor that has been reported to be closely associated with central and peripheral inflammation. The levels of YY1 and IL-1β were significantly increased in blood samples from depressed individuals, and significantly decreased after treatment with Vortioxetine. Meanwhile, it was found that the level of YY1 in plasma was negatively correlated with visual learning reasoning and problem solving in MDD patients, and positively correlated with the level of IL-1β in plasma. CUMS animals showed depressive-like behavior. Compared with the control group, MicroPET analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum and mPFC was reversed after treatment. After treatment, these changes were reversed. In conclusion, Our study suggested that YY1-NF-κB - IL-1β inflammatory pathway may play an essential part on both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in the emotion regulation and cognition related brain regions. These findings provide new evidence for the inflammatory mechanisms of depression.

Major depressive disorder (MDD) is a devastating mental illness and the leading cause of disability worldwide. Previous studies have suggested that synaptic plasticity in the hippocampus plays an important role in depression pathogenesis. Reelin is expressed mainly in the frontal lobe and hippocampus, and is closely associated with neurodevelopment and synaptic plasticity. However, few studies have investigated its role in MDD combining clinical trials and animal experiments. We show that in a clinical trial, plasma reelin levels decreased in patients with first-episode drug-naïve MDD and increased after treatment; further, plasma reelin levels allowed to distinguish drug-naïve patients with first-episode MDD from healthy individuals. In rats, chronic mild and unpredictable stress led to a decrease in both reelin mRNA and protein levels in the hippocampus, which could be reversed by vortioxetine. Subsequent experiments confirmed that the reelin-ApoER2-NR2A /NR2B pathway regulates hippocampal synaptic plasticity and may be involved in depression or antidepressant responses. Our work contributes to a deeper understanding of MDD pathogenesis and provides new evidence that reelin should be considered a potential therapeutic target for MDD.

Background Cognitive impairment has long challenged the patients with major depressive disorder (MDD), hypocretins and inflammation have recently been implicated in cognitive function. However, limited studies have compressively assessed their associations with cognitive impairment in MDD. Methods A total of 100 MDD patients and 100 healthy controls (HC) were recruited for this study. They were tested with HAMD, HAMA, and MCCB scales. The plasma level of selected inflammatory factors (IL-1β, IL-6, and TNF-α) and hypocretin-1 were determined using enzyme-linked immunosorbent assay (ELISA). Correlation analysis was performed to explore the relationship between the plasma level of the factors and clinical performances. Results Patients with MDD showed cognitive impairment in each MCCB subdomain except working memory compared with HC. The levels of IL-6, IL-1β and hypocretin-1 in MDD patients were higher than HC. Besides, IL-1β levels was negatively correlated with overall cognitive function in the combined group. Hypocretin-1 was positively correlated with socially cognitive impairment in MDD patients. A negative correlation between plasma hypocretin-1 levels and HAMA scales was also observed in MDD patients. Limitation The study was cross-sectional, thereby limiting causal inference, and had a relatively small sample size. There are no subcategories for MDD based on characteristics. Conclusion IL-1β, IL-6 and Hypocretin-1 were reported as potential factors involved in MDD pathology. Hypocretin-1 could contribute to the biological mechanisms of anxiety relief. Hypocretin-1, therefore, may be important in exploring the pathological mechanisms of social cognitive impairment in MDD patients. Conclusively, this study provides new insights for exploring cognitive impairment in depression.

Background: The pathophysiology of major depressive disorder (MDD) remains obscure. Recently, the microbiota-gut-brain (MGB) axis’s role in MDD has an increasing attention. But there are very few studies on the correlations of the gut microbiota with all three omics, including immunology, metabolomics, and brain structure in MDD. Methods: The data of metagenomics, metabolomic, inflammatory factors, and MRI scanning are collected from the two groups including 24 drug-naive MDD patients and 26 healthy controls (HCs). Then, the correlation analysis is performed in all omics. Findings: The results confirmed that there are many markedly altered differences, such as elevated Actinobacteria abundance, plasma IL-1β concentration, lipid, vitamin, and carbohydrate metabolism disorder, and diminished grey matter volume (GMV) of inferior frontal gyrus (IFG) in the MDD patients. Notably, three kinds of discriminative bacteria, Ruminococcus bromii, Lactococcus chungangensis, and Streptococcus gallolyticus have an extensive correlation with metabolome, immunology, GMV, and clinical symptoms. All three microbiota are closely related to IL-1β and lipids (for example, phosphoethanolamine (PEA)). Besides, Lactococcus chungangensis is negatively related to the GMV of left IFG. Interpretation: Overall, this study demonstrate that the effects of gut microbiome exert in MDD is multifactorial. Funding: This work was supported by the National Natural Science Foundation of China (No. 81601182), the grant 2015C03040 of the major subject of Zhejiang Province, and the Natural Science Foundation of Zhejiang Province (LQ20H090010). Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: Ethical approval was obtained from the local Ethics Committee at the First Affiliated Hospital, College of Medicine, Zhejiang University, China.

Hypocretin (also called orexin) regulates various functions, such as sleep-wake rhythms, attention, cognition, and energy balance, which show significant changes in schizophrenia (SCZ). We aimed to identify alterations in the hypocretin system in SCZ patients. We measured plasma hypocretin-1 levels in SCZ patients and healthy controls and found significantly decreased plasma hypocretin-1 levels in SCZ patients, which was mainly due to a significant decrease in female SCZ patients compared with female controls. In addition, we measured postmortem hypothalamic hypocretin-1-immunoreactivity (ir), ventricular cerebrospinal fluid (CSF) hypocretin-1 levels, and hypocretin receptor (Hcrt-R) mRNA expression in the superior frontal gyrus (SFG) in SCZ patients and controls We observed a significant decrease in the amount of hypothalamic hypocretin-1 ir in SCZ patients, which was due to decreased amounts in female but not male patients. Moreover, Hcrt-R2 mRNA in the SFG was decreased in female SCZ patients compared with female controls, while male SCZ patients showed a trend of increased Hcrt-R1 mRNA and Hcrt-R2 mRNA expression compared with male controls. We conclude that central hypocretin neurotransmission is decreased in SCZ patients, especially female patients, and this is reflected in the plasma.

Background: This is an intervention study which explores the effect of using virtual reality supermarket training system (VRSTS) to improve cognitive function deficiency and clinical symptoms in Han Chinese patients with schizophrenia in the remission stage. Methods:68 patients with schizophrenia in the remission stage were recruited for the interventional study and were randomly allocated to either virtual reality training (VRT) group or treatment-as-usual (TAU) group. For VRT group, patients received training with VRSTS for two weeks and antipsychotic treatment as usual while TAU group only received antipsychotic treatment as usual. Cognitive function and clinical symptoms before and after intervention were assessed by MATRICS Consensus Cognitive Battery (MCCB), Positive and Negative Syndrome Scale (PANSS), and the Personal and Social Performance Scale (PSP).Results:Results showed (1) VRSTS could improve MCCB composite scores and 4 out of 7 cognitive domains: speed of processing, working memory, visual learning, reasoning and problem solving, and (2) VRSTS could alleviate general psychopathology symptoms of PANSS but did not exert effects on positive and negative symptoms among patients with schizophrenia in the remission stageConclusion:A therapeutic effect of VRSTS was observed in patients with schizophrenia in the remission stage. It may improve cognitive impairment and general psychopathology symptoms.Trial registration: China Clinical Trial Registry, ChiVTR1800016121. Registered 13 May 2018, http://www.chictr.org.cn/showproj.aspx?proj=27233