Schizophrenia is characterized by the distributed dysconnectivity of resting-state multiple brain networks. However, the abnormalities of intra- and inter-network functional connectivity (FC) in schizophrenia and its relationship to symptoms remain unknown. The aim of the present study is to compare the intra- and inter-connectivity of the intrinsic networks between a large sample of patients with schizophrenia and healthy controls. Using the Region of interest (ROI) to ROI FC analyses, the intra- and inter-network FC of the eight resting state networks [default mode network (DMN); salience network (SN); frontoparietal network (FPN); dorsal attention network (DAN); language network (LN); visual network (VN); sensorimotor network (SMN); and cerebellar network (CN)] were investigated in 196 schizophrenia and 169-healthy controls. Compared to the healthy control group, the schizophrenia group exhibited increased intra-network FC in the DMN and decreased intra-network FC in the CN. Additionally, the schizophrenia group showed the decreased inter-network FC mainly involved the SN-DMN, SN-LN and SN-CN while increased inter-network FC in the SN-SMN and SN-DAN (p < 0.05, FDR-corrected). Our study suggests widespread intra- and inter-network dysconnectivity among large-scale RSNs in schizophrenia, mainly involving the DMN, SN and SMN, which may further contribute to the dysconnectivity hypothesis of schizophrenia.

Major depressive disorder (MDD) is common, and successful treatment remains challenging. Resveratrol, a naturally occurring polyphenol, has been shown to alleviate depression-like behaviors, but the underlying mechanisms remain unclear. We previously developed a new model of depression by inducing hippocampal ferroptosis in rats, suggesting that ferroptosis may be involved in the development of MDD. Here, we further explored the antidepressant-like effect of resveratrol and its association with ferroptosis. Male rats were exposed to chronic unpredictable mild stress (CUMS), with or without resveratrol, followed by comprehensive behavioral testing. In PC12 cells in vitro, LY294002 (an AKT inhibitor) and ML385 (an NRF2 inhibitor) were used to elucidate the involvement of AKT/NRF2 signaling in resveratrol-mediated ferroptosis. mRNA and protein levels of AKT/NRF2 pathway and ferroptosis-related targets were measured. Ferroptosis was quantified by measuring malondialdehyde (MDA), glutathione (GSH), and Fe²⁺ content and superoxide dismutase (SOD) activity. Resveratrol ameliorated depression-like behaviors in rats, simultaneously restoring AKT/NRF2 pathway and ferroptosis-related targets in the hippocampus downregulated by CUMS. Elevated markers of oxidative stress in plasma were attenuated by resveratrol. Furthermore, erastin induced ferroptosis and inhibited AKT/NRF2 signaling in PC12 cells, which was counteracted by resveratrol. Additionally, the impact of resveratrol on erastin-induced ferroptosis was reversed by LY294002 and ML385. This study demonstrates that resveratrol ameliorates depression-like behaviors by inhibiting ferroptosis via the AKT/NRF2 pathway.

Objectives: Childhood trauma (CT) is a known risk factor for major depressive disorder (MDD), but the mechanisms linking CT and MDD remain unknown. The purpose of this study was to examine the influence of CT and depression diagnosis on the subregions of the anterior cingulate cortex (ACC) in MDD patients.Methods: The functional connectivity (FC) of ACC subregions was evaluated in 60 first-episode, drug-naïve MDD patients (40 with moderate-to-severe and 20 with no or low CT), and 78 healthy controls (HC) (19 with moderate-to-severe and 59 with no or low CT). The correlations between the anomalous FC of ACC subregions and the severity of depressive symptoms and CT were investigated.Results: Individuals with moderate-to severe CT exhibited increased FC between the caudal ACC and the middle frontal gyrus (MFG) than individuals with no or low CT, regardless of MDD diagnosis. MDD patients showed lower FC between the dorsal ACC and the superior frontal gyrus (SFG) and MFG. They also showed lower FC between the subgenual/perigenual ACC and the middle temporal gyrus (MTG) and angular gyrus (ANG) than the HCs, regardless of CT severity. The FC between the left caudal ACC and the left MFG mediated the correlation between the Childhood Trauma Questionnaire (CTQ) total score and HAMD-cognitive factor score in MDD patients.Conclusion: Functional changes of caudal ACC mediated the correlation between CT and MDD. These findings contribute to our understanding of the neuroimaging mechanisms of CT in MDD.

Resveratrol, a plant-derived polyphenol, exhibits significant antidepressant effects and notably enhances neuroplasticity in neurological diseases. However, whether the antidepressant function of resveratrol is related to neuroplasticity remains uncertain, and the underlying mechanisms is poorly understood. This study aims to investigate the role and mechanism of resveratrol in neuroplasticity in depression. Here, we adopted the chronic unpredictable mild stress (CUMS) model and resveratrol intervention by oral gavage. Thereafter, behavioral tests confirmed resveratrol’s antidepressant effect, and Nissl staining, Golgi staining, and Western blotting (WB) were employed to assess the neuronal plasticity. Moreover, proteomic analysis and WB were used to screen and identify the key proteins. To investigate the downstream target of ELAV-like RNA-binding protein 4 (ELAVL4) (one of candidate genes), the RNA Interactome Database and the National Center for Biotechnology Information databases were utilized to predict the targets of ELAVL4. Finally, Quantitative PCR, WB, and Immunofluorescence were used to verify the prediction. Our results indicate that resveratrol alleviates CUMS-induced depressive-like behaviors accompanied by the restoration of impaired hippocampal neuroplasticity. Then, proteomic analysis shows that 351 differentially expressed proteins (DEPs) decrease after CUMS, while 24 DEPs increase remarkably with the resveratrol treatment. Among which, ELAVL4 is downregulated by CUMS, simultaneously increasing after resveratrol intervention, which acts as a protective protein in this process. Finally, brain-derived neurotrophic factor (Bdnf) mRNA is predicted to be the potential target of ELAVL4 and validated by molecular technologies. In conclusion, our findings demonstrate that resveratrol’s antidepressant efficacy is closely associated with ELAVL4, an RNA-binding protein, a mediated neuroplasticity pathway, potentially intersecting with the Bdnf mRNA. Overall, this research sheds light on the role of the ELAVL4-Bdnf mRNA pathway through neuroplasticity in resveratrol’s antidepressant action, which provides an mRNA regulation perspective for the development of novel antidepressants and understanding depression pathology.

The growing popularity of internet gaming among adolescents and young adults has driven an increase in both casual and excessive gaming behavior. Nevertheless, it remains unclear how progressive increases in internet gaming engagement led to changes within and between brain networks. This study aims to investigate these connectivity alterations across varying levels of gaming involvement. In this cross-sectional study, 231 participants were recruited and classified into three groups according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for Internet Gaming Disorder (IGD): IGD group, highly engaged gaming(HEG) group, and lowly engaged gaming (LEG) group. Resting-state fMRI data from 217 participants (143 males, 74 females) were included in the final analysis. Independent component analysis was used to examine differences in intra- and inter-network functional connectivity (FC)across the three groups. No significant differences were found in intra-network FC across the three groups. However, significant inter-network differences between the dorsal attention network(dAN)and the visual network (VN) among the three groups were observed. The HEG group exhibited significantly higher dAN-VN functional network connectivity (FNC) compared to the LEG group. Linear correlation analyses showed no significant correlation between the dAN-VN FNC values and IGD-20T scores. Throughout the development of IGD, increasing levels of engagement are associated with a rise and subsequent decline in FNC of DAN-VN. This pattern may reflect top-down attentional regulation in the early stages of addiction, followed by attentional bias as addiction progresses.

Objectives: Major Depressive Disorder (MDD) is significantly influenced by childhood trauma (CT), affecting brain anatomy and functionality. Despite the unique disease trajectory in MDD patients with CT, the underlying neurobiological mechanisms remain unclear. Our objective is to investigate CT’s impact on the white matter structure of the brain in patients with MDD.Methods: This research employed tract-based spatial statistics (TBSS) to detect variations between groups in Fractional Anisotropy (FA) throughout the whole brain in 71 medication-free MDD patients and 97 HCs. Participants filled out the Childhood Trauma Questionnaire (CTQ) and assessments for depression and anxiety symptoms. The relationship between FA and CTQ scores was explored with partial correlation analysis, adjusting for factors such as age, gender, educational background, and length of illness.Results: Compared to HCs, the MDD group showed decreased FA values in the right posterior limb of the internal capsule (PLIC), the inferior fronto-occipital fasciculus (IFOF), and bilateral superior longitudinal fasciculus (SLF). Simple effects analysis revealed that compared to HC-CT, the MDD-CT group demonstrated decreased FA values in right PLIC, IFOF, and bilateral SLF. The MDD-nCT group showed decreased FA values in right PLIC and IFOF compared to HC-nCT. The total scores and subscale scores of CTQ were negatively correlated with the FA in the right SLF.Conclusion: The right SLF may potentially be influenced by CT during the brain development of individuals with MDD. These results enhance our knowledge of the role of the SLF in the pathophysiology of MDD and the neurobiological mechanisms by which CT influences MDD.