Effects of autotaxin and lysophosphatidic acid deficiencies on depression-like behaviors in mice exposed to chronic unpredictable mild stress.

The involvement of lipids in the mechanism of depression has triggered extensive discussions. Earlier studies have identified diminished levels of lysophosphatidic acid (LPA) and autotaxin (ATX) in individuals experiencing depression. However, the exact significance of this phenomenon in relation to depression remains inconclusive. This study seeks to explore the deeper implications of these observations. We assessed alterations in ATX and LPA in both the control group and the chronic unpredictable mild stress (CUMS) model group. Additionally, the impact of ATX adeno-associated virus (AAV-ATX) injection into the hippocampus was validated through behavioral tests in CUMS-exposed mice. Furthermore, we probed the effects of LPA on synapse-associated proteins both in HT22 cells and within the mouse hippocampus. The mechanisms underpinning the LPA-triggered shifts in protein expression were further scrutinized. Hippocampal tissues were augmented with ATX to assess its potential to alleviate depression-like behavior by modulating synaptic-related proteins. Our findings suggest that the decrement in ATX and LPA levels alters the expression of proteins associated with synaptic plasticity in vitro and in vivo, such as synapsin-I (SYN), synaptophysin (SYP), and brain-derived neurotrophic factor (BDNF). Moreover, we discerned a role for the ERK/CREB signaling pathway in mediating the effects of ATX and LPA. Importantly, strategic supplementation of ATX effectively mitigated depression-like behaviors. This study indicates that the ATX-LPA pathway may influence depression-like behaviors by modulating synaptic plasticity in the brains of CUMS-exposed mice. These insights augment our understanding of depression's potential pathogenic mechanism in the context of lipid metabolism and propose promising therapeutic strategies for ameliorating the disease.

Oligodendrocyte-derived exosomes-containing SIRT2 ameliorates depressive-like behaviors and restores hippocampal neurogenesis and synaptic plasticity via the AKT/GSK-3ß pathway in depressed mice.

AIMS: To investigate the antidepressant role of oligodendrocyte-derived exosomes (ODEXs)-containing sirtuin 2 (SIRT2) and the underlying mechanism both in vivo and in vitro. METHODS: Oligodendrocyte-derived exosomes isolated from mouse serum were administered to mice with chronic unpredictable mild stress (CUMS)-induced depression via the tail vein. The antidepressant effects of ODEXs were assessed through behavioral tests and quantification of alterations in hippocampal neuroplasticity. The role of SIRT2 was confirmed using the selective inhibitor AK-7. Neural stem/progenitor cells (NSPCs) were used to further validate the impact of overexpressed SIRT2 and ODEXs on neurogenesis and synapse formation in vitro. RESULTS: Oligodendrocyte-derived exosome treatment alleviated depressive-like behaviors and restored neurogenesis and synaptic plasticity in CUMS mice. SIRT2 was enriched in ODEXs, and blocking SIRT2 with AK-7 reversed the antidepressant effects of ODEXs. SIRT2 overexpression was sufficient to enhance neurogenesis and synaptic protein expression. Mechanistically, ODEXs mediated transcellular delivery of SIRT2, targeting AKT deacetylation and AKT/GSK-3ß signaling to regulate neuroplasticity. CONCLUSION: This study establishes how ODEXs improve depressive-like behaviors and hippocampal neuroplasticity and might provide a promising therapeutic approach for depression.

The Neuroprotective Effects of BMSC-Derived Exosomes against Glutamate-Induced HT22 Cell Cytotoxicity.

Many central nervous system diseases are closely related to nerve damage caused by dysregulation of the endogenous neurotransmitter glutamate. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) play an important role in improving injury and regeneration functions. However, its mechanism remains unknown. Therefore, the aim of this study is to investigate whether and how BMSC-Exos improve neurotoxicity caused by glutamate and to fill the gap in the literature. In this study, glutamate-treated HT22 cells were first exposed to mouse-derived BMSC-Exos at different concentrations to observe their effects on HT22 apoptosis. Next, we treated glutamate-treated HT22 cells with mouse-derived BMSC-Exos. We then inhibited the PI3K/Akt/mTOR signaling pathways using the PI3K/Akt inhibitor and the mTOR inhibitor, respectively, and observed the protective effect of mouse-derived BMSC-Exos on HT22 cells treated with glutamate. Our results show that BMSC-Exos reduced apoptosis triggered by glutamate stimulation, increased cell vitality, and decreased the levels of proapoptotic proteins while increasing the levels of anti-apoptotic proteins. The protective effect of BMSC-Exos was weakened when PI3K/Akt inhibitor and mTOR inhibitor were added. To sum up, we draw the following conclusions: BMSC-Exos can reduce neuronal apoptosis and apoptosis-related protein expression after glutamate stimulation by regulating the PI3K/Akt/mTOR signaling pathway.

Elevated triglycerides and low triiodothyronine: Key risk factors for coronary artery calcification in patients with schizophrenia.

OBJECTIVE: Coronary artery calcification (CAC) is a well-established independent predictor of coronary heart disease, and patients with schizophrenia have significantly higher rates compared to the general population. We performed this study to examine the population-specific risk factors associated with CAC in patients with schizophrenia. METHODS: In this cross-sectional study, patients with schizophrenia who underwent low-dose chest CT scans between January 2020 and December 2021 were analyzed. Ordinary CAC scores and results of routine blood tests were obtained. Logistic regression was used to calculate the odds ratio (OR) for potential risk factors in patients with and without CAC, while the negative binomial additive model was used to explore the dose-response relationship between risk factors and CAC score. RESULTS: Of the 916 patients, 233 (25.4 %) had CAC, while 683 (74.6 %) did not. After adjusting for confounding factors, higher triglyceride levels (OR = 1.20, 95 % confidence interval (CI): 1.04 to 1.38, p = 0.013) and low triiodothyronine levels (OR = 0.50, 95 % CI: 0.29 to 0.84; p = 0.010) were identified as risk factors for CAC. Both triglycerides (p = 0.021) and triiodothyronine (p = 0.010) were also found to have significant dose-response relationships with CAC scores according to the negative binomial additive model in the exploratory analysis. CONCLUSIONS: This study highlights elevated serum triglycerides and decreased triiodothyronine levels as population-specific risk factors for CAC in patients with schizophrenia, suggest the need for close monitoring of CAC in patients with schizophrenia and further prospective trials to provide additional evidence on this topic.

Altered in vivo early neurogenesis traits in patients with depression: Evidence from neuron-derived extracellular vesicles and electroconvulsive therapy.

BACKGROUND: The neurogenesis hypothesis is a promising candidate etiologic hypothesis for depression, and it is associated with electroconvulsive therapy (ECT). However, human in vivo molecular-level evidence is lacking. OBJECTIVE: We used neuron-derived extracellular vesicles (NDEVs) as a "window to the neurons" to explore the in vivo neurogenesis status associated with ECT in patients with treatment-resistant depression (TRD). METHODS: In this study, we enrolled 40 patients with TRD and 35 healthy controls (HCs). We isolated NDEVs from the plasma of each participant to test the levels of doublecortin (DCX), a marker of neurogenesis, and cluster of differentiation (CD) 81, a marker of EVs. We also assessed the plasma levels of brain-derived neurotrophic factor (BDNF), a protein that is known to be associated with ECT and neuroplastic processes. RESULTS: Our findings indicated that both the levels of DCX in NDEVs and BDNF in plasma were significantly lower in TRD patients compared to HCs at baseline, but increased following ECTs. Conversely, levels of CD81 in NDEVs were found higher in TRD patients at baseline, but did not change after the ECT treatments. Exploratory analyses revealed that lower levels of BDNF in plasma and DCX in NDEVs, along with higher CD81 levels in NDEVs, were associated with more severe depressive symptoms and reduced cognitive function at baseline. Furthermore, higher baseline CD81 concentrations in NDEVs were correlated with greater decreases in depression symptoms. CONCLUSIONS: We first present human in vivo evidence of early neurogenesis using DCX through NDEVs: decreased in TRD patients, increased after ECTs.

Interpretable Machine Learning Model to Predict Bone Cement Leakage in Percutaneous Vertebral Augmentation for Osteoporotic Vertebral Compression Fracture Based on SHapley Additive exPlanations.

STUDY DESIGN: Retrospective study. OBJECTIVES: Our objective is to create comprehensible machine learning (ML) models that can forecast bone cement leakage in percutaneous vertebral augmentation (PVA) for individuals with osteoporotic vertebral compression fracture (OVCF) while also identifying the associated risk factors. METHODS: We incorporated data from patients (n = 425) which underwent PVA. To predict cement leakage, we devised six models based on a variety of parameters. Evaluate and juxtapose the predictive performances relied on measures of discrimination, calibration, and clinical utility. SHapley Additive exPlanations (SHAP) methodology was used to interpret model and evaluate the risk factors associated with cement leakage. RESULTS: The occurrence rate of cement leakage was established at 50.4%. A binary logistic regression analysis identified cortical disruption (OR 6.880, 95% CI 4.209-11.246), the basivertebral foramen sign (OR 2.142, 95% CI 1.303-3.521), the fracture type (OR 1.683, 95% CI 1.083-2.617), and the volume of bone cement (OR 1.198, 95% CI 1.070-1.341) as independent predictors of cement leakage. The XGBoost model outperformed all others in predicting cement leakage in the testing set, with AUC of .8819, accuracy of .8025, recall score of .7872, F1 score of .8315, and a precision score of .881. Several important factors related to cement leakage were drawn based on the analysis of SHAP values and their clinical significance. CONCLUSION: The ML based predictive model demonstrated significant accuracy in forecasting bone cement leakage for patients with OVCF undergoing PVA. When combined with SHAP, ML facilitated a personalized prediction and offered a visual interpretation of feature importance.

Human in vivo evidence of reduced astrocyte activation and neuroinflammation in patients with treatment-resistant depression following electroconvulsive therapy.

AIM: The current study aimed to investigate the neuroinflammatory hypothesis of depression and the potential anti-inflammatory effect of electroconvulsive therapy (ECT) in vivo, utilizing astrocyte-derived extracellular vesicles (ADEVs) isolated from plasma. METHODS: A total of 40 patients with treatment-resistant depression (TRD) and 35 matched healthy controls were recruited at baseline, and 34 patients with TRD completed the post-ECT visits. Blood samples were collected at baseline and post-ECT. Plasma ADEVs were isolated and confirmed, and the concentrations of two astrocyte markers (glial fibrillary acidic protein [GFAP] and S100ß), an extracellular vesicle marker cluster of differentiation 81 (CD81), and nine inflammatory markers in ADEVs were measured as main analyses. In addition, correlation analysis was conducted between clinical features and ADEV protein levels as exploratory analysis. RESULTS: At baseline, the TRD group exhibited significantly higher levels of two astrocyte markers GFAP and S100ß, as well as CD81 compared with the healthy controls. Inflammatory markers interferon γ (IFN-γ), interleukin (IL) 1ß, IL-4, IL-6, tumor necrosis factor α, IL-10, and IL-17A were also significantly higher in the TRD group. After ECT, there was a significant reduction in the levels of GFAP, S100ß, and CD81, along with a significant decrease in the levels of IFN-γ and IL-4. Furthermore, higher levels of GFAP, S100ß, CD81, and inflammatory cytokines were associated with more severe depressive symptoms and poorer cognitive function. CONCLUSION: This study provides direct insight supporting the astrocyte activation and neuroinflammatory hypothesis of depression using ADEVs. ECT may exert an anti-inflammatory effect through inhibition of such activation of astrocytes.

The needle in the haystack: Identifying and validating common genes of depression, insomnia, and inflammation.

BACKGROUND: Insomnia, inflammation, and depression are often co-occurring conditions. The mechanisms underlying these conditions remain unclear. MATERIALS AND METHODS: We collected microarray datasets of depression and insomnia from GEO and analyzed them for differentially expressed genes (DEGs). We then overlapped the DEGs with a list of inflammatory response-related genes to identify genes associated with all three conditions. We next performed analyses of enrichment analyses, KEGG mapping, and protein-protein interaction to identify hub genes. Furthermore, we established a depression rat model with inflammation and insomnia to validate the potential genes. At last, a two-sample Mendelian randomization (MR) study was conducted to confirm the association of identified target genes with depression outcomes. RESULTS: We obtained 32 common DEGs associated with the depression, insomnia and inflammatory, and found that the PI3K-AKT signaling pathway might be involved in the inflammatory response in insomnia and depression. CREB1, CYBB, FYN, and CCR5 were identified as targets for the next validation. In model rats, the CCR5 and PI3K-AKT pathways were significantly up-regulated, while the model group exhibited significantly lower hippocampal p-CREB protein expression. The MR study suggested a potential causal relationship between CREB1 and the risk of depression (OR = 1.11, p = 0.013). LIMITATIONS: The identified potential genes and pathways require further laboratory and clinical evidence verification. CONCLUSION: We identified four potential inflammatory related-genes (CREB1, CYBB, FYN, and CCR5). CREB1 may be a potential inflammatory response-related biomarker and drug target for depression and insomnia, as validated by the followed rat model and MR study.

Machine Learning Prediction Model and Risk Factor Analysis of Reoperation in Recurrent Lumbar Disc Herniation Patients After Percutaneous Endoscopic Lumbar Discectomy.

OBJECTIVE: To investigate the risk factors of reoperation after percutaneous endoscopic lumbar discectomy (PELD) due to recurrent lumbar disc herniation (rLDH) and to establish a set of individualized prediction models. METHODS: Patients who underwent PELD successfully from January 2016 to February 2022 in a single institution were enrolled in this study. Six methods of machine learning (ML) were used to establish an individualized prediction model for reoperation in rLDH patients after PELD, and these models were compared with logistics regression model to select optimal model. RESULTS: A total of 2603 patients were enrolled in this study. 57 patients had repeated operation due to rLDH and 114 patients were selected from the remaining 2546 nonrecurrent patients as matched controls. Multivariate logistic regression analysis showed that disc herniation type (P < .001), Modic changes (type II) (P = .003), sagittal range of motion (sROM) (P = .022), facet orientation (FO) (P = .028) and fat infiltration (FI) (P = .001) were independent risk factors for reoperation in rLDH patients after PELD. The XGBoost AUC was of 90.71%, accuracy was approximately 88.87%, sensitivity was 70.81%, specificity was 97.19%. The traditional logistic regression AUC was 77.4%, accuracy was about 77.73%, sensitivity was 47.15%, specificity was 92.12%. CONCLUSION: This study showed that disc herniation type (extrusion, sequestration), Modic changes (type II), a large sROM, a large FO and high FI were independent risk factors for reoperation in LDH patients after PELD. The prediction efficiency of XGBoost model was higher than traditional Logistic regression analysis model.

Young Adults with Major Depression Show Altered Microbiome.

There is growing basic and clinical evidence that major depressive disorder (MDD) is associated with gut microbiome alterations, but clinical studies have tended not to adjust for confounding factors. And few studies on the gut microbiome focused on young adults with MDD. Here we performed a pilot study to compare the gut microbiome of young adults with MDD with healthy controls. Shotgun metagenomic sequencing was performed on stool samples obtained from 40 young adults with MDD and 42 healthy controls. After controlling for confounding factors including sex, age, BMI, alcohol or cigarette consumption, bowel movement quality, exercise or defecation frequency, we compared microbiome diversity between groups, identified differentially abundant taxa, and further compared functional differences through gut-brain and gut-metabolic module analysis. There were no significant differences in overall gut microbiome structure and function in young adults with MDD compared with controls. Abundance of Sutterellaceae and species belonging to Clostridium, Eubacterium, and Ruminococcus were significantly different between groups. The cysteine degradation I pathway was increased in MDD. After controlling for most confounding factors, this pilot study provides new evidence on the specific, often subtle gut dysbiosis affecting young adults with depression.

Trajectories of Efficacy and Cognitive Function During Electroconvulsive Therapy Course in Young Adults with Treatment-Resistant Depression.

Objective: Little is known about the effectiveness and cognitive side-effects of electroconvulsive therapy (ECT) in young adults with treatment-resistant depression (TRD). The primary aim of this prospective longitudinal observational trial was to examine the clinical features and cognitive outcomes of young adults with TRD undergoing ECT. Methods: Changes in depressive symptoms and objective and subjective cognitive function were assessed using repeated evaluation at baseline, after each ECT session, and at one-month follow-up using the Montgomery-Äsberg Depression Rating Scale (MADRS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Forward Digital Span Test (FDST), and part of the Columbia Subjective Side Effects Schedule. Results: Of 41 inpatients, 35 (85.4%) and 12 (29.3%) met the criteria for response and remission after ECT, respectively. The greatest clinical improvements occurred during the first 3-4 ECT sessions. While 34 patients reported subjective cognitive impairment increased with ECT, immediate and delayed memory (RBANS) significantly increased after ECT, consistent with FDST results. Objective cognition significantly improved during follow-up, but subjective cognition remained impaired. Conclusion: ECT is effective in young adults with TRD. Although subjective cognitive impairment increased during treatment, objective cognitive impairments were not observed.

Hyper-inflammation of astrocytes in patients of major depressive disorder: Evidence from serum astrocyte-derived extracellular vesicles.

Astrocyte-derived extracellular vesicles (ADEs) allow the in vivo probing of the inflammatory status of astrocytes practical. Serum sample and ADEs were used to test the inflammatory hypothesis in 70 patients with major depressive disorder (MDD) and 70 matched healthy controls (HCs). In serum, tumor necrosis factor α (TNF-α) and interleukin (IL)-17A were significantly increased, where as IL-12p70 was significantly reduced in the MDD patients compared with HCs. In ADEs, all inflammatory markers (Interferon-γ, IL-12p70, IL-1ß, IL-2, IL-4, IL-6, TNF-α, and IL-17A) except IL-10 were significantly increased in the MDD patients, the Hedge's g values of elevated inflammatory markers varied from 0.48 to 1.07. However, there were no differences of all inflammatory markers whether in serum or ADEs between MDD-drug free and medicated subgroups. The association of inflammatory biomarkers between ADEs and serum did not reach statistically significance after multi-comparison correction neither in the HCs nor MDD patients. The spearman coefficients between inflammatory factors and clinical characteristics in the MDD patients, such as onset age, disease course, current episode duration, and severity of depression, were nonsignificant after multi-comparison correction. In the receiver operating characteristic curves analysis, the corrected partial area under the curve (pAUC) of each inflammatory markers in ADEs ranged from 0.522 to 0.696, and the combination of these inflammatory factors achieved a high pAUC (>0.9). Our findings support the inflammatory glial hypothesis of depression, and suggests that in human ADEs could be a useful tool to probe the in vivo astrocyte status.

The relationship between vitamin D levels in seasonal variations and Chinese patients with first-episode drug-naive depression.

BACKGROUND: Vitamin D deficiency is highly prevalent worldwide and is associated with various diseases, including depression. Previous studies on vitamin D and depression have different conclusions. OBJECTIVES: Our study aimed to examine the association between vitamin D levels in seasonal variation and depression. METHODS: A total of 324 patients with first-episode depression aged 18-50 years were recruited for our study. Vitamin D levels were recorded, and PHQ-9 scale evaluation was performed in different seasons. Seasonal variations in vitamin D levels and depressive symptoms were examined. RESULTS: The cohort comprised 77 males and 247 females. 98.1% of patients had insufficient or deficient vitamin D levels. The median vitamin D level was 12 ng/mL; 14.5 ng/mL in summer and 13 ng/mL in autumn, which was significantly higher than 9 ng/mL in spring, and the correlation between vitamin D level and PHQ-9 score was more significant in spring but not in summer and autumn. LIMITATIONS: Our study used cross-sectional data and could not examine the causal relationship of the vitamin D level and depressive symptoms. There are also some possible influencing factors, such as the dietary habits, outdoor sports, and the use of sunscreen were not investigated. CONCLUSION: Observational data showed that the vitamin D level of depression is lower than the normal (30 ng/mL), and it is closely related to depressive symptoms in spring. The seasonal variations in vitamin D levels might play a critical role in Chinese patients with first-episode depression.

Violent behavior and the network properties of psychopathological symptoms and real-life functioning in patients with schizophrenia.

Objective: To assess the interplay among psychopathological symptoms and real-life functioning, and to further detect their influence with violent behavior in patient with schizophrenia. Methods: A sample of 1,664 patients with post-violence assessments and their propensity score-matched controls without violence from a disease registration report system of community mental health service in Guangdong, China, were studied by network analysis. Ising-Model was used to estimate networks of psychopathological symptoms and real-life functioning. Then, we tested whether network properties indicated the patterns of interaction were different between cases and controls, and calculated centrality indices of each node to identify the central nodes. Sensitivity analysis was conducted to examine the difference of interaction patterns between pre-violence and post-violence assessments in violence cases. Results: Some nodes in the same domain were highly positive interrelations, while psychopathological symptoms were negatively related to real-life functioning in all networks. Many symptom-symptom connections and symptom-functioning connections were disconnected after the violence. The network density decreased from 23.53% to 12.42% without statistical significance (p = 0.338). The network structure, the global network strength, and the global clustering coefficient decreased significantly after the violence (p < 0.001, p = 0.019, and p = 0.045, respectively). Real-life functioning had a higher node strength. The strength of sleeping, lack of spontaneity and flow of conversation, and preoccupation were decreased in post-violence network of patients. Conclusion: The decreasing connectivity may indicate an increased risk of violence and early warning for detecting violence. Interventions and improving health state based on nodes with high strength might prevent violence in schizophrenia patients.

Improved Safety of Hybrid Electroconvulsive Therapy Compared With Standard Electroconvulsive Therapy in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Parallel-Group Pilot Trial.

Objectives: ECT is a rapid and effective treatment for depression. While efficacy is often remarkable over the initial 3-4 sessions, the efficacy of later sessions is less rapid, and the side-effects, especially cognitive impairment limit its use. To preliminarily compare the efficacy and acceptability of a novel hybrid-ECT (HECT) protocol for patients with major depressive disorder (MDD) with standard ECT, we conducted this pilot trial. Methods: Thirty patients were randomly assigned to ECT or HECT. Both arms received three ECT sessions (phase 1) but, in phase 2, the HECT arm received low-charge electrotherapy instead of ECT. The primary outcome was the change in 24-item Hamilton depression rating scale (HAMD-24) scores between baseline and the end of treatment. Cognitive function was assessed by repeatable battery for the assessment of neuropsychological status (RBANS), Stroop color word, and orientation recovery tests (ORT). Safety was measured by the drop-out rate and adverse events (AEs). Four visits were conducted at baseline, post-phase 1, post-phase 2, and at 1-month follow-up. Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/), identifier: ChiCTR1900027701. Results: Patients in both arms showed significant within-group improvements in HAMD-24, but the between-group differences were non-significant. Participants in the HECT arm outperformed ECT patients for most cognitive tests at the end of treatment or at follow-up. There was a significantly lower AE rate and shorter ORT in phase 2 of the HECT ar. Conclusion: In this pilot trial, HECT was associated with fewer AEs and better cognitive function including executive and memory function, but its possible similar antidepressive efficacy needs to be further investigated in future.

Parkin-mediated mitophagy protects against TNF-α-induced stress in bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMSCs) have been investigated as cellular therapeutics for intervertebral disc degeneration. However, transplanted BMSCs are prone to be damaged. TNF-α is reported to extensively promote degeneration process. Nevertheless, the relationship between BMSCs senescence and TNF-α-induced stress has not been elucidated. Previous studies showed that mitophagy is a crucial factor in maintaining cellular homeostasis. Hence, we sought to clarify the role and mechanism of mitophagy in TNF-α-induced biological changes of BMSCs. Here, we found that TNF-α caused transient senescent damage in the early stage. Meanwhile, Parkin-mediated mitophagy was initiated and weakened the damage through maintaining mitochondria homeostasis. After inhibiting mitophagy by knockdown of Parkin, TNF-α irreversibly caused cellular senescence. These results suggested that Parkin-mediated mitophagy played protective role in BMSCs in response to TNF-α, which could be a crucial therapeutic target in the future.

The integrated understanding of structural and functional connectomes in depression: A multimodal meta-analysis of graph metrics.

BACKGROUND: From the perspective of information processing, an integrated understanding of the structural and functional connectomes in depression patients is important, a multimodal meta-analysis is required to detect the robust alterations in graph metrics across studies. METHODS: Following a systematic search, 952 depression patients and 1447 controls in nine diffusion magnetic resonance imaging (dMRI) and twelve rest state functional MRI (rs-fMRI) studies with high methodological quality met the inclusion criteria and were included in the meta-analysis. RESULTS: Regarding the dMRI results, no significant differences of meta-analytic metrics were found; regarding the rs-fMRI results, the modularity and local efficiency were found to be significantly lower in the depression group than in the controls (Hedge's g = -0.330 and -0.349, respectively). CONCLUSION: Our findings suggested a lower modularity and network efficiency in the rs-fMRI network in depression patients, indicating that the pathological imbalances in brain connectomes needs further exploration. LIMITATIONS: Included number of trials was low and heterogeneity should be noted.