Study on the Interaction Between C3 Gene Polymorphism and Environment in Patients with Type 2 Diabetes Combined with Coronary Artery Disease.

Objective: This study was conducted to investigate the combined effect of genetic variation in the C3 gene and environmental factors on the risk of type 2 diabetes mellitus(T2DM) and coronary artery disease(CAD) in a population from Xinjiang, China. Methods: We conducted a hospital-based case-control study with 896 participants (217 with T2DM+CAD and 679 healthy controls). A polymerase chain reaction-ligase detection reaction was used to identify and genotype TagSNPs in the C3 gene, and the influence of the interaction of two SNP loci (rs1047286 and rs11569562) with the environment on T2DM combined with CAD was evaluated through clinical data, statistical analysis of gene frequencies, and the formation of a gene-environment interaction model. Results: We find that rs11569562 GG is an independent protective factor for T2DM and CAD (OR=0.353, p=0.012), and the variants at its locus may be closely associated with Activated Partial Thromboplastin Time (APTT), lipoprotein a (Lp(a)), Apolipoprotein A (APOA), Aspartate Aminotransferase (AST), Aspartate Aminotransferase (ALT) and AST/ALT levels (all P < 0.05); its GG genotype has significantly lower Gensini score and number of stenoses than the GA and AA genotypes. Multifactorial dimensionality reduction (MDR) finds a strong correlation between rs11569562 and AST (antagonistic effect) (4.44%); the role of rs11569562's influence remains strong in terms of the independent effects of each attribute (1.72%). Conclusions: In this study, we find that variants in the C3 gene loci rs11569562 are associated with the incidence of type 2 diabetes mellitus combined with coronary heart disease in a Chinese population. It is expected to be an independent predictor of type 2 diabetes mellitus combined with coronary heart disease in the Chinese population. Rs11569562 may be associated with lipid levels and coagulation molecules. Clinical Trial Registration: This trial registered on in 2014 at the China Clinical Trials Registry (ChiCTR-TRC-14005114).

The efficacy of electroconvulsive therapy in adolescent major depressive disorder with suicidal ideation: A propensity score-matched, retrospective cohort study.

BACKGROUND: More evidence is needed to validate the use of ECT in adolescent depression. This study aims to compare the effectiveness of electroconvulsive therapy (ECT) to conventional medication therapy for adolescents with major depression with suicidal ideation. METHODS: In this retrospective cohort study, we reviewed inpatient records from the First Affiliated Hospital of Chongqing Medical University spanning December 2016 to June 2021. We focused on adolescents diagnosed with severe depression presenting with suicidal tendencies. To equalize baseline differences between patients, we used the one-to-one propensity score matching to match patients who received ECT treatment with those who did not. Multivariate regression analysis was utilized to adjust for potential confounders, and subgroup analyses and sensitivity analyses were conducted to verify the robustness of our findings. RESULTS: Of the 626 patients in this study, 474 underwent ECT treatment while 152 received medication treatment, all aged between 10 and 18 years. Once matched, each group contained 143 patients. The ECT group demonstrated a significantly higher response rate and greater reductions in both Hamilton Depression Rating Scale and Hamilton Anxiety Scale scores (all P < 0.001). Additionally, the ECT group was more effective in reducing suicidal ideation, with fewer individuals retaining such ideation at discharge. In the multivariable regression analysis, both ECT treatment and shorter disease duration were independently linked to enhanced antidepressant efficacy. Subgroup analyses and sensitivity analyses verified the robustness of the main study effect. CONCLUSIONS: For adolescents with major depressive disorder and suicidal ideation, combining ECT with pharmacotherapy is more effective than pharmacotherapy alone before medications reach full effect.

Functional Abnormality of the Reward System in Depressed Adolescents and Young Adults with and without Suicidal Behavior.

OBJECTIVE: To identify local and functional connectivity abnormalities in the brain's reward network in depressed adolescents and young adults with and without suicidal behavior. METHODS: Magnetic resonance imaging data were obtained from 41 major depressive disorder (MDD) patients with suicidal behavior (sMDD, males/females: 12/29), 44 MDD patients without suicidal behavior (nMDD, males/females: 13/32), and 52 healthy controls (HCs, males/females: 17/35). The Young Mania Scale, Hamilton Depression Scale, Columbia Suicide Scale, and Scale for Suicide Ideation were used to evaluate emotional state and suicidal ideation and behaviors. The amplitude of low frequency fluctuations (ALFF), regional homogeneity (ReHo) and functional connectivity of 11 regions of interest (ROIs) in the reward network were determined. RESULTS: ALFF values in the vmPFC of the nMDD group were significantly lower than those in the HC group (p = 0.031). The ReHo values of the nMDD group were lower in the lVS but higher in the vmPFC than those of the HC group (P = 0.018 and 0.025, respectively). Functional connectivity of the AC with the vmPFC, lVS, rVS, and vmPFC was increased in the sMDD group compared with that in the nMDD group (P = 0.038, 0.034, 0.006, respectively). CONCLUSION: Local and functional connectivity abnormalities in the reward network were found in the MDD groups. However, increased functional connectivity was found in only the sMDD group.

Personality traits predict treatment outcome of an antidepressant in untreated adolescents with depression: An 8-week, open-label, flexible-dose study.

BACKGROUND: Antidepressant response in adults with major depressive disorder (MDD) is probably influenced by personality dimensions. However, personality dimensions in depression and their association with antidepressant treatment in adolescents are relatively unknown. We sought to investigate whether personality traits (PTs) can influence antidepressant treatment response in adolescents with depression. METHODS: Eighty-two adolescents with MDD who had completed the 8 weeks of treatment with selective serotonin reuptake inhibitors (SSRI) were enrolled. The Revised NEO Five-Factor Inventory (NEO-FFI-R) was used to measure their personality at baseline, and the 17-item Hamilton Depression Rating Scale (HAMD-17) and Children's Depression Rating Scale-Revised (CDRS-R) were used to evaluate depressive symptoms at baseline and 8 weeks. Moreover, logistic regression was performed to investigate the relationship between personality dimensions and antidepressant response. Receiver operating characteristic analyses were employed to determine the accuracy of a PT-based model in predicting the antidepressant response rate. RESULTS: Adolescents with MDD had significantly different PTs at baseline. Multivariable logistic regression analysis showed that extroversion scores were associated with response to antidepressant treatment, the lower the extroversion score, the better the response to antidepressant treatment, after correcting for variables with significant differences and trends or all potential confounding variables. It was also found that the combination of disease duration, extraversion-gregariousness, and agreeableness-trust effectively predicted antidepressant response in adolescents with MDD, with a sensitivity of 79.4 % and specificity of 68.7 %. CONCLUSION: Personality dysfunction in adolescents is associated with MDD. The antidepressant treatment response is influenced by the degree of extroversion in adolescents with MDD.

FOXO3a functions as a transcriptional and co-transcriptional splicing regulator in vascular endothelial cell lines.

Recent studies have indicated a connection between Forkhead box O3a protein and coronary artery disease, yet the exact role of FOXO3a in the regulation of metabolic processes and apoptosis in vascular endothelial cells is still unknown. Therefore, we investigated the role of FOXO3a on target genes in a human vascular endothelial cell line. Through the utilization of high-throughput sequencing technology, we analyzed gene expression profiles and alternative splicing patterns in human vascular endothelial cells with FOXO3a over expression. This study identified 419 DEGs between FOXO3a-OE HUVEC model and control cells. KEGG analysis indicated that the upregulated genes were mainly enriched in inflammation-related signaling pathways, and the downregulated genes were enriched in lipid metabolism-related pathways.

Electroconvulsive therapy for adolescents with severe depressive episode and suicidality: retrospective comparison between responders and non-responders.

BACKGROUND: For adolescents with major depression who exhibit suicidal tendencies, Electroconvulsive Therapy (ECT) is increasingly adopted in clinical practice. Yet, the precise mechanisms behind its effectiveness remain elusive, and studies on factors that influence treatment outcomes are scarce. METHODS: In this retrospective comparative study, we included all adolescent severe depressive episode patients with suicidal tendencies admitted to the Psychiatry Department of the First Affiliated Hospital of Chongqing Medical University between 2017 and 2021 and received ECT treatment. By collecting data on personal history, medical history, and standard treatment features, we established demographic, disease, medication, and ECT treatment factors variables. Patients were divided into effective and ineffective groups based on the Clinical Global Impressions-Improvement (CGI-I) scale scores, and differences between outcomes were compared. Logistic regression analyses were used to identify factors independently associated with ineffectiveness. RESULTS: A total of 494 adolescent severe depressive episode patients with suicidal behavior who received ECT were included in this study. According to CGI-I scores, the treatment was effective in 361 patients (73.1%) and ineffective in 133 patients (26.9%). Logistic regression analyses showed that 8 to 12 and 12 to 16 ECT sessions reduced the risk of ineffectiveness compared to fewer than 4 sessions. The risk of ineffectiveness decreased with age and increased with comorbidity with obsessive-compulsive disorder (OCD). Compared to sertraline, escitalopram was associated with a heightened risk of futility, whereas olanzapine and aripiprazole demonstrated a reduced risk when contrasted with quetiapine. CONCLUSIONS: ECT's ineffectiveness in treating adolescent severe depressive episode with suicidal behavior decreases with age, and comorbidity with OCD significantly increases the risk of treatment failure. Fewer than 8 ECT sessions may hinder achieving satisfactory results.

Subanesthetic Dose of Ketamine Administered Before Each Electroconvulsive Therapy Session Improves Antidepressant and Sleep Quality Outcomes: A Randomized, Controlled Trial.

OBJECTIVES: The main purpose of this trial is to explore the effects of subanesthetic dose of ketamine on sleep quality and symptoms in patients with major depressive disorder undergoing bitemporal electroconvulsive therapy (ECT). METHODS: Seventy-one patients with major depressive disorder and sleep disturbance were randomly divided into 2 groups, namely, the ECT without ketamine group (group ES), receiving routine ECT and saline (3 mL) at each ECT session, and the ECT-assisted ketamine group (group KS), which received ECT and ketamine (3 mL) at each ECT session. The 24 Hamilton Depression Rating Scale was used to assess depressive symptoms and the Chinese Pittsburgh Sleep Quality Index was used to evaluate sleep quality. RESULTS: The patients in group KS required shorter ECT treatment sessions. Patients in group ES had lower sleep efficiency, longer sleep latency, and required more sleep medication than patients in group KS at the end of the ECT course. CONCLUSIONS: Subanesthetic dose of ketamine improved sleep quality and enhanced ECT therapeutic effects in patients with sleep disturbance.

Psychiatric symptoms in a female with subacute combined degeneration of the spinal cord (SCD): a case report.

BACKGROUND: Subacute combined degeneration of the spinal cord (SCD) is mainly caused by deficiency of Vitamin B12 and characterized by deep hypoesthesia, sensory ataxia and spasmodic paralysis of lower limbs. SCD often accompanies with megaloblastic anemia. Psychiatric symptoms could be the initial manifestations of SCD by lack of Vitamin B12, but are rarely considered secondary to physical discomfort and psychological factors in SCD. Additionally, treatment experience for psychiatric symptoms in SCD remains little reported. CASE REPORT: We presented a case of a 37-year-old female who complained of being persecuted and controlled for one week and thus was admitted to the psychiatry department. Before that, she had went through persistent paresthesia and numbness of her lower extremities for two-month. Low Vitamin B12 level and hemoglobin concentration, neurologic symptoms and bone marrow smear results supported the clinical diagnosis of SCD and megaloblastic anemia. With supplementation of Vitamin B12 and blood transfusion and short-term prescription of antipsychotics and antidepressants, physical symptoms were improved and psychological symptoms disappeared within 2 weeks. CONCLUSIONS: Psychiatric symptoms of SCD could be generated from lack of Vitamin B12, anemia and neurologic symptoms, where short-term use of antipsychotics and antidepressants may be effective.

Association Between Serum Uric Acid Levels and Suicide Attempts in Adolescents and Young Adults with Major Depressive Disorder: A Retrospective Study.

Purpose: Uric acid (UA) is thought to exert neuroprotective roles. The purpose of this study was to examine the association of serum UA with suicide attempts (SA) in adolescents and young adults with major depressive disorder (MDD). Patients and Methods: We retrospectively recruited 533 participants with MDD aged 13 to 25 years, of which 168 had a history of SA in the past three months and 365 did not have a history of SA. Serum UA levels were measured using the uricase-peroxidase coupling method. In addition to overall serum UA level comparison in MDD individuals with and without SA, a stratified analysis by biological sex was carried out. Results: Compared to MDD individuals without a history of SA, serum UA levels were significantly lower in MDD individuals with SA (P < 0.001). Female MDD, but not male MDD individuals, with SA exhibited lower levels of UA than those without SA (P < 0.01). Importantly, serum UA remained significantly associated with SA in MDD individuals (OR = 0.996, 95% CI: 0.993~0.999, P < 0.01) when controlling for possible confounding variables. Conclusion: This research identifies a relationship between serum UA levels and SA in adolescents and young adults with MDD. UA may represent a biological risk marker for SA, in particular for female MDD individuals.

Changes in the amplitude of low-frequency fluctuations in specific frequency bands in major depressive disorder after electroconvulsive therapy.

BACKGROUND: Major depressive disorder (MDD) tends to have a high incidence and high suicide risk. Electroconvulsive therapy (ECT) is currently a relatively effective treatment for MDD. However, the mechanism of efficacy of ECT is still unclear. AIM: To investigate the changes in the amplitude of low-frequency fluctuations in specific frequency bands in patients with MDD after ECT. METHODS: Twenty-two MDD patients and fifteen healthy controls (HCs) were recruited to this study. MDD patients received 8 ECT sessions with bitemporal placement. Resting-state functional magnetic resonance imaging was adopted to examine regional cerebellar blood flow in both the MDD patients and HCs. The MDD patients were scanned twice (before the first ECT session and after the eighth ECT session) to acquire data. Then, the amplitude of low-frequency fluctuations (ALFF) was computed to characterize the intrinsic neural oscillations in different bands (typical frequency, slow-5, and slow-4 bands). RESULTS: Compared to before ECT (pre-ECT), we found that MDD patients after the eighth ECT (post-ECT) session had a higher ALFF in the typical band in the right middle frontal gyrus, posterior cingulate, right supramarginal gyrus, left superior frontal gyrus, and left angular gyrus. There was a lower ALFF in the right superior temporal gyrus. Compared to pre-ECT values, the ALFF in the slow-5 band was significantly increased in the right limbic lobe, cerebellum posterior lobe, right middle orbitofrontal gyrus, and frontal lobe in post-ECT patients, whereas the ALFF in the slow-5 band in the left sublobar region, right angular gyrus, and right frontal lobe was lower. In contrast, significantly higher ALFF in the slow-4 band was observed in the frontal lobe, superior frontal gyrus, parietal lobe, right inferior parietal lobule, and left angular gyrus. CONCLUSION: Our results suggest that the abnormal ALFF in pre- and post-ECT MDD patients may be associated with specific frequency bands.

Serum extracellular vesicle microRNA dysregulation and childhood trauma in adolescents with major depressive disorder.

Major depressive disorder (MDD) seriously endangers adolescent mental and physical health. Extracellular vesicles (EVs) are mediators of cellular communication and are involved in many physiological brain processes. Although EV miRNAshave been implicated in adults with major psychiatric disorders, investigation into their effects in adolescent MDDremains scarce. In discovery set, we conducted a genome-wide miRNA sequencing of serum EVs from 9 untreated adolescents with MDD and 8 matched healthy controls (HCs), identifying 32 differentially expressed miRNAs (18 upregulated and 14 downregulated). In the validation set, 8 differentially expressed and highly enriched miRNAs were verified in independent samples using RT-PCR, with 4 (miR-450a-2-3p, miR-3691-5p, miR-556-3p, and miR-2115-3p) of the 8 miRNAs found to be significantly elevated in 34 untreated adolescents with MDD compared with 38 HCs and consistent with the sequencing results. After the Bonferroni correction, we found that three miRNAs (miR-450a-2-3p, miR-556-3p, and miR-2115-3p) were still significantly different. Among them, miR-450a-2-3p showed the most markeddifferential expression and was able to diagnose disease with 67.6% sensitivity and 84.2% specificity. Furthermore, miR-450a-2-3p partially mediated the associations between total childhood trauma, emotional abuse, and physical neglect and adolescent MDD. We also found that the combination of miR-450a-2-3p and emotional abuse could effectively diagnose MDD in adolescents with 82.4% sensitivity and 81.6% specificity. Our data demonstrate the association of serum EV miRNA dysregulation with MDD pathophysiology and, furthermore, show that miRNAs may mediate the relationship between early stress and MDD susceptibility. We also provide a valid integrated model for the diagnosis of adolescent MDD.

Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Current progress in neuroimaging research for the treatment of major depression with electroconvulsive therapy.

Electroconvulsive therapy (ECT) uses a certain amount of electric current to pass through the head of the patient, causing convulsions throughout the body, to relieve the symptoms of the disease and achieve the purpose of treatment. ECT can effectively improve the clinical symptoms of patients with major depression, but its therapeutic mechanism is still unclear. With the rapid development of neuroimaging technology, it is necessary to explore the neurobiological mechanism of major depression from the aspects of brain structure, brain function and brain metabolism, and to find that ECT can improve the brain function, metabolism and even brain structure of patients to a certain extent. Currently, an increasing number of neuroimaging studies adopt various neuroimaging techniques including functional magnetic resonance imaging (MRI), positron emission tomography, magnetic resonance spectroscopy, structural MRI, and diffusion tensor imaging to reveal the neural effects of ECT. This article reviews the recent progress in neuroimaging research on ECT for major depression. The results suggest that the neurobiological mechanism of ECT may be to modulate the functional activity and connectivity or neural structural plasticity in specific brain regions to the normal level, to achieve the therapeutic effect.

Impaired robust interhemispheric function integration of depressive brain from REST-meta-MDD database in China.

BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Disrupted intrinsic functional brain topology in patients with major depressive disorder.

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Disrupted hemispheric connectivity specialization in patients with major depressive disorder: Evidence from the REST-meta-MDD Project.

BACKGROUND: Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied. METHODS: Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes). RESULTS: Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities. LIMITATIONS: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results. CONCLUSIONS: Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

Author Correction: Predicting individual responses to the electroconvulsive therapy with hippocampal subfield volumes in major depression disorder.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Resting-state functional connectivity of the anterior cingulate cortex in young adults depressed patients with and without suicidal behavior.

Functional alterations in the subregions of the anterior cingulate cortex (ACC) have been observed in patients with major depressive disorder (MDD). Studies have shown that higher depressive symptoms are associated with altered functional connectivity (FC) in different ACC sub-regions. Suicide is highly prevalent in patients with MDD; however, it is unclear whether suicidal behavior is associated with the FC alterations in the subregions of the ACC in these indibiduals. Seventy-six patients with MDD (41 with and 35 without a history of suicidal behavior) underwent functional magnetic resonance imaging (fMRI) and were assessed using the Hamilton Rating Scale for Depression (HAMD), the Scale for Suicide Ideation (SSI), and the Columbia Scale for Rating of Suicide Severity. We investigated the FC between the ACC subregions and other brain regions in young MDD patients with and without a history of suicidal behavior. The FC in the subregions of the ACC-superior frontal gyrus differed significantly between the two groups. Additionally, the anterior sgACC-right caudate FC and the pgACC-left insula FC were found to be abnormal in the suicidal MDD group. Interestingly, the suicidal ideation score positively correlated with decreased FC in the pgACC-superior frontal gyrus in both groups, but it negatively correlated with increased FC in the anterior sgACC-superior frontal gyrus in the non-suicidal MDD group. Our findings indicate that altered connections of subregions in the ACC may be involved in the neurological mechanisms underlying suicide in young adults with MDD.

Altered resting-state dynamic functional brain networks in major depressive disorder: Findings from the REST-meta-MDD consortium.

BACKGROUND: Major depressive disorder (MDD) is known to be characterized by altered brain functional connectivity (FC) patterns. However, whether and how the features of dynamic FC would change in patients with MDD are unclear. In this study, we aimed to characterize dynamic FC in MDD using a large multi-site sample and a novel dynamic network-based approach. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from a total of 460 MDD patients and 473 healthy controls, as a part of the REST-meta-MDD consortium. Resting-state dynamic functional brain networks were constructed for each subject by a sliding-window approach. Multiple spatio-temporal features of dynamic brain networks, including temporal variability, temporal clustering and temporal efficiency, were then compared between patients and healthy subjects at both global and local levels. RESULTS: The group of MDD patients showed significantly higher temporal variability, lower temporal correlation coefficient (indicating decreased temporal clustering) and shorter characteristic temporal path length (indicating increased temporal efficiency) compared with healthy controls (corrected p < 3.14×10-3). Corresponding local changes in MDD were mainly found in the default-mode, sensorimotor and subcortical areas. Measures of temporal variability and characteristic temporal path length were significantly correlated with depression severity in patients (corrected p < 0.05). Moreover, the observed between-group differences were robustly present in both first-episode, drug-naïve (FEDN) and non-FEDN patients. CONCLUSIONS: Our findings suggest that excessive temporal variations of brain FC, reflecting abnormal communications between large-scale bran networks over time, may underlie the neuropathology of MDD.