Uncovering the Neural Correlates of Anhedonia Subtypes in Major Depressive Disorder: Implications for Intervention Strategies.

Major depressive disorder (MDD) represents a serious public health concern, negatively affecting individuals' quality of life and making a substantial contribution to the global burden of disease. Anhedonia is a core symptom of MDD and is associated with poor treatment outcomes. Variability in anhedonia components within MDD has been observed, suggesting heterogeneity in psychopathology across subgroups. However, little is known about anhedonia subgroups in MDD and their underlying neural correlates across subgroups. To address this question, we employed a hierarchical cluster analysis based on Temporal Experience of Pleasure Scale subscales in 60 first-episode, drug-naive MDD patients and 32 healthy controls. Then we conducted a connectome-wide association study and whole-brain voxel-wise functional analyses for identified subgroups. There were three main findings: (1) three subgroups with different anhedonia profiles were identified using a data mining approach; (2) several parts of the reward network (especially pallidum and dorsal striatum) were associated with anticipatory and consummatory pleasure; (3) different patterns of within- and between-network connectivity contributed to the disparities of anhedonia profiles across three MDD subgroups. Here, we show that anhedonia in MDD is not uniform and can be categorized into distinct subgroups, and our research contributes to the understanding of neural underpinnings, offering potential treatment directions. This work emphasizes the need for tailored approaches in the complex landscape of MDD. The identification of homogeneous, stable, and neurobiologically valid MDD subtypes could significantly enhance our comprehension and management of this multifaceted condition.

Maternal Vitamin D and Inulin Supplementation in Oxidized Oil Diet Improves Growth Performance and Hepatic Innate Immunity in Offspring Mice.

Dietary oxidized fat contains harmful materials such as hydrogen peroxide and malondialdehyde (MDA). Excessive oxidized fat intake during pregnancy and lactation not only leads to maternal body injury but also damages offspring health. Our previous study demonstrated that vitamin D (VD) had antioxidative capability in sows. This study was conducted to investigate the effect of maternal VD and inulin supplementation in oxidized oil diet on the growth performance and oxidative stress of their offspring. Sixty 5-month-old C57BL/6N female mice were randomly divided into five groups: Control group (basal diet, n = 12), OF group (oxidized-soybean-oil-replaced diet, n = 12), OFV group (oxidized-soybean-oil-replaced diet + 7000 IU/kg VD, n = 12), OFI group (oxidized-soybean-oil-replaced diet + 5% inulin, n = 12) and OFVI group (oxidized-soybean-oil-replaced diet + 7000 IU/kg VD + 5% inulin, n = 12). Mice were fed with the respective diet during pregnancy and lactation. The offspring were then slaughtered on day 21 of age at weaning. Results showed that a maternal oxidized oil diet impaired body weight and liver weight gain of offspring during lactation compared to the control group, while maternal VD, inulin or VD and inulin mixture supplementation reversed this effect. In addition, the activity of T-AOC in the liver of offspring was lower in the OF group than that in the control group, but could be restored by maternal VD and inulin mixture supplementation. Furthermore, the gene expression of both proinflammatory and anti-inflammatory cytokines, such as Il-6, Tnfα and Il-10, in offspring liver were downregulated by a maternal oxidized oil diet compared with the control group, but they were restored by maternal VD or VD and inulin mixture supplementation. The expressions of Vdr and Cyp27a1 were decreased by a maternal oxidized oil diet compared with the control group, while they could be increased by VD or VD and inulin mixture supplementation. Conclusion: maternal oxidized oil diet intake could impair the growth performance by inducing oxidative stress, but this can be relieved by maternal VD and inulin supplementation.

Abnormal long- and short-range functional connectivity in patients with first-episode drug-naïve melancholic and non-melancholic major depressive disorder.

BACKGROUND: We attempted to explore the common and distinct long- and short-range functional connectivity (FC) patterns of melancholic and non-melancholic major depressive disorder (MDD) and their associations with clinical characteristics. METHODS: Fifty-nine patients with first-episode drug-naïve MDD, including 31 patients with melancholic features and 28 patients with non-melancholic features, underwent resting-state functional magnetic resonance imaging (fMRI) scanning to examine long- and short-range FC. Thirty-two healthy volunteers were recruited as controls. The support vector machines (SVM) was applied to distinguish the melancholic patients from the non-melancholic patients by using the FC of abnormal brain regions. RESULTS: Compared to healthy volunteers, patients with MDD showed increased long-range positive FC (lpFC) in the right insula/inferior frontal gyrus and left insula. Relative to non-melancholic patients, melancholic patients displayed decreased lpFC in the right lingual gyrus, decreased short-range positive FC (spFC) in the right middle temporal gyrus and right superior parietal lobule, increased lpFC in the left inferior parietal lobule, and increased spFC in the left middle occipital gyrus/inferior occipital gyrus, left cerebellum VII/IX, and bilateral cerebellum CrusII. Increased lpFC in the left inferior parietal lobule in melancholic patients was correlated with the TEPS abstract anticipatory scores. SVM results showed that FCs of five combinations within different brain regions could distinguish melancholic patients from non-melancholic patients. CONCLUSIONS: FC abnormalities in the default mode network and parietal-occipital brain regions may underlie the neurobiology of melancholic MDD. An increased lpFC in the left inferior parietal lobule correlated with anhedonia may be a distinctive neurobiological feature of melancholic MDD.

Overlapping and segregated changes of functional hubs in melancholic depression and non-melancholic depression.

BACKGROUND: Previous research found associations between neuropsychiatric disorders and patterns of highly connected "hub" nodes, which are crucial in coordinating brain functions. Melancholic depression is considered a relatively distinct and homogenous subtype of major depressive disorder (MDD), which responds better to pharmacological treatments than placebos or psychotherapies. Accordingly, melancholic depression probably has distinct neuropathological underpinnings. This study aims to examine the overlapping and segregated changes of functional hubs in melancholic and non-melancholic MDD. METHODS: Thirty-one melancholic patients, 28 non-melancholic patients, and 32 healthy controls were included. Resting-state functional imaging data were analyzed using global functional connectivity. RESULTS: Both melancholic and non-melancholic patients had increased GFC in the bilateral insula and decreased GFC in the PCC/precuneus compared to HCs. The distinction was that melancholic patients showed increased GFC in the bilateral thalamus, right inferior parietal lobule (IPL), and left cerebellum Crus I and decreased GFC in the left temporal lobe, whereas non-melancholic patients showed increased GFC in the left superior parietal lobe. Additionally, compared with non-melancholic patients, melancholic individuals displayed significant increases of GFC in the left IPL and cerebellum. CONCLUSION: Increased GFC of the insula and decreased GFC of the PCC and precuneus are the common abnormalities of melancholic and non-melancholic MDD. Hyperconnectivity of the IPL and cerebellum might be distinctive neuropathological features of melancholic MDD.

The Psychopathology of Worthlessness in Depression.

Background: Despite common dissatisfaction with the syndromic heterogeneity of major depression, investigations into its symptom structure are scarce. Self-worthlessness/inadequacy is a distinctive and consistent symptom of major depression across cultures. Aims: We investigated whether self-worthlessness is associated with self-blaming attribution-related symptoms or is instead an expression of reduced positive feelings overall, as would be implied by reduced positive affect accounts of depression. Methods: 44,161 undergraduate students in Study 1, and 215 patients with current Major Depressive Disorder (MDD) and 237 age-matched healthy control participants in Study 2 completed the well-validated Symptom Check List-90. Depression-relevant items were used to construct regularized partial correlation networks with bootstrap estimates of network parameter variability. Results: Worthlessness co-occurred more strongly with other symptoms linked to self-blaming attributions (hopelessness, and self-blame), displaying a combined edge weight with these symptoms which was significantly stronger than the edge weight representing its connection with reduced positive emotion symptoms (such as reduced pleasure/interest/motivation, difference in edge weight sum in Study 1 = 2.95, in Study 2 = 1.64; 95% confidence intervals: Study 1: 2.6-3.4; Study 2: 0.02-3.5; Bonferroni-corrected p < 0.05). Conclusions: This confirms the prediction of the revised learned helplessness model that worthlessness is most strongly linked to hopelessness and self-blame. In contrast, we did not find a strong and direct link between anhedonia items and a reduction in self-worth in either study. This supports worthlessness as a primary symptom rather than resulting from reduced positive affect.

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.

Anhedonia reduction correlates with increased ventral caudate connectivity with superior frontal gyrus in depression.

This study was to investigate the relationship between the ventral caudate connectivity and anhedonia. Nineteen depressed patients and 16 healthy controls participated in two identical functional magnetic resonance imaging scans during a 1-year period to determine the resting-state functional connectivity changes using a seed-based approach. Patients showed increased left ventral caudate functional connectivity with superior frontal gyrus over time and the increased connectivity was associated with anhedonia improvement. None of these associations were observed in healthy controls. The findings suggest that left ventral caudate may serve as a potential target to improve the severity of anhedonia.

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.

The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder.

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.

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.

Abnormal Default-Mode Network Homogeneity in Melancholic and Nonmelancholic Major Depressive Disorder at Rest.

Background: Melancholic depression has been assumed as a severe type of major depressive disorder (MDD). We aimed to explore if there were some distinctive alterations in melancholic MDD and whether the alterations could be used to discriminate the melancholic MDD and nonmelancholic MDD. Methods: Thirty-one outpatients with melancholic MDD, thirty-three outpatients with nonmelancholic MDD, and thirty-two age- and gender-matched healthy controls were recruited. All participants were scanned by resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with the network homogeneity (NH) and support vector machine (SVM) methods. Results: Both patient groups exhibited increased NH in the right PCC/precuneus and right angular gyrus and decreased NH in the right middle temporal gyrus compared with healthy controls. Compared with nonmelancholic patients and healthy controls, melancholic patients exhibited significantly increased NH in the bilateral superior medial frontal gyrus and decreased NH in the left inferior temporal gyrus. But merely for melancholic patients, the NH of the right middle temporal gyrus was negatively correlated with TEPS total and contextual anticipatory scores. SVM analysis showed that a combination of NH values in the left superior medial frontal gyrus and left inferior temporal gyrus could distinguish melancholic patients from nonmelancholic patients with accuracy, sensitivity, and specificity of 79.66% (47/59), 70.97% (22/31), and 89.29%(25/28), respectively. Conclusion: Our findings showed distinctive network homogeneity alterations in melancholic MDD which may be potential imaging markers to distinguish melancholic MDD and nonmelancholic MDD.

Shared and distinct homotopic connectivity changes in melancholic and non-melancholic depression.

OBJECTIVE: Previous studies have revealed different neuroimaging features between melancholic and non-melancholic major depressive disorder (MDD). However, homotopic connectivity of melancholic and non-melancholic MDD remains unknown. The present study aimed to explore common and distinct homotopic connectivity patterns of melancholic and non-melancholic MDD and their associations with clinical characteristics. METHODS: Sixty-four patients with MDD and thirty-two healthy controls were scanned by resting-state functional magnetic resonance imaging (fMRI). Voxel-mirrored homotopic connectivity (VMHC) and pattern classification were applied to analyze the imaging data. RESULTS: Relative to healthy controls, melancholic patients displayed decreased VMHC in the fusiform gyrus, posterior cingulate cortex (PCC), superior occipital gyrus (SOG), postcentral gyrus and precentral/postcentral gyrus, and non-melancholic patients displayed decreased VMHC in the PCC. Compared with non-melancholic patients, melancholic patients displayed reduced VMHC in the precentral gyrus and precentral/postcentral gyrus. Support vector machine (SVM) results exhibited VMHC in the precentral gyrus could distinguish melancholic patients from non-melancholic patients with more than 0.6 for specificity, sensitivity and accuracy. CONCLUSION: The study demonstrated common and distinct homotopic connectivity patterns in melancholic and non-melancholic patients. Decreased VMHC in the PCC may be a state-related change for depression, and reduced VMHC in the precentral gyrus and postcentral gyrus may be a distinctive neurobiological feature for melancholic MDD. VMHC in precentral gyrus might be served as potential imaging markers to discriminate melancholic patients from non-melancholic MDD.

Disrupted Regional Homogeneity in Melancholic and Non-melancholic Major Depressive Disorder at Rest.

Background: Melancholic depression has been viewed as one severe subtype of major depressive disorder (MDD). However, it is unclear whether melancholic depression has distinct changes in brain imaging. We aimed to explore specific or distinctive alterations in melancholic MDD and whether the alterations could be used to separate melancholic MDD from non-melancholic MDD or healthy controls. Materials and Methods: Thirty-one outpatients with melancholic MDD and thirty-three outpatients with non-melancholic MDD and thirty-two age- and gender-matched healthy controls were recruited. All participants were scanned by resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with the regional homogeneity (ReHo) and support vector machine (SVM) methods. Results: Melancholic MDD patients exhibited lower ReHo in the right superior occipital gyrus/middle occipital gyrus than non-melancholic MDD patients and healthy controls. Merely for non-melancholic MDD patients, decreased ReHo in the right middle frontal gyrus was negatively correlated with the total HRSD-17 scores. SVM analysis results showed that a combination of abnormal ReHo in the right fusiform gyrus/cerebellum Crus I and the right superior occipital gyrus/middle occipital gyrus exhibited the highest accuracy of 83.05% (49/59), with a sensitivity of 90.32% (28/31), and a specificity of 75.00% (21/28) for discriminating patients with melancholic MDD from patients with non-melancholic MDD. And a combination of abnormal ReHo in the right fusiform gyrus/cerebellum VI and left postcentral gyrus/precentral gyrus exhibited the highest accuracy of 98.41% (62/63), with a sensitivity of 96.77% (30/31), and a specificity of 100.00%(32/32) for separating patients with melancholic MDD from healthy controls. Conclusion: Our findings showed the distinctive ReHo pattern in patients with melancholic MDD and found brain area that may be associated with the pathophysiology of non-melancholic MDD. Potential imaging markers for discriminating melancholic MDD from non-melancholic MDD or healthy controls were reported.

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.

Differentiating Melancholic and Non-melancholic Major Depressive Disorder Using Fractional Amplitude of Low-Frequency Fluctuations.

BACKGROUND: Melancholic major depressive disorder (MDD) is a network-based brain disorder. However, whether or not network-based changes can be applied to differentiate melancholic (MEL) from non-melancholic (NMEL) MDD remains unclear. METHODS: Thirty-one MEL patients, 28 NMEL patients, and 32 matched healthy controls (HCs) were scanned using resting-state functional magnetic resonance imaging. Patients were assessed by the Chinese version of Snaith-Hamilton Pleasure Scale (SHAPS-C) and Temporal Experience of Pleasure Scale (TEPS). Fractional amplitude of low-frequency fluctuations (fALFF) and correlation analysis were used to analyze the data. RESULTS: Compared with HCs, the MEL group had significantly higher fALFF values in the bilateral inferior frontal gyrus and right supplementary motor area (SMA) and significantly lower fALFF values in the right inferior occipital gyrus (IOG), right middle temporal gyrus (MTG)/left IOG, and bilateral superior occipital gyrus (SOG)/MTG. On the other hand, the NMEL group showed significantly higher fALFF values in the bilateral SMA and significantly lower fALFF values in the bilateral posterior cingulate cortex/precuneus relative to HCs. Compared with the NMEL group, the MEL group showed significantly lower fALFF values in the left anterior cingulate cortex (ACC). A correlation was found between the fALFF values of the right SMA and the SHAPS-C in the MEL group. In addition, correlations were observed between the fALFF values of the left ACC and the TEPS contextual consummatory and total scores in all patients. CONCLUSION: Our study uncovered that MDD exhibited altered brain activity in extensive brain networks, including the default-mode network, frontal-striatal network, reward system, and frontal-limbic network. Decreased fALFF in the left ACC might be applied to differentiate the two subtypes of MDD.

Conductive polyaniline-mediated efficient electron transfer in Z-scheme photocatalysts for enhanced overall water splitting.

Here, we demonstrate that conductive polyaniline (PANI) can function as a solid redox mediator to efficiently shuttle photogenerated electrons from BiVO4 to Ru/SrTiO3:Rh, thus greatly promoting the separation of electrons and holes and nearly quadrupling the overall water splitting activity under visible light irradiation (λ ≥ 420 nm).

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.

Biotypes of major depressive disorder: Neuroimaging evidence from resting-state default mode network patterns.

BACKGROUND: Major depressive disorder (MDD) is heterogeneous disorder associated with aberrant functional connectivity within the default mode network (DMN). This study focused on data-driven identification and validation of potential DMN-pattern-based MDD subtypes to parse heterogeneity of the disorder. METHODS: The sample comprised 1397 participants including 690 patients with MDD and 707 healthy controls (HC) registered from multiple sites based on the REST-meta-MDD Project in China. Baseline resting-state functional magnetic resonance imaging (rs-fMRI) data was recorded for each participant. Discriminative features were selected from DMN between patients and HC. Patient subgroups were defined by K-means and principle component analysis in the multi-site datasets and validated in an independent single-site dataset. Statistical significance of resultant clustering were confirmed. Demographic and clinical variables were compared between identified patient subgroups. RESULTS: Two MDD subgroups with differing functional connectivity profiles of DMN were identified in the multi-site datasets, and relatively stable in different validation samples. The predominant dysfunctional connectivity profiles were detected among superior frontal cortex, ventral medial prefrontal cortex, posterior cingulate cortex and precuneus, whereas one subgroup exhibited increases of connectivity (hyperDMN MDD) and another subgroup showed decreases of connectivity (hypoDMN MDD). The hyperDMN subgroup in the discovery dataset had age-related severity of depressive symptoms. Patient subgroups had comparable demographic and clinical symptom variables. CONCLUSIONS: Findings suggest the existence of two neural subtypes of MDD associated with different dysfunctional DMN connectivity patterns, which may provide useful evidence for parsing heterogeneity of depression and be valuable to inform the search for personalized treatment strategies.

Reduced default mode network functional connectivity in patients with recurrent major depressive disorder.

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

Association between T-182C, G1287A polymorphism in NET gene and suicidality in major depressive disorder in Chinese patients.

Objective: Previous studies have implicated norepinephrine transporter gene (NET) polymorphisms in the etiology of major depressive disorder (MDD). A functional NET T-182C polymorphism (rs2242446) in the promoter region and a synonymous polymorphisms G1287A in the exon 9 (rs5569) were associated with MDD in different populations. However, few studies have focused on the relationship between these polymorphisms and MDD patients with suicidality. The objective of the present study was to examine whether the two polymorphisms are associated with MDD patients with suicidality in the Han Chinese population. Methods: Two hundred and sixty-three suicidal depressed patients and 241 non-suicidal depressed patients who met DSM-IV criteria for MDD were recruited from our hospital. Three hundred and three unrelated, age- and sex-matched healthy control subjects participated in this case-control study. Suicidality was assessed using Mini International Neuropsychiatric Interview (MINI) and the Hamilton rating scale for depression (HAMD). Genotypes of T-182C polymorphism (rs2242446) and G1287A (rs5569) were screened by polymerase chain reaction. Results: No statistical significant differences between patients and controls were found for any of the analysed polymorphisms, either in the genotype or allele distribution. Conclusions: Our results suggest that the investigated polymorphisms are not major susceptibility factors in the etiology of MDD with suicidality. However, the results must be verified in larger samples and different ethnicities.