Identification Of Major Depressive Disorder Research Articles

Identifying neuroimaging biomarkers in major depressive disorder using machine learning algorithms and functional near-infrared spectroscopy (fNIRS) during verbal fluency task

One of the most prevalent psychiatric disorders is major depressive disorder (MDD), which increases the probability of suicidal ideation or untimely demise. Abnormal frontal hemodynamic changes detected by functional near-infrared spectroscopy (fNIRS) during verbal fluency task (VFT) have the potential to be used as an objective indicator for assessing clinical symptoms. However, comprehensive quantitative and objective assessment instruments for individuals who exhibit symptoms suggestive of depression remain undeveloped. Drawing from a total of 467 samples in a large-scale dataset comprising 289 MDD patients and 178 healthy controls, fNIRS measurements were obtained throughout the VFT. To identify unique MDD biomarkers, this research introduced a data representation approach for extracting spatiotemporal features from fNIRS signals, which were subsequently utilized as potential predictors. Machine learning classifiers (e.g., Gradient Boosted Decision Trees (GBDT) and Multilayer Perceptron) were implemented to assess the ability to predict selected features. The mean and standard deviation of the cross-validation indicated that the GBDT model, when combined with the 180-feature pattern, distinguishes patients with MDD from healthy controls in the most effective manner. The accuracy of correct classification for the test set was 0.829 ± 0.053, with an AUC of 0.895 (95 % CI: 0.864–0.925) and a sensitivity of 0.914 ± 0.051. Channels that made the most important contribution to the identification of MDD were identified using Shapley Additive Explanations method, located in the frontopolar area and the dorsolateral prefrontal cortex, as well as pars triangularis Broca's area. Assessment of abnormal prefrontal activity during the VFT in MDD serves as an objectively measurable biomarker that could be utilized to evaluate cognitive deficits and facilitate early screening for MDD. The model suggested in this research could be applied to large-scale case-control fNIRS datasets to detect unique characteristics of MDD and offer clinicians an objective biomarker-based analytical instrument to assist in the evaluation of suspicious cases.

Graph Autoencoders for Embedding Learning in Brain Networks and Major Depressive Disorder Identification.

Brain functional connectivity (FC) networks inferred from functional magnetic resonance imaging (fMRI) have shown altered or aberrant brain functional connectome in various neuropsychiatric disorders. Recent application of deep neural networks to connectome-based classification mostly relies on traditional convolutional neural networks (CNNs) using input FCs on a regular Euclidean grid to learn spatial maps of brain networks neglecting the topological information of the brain networks, leading to potentially sub-optimal performance in brain disorder identification. We propose a novel graph deep learning framework that leverages non-Euclidean information inherent in the graph structure for classifying brain networks in major depressive disorder (MDD). We introduce a novel graph autoencoder (GAE) architecture, built upon graph convolutional networks (GCNs), to embed the topological structure and node content of large fMRI networks into low-dimensional representations. For constructing the brain networks, we employ the Ledoit-Wolf (LDW) shrinkage method to efficiently estimate high-dimensional FC metrics from fMRI data. We explore both supervised and unsupervised techniques for graph embedding learning. The resulting embeddings serve as feature inputs for a deep fully-connected neural network (FCNN) to distinguish MDD from healthy controls (HCs). Evaluating our model on resting-state fMRI MDD dataset, we observe that the GAE-FCNN outperforms several state-of-the-art methods for brain connectome classification, achieving the highest accuracy when using LDW-FC edges as node features. The graph embeddings of fMRI FC networks also reveal significant group differences between MDD and HCs. Our framework demonstrates the feasibility of learning graph embeddings from brain networks, providing valuable discriminative information for diagnosing brain disorders.

Cross-Silo, Privacy-Preserving, and Lightweight Federated Multimodal System for the Identification of Major Depressive Disorder Using Audio and Electroencephalogram.

In this day and age, depression is still one of the biggest problems in the world. If left untreated, it can lead to suicidal thoughts and attempts. There is a need for proper diagnoses of Major Depressive Disorder (MDD) and evaluation of the early stages to stop the side effects. Early detection is critical to identify a variety of serious conditions. In order to provide safe and effective protection to MDD patients, it is crucial to automate diagnoses and make decision-making tools widely available. Although there are various classification systems for the diagnosis of MDD, no reliable, secure method that meets these requirements has been established to date. In this paper, a federated deep learning-based multimodal system for MDD classification using electroencephalography (EEG) and audio datasets is presented while meeting data privacy requirements. The performance of the federated learning (FL) model was tested on independent and identically distributed (IID) and non-IID data. The study began by extracting features from several pre-trained models and ultimately decided to use bidirectional short-term memory (Bi-LSTM) as the base model, as it had the highest validation accuracy of 91% compared to a convolutional neural network and LSTM with 85% and 89% validation accuracy on audio data, respectively. The Bi-LSTM model also achieved a validation accuracy of 98.9% for EEG data. The FL method was then used to perform experiments on IID and non-IID datasets. The FL-based multimodal model achieved an exceptional training and validation accuracy of 99.9% when trained and evaluated on both IID and non-IIID datasets. These results show that the FL multimodal system performs almost as well as the Bi-LSTM multimodal system and emphasize its suitability for processing IID and non-IIID data. Several clients were found to perform better than conventional pre-trained models in a multimodal framework for federated learning using EEG and audio datasets. The proposed framework stands out from other classification techniques for MDD due to its special features, such as multimodality and data privacy for edge machines with limited resources. Due to these additional features, the framework concept is the most suitable alternative approach for the early classification of MDD patients.

Evaluation of bidirectional relationships between risk preference and mood disorders: A 2-sample Mendelian randomization study

BackgroundRisk preference is often defined as the tendency to engage in risky activities. Increasing evidence shows that risk preference is associated with mood disorders. However, the causality and direction of this association are not clear. MethodsGenome-wide association study summary data of risk preference in 939,908 participants from UK Biobank and 23andMe were used to identify general risk preference. Data for 413,466 individuals taken from The Psychiatric Genomics Consortium were used to identify bipolar disorder (BP). Data for 807,553 individuals taken from The Psychiatric Genomics Consortium were used to identify major depressive disorder (MDD). The weighted median, inverse-variance weighting, and Mendelian randomization-Egger methods were used for the Mendelian randomization analysis to estimate a causal effect and detect directional pleiotropy. ResultsGWAS summary data were obtained from three combined samples, containing 939,908, 413,466 and 807,553 individuals of European ancestry. Mendelian randomization evidence suggested that risk preference increased the onset of BP, and BP also increased risk preference (P < 0.001). In contrast, there were no reliable results to describe the relationship of risk preference with MDD (P > 0.05). Furthermore, there was no significant relationship between MDD and risk preference. ConclusionUsing large-scale GWAS data, robust evidence supports a mutual relationship between risk preference and BP, but no relationship between risk preference and MDD was observed. This study indicates a potential marker for the early identification of MDD and BP. Additionally, it shows that reducing risk preferences for patients with BP may be a valuable intervention for treating BP.

Resting-state cerebral blood flow and functional connectivity abnormalities in depressed patients with childhood maltreatment: Potential biomarkers of vulnerability?

Childhood maltreatment (CM) is an important risk factor for major depressive disorder (MDD). This study aimed to explore the specific effect of CM on cerebral blood flow (CBF) and brain functional connectivity (FC) in MDD patients. A total of 150 subjects were collected including 55 MDD patients with CM, 34 MDD patients without CM, 19 healthy controls (HC) with CM, and 42 HC without CM. All subjects completed MRI scans and neuropsychological tests. Two-way analysis of covariance was used to detect the main and interactive effects of disease and CM on CBF and FC across subjects. Then, partial correlation analyses were conducted to explore the behavioral significance of altered CBF and FC in MDD patients. Finally, a support vector classifier model was applied to differentiate MDD patients. MDD patients represented increased CBF in bilateral temporal lobe and decreased CBF in right visual cortex. Importantly, significant depression-by-CM interactive effects on CBF were primarily located in the frontoparietal regions, including orbitofrontal cortex (OFC), lateral prefrontal cortex (PFC), and parietal cortex. Moreover, significant FC abnormalities were seen in OFC-PFC and frontoparietal-visual cortex. Notably, the abnormal CBF and FC were significantly associated with behavioral performance. Finally, a combination of altered CBF and FC behaved with a satisfactory classification ability to differentiate MDD patients. These results highlight the importance of frontoparietal and visual cortices for MDD with CM experience, proposing a potential neuroimaging biomarker for MDD identification.

Multi-view graph network learning framework for identification of major depressive disorder

Functional connectivity (FC) derived from resting-state functional magnetic resonance imaging (rs-fMRI) exhibits non-Euclidean topological structures, which have pathological foundations and serve as ideal objective data for intelligent diagnosis of major depressive disorder (MDD) patients. Additionally, the fully connected FC demonstrates uniform spatial structures. To learn and integrate information from these two structural forms for a more comprehensive identification of MDD patients, we propose a novel hierarchical learning structure called Multi-View Graph Neural Network (MV-GNN). In MV-GNN, the collaborative FC of subjects is filtered and reconstructed from topological view to obtain the reconstructed FC, incorporating various threshold values to calculate the topological attributes of brain regions. ROC analysis is performed on the average scores of these attributes for MDD and healthy control (HC) groups to determine an efficient threshold. Group differences analysis is conducted on the efficient topological attributes of brain regions, followed by their selection. These efficient attributes, along with the reconstructed FC, are combined to construct a graph view using self-attention graph pooling and graph convolutional neural networks, enabling efficient embedding. To extract efficient FC pattern difference information from spatial view, a dual leave-one-out cross-feature selection method is proposed. It selects and extracts relevant information from uniformly sized FC structures’ high-dimensional spatial features, constructing a relationship view between brain regions. This approach incorporates both the whole graph topological view and spatial relationship view in a multi-layered structure, fusing them using gating mechanisms. By incorporating multiple views, it enhances the inference of whether subjects suffer from MDD and reveals differential information between MDD and HC groups across different perspectives. The proposed model structure is evaluated through leave-one-site cross-validation and achieves an average accuracy of 65.61% in identifying MDD patients at a single-center site, surpassing state-of-the-art methods in MDD recognition. The model provides valuable discriminatory information for objective diagnosis of MDD and serves as a reference for pathological foundations.

Estimation of Discriminative Multimodal Brain Network Connectivity Using Message-Passing-Based Nonlinear Network Fusion.

Effective estimation of brain network connectivity enables better unraveling of the extraordinary complexity interactions of brain regions and helps in auxiliary diagnosis of psychiatric disorders. Considering different modalities can provide comprehensive characterizations of brain connectivity, we propose the message-passing-based nonlinear network fusion (MP-NNF) algorithm to estimate multimodal brain network connectivity. In the proposed method, the initial functional and structural networks were computed from fMRI and DTI separately. Then, we update every unimodal network iteratively, making it more similar to the others in every iteration, and finally converge to one unified network. The estimated brain connectivities integrate complementary information from multiple modalities while preserving their original structure, by adding the strong connectivities present in unimodal brain networks and eliminating the weak connectivities. The effectiveness of the method was evaluated by applying the learned brain connectivity for the classification of major depressive disorder (MDD). Specifically, 82.18% classification accuracy was achieved even with the simple feature selection and classification pipeline, which significantly outperforms the competing methods. Exploration of brain connectivity contributed to MDD identification suggests that the proposed method not only improves the classification performance but also was sensitive to critical disease-related neuroimaging biomarkers.

Multidimensional voiceprint feature assessment system for identifying the depression in children and adolescents: a diagnostic test.

We designed a diagnostic test to evaluate the effectiveness and accuracy of a multidimensional voiceprint feature diagnostic assessment (MVFDA) system vs. the 24-item Hamilton Rating Scale for Depression (HAMD-24) for adjunctive diagnosis of children and adolescents with major depressive disorder (MDD). This study included 55 children aged 6-16 years who were clinically diagnosed with MDD according to the DSM-5 and analyzed by professional physicians, and 55 healthy children (typically developing). Each subject completed a voice recording and was scored on the HAMD-24 scale by a trained rater. We calculated the validity indices, including sensitivity, specificity, Youden's index, likelihood ratio, and other indices including predictive value, diagnostic odds ratio, diagnostic accuracy, and area under the curve (AUC), to assess the effectiveness of the MVFDA system in addition to the HAMD-24. The sensitivity (92.73 vs. 76.36%) and the specificity (90.91 vs. 85.45%) of the MVFDA system are significantly higher than those of the HAMD-24. The AUC of the MVFDA system is also higher than that of the HAMD-24. There is a statistically significant difference between the groups (p < 0.05), and both of them have high diagnostic accuracy. In addition, the diagnostic efficacy of the MVFDA system is higher than that of HAMD-24 in terms of the Youden index, diagnostic accuracy, likelihood ratio, diagnostic odds ratio, and predictive value. The MVFDA has performed well in clinical diagnostic trials for the identification of MDD in children and adolescents by capturing objective sound features. Compared with the scale assessment method, the MVFDA system could be further promoted in clinical practice due to its advantages of simple operation, objective rating, and high diagnostic efficiency.

Ensemble graph neural network model for classification of major depressive disorder using whole-brain functional connectivity.

Major depressive disorder (MDD) is characterized by impairments in mood and cognitive functioning, and it is a prominent source of global disability and stress. A functional magnetic resonance imaging (fMRI) can aid clinicians in their assessments of individuals for the identification of MDD. Herein, we employ a deep learning approach to the issue of MDD classification. Resting-state fMRI data from 821 individuals with MDD and 765 healthy controls (HCs) is employed for investigation. An ensemble model based on graph neural network (GNN) has been created with the goal of identifying patients with MDD among HCs as well as differentiation between first-episode and recurrent MDDs. The graph convolutional network (GCN), graph attention network (GAT), and GraphSAGE models serve as a base models for the ensemble model that was developed with individual whole-brain functional networks. The ensemble's performance is evaluated using upsampling and downsampling, along with 10-fold cross-validation. The ensemble model achieved an upsampling accuracy of 71.18% and a downsampling accuracy of 70.24% for MDD and HC classification. While comparing first-episode patients with recurrent patients, the upsampling accuracy is 77.78% and the downsampling accuracy is 71.96%. According to the findings of this study, the proposed GNN-based ensemble model achieves a higher level of accuracy and suggests that our model produces can assist healthcare professionals in identifying MDD.

Functional connectivity signatures of major depressive disorder: machine learning analysis of two multicenter neuroimaging studies

The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep learning algorithms to differentiate patients with MDD from healthy controls and identify neurophysiological signatures of depression in two of the largest resting-state datasets for MDD. We obtained resting-state functional magnetic resonance imaging data from the REST-meta-MDD (N = 2338) and PsyMRI (N = 1039) consortia. Classification of functional connectivity matrices was done using support vector machines (SVM) and graph convolutional neural networks (GCN), and performance was evaluated using 5-fold cross-validation. Features were visualized using GCN-Explainer, an ablation study and univariate t-testing. The results showed a mean classification accuracy of 61% for MDD versus controls. Mean accuracy for classifying (non-)medicated subgroups was 62%. Sex classification accuracy was substantially better across datasets (73–81%). Visualization of the results showed that classifications were driven by stronger thalamic connections in both datasets, while nearly all other connections were weaker with small univariate effect sizes. These results suggest that whole brain resting-state connectivity is a reliable though poor biomarker for MDD, presumably due to disease heterogeneity as further supported by the higher accuracy for sex classification using the same methods. Deep learning revealed thalamic hyperconnectivity as a prominent neurophysiological signature of depression in both multicenter studies, which may guide the development of biomarkers in future studies.

Unsupervised cross-domain functional MRI adaptation for automated major depressive disorder identification.

Resting-state functional magnetic resonance imaging (rs-fMRI) data have been widely used for automated diagnosis of brain disorders such as major depressive disorder (MDD) to assist in timely intervention. Multi-site fMRI data have been increasingly employed to augment sample size and improve statistical power for investigating MDD. However, previous studies usually suffer from significant inter-site heterogeneity caused for instance by differences in scanners and/or scanning protocols. To address this issue, we develop a novel discrepancy-based unsupervised cross-domain fMRI adaptation framework (called UFA-Net) for automated MDD identification. The proposed UFA-Net is designed to model spatio-temporal fMRI patterns of labeled source and unlabeled target samples via an attention-guided graph convolution module, and also leverage a maximum mean discrepancy constrained module for unsupervised cross-site feature alignment between two domains. To the best of our knowledge, this is one of the first attempts to explore unsupervised rs-fMRI adaptation for cross-site MDD identification. Extensive evaluation on 681 subjects from two imaging sites shows that the proposed method outperforms several state-of-the-art methods. Our method helps localize disease-associated functional connectivity abnormalities and is therefore well interpretable and can facilitate fMRI-based analysis of MDD in clinical practice.

High-order brain functional network for electroencephalography-based diagnosis of major depressive disorder.

Brain functional network (BFN) based on electroencephalography (EEG) has been widely used to diagnose brain diseases, such as major depressive disorder (MDD). However, most existing BFNs only consider the correlation between two channels, ignoring the high-level interaction among multiple channels that contain more rich information for diagnosing brain diseases. In such a sense, the BFN is called low-order BFN (LO-BFN). In order to fully explore the high-level interactive information among multiple channels of the EEG signals, a scheme for constructing a high-order BFN (HO-BFN) based on the “correlation’s correlation” strategy is proposed in this paper. Specifically, the entire EEG time series is firstly divided into multiple epochs by sliding window. For each epoch, the short-term correlation between channels is calculated to construct a LO-BFN. The correlation time series of all channel pairs are formulated by these LO-BFNs obtained from all epochs to describe the dynamic change of short-term correlation along the time. To construct HO-BFN, we cluster all correlation time series to avoid the problems caused by high dimensionality, and the correlation of the average correlation time series from different clusters is calculated to reflect the high-order correlation among multiple channels. Experimental results demonstrate the efficiency of the proposed HO-BFN in MDD identification, and its integration with the LO-BFN can further improve the recognition rate.

3D FRN-ResNet: An Automated Major Depressive Disorder Structural Magnetic Resonance Imaging Data Identification Framework.

Major Depressive Disorder (MDD) is the most prevalent psychiatric disorder, seriously affecting people’s quality of life. Manually identifying MDD from structural magnetic resonance imaging (sMRI) images is laborious and time-consuming due to the lack of clear physiological indicators. With the development of deep learning, many automated identification methods have been developed, but most of them stay in 2D images, resulting in poor performance. In addition, the heterogeneity of MDD also results in slightly different changes reflected in patients’ brain imaging, which constitutes a barrier to the study of MDD identification based on brain sMRI images. We propose an automated MDD identification framework in sMRI data (3D FRN-ResNet) to comprehensively address these challenges, which uses 3D-ResNet to extract features and reconstruct them based on feature maps. Notably, the 3D FRN-ResNet fully exploits the interlayer structure information in 3D sMRI data and preserves most of the spatial details as well as the location information when converting the extracted features into vectors. Furthermore, our model solves the feature map reconstruction problem in closed form to produce a straightforward and efficient classifier and dramatically improves model performance. We evaluate our framework on a private brain sMRI dataset of MDD patients. Experimental results show that the proposed model exhibits promising performance and outperforms the typical other methods, achieving the accuracy, recall, precision, and F1 values of 0.86776, 0.84237, 0.85333, and 0.84781, respectively.

Multivariate Machine Learning Analyses in Identification of Major Depressive Disorder Using Resting-State Functional Connectivity: A Multicentral Study.

Diagnosis of major depressive disorder (MDD) using resting-state functional connectivity (rs-FC) data faces many challenges, such as the high dimensionality, small samples, and individual difference. To assess the clinical value of rs-FC in MDD and identify the potential rs-FC machine learning (ML) model for the individualized diagnosis of MDD, based on the rs-FC data, a progressive three-step ML analysis was performed, including six different ML algorithms and two dimension reduction methods, to investigate the classification performance of ML model in a multicentral, large sample dataset [1021 MDD patients and 1100 normal controls (NCs)]. Furthermore, the linear least-squares fitted regression model was used to assess the relationships between rs-FC features and the severity of clinical symptoms in MDD patients. Among used ML methods, the rs-FC model constructed by the eXtreme Gradient Boosting (XGBoost) method showed the optimal classification performance for distinguishing MDD patients from NCs at the individual level (accuracy = 0.728, sensitivity = 0.720, specificity = 0.739, area under the curve = 0.831). Meanwhile, identified rs-FCs by the XGBoost model were primarily distributed within and between the default mode network, limbic network, and visual network. More importantly, the 17 item individual Hamilton Depression Scale scores of MDD patients can be accurately predicted using rs-FC features identified by the XGBoost model (adjusted R2 = 0.180, root mean squared error = 0.946). The XGBoost model using rs-FCs showed the optimal classification performance between MDD patients and HCs, with the good generalization and neuroscientifical interpretability.

Sex Difference in Peripheral Inflammatory Biomarkers in Drug-Naïve Patients with Major Depression in Young Adulthood.

The number of patients with major depressive disorder (MDD) is increasing worldwide. In particular, the early onset of MDD from adolescence to young adulthood is more problematic than the later onset. The specific and expeditious identification of MDD before the occurrence of severe symptoms is significant for future interventions or therapies; however, there is no accurate diagnostic marker that has sufficient sensitivity and specificity for clinical use. In the present study, to identify the possibility of blood markers for depression, we first measured the baseline inflammatory biomarkers in the peripheral blood of 50 treatment-naïve young adults with MDD and 50 matched healthy controls. We then analyzed the correlation between prospective biomarkers and depressive symptoms using scores from various clinical depression indices. We also identified differential responses between males and females in prospective biomarkers. In young adulthood, men with MDD had increased peripheral interleukin (IL)-17 levels, whereas women with MDD had significantly increased IL-1β, IL-6, and C-reactive protein (CRP) levels compared with healthy controls. However, tumor necrosis factor-α (TNF-α), CCL1, CCL2, adiponectin, and cortisol were not significantly different in young adult individuals with MDD. Higher levels of IL-17 in the male group and of IL-1β, IL-6, and CRP in the female group may have been associated with the clinical symptoms of MDD, including depressive moods, hopelessness, suicidal ideation, low self-esteem, and reduced psychological resilience. Our findings will be useful in developing diagnostic tools or treatments for MDD in young adulthood.

The Developmental and Translational Study on Biomarkers and Clinical Characteristics-based Diagnostic and Therapeutic Identification of Major Depressive Disorder: Study Protocol for a Multicenter Randomized Controlled Trial in China.

BackgroundMajor depressive disorder (MDD) is a heterogeneous mental disease that encompasses different subtypes and specifiers. Clinically targeted treatments have not been identified yet, although standardized strategies are recommended by several clinical guidelines. The main aim of this study is to respectively identify the precise treatment for three different subtypes of MDD (ie, melancholic, atypical, and anxious).MethodsAn 8-to-12-week, multicenter randomized controlled trial (RCT) with a parallel group design will be conducted to determine the most effective and appropriate treatment. A total of 750 adults diagnosed with MDD will be recruited, categorized into melancholic, atypical or anxious type based on the assessment of the Inventory of Depressive Symptomatology (IDS30) and the Hamilton Anxiety Scale (HAMA), and 1:1 randomly assigned to different intervention groups. Blood draw, EEG test, and MRI scan will be performed at baseline and endpoint. Clinical symptom and side-effects will be evaluated at critical decision points (CDP) including weeks two, four, six, eight, and 12 after treatment. The primary outcome is total score and reduction rate of the 17-Hamilton Depression Rating Scale (17-HDRS). The secondary outcomes include the scores of the Quick Inventory of Depressive Symptomatology-self-report (QIDS-SR), IDS30, HAMA and the Treatment Emergent Symptom Scale (TESS). All the data will be analyzed by SAS software.DiscussionThe study commenced recruitment in August 2017 and is currently ongoing.Trial RegistrationClinicalTrials.gov Identifier: NCT03219008 (July 17, 2017).

Diagnosis of major depressive disorder using whole-brain effective connectivity networks derived from resting-state functional MRI

Objective. It is important to improve identification accuracy for possible early intervention of major depressive disorder (MDD). Recently, effective connectivity (EC), defined as the directed influence of spatially distant brain regions on each other, has been used to find the dysfunctional organization of brain networks in MDD. However, little is known about the ability of whole-brain resting-state EC features in identification of MDD. Here, we employed EC by whole-brain analysis to perform MDD diagnosis. Approach. In this study, we proposed a high-order EC network capturing high-level relationship among multiple brain regions to discriminate 57 patients with MDD from 60 normal controls (NC). In high-order EC networks and traditional low-order EC networks, we utilized the network properties and connection strength for classification. Meanwhile, the support vector machine (SVM) was employed for model training. Generalization of the results was supported by 10-fold cross-validation. Main results. The classification results showed that the high-order EC network performed better than the low-order EC network in diagnosing MDD, and the integration of these two networks yielded the best classification precision with 95% accuracy, 98.83% sensitivity, and 91% specificity. Furthermore, we found that the abnormal connections of high-order EC in MDD patients involved multiple widely concerned functional subnets, particularly the default mode network and the cerebellar network. Significance. The current study indicates whole-brain EC networks, measured by our high-order method, may be promising biomarkers for clinical diagnosis of MDD, and the complementary between high-order and low-order EC will better guide patients to get early interventions as well as treatments.

Machine Learning Approaches for MDD Detection and Emotion Decoding Using EEG Signals.

Emotional decoding and automatic identification of major depressive disorder (MDD) are helpful for the timely diagnosis of the disease. Electroencephalography (EEG) is sensitive to changes in the functional state of the human brain, showing its potential to help doctors diagnose MDD. In this paper, an approach for identifying MDD by fusing interhemispheric asymmetry and cross-correlation with EEG signals is proposed and tested on 32 subjects [16 patients with MDD and 16 healthy controls (HCs)]. First, the structural features and connectivity features of the θ-, α-, and β-frequency bands are extracted on the preprocessed and segmented EEG signals. Second, the structural feature matrix of the θ-, α-, and β-frequency bands are added to and subtracted from the connectivity feature matrix to obtain mixed features. Finally, the structural features, connectivity features, and the mixed features are fed to three classifiers to select suitable features for the classification, and it is found that our mode achieves the best classification results using the mixed features. The results are also compared with those from some state-of-the-art methods, and we achieved an accuracy of 94.13%, a sensitivity of 95.74%, a specificity of 93.52%, and an F1-score (f1) of 95.62% on the data from Beijing Anding Hospital, Capital Medical University. The study could be generalized to develop a system that may be helpful in clinical purposes.

Identifying resting-state effective connectivity abnormalities in drug-naïve major depressive disorder diagnosis via graph convolutional networks.

Major depressive disorder (MDD) is a leading cause of disability; its symptoms interfere with social, occupational, interpersonal, and academic functioning. However, the diagnosis of MDD is still made by phenomenological approach. The advent of neuroimaging techniques allowed numerous studies to use resting‐state functional magnetic resonance imaging (rs‐fMRI) and estimate functional connectivity for brain‐disease identification. Recently, attempts have been made to investigate effective connectivity (EC) that represents causal relations among regions of interest. In the meantime, to identify meaningful phenotypes for clinical diagnosis, graph‐based approaches such as graph convolutional networks (GCNs) have been leveraged recently to explore complex pairwise similarities in imaging/nonimaging features among subjects. In this study, we validate the use of EC for MDD identification by estimating its measures via a group sparse representation along with a structured equation modeling approach in a whole‐brain data‐driven manner from rs‐fMRI. To distinguish drug‐naïve MDD patients from healthy controls, we utilize spectral GCNs based on a population graph to successfully integrate EC and nonimaging phenotypic information. Furthermore, we devise a novel sensitivity analysis method to investigate the discriminant connections for MDD identification in our trained GCNs. Our experimental results validated the effectiveness of our method in various scenarios, and we identified altered connectivities associated with the diagnosis of MDD.

Quantitative Identification of Major Depression Based on Resting-State Dynamic Functional Connectivity: A Machine Learning Approach.

IntroductionDeveloping a machine learning-based approach which could provide quantitative identification of major depressive disorder (MDD) is essential for the diagnosis and intervention of this disorder. However, the performances of traditional algorithms using static functional connectivity (SFC) measures were unsatisfactory. In the present work, we exploit the hidden information embedded in dynamic functional connectivity (DFC) and developed an accurate and objective image-based diagnosis system for MDD.MethodsMRI images were collected from 99 participants including 56 healthy controls and 43 MDD patients. DFC was calculated using a sliding-window algorithm. A non-linear support vector machine (SVM) approach was then used with the DFC matrices as features to distinguish MDD patients from healthy controls. The spatiotemporal characteristics of the most discriminative features were then investigated.ResultsThe area under the curve (AUC) of the SVM classifier with DFC measures reached 0.9913, while this value is only 0.8685 for the algorithm using SFC measures. Spatially, the most discriminative 28 connections distributed in the visual network (VN), somatomotor network (SMN), dorsal attention network (DAN), ventral attention network (VAN), limbic network (LN), frontoparietal network (FPN), and default mode network (DMN), etc. Notably, a large portion of these connections were associated with the FPN, DMN, and VN. Temporally, the most discriminative connections transited from the cortex to deeper regions.ConclusionThe results clearly suggested that DFC is superior to SFC and provide a reliable quantitative identification method for MDD. Our findings may furnish a better understanding of the neural mechanisms of MDD as well as improve accurate diagnosis and early intervention of this disorder.