Processing In Major Depressive Disorder Research Articles

222. Repetitive Negative Thinking Modulates Error Processing in Major Depressive Disorder With and Without Anxiety Disorder

222. Repetitive Negative Thinking Modulates Error Processing in Major Depressive Disorder With and Without Anxiety Disorder

The interplay between polygenic score for tumor necrosis factor-α, brain structural connectivity, and processing speed in major depression.

Reduced processing speed is a core deficit in major depressive disorder (MDD) and has been linked to altered structural brain network connectivity. Ample evidence highlights the involvement of genetic-immunological processes in MDD and specific depressive symptoms. Here, we extended these findings by examining associations between polygenic scores for tumor necrosis factor-α blood levels (TNF-α PGS), structural brain connectivity, and processing speed in a large sample of MDD patients. Processing speed performance of n = 284 acutely depressed, n = 177 partially and n = 198 fully remitted patients, and n = 743 healthy controls (HC) was estimated based on five neuropsychological tests. Network-based statistic was used to identify a brain network associated with processing speed. We employed general linear models to examine the association between TNF-α PGS and processing speed. We investigated whether network connectivity mediates the association between TNF-α PGS and processing speed. We identified a structural network positively associated with processing speed in the whole sample. We observed a significant negative association between TNF-α PGS and processing speed in acutely depressed patients, whereas no association was found in remitted patients and HC. The mediation analysis revealed that brain connectivity partially mediated the association between TNF-α PGS and processing speed in acute MDD. The present study provides evidence that TNF-α PGS is associated with decreased processing speed exclusively in patients with acute depression. This association was partially mediated by structural brain connectivity. Using multimodal data, the current findings advance our understanding of cognitive dysfunction in MDD and highlight the involvement of genetic-immunological processes in its pathomechanisms.

Aberrant dynamic functional connectivity of thalamocortical circuitry in major depressive disorder.

Thalamocortical circuitry has a substantial impact on emotion and cognition. Previous studies have demonstrated alterations in thalamocortical functional connectivity (FC), characterized by region-dependent hypo- or hyper-connectivity, among individuals with major depressive disorder (MDD). However, the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear. Hence, we analyzed dynamic FC (dFC) between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls (HCs) to investigate time-varying changes in thalamocortical FC in patients with MDD. Moreover, dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time. Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated. We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks, compared with the HCs. In addition, MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration. The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort. Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms. Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients. The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.

Distorted Cognitive Process in Major Depressive Disorder and Relevant Interventions

This paper mainly discussed cognitive distortions of major depression and the methods of intervention for major depression. Then, this paper also contains different studies and different findings that indicate different cognitive patterns and processes of patients with major depression. For example, patients with major depression will be more sensitive to stressful events. Expectations have a significant correlation with major depression. Due to the existence of cognitive dissonance, people tend to reduce this dissonance by changing inconsistent cognition, according to social psychology. An individual's self-esteem level can predict the expectation of future performance. At the same time, some papers have also studied the relationship between mind wandering and major depression, as well as the ambulatory heart rate and variability. There are also relevant studies that found that people with depression post more negative language on social media. Among them, researchers have also developed intervention methods for these cognitive errors. At the same time, it is also important for psychologists to pay attention to patients' expectations when treating patients' mental illness, as the source of most of rumination and loss is to do with the patient's high expectations. Patients struggle to keep track of their most accurate emotions from moment to moment as well. This review can provide some guidance to the design of effective treatment for at-risk individuals.

Abnormal neurophysiological sensitivity to rewards in depression is moderated by sex and age in middle adulthood

A candidate pathophysiological process in major depressive disorder is diminished neural reactivity to reward delivery, which is theorized to give rise to anhedonia. Reduced amplitude in the reward positivity (RewP), which captures initial reward evaluation, has been linked to current symptoms of depression among child, adolescent, and young adult samples. However, the developmental trajectory of this association is incomplete, with relatively few studies in middle and older adulthood. Further, emerging evidence in the literature also suggests that this association may be linked to female sex-specific processes, but no studies to date have directly contrasted the effect of sex on the depression-RewP association. The current study sought to address these gaps by testing how sex and age may moderate the depression-RewP association within a mature adult community sample. Symptoms of depression were evaluated using a survey and a clinical interview, and the RewP was elicited using a simple guessing task. There was a three-way interaction between depression symptom severity, age, and sex in predicting RewP amplitude. This was driven by younger (late 30’s to early 40’s) female-sexed people such that for this group, elevated symptoms of depression were associated with blunting of the RewP. This association tapered around age 50. This effect was specific to clinician-rated rather than self-reported depressive symptom severity. This pattern of effects suggests that among female-sexed people, developmental processes continue to shape the association between reward responsiveness and depression throughout middle adulthood.

Altered beta band spatial-temporal interactions during negative emotional processing in major depressive disorder: An MEG study

BackgroundThe mood-concordance bias is a key feature of major depressive disorder (MDD), but the spatiotemporal neural activity associated with emotional processing in MDD remains unclear. Understanding the dysregulated connectivity patterns during emotional processing and their relationship with clinical symptoms could provide insights into MDD neuropathology. MethodsWe enrolled 108 MDD patients and 64 healthy controls (HCs) who performed an emotion recognition task during magnetoencephalography recording. Network-based statistics (NBS) was used to analyze whole-brain functional connectivity (FC) across different frequency ranges during distinct temporal periods. The relationship between the aberrant FC and affective symptoms was explored. ResultsMDD patients exhibited decreased FC strength in the beta band (13–30 Hz) compared to HCs. During the early stage of emotional processing (0-100 ms), reduced FC was observed between the left parahippocampal gyrus and the left cuneus. In the late stage (250-400 ms), aberrant FC was primarily found in the cortex-limbic-striatum systems. Moreover, the FC strength between the right fusiform gyrus and left thalamus, and between the left calcarine fissure and left inferior temporal gyrus were negatively associated with Hamilton Depression Rating Scale (HAMD) scores. LimitationsMedication information was not involved. ConclusionMDD patients exhibited abnormal temporal-spatial neural interactions in the beta band, ranging from early sensory to later cognitive processing stages. These aberrant interactions involve the cortex-limbic-striatum circuit. Notably, aberrant FC in may serve as a potential biomarker for assessing depression severity.

Trying to name what doesn't change: Neural nonresponse to Cognitive Therapy for depression.

Theoretical models of neural mechanisms underlying Cognitive Behavior Therapy (CBT) for major depressive disorder (MDD) propose that psychotherapy changes neural functioning of prefrontal cortical structures associated with cognitive-control processes (DeRubeis, Siegle, & Hollon, ); however, MDD is persistent and characterized by long-lasting vulnerabilities to recurrence after intervention, suggesting that underlying neural mechanisms of MDD remain despite treatment. It follows that identification of treatment-resistant aberrant neural processes in MDD may inform clinical and research efforts targeting sustained remission. Thus, we sought to identify brain regions showing aberrant neural functioning in MDD that either (1) fail to exhibit substantive change (nonresponse) or (2) exhibit functional changes (response) following CBT. To identify treatment-resistant neural processes (as well as neural processes exhibiting change after treatment), we collected functional magnetic resonance imaging (fMRI) data of MDD patients (n = 58) before and after CBT as well as never-depressed controls (n = 35) before and after a similar amount of time. We evaluated fMRI data using conjunction analyses, which utilized several contrast-based criteria to characterize brain regions showing both differences between patients and controls at baseline and nonresponse or response to CBT. Findings revealed nonresponse in a cerebellar region and response in prefrontal and parietal regions. Results are consistent with prior theoretical models of CBT's direct effect on cortical regulatory processes but expand on them with identification of additional regions (and associated neural systems) of response and nonresponse to CBT.

Treatment with the second-generation antipsychotic quetiapine is associated with increased subgenual ACC activation during reward processing in major depressive disorder

BackgroundThe second-generation antipsychotic (SGA) quetiapine is an essential option for antidepressant augmentation therapy in major depressive disorder (MDD), yet neurobiological mechanisms behind its antidepressant properties remain unclear. As SGAs interfere with activity in reward-related brain areas, including the anterior cingulate cortex (ACC) — a key brain region in antidepressant interventions, this study examined whether quetiapine treatment affects ACC activity during reward processing in MDD patients. MethodsUsing the ACC as region of interest, an independent t-test comparing reward-related BOLD response of 51 quetiapine-taking and 51 antipsychotic-free MDD patients was conducted. Monetary reward outcome feedback was measured in a card-guessing paradigm using pseudorandom blocks. Participants were matched for age, sex, and depression severity and analyses were controlled for confounding variables, including total antidepressant medication load, illness chronicity and acute depression severity. Potential dosage effects were examined in a 3 × 1 ANOVA. Differences in ACC-related functional connectivity were assessed in psycho-physiological interaction (PPI) analyses. ResultsLeft subgenual ACC activity was significantly higher in the quetiapine group compared to antipsychotic-free participants and dependent on high-dose quetiapine intake. Results remained significant after controlling for confounding variables. The PPI analysis did not yield significant group differences in ACC-related functional connectivity. LimitationsCausal interpretation is limited due to cross-sectional findings. ConclusionElevated subgenual ACC activity to rewarding stimuli may represent a neurobiological marker and potential key interface of quetiapine's antidepressant effects in MDD. These results underline ACC activity during reward processing as an investigative avenue for future research and therapeutic interventions to improve MDD treatment outcomes.

Bilateral theta-burst stimulation on emotional processing in major depressive disorder: A functional neuroimaging study from a randomized, double-blind, sham-controlled trial.

Bilateral theta-burst stimulation (biTBS; intermittent TBS over the left dorsolateral prefrontal cortex [DLPFC] and continuous TBS over the right DLPFC) has demonstrated efficacy in improving symptoms in patients with major depressive disorder (MDD). However, the underlying brain mechanisms remain unknown. The authors aimed to investigate the antidepressant efficacy of biTBS monotherapy and its effects on the brain responses measured by functional magnetic resonance imaging (fMRI) during emotional processing in MDD. The authors conducted a double-blind, randomized, sham-controlled trial of patients with MDD who exhibited no responses to at least one adequate antidepressant treatment for the prevailing episode. Recruited patients were randomly assigned to 10 biTBS monotherapy or sham stimulation sessions. The fMRI scans during performing emotional recognition task were obtained at baseline and after 10 sessions of treatment. Depressive symptoms were assessed using the 21-item Hamilton Rating Scale for Depression at baseline and the weeks 4, 8, 12, 16, 20, and 24 week. The biTBS group (n=17) exhibited significant decreases in depression scores compared with the sham group (n=11) at week 8 (70% vs 40%; P=0.02), and the significant differences persisted during the 24-week follow-up periods. At week 4, when the treatment course was completed, patients in the biTBS group, but not in the sham group, exhibited increased brain activities over the left superior and middle frontal gyrus during negative emotional stimuli. The authors' findings provide the first evidence regarding the underlying neural mechanisms of biTBS therapy to improve clinical symptoms in patients with MDD.

Behavioral and electrophysiological analyses of self-referential neural processing in major depressive disorder.

Cognitive theories suggest that patients with major depressive disorder (MDD) constantly negatively evaluate their self-referential information. Unlike Westerners with an independent self, self-representation is strongly influenced by cultural differences; the Chinese self may include others (interdependent self). This study uses a self-referential effect task combined with event-related potentials (ERP), and 34 patients with MDD and 54 healthy controls (HC) were asked to judge whether an adjective was suitable for describing the self, mother, or a public person, followed by an unexpected recognition task. They were required to judge whether a word was presented during the encoding phase. The results reveal that during the encoding phase, for both self- and mother-referential adjectives, patients with MDD endorsed fewer positive adjectives and more negative adjectives than the HCs. During the recognition phase, both groups showed a typical task effect (self=mother>other), while patients recognized more self-referential adjectives than the HCs. ERP data reveal that patients with MDD show larger P2 amplitudes during the encoding stage than healthy individuals. During the recognition phase, negative adjectives evoked larger P2 amplitudes in patients than in HCs under the self-referential condition. These findings shed important light on the information processes that may contribute to our understanding of depression and may offer implications for clinical interventions.

Higher serum interleukin-12 levels are associated with the pathophysiology of major depressive disorder: A case-control study results.

Major depressive disorder (MDD) is the fourth biggest health-related concern that dramatically impacts individuals' mental and physical health. Alteration of serum proinflammatory cytokine levels may take part in the development and progression of MDD. We aimed to explore and compare the role of interleukin-12 (IL-12) in MDD patients and healthy controls (HCs) and its involvement with the disease severity. The present study included 85 patients and 87 age-sex matched HCs. A qualified psychiatrist utilized the diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria to diagnose patients and evaluate HCs. We applied the Ham-D rating scale to measure the severity of depression. Serum IL-12 levels were measured using ELISA kits. We observed a notable increase in the serum levels of IL-12 in MDD patients compared to HCs (164.27 ± 10.18 pg/ml and 82.55 ± 4.40 pg/ml; p < 0.001). Moreover, we noticed a positive correlation between serum IL-12 levels and Ham-D scores in MDD patients (r = 0.363; p = 0.001). Receiver operating characteristicanalysis showed a good predictive performance (AUC = 0.871; p < 0.001)at the cut-off point of 53.46 pg/ml for serum IL-12. The current study findings support that IL-12 levels are involved with the pathogenesis and inflammatory process in MDD. At the same time, this involvement may make this cytokine eligible for the risk evaluation of MDD. However, we recommend further interventional studies to explore more accurate associations between IL-12 and depressive disorder.

Decomposing Working Memory in Recurrent Major Depression: Impaired Encoding and Limited Maintenance Immune-to-Encoding Constraint.

It is generally believed that working memory (WM) is dysfunctional in depression. However, whether this impaired performance originates from impaired encoding, maintenance or both stages is still unclear. Here, we aimed to decompose the abnormal characteristics of encoding and maintenance in patients with recurrent major depressive disorder (MDD). Thirty patients and thirty-nine healthy controls completed a spatial working memory task where the encoding time and the retention time could vary under different load levels. Encoding performance was assessed by comparing accuracies between short and long encoding times, and maintenance performance was assessed by comparing accuracies between short and long retention times. The results show a lower performance in depression than the controls. However, while the decreased accuracy by long retention (vs. short retention) was increased by a short encoding time in the control group, the retention performance of the depression group did not further suffer from the short encoding time. The generally impaired encoding, together with limited maintenance of immunity against the constrained encoding time, suggests a common bias for fixed internal processing over external processing in recurrent MDD. The paradigm provided in this study can be a convenient and efficient clinical test for assessing the WM encoding and maintenance function.

The Influence of Alcohol on Rumination and Metacognitions in Major Depressive Disorder.

Comorbidity between major depressive disorder (MDD) and alcohol use disorder (AUD) is highly prevalent but reasons for this association are unclear. Rumination may activate metacognitive beliefs that contribute to the development and maintenance of rumination and depression. Negative metacognitions can further lead to other dysfunctional coping strategies (i.e., consumption of alcohol). We examined whether alcohol reduces (state) metacognitions, rumination and other disorder-specific processes in a group of individuals suffering from MDD. In an experiment with three randomized conditions we investigated whether the consumption of alcohol, placebo or no alcohol (orange juice) affects (meta-)cognitions, depressive symptoms and / or psychophysiological variables while participants ruminate. Voluntary rumination increased self-reported sadness, tension and rumination, tensed facial muscles and increased heart rate, but did not affect (state) metacognitions and heart rate variability. The consumption of alcohol did not influence rumination, metacognitions, depressive or psychophysiological measures. We recruited a depressed population but excluded pathological alcohol use due to ethical considerations. We found no evidence that alcohol consumption affects rumination, metacognitions and other disorder-specific processes in MDD. However, rumination had a negative effect on various depression-specific processes, although it did not activate (negative state) metacognitions.

Structural covariance network of the hippocampus-amygdala complex in medication-naïve patients with first-episode major depressive disorder.

The hippocampus and amygdala are densely interconnected structures that work together in multiple affective and cognitive processes that are important to the etiology of major depressive disorder (MDD). Each of these structures consists of several heterogeneous subfields. We aim to explore the topologic properties of the volume-based intrinsic network within the hippocampus-amygdala complex in medication-naïve patients with first-episode MDD. High-resolution T1-weighted magnetic resonance imaging scans were acquired from 123 first-episode, medication-naïve, and noncomorbid MDD patients and 81 age-, sex-, and education level-matched healthy control participants (HCs). The structural covariance network (SCN) was constructed for each group using the volumes of the hippocampal subfields and amygdala subregions; the weights of the edges were defined by the partial correlation coefficients between each pair of subfields/subregions, controlled for age, sex, education level, and intracranial volume. The global and nodal graph metrics were calculated and compared between groups. Compared with HCs, the SCN within the hippocampus-amygdala complex in patients with MDD showed a shortened mean characteristic path length, reduced modularity, and reduced small-worldness index. At the nodal level, the left hippocampal tail showed increased measures of centrality, segregation, and integration, while nodes in the left amygdala showed decreased measures of centrality, segregation, and integration in patients with MDD compared with HCs. Our results provide the first evidence of atypical topologic characteristics within the hippocampus-amygdala complex in patients with MDD using structure network analysis. It provides more delineate mechanism of those two structures that underlying neuropathologic process in MDD.

The effects of transient receptor potential cation channel inhibition by BI 1358894 on cortico-limbic brain reactivity to negative emotional stimuli in major depressive disorder

Abnormal emotional processing in major depressive disorder (MDD) has been associated with increased activation to negative stimuli in cortico-limbic brain regions. The authors investigated whether treatment with BI 1358894, a small-molecule inhibitor of the transient receptor potential cation channel subfamily C leads to attenuated activity in these areas in MDD patients. 73 MDD patients were randomized to receive a single oral dose of BI 1358894 (100 mg), citalopram (20 mg), or matching placebo. Brain responses to emotional faces and scenes were investigated using functional magnetic resonance imaging. Primary endpoints were BOLD signal changes in response to negative faces in cortico-limbic brain regions, i.e. bilateral amygdala (AMY), dorsolateral prefrontal cortex, anterior insula (AI), and anterior cingulate cortex. Secondary endpoints were BOLD signal changes in response to negative scenes. For each region, separate ANOVA models were computed for the comparison of treatments (BI 1358894 or citalopram) vs. placebo. The adjusted treatment differences in the % BOLD signal changes in the faces task showed that BI 1358894 induced signal reduction in bilateral AMY and left AI. In the scenes task, BI 1358894 demonstrated significant signal reduction in bilateral AMY, AI, anterior cingulate cortex and left dorsolateral prefrontal cortex. Citalopram failed to induce any significant reductions in BOLD signal in both tasks. BI 1358894-mediated inhibition of the transient receptor potential cation channel subfamily resulted in strong signal reduction in cortico-limbic brain regions, thereby supporting development of this mechanism of action for MDD patients.

Exercise as a Potential Therapeutic Strategy to Target the Clinical Link Between Depression and Alzheimer's Disease: A Narrative Review.

Alzheimer's disease (AD) and major depressive disorder (MDD) affect millions worldwide and both cause significant morbidity and mortality. While clinically distinctive, patients with MDD can present with memory dysfunction and patients with AD commonly report symptoms of depression. Additionally, brain pathology in MDD and AD both demonstrate decreased hippocampal volumes, and severe disease is associated with smaller hippocampal volumes in both disorders. Hippocampal neurogenesis occurs daily in healthy individuals, an impaired process in AD and MDD. MDD is thus suggested to be a risk factor for developing AD later in life; moreover, depression onset alongside AD indicates a worse prognosis. Treatment options that target hippocampal neurogenesis are being evaluated for both diseases, and aerobic exercise has shown promising results. We searched PubMed for relevant review articles published since 2000 encompassing the topics of hippocampal neurogenesis and exercise in relation to depression and AD, including novel clinical trials if they contributed information not in the chosen reviews. While much data indicates that exercise increases hippocampal neurogenesis in both MDD and AD, mood improvement in MDD, mild quality of life and cognitive improvement in AD, and reduced risk of those with MDD developing AD in response to various exercise regimens, this result was not universal. Some data indicated no difference between exercise groups and controls. Further randomized control trials into exercise as an intervention in treating MDD and preventing AD is required. However, exercise is a low-risk, affordable treatment option and is a feasible additive therapy in patients with AD and MDD.

Association of DNA Methylation of the NLRP3 Gene with Changes in Cortical Thickness in Major Depressive Disorder.

The Nod-like receptor pyrin containing 3 (NLRP3) inflammasome has been reported to be a convergent point linking the peripheral immune response induced by psychological stress and neuroinflammatory processes in the brain. We aimed to identify differences in the methylation profiles of the NLRP3 gene between major depressive disorder (MDD) patients and healthy controls (HCs). We also investigated the correlation of the methylation score of loci in NLRP3 with cortical thickness in the MDD group using magnetic resonance imaging (MRI) data. A total of 220 patients with MDD and 82 HCs were included in the study, and genome-wide DNA methylation profiling of the NLRP3 gene was performed. Among the total sample, 88 patients with MDD and 74 HCs underwent T1-weighted structural MRI and were included in the neuroimaging–methylation analysis. We identified five significant differentially methylated positions (DMPs) in NLRP3. In the MDD group, the methylation scores of cg18793688 and cg09418290 showed significant positive or negative correlations with cortical thickness in the occipital, parietal, temporal, and frontal regions, which showed significant differences in cortical thickness between the MDD and HC groups. Our findings suggest that NLRP3 DNA methylation may predispose to depression-related brain structural changes by increasing NLRP3 inflammasome-related neuroinflammatory processes in MDD.

Chemokine receptor 4 expression on blood T lymphocytes predicts severity of major depressive disorder

BackgroundChemokines and their receptors regulate inflammatory processes in major depressive disorder (MDD). Here, we characterize the expression pattern of the C-C chemokine receptor 4 (CCR4) and its ligands CCL17 and CCL22 in MDD and its clinical relevance in predicting disease severity. MethodsExpression of CCR4 on peripheral blood lymphocytes and serum CCL17/CCL22 levels were measured using multiparameter flow cytometry and multiplex assays in 33 depressed inpatients at baseline (T0) and after 6-week multimodal treatment (T1) compared with 21 healthy controls (HC). Using stratified and correlation analysis, we examined the associations of CCR4-CCL17/CCL22 expression with depression severity and symptoms according to standard clinical rating scales and questionnaires. Additionally, we assessed whether polygenic risk score (PRS) for psychiatric disorders and chronotype are associated with disease status or CCR4-CCL17/CCL22 expression. Regression analysis was performed to assess the capacity of CCR4 and PRS in predicting disease severity. ResultsCompared with HC, MDD patients showed significantly decreased CCR4 expression on T cells (T0 and T1), whereas CCL17/CCL22 serum levels were increased. Stratified and correlation analysis revealed an association of CCR4 expression on CD4+ T cells with depression severity as well as Beck Depression Inventory-II items including loss of pleasure, agitation and cognitive deficits. CCR4 expression levels on CD4+ T cells together with cross-disorder and chronotype PRS significantly predicted disease severity. LimitationsThis exploratory study with small sample size warrants future studies. ConclusionsThis newly identified CCR4-CCL17/CCL22 signature and its predictive capacity for MDD severity suggest its potential functional involvement in the pathophysiology of MDD.

Interoception Dysfunction Contributes to the Negative Emotional Bias in Major Depressive Disorder.

BackgroundPrevious research studies have demonstrated that impaired interoception is involved in emotional information processing in major depressive disorder (MDD). Heartbeat-evoked potential (HEP) amplitudes, an index for interoception, could be manipulated by emotional faces in healthy people. Considering negative emotional bias is the core characteristic in MDD, we hypothesized that interoception dysfunction was associated with the negative emotional bias in MDD.MethodsAn electroencephalogram (EEG) study under an emotional faces task was applied to explore the relationship between interoception and emotional bias. HEPs before emotional faces stimuli were used to predict the late positive potential (LPP) amplitudes and it worked as an index of emotional bias. Twenty-seven patients with MDD and 27 healthy controls (HCs) participated in this study. Source analysis gave an auxiliary description for results in sensory level.ResultsMajor depressive disorders (MDDs) had poor performance in the heartbeat count task (HCT) and attenuate HEP average amplitudes (455–550 ms). Compared with HCs, cluster-based permutation t-tests revealed that MDDs had attenuated LPP amplitudes (300–1,000 ms) over centroparietal regions and enhanced LPP amplitudes over frontocentral regions. Furthermore, abnormal attenuated HEPs could predict aberrant LPPs under sad face stimuli in MDDs, which could be associated with the dysfunction of the anterior cingulate cortex (ACC) and right insula.ConclusionMediated by ACC and insula, interoception dysfunction contributes to the negative emotional bias of MDD, highlighting the importance of interoception in the disorder.

MicroRNA-Messenger RNA Regulatory Network Mediates Disrupted TH17 Cell Differentiation in Depression.

Accumulating evidence indicates an important role for microRNA (miRNA)–messenger RNA (mRNA) regulatory networks in human depression. However, the mechanisms by which these networks act are complex and remain poorly understood. We used data mining to identify differentially expressed miRNAs from GSE81152 and GSE152267 datasets, and differentially expressed mRNAs were identified from the Netherlands Study of Depression and Anxiety, the GlaxoSmithKline-High-Throughput Disease-specific target Identification Program, and the Janssen-Brain Resource Company study. We constructed a miRNA–mRNA regulatory network based on differentially expressed mRNAs that intersected with target genes of differentially expressed miRNAs, and then performed bioinformatics analysis of the network. The key candidate genes were assessed in the prefrontal cortex of chronic social defeat stress (CSDS) depression mice by quantitative real-time polymerase chain reaction (qRT-PCR). Three differentially expressed miRNAs were commonly identified across the two datasets, and 119 intersecting differentially expressed mRNAs were identified. A miRNA–mRNA regulatory network including these three key differentially expressed miRNAs and 119 intersecting differentially expressed mRNAs was constructed. Functional analysis of the intersecting differentially expressed mRNAs revealed that an abnormal inflammatory response characterized by disturbed T-helper cell 17 (Th17) differentiation was the primary altered biological function. qRT-PCR validated the decreased expression of Th17 cell differentiation-related genes, including interleukin (IL)17A, IL21, IL22, and IL1β, and the increased expression of retinoic acid receptor-related orphan receptor gamma-t (RORγt) in CSDS mice, which showed significant depressive- and anxiety-like behaviors. This study indicates that an abnormal inflammatory response characterized by disturbed Th17 cell differentiation is the primary altered biological process in major depressive disorder. Our findings indicate possible biomarkers and treatment targets and provide novel clues to understand the pathogenesis of major depressive disorder.