Major Depressive Disorder Individuals Research Articles

Insulin resistance, clinical presentation and resistance to selective serotonin and noradrenaline reuptake inhibitors in major depressive disorder.

The understanding of mechanisms underlying non-response to antidepressants is limited. The latest data highlights the role of insulin resistance (IR) in major depressive disorder (MDD) pathophysiology, presentation, and treatment efficacy. This work aimed to assess IR in MDD and explore the relationships between IR, MDD presentation and non-response to selective serotonin and noradrenaline reuptake inhibitors (SNRI). 67 MDD individuals: 36 responsive (MDD T[+]), 31 non-responsive (MDD T[-]) to SNRI and 30 healthy controls were recruited. The treatment response criteria were: Clinical Global Impression Scale-Improvement score of 1 or 2 after ≥ 8 weeks of treatment. Participants were assessed by physician and self-report tools measuring depression, anhedonia, anxiety, bipolarity, sleep quality. Blood samples were collected to assess fasting glucose and insulin levels and calculate HOMA-IR (homeostasis model assessment of insulin resistance). MDD T[-] vs. MDD T[+] had significantly higher body mass index, insulin levels, and HOMA-IR. MDD T[-] presented higher levels of depressed mood, appetite/weight changes, loss of interest, energy, overall depressive symptoms, and sleep impairment; some evaluations suggested higher anhedonia and anxiety in MDD T[-] vs. MDD T[+]. Insulin and IR were weakly but significantly correlated with the severity of psychomotor symptoms, energy level, thoughts of death/suicide, self-criticism, appetite/weight, depressed mood symptoms, sleep problems. IR was weakly but significantly correlated with anhedonia. IR appears to be linked to depressive symptoms characteristic of the "metabolic" MDD subtype, such as psychomotor changes, energy level, anhedonia, sleep problems, appetite/weight changes, state and trait anxiety, sleep quality, and non-response to SNRI.

Low-grade inflammation and serotonin 4 receptor binding in the healthy and the depressed brain

Inflammatory status affects healthy brain function and also low-grade inflammation putatively contributes to the pathophysiology of Major Depressive Disorder (MDD). This psychoneuro-immunological interplay is complex, bidirectional, and not fully understood. Also, it is not clear to what extent depressive states induce inflammation and/or if increased inflammation leads to depressive symptoms by affecting brain biology including serotonin signaling. The serotonin 4 receptor (5-HT4R) is an interesting new antidepressant target; direct stimulation has antidepressant-like, and pro-cognitive effects, and may also index serotonin tone at least in the adult healthy brain.Here, we investigate whether a peripheral marker of low-grade inflammation (hsCRP) is associated with 5-HT4R brain binding in both a healthy and in an unmedicated MDD group. 5-HT4R PET imaging data and hsCRP measures from 112 healthy and 79 unmedicated MDD individuals were available from the Cimbi database. We evaluated the associations between hsCRP level and 5-HT4R binding in three regions of interest (neocortex, hippocampus, and neostriatum) using multiple linear regression models adjusted for relevant covariates.We did not observe a statistically significant association between hsCRP and 5-HT4R binding. This applied to both the healthy and the MDD group.Our findings do not support a coupling between low-grade inflammation and brain 5-HT4R availability, which suggests that the serotonergic system is not sensitive to low-grade inflammation captured by hsCRP, neither in healthy nor in depressed states. Future studies are needed to test if the brain serotonin system is coupled to other inflammatory markers, for instance in conditions with high-grade and/or prolonged immunoactivation.

The impact of major depressive disorder on glycaemic control in type 2 diabetes: a longitudinal cohort study using UK Biobank primary care records

BackgroundThis study evaluates longitudinal associations between glycaemic control, measured by mean and within-patient variability of glycated haemaglobin (HbA1c) levels, and major depressive disorder (MDD) in individuals with type 2 diabetes (T2D), focusing on the timings of these diagnoses.MethodsIn UK Biobank, T2D was defined using self-report and linked health outcome data, then validated using polygenic scores. Repeated HbA1c measurements (mmol/mol) over the 10 years following T2D diagnosis were outcomes in mixed effects models, with disease duration included using restricted cubic splines. Four MDD exposures were considered: MDD diagnosis prior to T2D diagnosis (pre-T2D MDD), time between pre-T2D MDD diagnosis and T2D, new MDD diagnosis during follow-up (post-T2D MDD) and time since post-T2D MDD diagnosis. Models with and without covariate adjustment were considered.ResultsT2D diagnostic criteria were robustly associated with T2D polygenic scores. In 11,837 T2D cases (6.9 years median follow-up), pre-T2D MDD was associated with a 0.92 increase in HbA1c (95% CI: [0.00, 1.84]), but earlier pre-T2D MDD diagnosis correlated with lower HbA1c. These pre-T2D MDD effects became non-significant after covariate adjustment. Post-T2D MDD individuals demonstrated increasing HbA1c with years since MDD diagnosis (β=0.51\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta =0.51$$\\end{document}, 95% CI: [0.17, 0.86]). Retrospectively, across study follow-up, within-patient variability in HbA1c was 1.16 (95% CI: 1.13–1.19) times higher in post-T2D MDD individuals.ConclusionsThe timing of MDD diagnosis is important for understanding glycaemic control in T2D. Poorer control was observed in MDD diagnosed post-T2D, highlighting the importance of depression screening in T2D, and closer monitoring for individuals who develop MDD after T2D.

Rumination and Overrecruitment of Cognitive Control Circuits in Depression

BackgroundRumination is associated with greater cognitive dysfunction and treatment resistance in major depressive disorder (MDD), but its underlying neural mechanisms are not well understood. Because rumination is characterized by difficulty in controlling negative thoughts, the current study investigated whether rumination was associated with aberrant cognitive control in the absence of negative emotional information. MethodsIndividuals with MDD (n = 176) and healthy control individuals (n = 52) completed the stop signal task with varied stop signal difficulty during functional magnetic resonance imaging. In the task, a longer stop signal asynchrony made stopping difficult (hard stop), whereas a shorter stop signal asynchrony allowed more time for stopping (easy stop). ResultsIn participants with MDD, higher rumination intensity was associated with greater neural activity in response to difficult inhibitory control in the frontoparietal regions. Greater activation for difficult inhibitory control associated with rumination was also positively related to state fear. The imaging results provide compelling evidence for the neural basis of inhibitory control difficulties in individuals with MDD with high rumination. ConclusionsThe association between higher rumination intensity and greater neural activity in regions involved in difficult inhibitory control tasks may provide treatment targets for interventions aimed at improving inhibitory control and reducing rumination in this population.

Impaired topology and connectivity of grey matter structural networks in major depressive disorder: evidence from a multi-site neuroimaging data-set.

Major depressive disorder (MDD) has been increasingly understood as a disruption of brain connectome. Investigating grey matter structural networks with a large sample size can provide valuable insights into the structural basis of network-level neuropathological underpinnings of MDD. Using a multisite MRI data-set including nearly 2000 individuals, this study aimed to identify robust topology and connectivity abnormalities of grey matter structural network linked to MDD and relevant clinical phenotypes. A total of 955 MDD patients and 1009 healthy controls were included from 23 sites. Individualised structural covariance networks (SCN) were established based on grey matter volume maps. Following data harmonisation, network topological metrics and focal connectivity were examined for group-level comparisons, individual-level classification performance and association with clinical ratings. Various validation strategies were applied to confirm the reliability of findings. Compared with healthy controls, MDD individuals exhibited increased global efficiency, abnormal regional centralities (i.e. thalamus, precentral gyrus, middle cingulate cortex and default mode network) and altered circuit connectivity (i.e. ventral attention network and frontoparietal network). First-episode drug-naive and recurrent patients exhibited different patterns of deficits in network topology and connectivity. In addition, the individual-level classification of topological metrics outperforms that of structural connectivity. The thalamus-insula connectivity was positively associated with the severity of depressive symptoms. Based on this high-powered data-set, we identified reliable patterns of impaired topology and connectivity of individualised SCN in MDD and relevant subtypes, which adds to the current understanding of neuropathology of MDD and might guide future development of diagnostic and therapeutic markers.

Understanding mechanisms of depression prevention: study protocol of a randomized cross-over trial to investigate mechanisms of mindfulness and positive fantasizing as intervention techniques for reducing perseverative cognition in remitted depressed individuals

BackgroundMajor Depressive Disorder (MDD) is one of the most prevalent psychiatric disorders, and involves high relapse rates in which persistent negative thinking and rumination (i.e., perseverative cognition [PC]) play an important role. Positive fantasizing and mindfulness are common evidence-based psychological interventions that have been shown to effectively reduce PC and subsequent depressive relapse. How the interventions cause changes in PC over time, is unknown, but likely differ between the two. Whereas fantasizing may change the valence of thought content, mindfulness may operate through disengaging from automatic thought patterns. Comparing mechanisms of both interventions in a clinical sample and a non-clinical sample can give insight into the effectivity of interventions for different individuals. The current study aims to 1) test whether momentary psychological and psychophysiological indices of PC are differentially affected by positive fantasizing versus mindfulness-based interventions, 2) test whether the mechanisms of change by which fantasizing and mindfulness affect PC differ between remitted MDD versus never-depressed (ND) individuals, and 3) explore potential moderators of the main effects of the two interventions (i.e., what works for whom).MethodsIn this cross-over trial of fantasizing versus mindfulness interventions, we will include 50 remitted MDD and 50 ND individuals. Before the start of the measurements, participants complete several individual characteristics. Daily-life diary measures of thoughts and feelings (using an experience sampling method), behavioural measures of spontaneous thoughts (using the Sustained Attention to Response Task), actigraphy, physiological measures (impedance cardiography, electrocardiography, and electroencephalogram), and measures of depressive mood (self-report questionnaires) are performed during the week before (pre-) the interventions and the week during (peri-) the interventions. After a wash-out of at least one month, pre- and peri-intervention measures for the second intervention are repeated.DiscussionThis is the first study integrating self-reports, behavioural-, and physiological measures capturing dynamics at multiple time scales to examine the differential mechanisms of change in PC by psychological interventions in individuals remitted from multiple MDD episodes and ND individuals. Unravelling how therapeutic techniques affect PC in remitted individuals might generate insights that allows development of personalised targeted relapse prevention interventions.Trial registrationClinicalTrials.gov: NCT06145984, November 16, 2023.

Abnormal energy metabolism, oxidative stress, and polyunsaturated fatty acid metabolism in depressed adolescents associated with childhood maltreatment: A targeted metabolite analysis

The purpose of this study was to explore the metabolomic differences between Major depressive disorder (MDD) and healthy individuals among adolescents and the association between childhood maltreatment (CM) and differentially abundant metabolites. The exploratory study included 40 first-episode drug-naïve adolescents with MDD and 20 healthy volunteers. We used the Beck Depression Inventory (BDI-13) to assess the severity of depression and the Childhood Trauma Questionnaire (CTQ) to assess the presence of childhood maltreatment. The plasma samples from all participants were collected for targeted metabolomics analysis using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC‒MS/MS) methods. Spearman correlation was applied to analyse the correlations between clinical variables and metabolites. We found 11 increased metabolites and 37 decreased metabolites that differed between adolescents with MDD and healthy individuals. Pathway enrichment analysis of differentially abundant metabolites showed abnormalities in energy metabolism and oxidative stress in MDD. Importantly, we found that creatine, valine, isoleucine, glutamic acid and pyroglutamic acid were negatively correlated with the BDI-13, while isocitric acid, fatty acid and acylcarnitine were negatively associated with CTQ, and 4-hydroxyproline was positively related to CTQ in adolescents with MDD. These studies provide new ideas for the pathogenesis and potential treatment of adolescents with MDD.

No association between serotonin 4 receptor brain binding and personality trait Neuroticism - A positron emission tomography study in depressed patients and healthy individuals

Serotonergic neurotransmission has been linked to normal personality functioning, including the five-factor personality trait Neuroticism, which is a robust risk factor for Major Depressive Disorder (MDD). The serotonin 4 receptor (5-HT4R) is involved in regulating mood and has been shown to be altered in patients with MDD and map onto anxiety levels and memory performance. We here evaluate the link between 5-HT4R levels and Neuroticism in patients with MDD and replicate a previous study in healthy individuals. Neuroticism scores and brain 5-HT4R binding potential assessed with [11C]SB207145 positron emission tomography (PET) imaging were available from the CIMBI database for 63 unmedicated patients with MDD (48 W) and 120 healthy individuals (67 W). We investigated the association between Neuroticism and 5-HT4R binding in six regions of interest: frontal cortex, anterior cingulate cortex, amygdala, hippocampus, neostriatum, and thalamus for each group. There was no association between regional 5-HT4R binding and total Neuroticism score in patients or healthy individuals (all padj > 0.99), although post hoc analyses indicated that in patients, Neuroticism facets of Depression (padj = 0.046) and Impulsivity (padj = 0.009) were positively associated with thalamic and frontal 5-HT4R binding respectively. While trait Neuroticism does not appear to be associated with brain 5-HT4R in either patients with MDD or healthy individuals, we found evidence that the facets Depression and Impulsiveness may be linked to regional 5-HT4R levels in patients.

PREVIDA- IMPACT OF VORTIOXETINE ON MAJOR DEPRESSIVE DISORDER AND PERCEIVED COGNITIVE DYSFUNCTION: A MULTICENTER STUDY

Objective: To find out how common cognitive impairment is in people with major depressive disorder (MDD) and assess how well vortioxetine works for treating both cognitive dysfunction and depressive symptoms. Study Design: Multi-centred, Cross-sectional, prospective follow up design Place & Duration of Study: The research took place over the course of 12 weeks at 16 different psychiatric outpatient clinics throughout Pakistan, from September 2020 to November 2020. Method: The study included 498 individuals with serious depressive disorder diagnoses. The degree of depression symptoms and cognitive impairment was assessed. Psychiatrists gave trial participants vortioxetine after completing the Clinical Global Impression-Severity scale (CGI-S), the Patient Health Questionnaire-9 (PHQ-9), and the Perceived Deficits Questionnaire (PDQ). The variables were reassessed one week (+/- 3 days), one month (+/- 7 days), and three months (+/- 14 days) after the treatment began. Results: After completing a 12-week course of therapy with vortioxetine, mean PHQ 9 and PDQ scores of MDD individuals showed significant improvements. This indicates that vortioxetine is effective in reducing depression symptoms as well as cognitive impairments in MDD patients. A strong connection was seen between PHQ-9 and PDQ scores, indicating a direct relationship between cognitive impairment and depressed symptoms. Conclusions: The results of the research demonstrate how well vortioxetine works to treat cognitive impairments in MDD patients while also reducing depressed symptoms. These findings demonstrate the possibility of vortioxetine as a beneficial therapeutic option for those with MDD diagnoses who also have cognitive impairment. Additional investigation is required to validate these findings and assess their suitability for other demographics.

Major Depression and the Perception of Affective Instrumental and Expressive Gestures: An fMRI Investigation

Major depressive disorder (MDD) is associated with biased perception of human movement. Gesture is important for communication and in this study we investigated neural correlates of gesture perception in MDD. We hypothesised different neural activity between individuals with MDD and typical individuals when viewing instrumental and expressive gestures that were negatively or positively valenced. Differences were expected in brain areas associated with gesture perception, including superior temporal, frontal, and emotion processing regions. We recruited 12 individuals with MDD and 12 typical controls matched on age, gender, and handedness. They viewed gestures displayed by stick figures while functional magnetic resonance imaging (fMRI) was performed. Results of a random effects three-way mixed ANOVA indicated that individuals with MDD had greater activity in the right claustrum compared to controls, regardless of gesture type or valence. Additionally, we observed main effects of gesture type and valence, regardless of group. Perceiving instrumental compared to expressive gestures was associated with greater activity in the left cuneus and left superior temporal gyrus, while perceiving negative compared to positive gestures was associated with greater activity in the right precuneus and right lingual gyrus. We also observed a two-way interaction between gesture type and valence in various brain regions.

The validity of the Edmonton Symptom Assessment System-Depression item for screening for depression in individuals with cancer pain: A cross-sectional study.

Depression is common in individuals with cancer and pain, negatively impacts quality of life, treatment adherence, tumor progression, and survival. The primary aims of this study were to (1) evaluate the validity of the Edmonton Symptom Assessment System's depression (ESAS-D) for detecting major depressive disorder (MDD) as diagnosed by a psychiatrist and (2) identify the best cutoff for this purpose in a sample of cancer pain individuals. The secondary aim was to compare ESAS-D with another commonly used screening measure (Patient Health Questionnaire-2 [PHQ-2]) for classifying individuals as meeting or not meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for depression. 49 cancer pain individuals completed the ESAS-D and PHQ-2 Within 2 weeks, a psychiatrist interviewed the participants and determined whether or not they met criteria for MDD based on the DSM-5. The ESAS-D demonstrated acceptable accuracy and validity for classifying MDD. A cutoff of ≥2 was identified as being best able to balance sensitivity (85%) and specificity (76%) and had an overall accuracy of 79%. A receiver operating characteristic curve analysis showed an area under the curve (AUC) of 0.81 (95% confidence interval [CI]: 0.68-0.94). The ESAS-D also compared favorably with the modified Thai PHQ-2 (sensitivity, 75%; specificity, 72%; overall accuracy, 73%; AUC, 0.74 [95% CI: 0.59-0.88]) for identifying MDD individuals. The ESAS-D showed acceptable sensitivity, specificity, and overall accuracy for screening for MDD in cancer and pain. It could therefore be used to screen for probable depression in this population.

Integrative bioinformatics and artificial intelligence analyses of transcriptomics data identified genes associated with major depressive disorders including NRG1

Major depressive disorder (MDD) is a common mental disorder and is amongst the most prevalent psychiatric disorders. MDD remains challenging to diagnose and predict its onset due to its heterogeneous phenotype and complex etiology. Hence, early detection using diagnostic biomarkers is critical for rapid intervention. In this study, a mixture of AI and bioinformatics were used to mine transcriptomic data from publicly available datasets including 170 MDD patients and 121 healthy controls. Bioinformatics analysis using gene set enrichment analysis (GSEA) and machine learning (ML) algorithms were applied. The GSEA revealed that differentially expressed genes in MDD patients are mainly enriched in pathways related to immune response, inflammatory response, neurodegeneration pathways and cerebellar atrophy pathways. Feature selection methods and ML provided predicted models based on MDD-altered genes with ≥75% of accuracy. The integrative analysis between the bioinformatics and ML approaches identified ten key MDD-related biomarkers including NRG1, CEACAM8, CLEC12B, DEFA4, HP, LCN2, OLFM4, SERPING1, TCN1 and THBS1. Among them, NRG1, active in synaptic plasticity and neurotransmission, was the most robust and reliable to distinguish between MDD patients and healthy controls amongst independent external datasets consisting of a mixture of populations. Further evaluation using saliva samples from an independent cohort of MDD and healthy individuals confirmed the upregulation of NRG1 in patients with MDD compared to healthy controls. Functional mapping to the human brain regions showed NRG1 to have high expression in the main subcortical limbic brain regions implicated in depression. In conclusion, integrative bioinformatics and ML approaches identified putative non-invasive diagnostic MDD-related biomarkers panel for the onset of depression.

Higher immune-related gene expression in major depression is independent of CRP levels: results from the BIODEP study

Compelling evidence demonstrates that some individuals suffering from major depressive disorder (MDD) exhibit increased levels of inflammation. Most studies focus on inflammation-related proteins, such as serum or plasma C-reactive protein (CRP). However, the immune-related modifications associated with MDD may be not entirely captured by CRP alone. Analysing mRNA gene expression levels, we aimed to identify broader molecular immune-related phenotypes of MDD. We examined 168 individuals from the non-interventional, case–control, BIODEP study, 128 with a diagnosis of MDD and 40 healthy controls. Individuals with MDD were further divided according to serum high-sensitivity (hs)CRP levels (n = 59 with CRP <1, n = 33 with CRP 1–3 and n = 36 with CRP >3 mg/L). We isolated RNA from whole blood and performed gene expression analyses using RT-qPCR. We measured the expression of 16 immune-related candidate genes: A2M, AQP4, CCL2, CXCL12, CRP, FKBP5, IL-1-beta, IL-6, ISG15, MIF, GR, P2RX7, SGK1, STAT1, TNF-alpha and USP18. Nine of the 16 candidate genes were differentially expressed in MDD cases vs. controls, with no differences between CRP-based groups. Only CRP mRNA was clearly associated with serum CRP. In contrast, plasma (proteins) IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-16, IL-17A, IFN-gamma and TNF-alpha, and neutrophils counts, were all differentially regulated between CRP-based groups (higher in CRP >3 vs. CRP <1 and/or controls), reflecting the gradient of CRP values. Secondary analyses on MDD individuals and controls with CRP values <1 mg/L (usually interpreted as 'no inflammation') confirmed MDD cases still had significantly different mRNA expression of immune-related genes compared with controls. These findings corroborate an immune-related molecular activation in MDD, which appears to be independent of serum CRP levels. Additional biological mechanisms may then be required to translate this mRNA signature into inflammation at protein and cellular levels. Understanding these mechanisms will help to uncover the true immune abnormalities in depression, opening new paths for diagnosis and treatment.

Early maladaptive schema domains and suicide risk in major depressive disorder: the mediating role of patients’ illness-related self-regulation processes and symptom severity

AbstractEarly maladaptive schemas (EMS), illness representations, and coping are associated with clinical outcomes of patients with major depressive disorder (MDD). However, the pathways that link these factors are largely unknown. The present prospective study aimed at investigating the possible mediating role of illness representations and coping in the associations among schema domains, symptom severity, and suicide risk in MDD. Participants were 135 patients diagnosed with MDD, aged 48.13 ± 14.12 (84.4% females). The Young Schema Questionnaire-Short Form 3 was used to measure schema domains at baseline. Illness representations and coping were measured at approximately five months later (mean = 5.04 ± 1.16 months) with the Illness Perception Questionnaire-Mental Health and the Brief COPE Inventory, respectively. MDD outcomes were measured about 10 months after the baseline assessment (mean = 9.44 ± 2.36 months) with the Beck Depression Inventory and the Risk Assessment Suicidality Scale. SPSS AMOS 27 was used to conduct path analysis. Serial mediation Structural Equation Modelling, controlling for age, education, marital status, working status, MDD duration, pharmacotherapy, and psychotherapy, revealed that Impaired Autonomy and Performance was positively linked to suicide risk. Negative MDD impact representations and symptom severity serially mediated the aforementioned association. Finally, problem-focused coping was negatively related to symptom severity and suicide risk. This study’s main limitation was modest sample size. Representations regarding the impact and severity of MDD mediate the effects of Impaired Autonomy and Performance on future suicide risk in MDD. Healing Impaired Autonomy and Performance domain of EMS, restructuring patients’ representations of high MDD impact, and enhancing problem-focused coping could significantly reduce symptom severity and suicide risk in Schema Therapy with MDD individuals.

The role of miRNA in diagnosing and clarifying the pathomechanisms in major depressive disorder

IntroductionThere are currently no diagnostic or treatment-guiding biomarkers for major depressive disorder (MDD). Microribonucleic acids (miRNA) may facilitate understanding the reorganisation of gene expression networks in MDD. Identifying miRNA and target mRNA pathways that contribute to MDD may open new therapeutic avenues, such as inhibiting endogenous miRNA or administering exogenous miRNA.ObjectivesThis study investigates how miRNAs can clarify the molecular mechanisms of MDD by comparing the miRNA levels in the blood serum of patients with MDD and healthy individuals. The study also investigates the discriminative ability of miRNAs to distinguish between depressed patients and healthy controls.MethodsSixty depressed patients were matched with 60 healthy controls based on age, gender, ethnicity, and years of education. The severity of depression was measured using the Hamilton Depression Rating Scale, and venous blood was collected for miRNA profiling. Using the QIAGEN Ingenuity Pathway Analysis, networks were constructed to identify the biological pathways associated with MDD influenced by the differentially expressed miRNAs. Analyses of the receiver operating characteristic (ROC) were performed to examine the capacity of miRNAs to distinguish between depressed and healthy individuals.ResultsSix miRNAs (miR-542-3p, miR-181b-3p, miR190a-5p, miR-33a-3p, miR-3690, and miR-6895-3p) were significantly down-regulated in untreated depressed patients compared to healthy controls. miR-542-3p has experimentally validated mRNA targets predicted to be associated with MDD. ROC analyses determined that a panel containing miR-542-3p, miR181b-3p, and miR-3690 distinguished between depressed and healthy individuals with an area under the curve value of 0.67.ConclusionsSpecific miRNAs, including miR-542-3p, miR181b-3p, and miR-3690, may be biomarkers with targets implicated in the pathophysiology of depression. They could also be used to distinguish accurately between depressed and healthy individuals.Disclosure of InterestNone Declared

Attenuated interoceptive processing in individuals with major depressive disorder and high repetitive negative thinking

Repetitive negative thinking (RNT) is a transdiagnostic symptom associated with poor outcomes in major depressive disorder (MDD). MDD is characterized by altered interoception, which has also been associated with poor outcomes. The present study investigated whether RNT is directly associated with altered interoceptive processing. Interoceptive awareness toward the heart and stomach was probed on the Visceral Interoceptive Attention (VIA) task with fMRI in MDD individuals who were propensity-matched on the severity of depression and anxiety symptoms and relevant demographics but different in RNT intensity (High RNT [H-RNT, n = 48] & Low RNT [L-RNT, n = 49]), and in matched healthy volunteers (HC, n = 27). Both H-RNT and L-RNT MDD individuals revealed reduced stomach interoceptive processing compared to HC in the left medial frontal region and insular cortex (H-RNT: β = −1.04, L-RNT: β = −0.97), perirhinal cortex (H-RNT: β = −0.99, L-RNT: β = −1.03), and caudate nucleus (H-RNT: β = −1.06, L-RNT: β = −0.89). However, H-RNT was associated with decreased right medial temporal lobe activity including the hippocampus and amygdala during stomach interoceptive trials (β = −0.61) compared to L-RNT. Insular interoceptive processing was similar in H-RNT and L-RNT participants (β = −0.07, p = 0.92). MDD individuals with high RNT exhibited altered gastric interoceptive responses in brain areas that are important for associating the information with specific contexts and emotions. Attenuated interoceptive processing may contribute to RNT generation, non-adaptive information processing, action selection, and thus poor treatment outcome.

Intensity of repetitive negative thinking in depression is associated with greater functional connectivity between semantic processing and emotion regulation areas.

Repetitive negative thinking (RNT), a cognitive process that encompasses past (rumination) and future (worry) directed thoughts focusing on negative experiences and the self, is a transdiagnostic construct that is especially relevant for major depressive disorder (MDD). Severe RNT often occurs in individuals with severe levels of MDD, which makes it challenging to disambiguate the neural circuitry underlying RNT from depression severity. We used a propensity score, i.e., a conditional probability of having high RNT given observed covariates to match high and low RNT individuals who are similar in the severity of depression, anxiety, and demographic characteristics. Of 148 MDD individuals, we matched high and low RNT groups (n = 50/group) and used a data-driven whole-brain voxel-to-voxel connectivity pattern analysis to investigate the resting-state functional connectivity differences between the groups. There was an association between RNT and connectivity in the bilateral superior temporal sulcus (STS), an important region for speech processing including inner speech. High relative to low RNT individuals showed greater connectivity between right STS and bilateral anterior insular cortex (AI), and between bilateral STS and left dorsolateral prefrontal cortex (DLPFC). Greater connectivity in those regions was specifically related to RNT but not to depression severity. RNT intensity is directly related to connectivity between STS and AI/DLPFC. This might be a mechanism underlying the role of RNT in perceptive, cognitive, speech, and emotional processing. Future investigations will need to determine whether modifying these connectivities could be a treatment target to reduce RNT.

MEG-based Classification and Grad-CAM Visualization for Major Depressive and Bipolar Disorders with Semi-CNN.

Major depressive disorder (MDD) and bipolar disorder (BD) are two major mood disorders with partly overlapped symptoms but different treatments. However, their misdiagnosis and mistreatment are common based on the DSM-V criteria, lacking objective and quantitative indicators. This study aimed to develop a novel approach that accurately classifies MDD and BD based on their resting-state magnetoencephalography (MEG) signals during euthymic phases. A revisited 3D CNN model, Semi-CNN, that could automatically detect brainwave patterns in spatial, temporal, and frequency domains was implemented to classify wavelet-transformed MEG signals of normal controls and MDD and BD patients. The model achieved a test accuracy of 96.05% and an average of 95.71% accuracy for 5-fold cross-validation. Furthermore, saliency maps of the model were estimated using Grad-CAM++ to visualize the proposed classification model and highlight disease-specific brain regions and frequencies. Clinical Relevance - Our model provides a stable pipeline that accurately classifies MDD, BD, and healthy individuals based on resting-state MEG signals during the euthymic phases, opening the potential for quantitative and accurate brain-based diagnosis for the highly misdiagnosed MDD/BD patients.

Help-Seeking Behaviors and Related Factors in Chinese Patients With Major Depressive Disorder: A Community-Based Cross-Sectional Study.

BackgroundAlthough evidence-based and effective treatments are available for people with major depressive disorder (MDD), a substantial number do not seek or receive help. Therefore, this study aimed to (1) investigate the total help-seeking rate and first-time help-seeking choices; (2) explore the perceived helpfulness of 23 potential sources; and (3) evaluate the factors related to help-seeking behaviors among patients with MDD.Materials and MethodsData came from the Tianjin Mental Health Survey (TJMHS), which included a representative sample of adult community residents (n = 11,748) in the Chinese municipality of Tianjin. Of these, 439 individuals were diagnosed with lifetime MDD according to the Diagnostic and Statistical Manual-fourth edition (DSM-IV) and administered a help-seeking questionnaire.ResultsIn a survey, 28.2% of patients with MDD living community reported that they had ever sought any help during their entire lifetime before the interview, with 8.2% seeking help in mental healthcare settings, 8.0% only in other healthcare settings, and 12.0% only in non-healthcare sources (e.g., family, friends, and spiritual advisor). Among help-seekers, the first help mainly was sought in non-healthcare sources (61.3%), followed by healthcare settings (25.8%) and mental healthcare settings (12.9%). The majority of MDD individuals thought the non-healthcare sources were not helpful and mental healthcare settings were helpful or possibly helpful to solve mental problems. Female, having 10–12 or higher education years, comorbid anxiety disorders were associated with increased help-seeking.ConclusionA small percentage of individuals with MDD living in community of Tianjin sought help. They preferred non-healthcare sources to healthcare settings. Demographic and clinical features were associated with help-seeking behaviors.

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

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