Major Depressive Disorder Patients Research Articles

Elevated SCN11A concentrations associated with lower serum lipid levels in patients with major depressive disorder

The pathogenesis of major depressive disorder (MDD) involves lipid metabolism. Our earlier research also revealed that MDD patients had much lower total cholesterol (TC) concentrations than healthy controls (HCs). However, it is still unclear why TC decreased in MDD. Here, based on the Ingenuity Knowledge Base’s ingenuity pathway analysis, we found that sodium voltage-gated channel alpha subunit 11A (SCN11A) might serve as a link between low lipid levels and MDD. We analyzed the TC levels and used ELISA kits to measure the levels of SCN11A in the serum from 139 MDD patients, and 65 HCs to confirm this theory and explore the potential involvement of SCN11A in MDD. The findings revealed that TC levels were considerably lower and SCN11A levels were remarkably increased in MDD patients than those in HCs, while they were significantly reversed in drug-treatment MDD patients than in drug-naïve MDD patients. There was no significant difference in SCN11A levels among MDD patients who used single or multiple antidepressants, and selective serotonin reuptake inhibitors or other antidepressants. Pearson correlation analysis showed that the levels of TC and SCN11A were linked with the Hamilton Depression Rating Scales score. A substantial association was also found between TC and SCN11A. Moreover, a discriminative model made up of SCN11A was discovered, which produced an area under a curve of 0.9571 in the training set and 0.9357 in the testing set. Taken together, our findings indicated that SCN11A may serve as a link between low lipid levels and MDD, and showed promise as a candidate biomarker for MDD.

Occurrence and characteristics of suicidal ideation in psychiatrically healthy individuals based on ecological momentary assessment.

Decedents with no known mental disorder comprise 5-40% of suicides, suggesting that suicide ideation (SI) and behavior may occur in the psychiatrically healthy with important implications for suicide risk screening. Healthy Volunteers (HV) and patients with Major Depressive Disorder (MDD) provided 7 days of Ecological Momentary Assessment (EMA) data about SI and stressors. Longitudinal mixed effects logistic regression models compared HV and patient SI and stressors. Mixed effects linear regression models compared HVs' and patients' SI score change from the previous epoch's SI score when each stressor occurred. HVs (n = 42) reported less frequent (p < 0.001) and less intense SI (p < 0.003) than patients (n = 80), yet did endorse SI and/or SI-related items in 44% of EMA epochs, endorsing SI items in 25% of epochs with non-zero SI scores. For 7 of 8 stressors, patients reported stressors more often than HVs (all p < 0.001) responding to them with increased SI (0.0001 < p < 0.0472). HVs were relatively resilient to stressors, reporting SI increases only in response to neglect (p < 0.0147). Although SI and SAs are documented among psychiatrically healthy individuals, scientific attention to these observations has been scant. Real-time SI measurement showed that HVs' SI was less pronounced than MDD patients', but was endorsed, nonetheless. Patients were more likely to report stressors than HVs, perhaps due to greater sensitivity to the environment, and reported SI in response to stressors, which was less common in HVs. Both MDD patients and HVs most often manifested passive SI (viz, "decreased wish to live"). However, passive SI (viz, "desire for death"), may predict suicide, even absent SI per se (thinking about killing yourself). This study validates the utility of real-time SI assessment, showing that HVs endorse SI items in 11% of epochs, which implies that suicide risk screening focused on those with mental disorders may be too narrow an approach.

An association study of m6A methylation with major depressive disorder

ObjectiveTo find the relationship between N6-methyladenosine (m6A) genes and Major Depressive Disorder (MDD).MethodsDifferential expression of m6A associated genes between normal and MDD samples was initially identified. Subsequent analysis was conducted on the functions of these genes and the pathways they may affect. A diagnostic model was constructed using the expression matrix of these differential genes, and visualized using a nomogram. Simultaneously, an unsupervised classification method was employed to classify all patients based on the expression of these m6A associated genes. Following this, common differential genes among different clusters were computed. By analyzing the functions of the common differential expressed genes among clusters, the role of m6A-related genes in the pathogenesis of MDD patients was elucidated.ResultsDifferential expression was observed in ELAVL1 and YTHDC2 between the MDD group and the control group. ELAVL1 was associated with comorbid anxiety in MDD patients. A linear regression model based on these two genes could accurately predict whether patients in the GSE98793 dataset had MDD and could provide a net benefit for clinical decision-making. Based on the expression matrix of ELAVL1 and YTHDC2, MDD patients were classified into three clusters. Among these clusters, there were 937 common differential genes. Enrichment analysis was also performed on these genes. The ssGSEA method was applied to predict the content of 23 immune cells in the GSE98793 dataset samples. The relationship between these immune cells and ELAVL1, YTHDC2, and different clusters was analyzed.ConclusionAmong all the m6A genes, ELAVL1 and YTHDC2 are closely associated with MDD, ELAVL1 is related to comorbid anxiety in MDD. ELAVL1 and YTHDC2 have opposite associations with immune cells in MDD.

Potential correlations between asymmetric disruption of functional connectivity and metabolism in major depressive disorder

ObjectivePrevious research has suggested a connection between major depressive disorder (MDD) and certain comorbidities, including gastrointestinal issues, thyroid dysfunctions, and glycolipid metabolism abnormalities. However, the relationships between these factors and asymmetrical alterations in functional connectivity (FC) in adults with MDD remain unclear. MethodWe conducted a study on a cohort of 42 MDD patients and 42 healthy controls (HCs). Participants underwent comprehensive clinical assessments, including evaluations of blood lipids and thyroid hormone levels, as well as resting-state functional magnetic resonance imaging (Rs-fMRI) scans. Data analysis involved correlation analysis to compute the parameter of asymmetry (PAS) for the entire brain's functional connectome. We then examined the interrelationships between abnormal PAS regions in the brain, thyroid hormone levels, and blood lipid levels. ResultsThe third-generation ultra-sensitive thyroid stimulating hormone (TSH3UL) level was found to be significantly lower in MDD patients compared to HCs. The PAS score of the left inferior frontal gyrus (IFG) decreased, while the bilateral posterior cingulate cortex (Bi-PCC) PAS increased in MDD patients relative to HCs. Notably, the PAS score of the left IFG negatively correlated with both TSH and total cholesterol (CHOL) levels. However, these correlations lose significance after the Bonferroni correction. ConclusionMDD patients demonstrated abnormal asymmetry in resting-state FC (Rs-FC) within the fronto-limbic system, which may be associated with CHOL and thyroid hormone levels.

The relationship between event-related potential components and suicide risk in major depressive disorder

BackgroundSuicide is a serious global issue, with major depressive disorder (MDD) being a significant risk factor for suicidal thoughts and behaviors. There is an urgent need to determine whether event-related potential components (ERPs) could be used as an indicator to assess suicidal risk. MethodsFrom 2020 to 2023, 258 participants in total were recruited into the study. All participants were divided into four groups: MDD patients at high (n = 66), moderate (n = 66), and low risk (n = 56) of suicide, and healthy controls (HCs)(n = 70). Each participant provided socio-demographic information and underwent evaluations using clinical psychological scales such as 7-item Generalized Anxiety Disorder (GAD-7), Health Questionnaire-9 items (PHQ-9), and Nurses' Global Assessment of Suicide Risk (NGASR). The auditory brainstem response test and ERP examination were performed for all subjects. ResultsOur study found that the amplitude of P2–P3 and N2–P3 was significantly reduced in MDD patients at moderate and high risk of suicide, and these were negatively correlated with NGASR total score (all P < 0.05). Point B latency was positively correlated with NGASR total score (P < 0.05). Patients with MDD patients at low risk for suicide had a lower A-B amplitude compared to HCs (P < 0.05). No differences were found in MMN or P50 components between the four groups (all P > 0.05). ConclusionsMDD patients at higher risk of suicide exhibited severe impairment of cognitive function. ERP indices, such as the amplitude of P2–P3 and N2–P3, could be associated with the risk of suicide in MDD patients.

Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia

BackgroundThis study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores.Methods46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman’s correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia.Results1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The β-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97.ConclusionThis study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP.

The influence of gender-specific factors influencing severe anxiety in psychotic major depression: role of thyroid hormones and depression severity.

Psychotic major depression (PMD) is characterized by major depressive disorder (MDD) accompanied by delusions or hallucinations. While the prevalence of PMD and its association with anxiety have been studied, gender-specific differences and the role of thyroid hormones in PMD-related anxiety remain less explored. A total of 1718 first-episode and drug-naïve MDD patients was assessed for the presence of PMD and severe anxiety. Clinical assessments, including Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impressions-Severity (CGI-S) scale, were conducted to assess depression, anxiety, psychotic symptoms, and clinical severity, respectively. Blood samples were collected to measure thyroid function parameters. The prevalence of severe anxiety was higher in PMD patients compared to non-psychotic MDD patients (71.3% vs. 5.3%). No significant gender differences were observed in the prevalence of severe anxiety among PMD patients. However, elevated thyroid-stimulating hormone (TSH) levels and increased depression severity (HAMD scores) were identified as independent risk factors for severe anxiety in female PMD patients. In contrast, no significant risk factors were found in male PMD patients. The area under the receiver operating characteristic (AUCROC) analysis revealed that the HAMD score and TSH level showed acceptable discriminatory capacity for distinguishing between female PMD patients with and without severe anxiety. This study highlights the heightened prevalence of severe anxiety in PMD patients, with TSH levels and depression severity emerging as gender-specific risk factors for anxiety in females. These findings suggest the importance of thyroid hormone assessment and tailored interventions for managing anxiety in female PMD patients.

Gender-related alterations of serum trace elements and neurometabolism in the anterior cingulate cortex of patients with major depressive disorder

BackgroundIt is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. Methods109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. ResultsIn individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. ConclusionsOur findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC.

Gray matter volume and corresponding covariance connectivity are biomarkers for major depressive disorder

The major depressive disorder (MDD) is a common and severe mental disorder. To identify a reliable biomarker for MDD is important for early diagnosis and prevention. Given easy access and high reproducibility, the structural magnetic resonance imaging (sMRI) is an ideal method to identify the biomarker for depression. In this study, sMRI data of first episode, treatment-naïve 66 MDD patients and 54 sex-, age-, and education-matched healthy controls (HC) were used to identify the differences in gray matter volume (GMV), group-level, individual-level covariance connections. Finally, the abnormal GMV and individual covariance connections were applied to classify MDD from HC. MDD patients showed higher GMV in middle occipital gyrus (MOG) and precuneus (PCun), and higher structural covariance connections between MOG and PCun. In addition, the Allen Human Brain Atlas (AHBA) was applied and revealed the genetic basis for the changes of gray matter volume. Importantly, we reported that GMV in MOG, PCun and structural covariance connectivity between MOG and PCun are able to discriminate MDD from HC. Our results revealed structural underpinnings for MDD, which may contribute towards early discriminating for depression.

Association of anhedonia with brain-derived neurotrophic factor and interleukin-10 in major depressive disorder

BackgroundAnhedonia, a core symptom of major depressive disorder (MDD), manifests in two forms: anticipatory and consummatory, reflecting a diminished capacity to anticipate or enjoy pleasurable activities. Prior studies suggest that brain-derived neurotrophic factor (BDNF) and interleukin-10 (IL-10) may play key roles in the emergence of anhedonia in MDD. The specific relationships between these biomarkers and the two forms of anhedonia remain unclear. This study investigated the potential links between BDNF, IL-10, and both forms of anhedonia in MDD patients. MethodsThis study included 43 participants diagnosed with MDD and 58 healthy controls. It involved detailed assessments of depression and anxiety levels, anticipatory and consummatory pleasure, cognitive functions, and a broad spectrum of plasma biomarkers, such as C-reactive protein, various interleukins, and BDNF. Using partial correlation, variables related to pleasant experiences were identified. Stepwise multiple linear regression analysis was applied to pinpoint the independent predictors of anhedonia in the MDD group. ResultsDemographically, both groups were comparable in terms of age, sex, body mass index, educational year, and marital status. Individuals with MDD displayed markedly reduced levels of anticipatory and consummatory pleasure, higher anxiety, and depression scores compared to healthy controls. Additionally, cognitive performance was notably poorer in the MDD group. These patients also had lower plasma diamine oxidase levels. Analysis linked anhedonia to impaired delayed memory. Regression results identified IL-10 and BDNF as independent predictors of anticipatory and consummatory anhedonia, respectively. ConclusionThese findings demonstrate that anticipatory and consummatory anhedonia are influenced by independent factors, thereby providing critical insights into the distinct neuroimmunological mechanisms that underlie various forms of anhedonia.Clinicl Trial Registration Number: NCT03790085

Diagnosis Support of Major Depressive Disorder using Event-Related Potentials during Affective Priming Tasks

Major Depressive Disorder (MDD) is a global problem. Currently, the most common diagnosis is based on criteria susceptible to the subjectivity of the patient and the clinician. A possible solution to this problem is to look for diagnostic biomarkers that can accurately and early detect this mental condition. Some researchers have focused on electroencephalogram (EEG) analysis to identify biomarkers. In this study we used a dataset composed of EEG recordings from 24 subjects with MDD and 29 healthy controls (HC), during the execution of affective priming tasks with three different emotional stimuli (images): fear, sadness, and happiness. We investigated abnormalities in depressed patients using a novel technique, by directly comparing Event-Related Potential (ERP) waveforms to find statistically significant differences between the MMD and HC groups. Compared to the control group (healthy subjects), we found out that for the emotions fear and happiness there is a decrease in cortical activity at temporal regions in MDD patients. Just the opposite, for the emotion sadness, an increase in MDD brain activity occurs in frontal and occipital regions. Our findings suggest that emotions regulate the attentional control of cognitive processing and are promising for clinical application in diagnosing patients with MDD more objectively.

Efficacy of addition of the anti-inflammatory, IV Glutathione to standard Ketamine IV therapy in Major Depressive Disorder

Efficacy of addition of the anti-inflammatory, IV Glutathione to standard Ketamine IV therapy in Major Depressive 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.

Association of clinical variables and thyroid-stimulating hormone with psychotic symptoms in patients with first-episode and drug-naïve major depressive disorder with elevated fasting blood glucose: preliminary exploratory study with a large sample.

Psychotic symptoms and elevated fasting blood glucose (FBG) are frequently observed in people with major depressive disorder (MDD), but there is a lack of research into this relationship within this cohort. This study aimed to preliminarily explore the prevalence of psychotic symptoms and their predictors among patients with MDD and elevated FBG. This study enrolled 1718 patients with first-episode and drug-naïve (FEDN) MDD. Sociodemographic data and physical and biochemical indicators were collected. Clinical symptoms were assessed with tools such as the Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression (HRSD) and Positive and Negative Syndrome Scale positive subscale. The odds ratio for psychotic symptoms in those with MDD and elevated FBG (18.7%) was 2.33 times higher than those with MDD without elevated FBG. Presence of psychotic symptoms was significantly correlated with HRSD score, suicide attempts, and total cholesterol and thyroid-stimulating hormone levels. The combination of HRSD score, suicide attempts and thyroid-stimulating hormone levels among patients with MDD and elevated FBG effectively distinguished between individuals with and without psychotic symptoms, achieving an area under the curve of 0.87. Psychotic symptoms are frequently observed among FEDN MDD patients with elevated FBG, and depressive symptoms, suicide attempts and thyroid-stimulating hormone levels are related to psychotic symptoms in this cohort.

Neural correlates of stress-reactive rumination in depression – the role of childhood trauma and social anxiety

Recent work showed an association of prefrontal dysfunctions in patients with Major Depressive Disorder (MDD) and social stress induced rumination. However, up to date it is unclear which etiological features of MDD might cause prefrontal dysfunctions. In the study at hand, we aimed to replicate recent findings, that showed prefrontal activation alterations during the Trier Social Stress Test (TSST) and subsequently increased stress-reactive rumination in MDD compared to healthy controls. Moreover, we aimed to explore the role of adverse childhood experiences and other clinical variables in this relationship. N=55 patients currently suffering from MDD and n=42 healthy controls (HC) underwent the TSST, while cortical activity in areas of the cognitive control network (CCN) was measured via functional near-infrared spectroscopy. The TSST successfully induced a stress reaction (physiologically, as well as indicated by subjective stress ratings) and state rumination in all subjects with moderate to large effect sizes. In comparison to HC, MDD patients showed elevated levels of state rumination with large effect sizes, as well as a typical pattern of reduced cortical oxygenation during stress in the CCN with moderate effect sizes. Self-reported emotional abuse and social anxiety were moderately positively associated with increased stress-reactive rumination. Within the MDD sample, emotional abuse was negatively and social anxiety positively associated with cortical oxygenation within the CCN with moderate to large effect sizes. In conclusion, our results replicate previous findings on MDD-associated hypoactivity during stress and extends the research toward specific subtypes of depression.

Altered asymmetry of functional connectome gradients in major depressive disorder.

Major depressive disorder (MDD) is a debilitating disease involving sensory and higher-order cognitive dysfunction. Previous work has shown altered asymmetry in MDD, including abnormal lateralized activation and disrupted hemispheric connectivity. However, it remains unclear whether and how MDD affects functional asymmetries in the context of intrinsic hierarchical organization. Here, we evaluate intra- and inter-hemispheric asymmetries of the first three functional gradients, characterizing unimodal-transmodal, visual-somatosensory, and somatomotor/default mode-multiple demand hierarchies, to study MDD-related alterations in overarching system-level architecture. We find that, relative to the healthy controls, MDD patients exhibit alterations in both primary sensory regions (e.g., visual areas) and transmodal association regions (e.g., default mode areas). We further find these abnormalities are woven in heterogeneous alterations along multiple functional gradients, associated with cognitive terms involving mind, memory, and visual processing. Moreover, through an elastic net model, we observe that both intra- and inter-asymmetric features are predictive of depressive traits measured by BDI-II scores. Altogether, these findings highlight a broad and mixed effect of MDD on functional gradient asymmetry, contributing to a richer understanding of the neurobiological underpinnings in MDD.

A Chinese adaptation of the Patient Health Questionnaire for Adolescents (PHQ-A): factor structure and psychometric properties

BackgroundTo examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD).MethodsA total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve.ResultsCFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively.ConclusionThe PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.

The digestion and dietary carbohydrate pathway contains 100% gene mutations enrichment among 117 patients with major depressive disorder.

Major depressive disorder (MDD) is partially inheritable while its mechanism is still uncertain. This cross-sectional study focused on gene pathways as a whole rather than polymorphisms of single genes. Deep sequencing and gene enrichment analysis based on pathways in Reactome database were obtained to reveal gene mutations. A total of 117 patients with MDD and 78 healthy controls were enrolled. The Digestion and Dietary Carbohydrate pathway (Carbohydrate pathway) was determined to contain 100% mutations in patients with MDD and 0 mutation in matched healthy controls. Findings revealed in the current study enable a better understanding of gene pathways mutations status in MDD patients, indicating a possible genetic mechanism of MDD development and a potential diagnostic or therapeutic target.

Effectiveness of Vortioxetine in Patients with Major Depressive Disorder Associated with Chronic Pain: An Observational Study in a Spanish Population.

Chronic pain (CP) and depression/anxiety often coexist, worsening each other's symptoms. Treating this comorbidity is challenging. Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are the first-line treatment options for this comorbidity, although sometimes they are not effective and/or well tolerated by patients, and there is little clinical evidence that selective serotonin reuptake inhibitors are useful for controlling CP. The antidepressant vortioxetine, with a multimodal mechanism that may help reduce pain, has proven clinical efficacy in patients with major depressive disorder (MDD). This study investigated vortioxetine's effectiveness for MDD and CP in clinical practice. This was a 3-month, multicenter, prospective, open-label, non-interventional pharmacoepidemiologic study. Patients (n = 64) with MDD (9-item Patient Health Questionnaire [PHQ-9] score ≥ 15) and CP (visual analogue scale [VAS] score ≥ 4) were treated with vortioxetine for 3months (initiated with 10mg/day, with flexible dosing thereafter [5-20mg/day]). VAS, Clinical Global Impression (CGI), and Patient Global Impression (PGI) scales were used at baseline and at 1 and 3months. Brief Pain Inventory (BPI), PHQ-9 scale, and Satisfaction with Medicines Questionnaire (SATMED-Q) were used at baseline and at 3months. Adverse Events (AEs) were recorded. Descriptive statistics, chi-square tests, and Student's t-tests were used for paired data. MDD patients showed a statistically significant improvement in VAS from baseline (mean [standard deviation (SD)]: 7.42 [0.69]) to 1month (mean [SD]: 6.1 [0.81], P < 0.001) and 3months (mean [SD]: 5.09 [1.26], P < 0.0001). Similarly, BPI and PHQ-9 scores showed significant improvement from baseline (mean [SD]: 6.20 [0.80] and 16.63 [1.47], respectively) to 3months (mean [SD]: 4.73 [0.98] and 7.30 [2.60], P < 0.0001, respectively). Patients showed clinical improvement with CGI and PGI scales and reported being satisfied with the treatment in the SATMED-Q. A few mild EAs were registered. Vortioxetine can relieve depressive and pain symptoms, with a good safety profile, in patients with MDD and CP.

Molecular mechanisms underlying structural plasticity of electroconvulsive therapy in major depressive disorder.

Although previous studies reported structural changes associated with electroconvulsive therapy (ECT) in major depressive disorder (MDD), the underlying molecular basis of ECT remains largely unknown. Here, we combined two independent structural MRI datasets of MDD patients receiving ECT and transcriptomic gene expression data from Allen Human Brain Atlas to reveal the molecular basis of ECT for MDD. We performed partial least square regression to explore whether/how gray matter volume (GMV) alterations were associated with gene expression level. Functional enrichment analysis was conducted using Metascape to explore ontological pathways of the associated genes. Finally, these genes were further assigned to seven cell types to determine which cell types contribute most to the structural changes in MDD patients after ECT. We found significantly increased GMV in bilateral hippocampus in MDD patients after ECT. Transcriptome-neuroimaging association analyses showed that expression levels of 726 genes were positively correlated with the increased GMV in MDD after ECT. These genes were mainly involved in synaptic signaling, calcium ion binding and cell-cell signaling, and mostly belonged to excitatory and inhibitory neurons. Moreover, we found that the MDD risk genes of CNR1, HTR1A, MAOA, PDE1A, and SST as well as ECT related genes of BDNF, DRD2, APOE, P2RX7, and TBC1D14 showed significantly positive associations with increased GMV. Overall, our findings provide biological and molecular mechanisms underlying structural plasticity induced by ECT in MDD and the identified genes may facilitate future therapy for MDD.