Major Depressive Disorder Group Research Articles

Volumetric Evaluation of Substantia Nigra in Major Depressive Disorder Using Atlas-Based Method

Aim: The substantia nigra pars compacta (SNc), a vital part of the brain that produces dopamine, is being closely studied due to its potential role in the monoamine hypothesis, which aims to explain the causes of Major Depressive Disorder (MDD). Dopamine, a chemical messenger in the brain, is linked to the monoamine hypothesis, suggesting that imbalances in these chemicals may contribute to MDD. This study aimed to calculate volumetric changes in the substantia nigra (SN), using brain magnetic resonance imaging (MRI) in individuals diagnosed with MDD. Material and Method: Sixty-six participants, comprising 33 individuals diagnosed with MDD (mean age=44.30±13.98 years) and 33 healthy individuals (mean age=46.27±14.94 years), were recruited from the university hospital psychiatry outpatient clinic. In the MDD group, there were 15 male participants (45%) and 18 female participants (55%). The healthy control group consisted of 28 males (84.8%) and 5 females (16.2%). Potential confounding factors, such as underlying chronic diseases, were ruled out by the clinician through a thorough examination of the patient's medical history, ensuring the study outcomes were not influenced. Three-dimensional brain MRI scans were conducted using a 1.5 Tesla MRI scanner. Volumes of the SN and midbrain were automatically computed using MRIStudio, an atlas-based image analysis program. Results: Statistically significant higher volumes were observed in the right SN in the MDD group compared to controls (0.146±0.045 cm³ vs. 0.122±0.035 cm³, p=0.02, p

Identification of shared gene signatures in major depressive disorder and triple-negative breast cancer.

Patients with major depressive disorder (MDD) have an increased risk of breast cancer (BC), implying that these two diseases share similar pathological mechanisms. This study aimed to identify the key pathogenic genes that lead to the occurrence of both triple-negative breast cancer (TNBC) and MDD. Public datasets GSE65194 and GSE98793 were analyzed to identify differentially expressed genes (DEGs) shared by both datasets. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape to identify key PPI genes using cytoHubba. Hub DEGs were obtained from the intersection of hub genes from a PPI network with genes in the disease associated modules of the Weighed Gene Co-expression Network Analysis (WGCNA). Independent datasets (TCGA and GSE76826) and RT-qPCR validated hub gene expression. A total of 113 overlapping DEGs were identified between TNBC and MDD. The PPI network was constructed, and 35 hub DEGs were identified. Through WGCNA, the blue, brown, and turquoise modules were recognized as highly correlated with TNBC, while the brown, turquoise, and yellow modules were similarly correlated with MDD. Notably, G3BP1, MAF, NCEH1, and TMEM45A emerged as hub DEGs as they appeared both in modules and PPI hub DEGs. Within the GSE65194 and GSE98793 datasets, G3BP1 and MAF exhibited a significant downregulation in TNBC and MDD groups compared to the control, whereas NCEH1 and TMEM45A demonstrated a significant upregulation. These findings were further substantiated by TCGA and GSE76826, as well as through RT-qPCR validation. This study identified G3BP1, MAF, NCEH1 and TMEM45A as key pathological genes in both TNBC and MDD.

Shared and distinct electroencephalogram microstate abnormalities across schizophrenia, bipolar disorder, and depression.

Microstates of an electroencephalogram (EEG) are canonical voltage topographies that remain quasi-stable for 90 ms, serving as the foundational elements of brain dynamics. Different changes in EEG microstates can be observed in psychiatric disorders like schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). However, the similarities and disparatenesses in whole-brain dynamics on a subsecond timescale among individuals diagnosed with SCZ, BD, and MDD are unclear. This study included 1112 participants (380 individuals diagnosed with SCZ, 330 with BD, 212 with MDD, and 190 demographically matched healthy controls [HCs]). We assembled resting-state EEG data and completed a microstate analysis of all participants using a cross-sectional design. Our research indicates that SCZ, BD, and MDD exhibit distinct patterns of transition among the four EEG microstate states (A, B, C, and D). The analysis of transition probabilities showed a higher frequency of switching from microstates A to B and from B to A in each patient group compared to the HC group, and less frequent transitions from microstates A to C and from C to A in the SCZ and MDD groups compared to the HC group. And the probability of the microstate switching from C to D and D to C in the SCZ group significantly increased compared to those in the patient and HC groups. Our findings provide crucial insights into the abnormalities involved in distributing neural assets and enabling proper transitions between different microstates in patients with major psychiatric disorders.

A comparison of the social cognition and neurocognitive characteristics of adolescents with suicide behavior, adolescent with depression and healthy controls.

Deficits in neurocognition and social-cognition have been suggested to be an endophenotype for suicidal behavior. We aimed to compare the social-cognition and neurocognitive characteristics of adolescents diagnosed with depression with and without suicidal behavior and to investigate whether these functions predict suicide. Adolescents diagnosed with Major Depressive Disorder (MDD) with suicidal behavior (n = 42); MDD without suicidal behavior (n = 44) and age- and sex-matched controls (n = 43) were included. The University of Pennsylvania Computerized Neurobehavioral Test Battery and Autism Spectrum Screening Questionnaire (ASSQ) were used to evaluate social-cognition and neurocognitive characteristics. Several neurocognitive domain values of MDD groups, were significantly different from the control group. Neutral emotion recognition task (p = 0.025) and ASSQ scores were found to be significantly impaired in the patient groups (p < 0.001). Logistic regression analysis showed that, only the increase in the Suicide Probability Scale score was found to be significant as a risk factor predicting suicide (p = 0.007, OR: 1.246). While the neurocognitive and social-cognitive performances of adolescents with MDD were significantly lower than the control group, these performances in the two depression groups were similar. When the predictors of suicidal behavior were examined, it was found that only the increase in suicidal ideation scores predicted suicide.

Cortical activation for adolescent-onset minor depression and major depressive disorder: an fNIRS study

BackgroundWhile depression is increasing worldwide, some patients are diagnosed as having Major Depressive Disorder (MDD), but others are diagnosed with minor depression, however, the potential neuro mechanism is unknown.MethodsSixty-two patients with minor depression, 44 adolescents with MDD and 54 healthy adolescents participated in this study. Functional near-infrared spectroscopy (fNIRS), both HAMD and HAMA data were collected from all of the participants.ResultsThe result indicates the pervasively decreased activation of BA, 11, 21, 45 and 46 were observed in the MDD group and reduced activation of BA 45 was observed in the minor depression group. However, cortical activation was not observed between the minor depression or MDD groups. Cortical activation was also not correlated with the depressive/anxious score in the minor and MDD groups separately.ConclusionsCortical activation was pervasively decreased in the MDD group and slightly reduced in the minor depression group, which may be a potential neural mechanism. As reduced cortical activation in minor depression, interventions in the early stages of minor depression may help slow or even modify the development of the illness.

Neuroimaging and epigenetic analysis reveal novel epigenetic loci in major depressive disorder.

Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD. A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci. In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (EML6, ZFP64, CLSTN3, KCNMA1, TAOK2, and NT5E). Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.

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.

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

Association of Lower Rostral Anterior Cingulate GABA+ and Dysregulated Cortisol Stress Response With Altered Functional Connectivity in Young Adults With Lifetime Depression: A Multimodal Imaging Investigation of Trait and State Effects.

Preclinical work suggests that excess glucocorticoids and reduced cortical γ-aminobutyric acid (GABA) may affect sex-dependent differences in brain regions implicated in stress regulation and depressive phenotypes. The authors sought to address a critical gap in knowledge, namely, how stress circuitry is functionally affected by glucocorticoids and GABA in current or remitted major depressive disorder (MDD). Multimodal imaging data were collected from 130 young adults (ages 18-25), of whom 44 had current MDD, 42 had remitted MDD, and 44 were healthy comparison subjects. GABA+ (γ-aminobutyric acid and macromolecules) was assessed using magnetic resonance spectroscopy, and task-related functional MRI data were collected under acute stress and analyzed using data-driven network modeling. Across modalities, trait-related abnormalities emerged. Relative to healthy comparison subjects, both clinical groups were characterized by lower rostral anterior cingulate cortex (rACC) GABA+ and frontoparietal network amplitude but higher amplitude in salience and stress-related networks. For the remitted MDD group, differences from the healthy comparison group emerged in the context of elevated cortisol levels, whereas the MDD group had lower cortisol levels than the healthy comparison group. In the comparison group, frontoparietal and stress-related network connectivity was positively associated with cortisol level (highlighting putative top-down regulation of stress), but the opposite relationship emerged in the MDD and remitted MDD groups. Finally, rACC GABA+ was associated with stress-induced changes in connectivity between overlapping default mode and salience networks. Lifetime MDD was characterized by reduced rACC GABA+ as well as dysregulated cortisol-related interactions between top-down control (frontoparietal) and threat (task-related) networks. These findings warrant further investigation of the role of GABA in the vulnerability to and treatment of MDD.

Cluster analysis dissecting cognitive deficits in older adults with major depressive disorder and the association with neurofilament light chain

BackgroundCognitive impairment is a growing problem with increasing burden in global aging. Older adults with major depressive disorder (MDD) have higher risk of dementia. Neurofilament light chain (NfL) has been proven as a potential biomarker in neurodegenerative disease, including dementia. We aimed to investigate the association between cognitive deficits and NfL levels in older adults with MDD.MethodsIn this cross-sectional study, we enrolled 39 MDD patients and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer’s type, as controls, from a tertiary psychiatric hospital. Both groups were over age 65 and with matched Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and each cognitive domain.ResultsIn the MDD group, participants had higher rate of family psychiatry history and current alcohol use habit compared with controls. Control group of neurocognitive disorders showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits clustered with that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster.ConclusionsWe noted the negative correlation between NfL levels and cognition in MDD patients clustered with neurodegenerative disorder, Alzheimer’s type. NfL could be a promising candidate as a biomarker to predict subtype of patients in MDD to develop cognitive decline. Further longitudinal studies and within MDD cluster analysis are required to validate our findings for clinical implications.

Identification of novel endoplasmic reticulum-related genes and their association with immune cell infiltration in major depressive disorder

BackgroundSeveral lines of evidence point to an interaction between genetic predisposition and environmental factors in the onset of major depressive disorder (MDD). This study is aimed to investigate the pathogenesis of MDD by identifying key biomarkers, associated immune infiltration using bioinformatic analysis and human postmortem sample. MethodsThe Gene Expression Omnibus (GEO) database of GSE98793 was adopted to identify hub genes linked to endoplasmic reticulum (ER) stress-related genes (ERGs) in MDD. Another GEO database of GSE76826 was employed to validate the novel target associated with ERGs and immune infiltration in MDD. Moreover, human postmortem sample from MDD patients was utilized to confirm the differential expression analysis of hub genes. ResultsWe discovered 12 ER stress-related differentially expressed genes (ERDEGs). A LASSO Cox regression analysis helped construct a diagnostic model for these ERDEGs, incorporating immune infiltration analysis revealed that three hub genes (ERLIN1, SEC61B, and USP13) show the significant and consistent expression differences between the two groups. Western blot analysis of postmortem brain samples indicated notably higher expression levels of ERLIN1 and SEC61B in the MDD group, with USP13 also tending to increase compared to control group. LimitationsThe utilization of the MDD gene chip in this analysis was sourced from the GEO database, which possesses a restricted number of pertinent gene chip samples. ConclusionsThese findings indicate that ERDEGs especially including ERLIN1, SEC61B, and USP13 associated the infiltration of immune cells may be potential diagnostic indicators for MDD.

SNORA69 is up-regulated in the lateral habenula of individuals with major depressive disorder

Major depressive disorder (MDD) is a complex and potentially debilitating illness whose etiology and pathology remains unclear. Non-coding RNAs have been implicated in MDD, where they display differential expression in the brain and the periphery. In this study, we quantified small nucleolar RNA (snoRNA) expression by small RNA sequencing in the lateral habenula (LHb) of individuals with MDD (n = 15) and psychiatrically-healthy controls (n = 15). We uncovered five snoRNAs that exhibited differential expression between MDD and controls (FDR < 0.01). Specifically, SNORA69 showed increased expression in MDD and was technically validated via RT-qPCR. We further investigated the expression of Snora69 in the LHb and peripheral blood of an unpredicted chronic mild stress (UCMS) mouse model of depression. Snora69 was specifically up-regulated in mice that underwent the UCMS paradigm. SNORA69 is known to guide pseudouridylation onto 5.8S and 18S rRNAs. We quantified the relative abundance of pseudouridines on 5.8S and 18S rRNA in human post-mortem LHb samples and found increased abundance of pseudouridines in the MDD group. Overall, our findings indicate the importance of brain snoRNAs in the pathology of MDD. Future studies characterizing SNORA69’s role in MDD pathology is warranted.

Temporal binding and sense of agency in major depression.

Alterations in the experience of controlling oneself and one's environment are of high relevance to understanding the psychopathology of depression. This study investigated the relationship between Temporal Binding for action-event sequences, sense of agency, self-efficacy and symptom severity in Major Depressive Disorder. We employed the Sense of Agency Scale (SoAS) and the General Self-Efficacy Scale (GSE) to assess explicit Sense of Agency and self-efficacy in a group of 42 persons diagnosed with Major Depressive Disorder (MDD) [20 identifying as female, 19 as male; mean age 37.8 years (± 13.3)] and 40 control persons without a psychiatric diagnosis (CG) [22 identifying as female, 20 as male; mean age 38.0 years ( ± 13.3)]. Depressive symptom severity was measured using the BDI-II. We additionally performed a temporal binding paradigm as a potential correlate to Sense of Agency. Participants partook in a time estimation task judging three intervals (250ms, 450ms, 650ms) while either observing or causing stimulus presentations. The underestimation of intervals following intentional actions causing stimulus presentations (compared to merely observing the stimulus presentation) is interpreted as temporal binding. SoAS scores demonstrated an inverse correlation with depressive symptoms (CG: p=.032, R2=.113; MDD: p<.001, R2=.260) and a positive correlation with GSE scores (CG: p<.001, R2=.379; MDD: p<.001, R2=.254). We found distinct differences in temporal binding between healthy participants and the Major Depressive Disorder group without significant correlation between temporal binding and the SoAS or GSE scores. The data suggest group differences in time estimation particular pertaining to time intervals involving intentional action and increasingly complex multisensory stimuli. We investigated parameters of subjective control, namely Sense of Agency and Self Efficacy. Here, we were able to reveal their inverse relationship with depressive symptoms in patients with major depressive disorder, highlighting a profound experience of loss of control with increasing symptom load. Deficits in experiencing control, particularly involving intentional motor actions (and more complex multisensory stimuli), appear to be more pronounced in Major Depressive Disorder, involving not only negative self-efficacy expectations but also an altered Sense of Agency and temporal binding. Temporal binding and SoAS scores did not correlate, adding to the growing evidence that the two measures may not be directly related. We propose that future research be directed at this contiguous relationship between Sense of Agency and Self Efficacy in Major Depressive Disorder.

Atypical brain aging and its association with working memory performance in major depressive disorder

BackgroundPatients with major depressive disorder (MDD) can present with altered brain structure and deficits in cognitive function similar to aging. Yet, the interaction between age-related brain changes and brain development in MDD remains understudied. In a cohort of adolescents and adults with and without MDD, we assessed brain aging differences and associations through a newly developed tool quantifying normative neurodevelopmental trajectories. Methods304 MDD participants and 236 non-depressed controls were recruited and scanned from three studies under the Canadian Biomarker Integration Network for Depression. Volumetric data were used to generate brain centile scores, which were examined for: a) differences in MDD relative to controls; b) differences in individuals with versus without severe childhood maltreatment; and c) correlations with depressive symptom severity, neurocognitive assessment domains, or escitalopram treatment response. ResultsBrain centiles were significantly lower in the MDD group compared to controls. It was also significantly correlated with working memory in controls, but not the MDD group. No significant associations were observed in depression severity or antidepressant treatment response with brain centiles. Likewise, childhood maltreatment history did not significantly affect brain centiles. ConclusionsConsistent with prior work on machine learning models that predict “brain age”, brain centile scores differed in people diagnosed with MDD, and MDD was associated with differential relationships between centile scores and working memory. The results support the notion of atypical development and aging in MDD, with implications on neurocognitive deficits associated with aging-related cognitive function.

Study on exosomes for identifying bipolar disorder in early stage: A cross-sectional and validation study protocol.

The difficulty is remained to accurately distinguish bipolar disorder (BD) from major depressive disorder (MDD) in early stage, with a delayed diagnosis for 5-10 years. BD patients are often treated with antidepressants systematically due to being diagnosed with MDD, affecting the disease course and clinical outcomes. The current study aims to explore the role of plasma exosomes as biomarker to distinguish BD from MDD in early stage. Two stages are included. The first stage is a cross-sectional study, comparing the concentrations of plasma exosome microRNA and related proteins among BD group, MDD group, and healthy controls (HC) group (n=40 respectively), to identify target biomarkers preliminarily. The "Latent Class Analysis" and "Receiver Operating Characteristic" analysis will be performed to determine the optimal concentration range for each biomarker. The second stage is to validate target markers in subjects, coming from an ongoing study focusing on patients with a first depressive episode. All target biomarkers will be test in plasma samples reserved at the initial stage to detect whether the diagnosis indicated by biomarker level is consistent with the diagnosis by DSM-5. Furthermore, the correlation between specific biomarkers and the manic episode, suicidal ideation, and adverse reactions will also be observed. Exosome-derived microRNA and related proteins have potential in serving as a good medium for exploring mental disorders because it can pass through the blood-brain barrier bidirectionally and convey a large amount of information stably. Improving the early diagnosis of BD would help implement appropriate intervention strategy as early as possible and significantly reduce the burden of disease.

Linking childhood trauma and dissociation to psychotic symptoms in major depressive disorder, bipolar disorders, and schizophrenia: A transdiagnostic examination using patient and clinician ratings.

Symptomatic overlap between dissociation and psychosis is well documented; however, the pathogenesis of these two phenomena might be distinct. Few studies have analyzed the relation of dissociative and psychotic symptoms transdiagnostically. The current study examines an emerging trauma-dissociation theoretical model that accounts for psychotic symptoms across affective disorders and schizophrenia (SCZ). Psychiatric inpatients with DSM-5 major depressive disorder (MDD), bipolar disorders (BD) currently in a major depressive episode, and SCZ, and healthy controls (HC) were recruited. Potentially traumatizing events in childhood, dissociative symptoms, and psychotic symptoms were assessed. In addition to participant's self-report, dissociative and psychotic symptoms were rated by psychiatrists blind to the hypothesis. Path analysis was conducted. Dissociation was commonly experienced by clinical participants, particularly for those with MDD or BD. For the SCZ group, ratings of dissociation differed between patient and clinician; specifically, patient-reported dissociation scores, but not clinician-rated scores, were higher than that of the HC group. Importantly, the links between childhood trauma, dissociation, and psychotic symptoms were not homogenous across the diagnostic groups. Dissociation mediated the relationship between childhood trauma and psychotic symptoms in the MDD and BD groups, but not the SCZ group. Depending on the psychiatric condition, dissociation and psychosis have different clinical implications. Childhood trauma and dissociation provide an account for psychotic symptoms in patients diagnosed with MDD and BD, but not with SCZ. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Leptin’s Inverse Association With Brain Morphology and Depressive Symptoms: A Discovery and Confirmatory Study Across Two Independent Samples

BackgroundMajor depressive disorder has a complex, bidirectional relationship with metabolic dysfunction, but the neural correlates of this association are not well understood. MethodsIn this cross-sectional investigation, we used a 2-step discovery and confirmatory strategy utilizing 2 independent samples (sample 1: 288 participants, sample 2: 196 participants) to examine the association between circulating indicators of metabolic health (leptin and adiponectin) and brain structures in individuals with major depressive disorder. ResultsWe found a replicable inverse correlation between leptin levels and cortical surface area within essential brain areas responsible for emotion regulation, such as the left posterior cingulate cortex, right pars orbitalis, right superior temporal gyrus, and right insula (standardized beta coefficient range: −0.27 to −0.49, puncorrected < .05). Notably, this relationship was independent of C-reactive protein levels. We also identified a significant interaction effect of leptin levels and diagnosis on the cortical surface area of the right superior temporal gyrus (standardized beta coefficient = 0.26 in sample 1, standardized beta coefficient = 0.30 in sample 2, puncorrected < .05). We also observed a positive correlation between leptin levels and atypical depressive symptoms in both major depressive disorder groups (r = 0.14 in sample 1, r = 0.29 in sample 2, puncorrected < .05). ConclusionsThe inverse association between leptin and cortical surface area in brain regions that are important for emotion processing and leptin’s association with sleep disturbances support the hypothesis that metabolic processes may be related to emotion regulation. However, the molecular mechanisms through which leptin may exert these effects should be explored further.

Characterizing Major Depressive Disorder (MDD) using alpha-band activity in resting-state electroencephalogram (EEG) combined with MATRICS Consensus Cognitive Battery (MCCB)

BackgroundThe diagnosis of major depressive disorder (MDD) is commonly based on the subjective evaluation by experienced psychiatrists using clinical scales. Hence, it is particularly important to find more objective biomarkers to aid in diagnosis and further treatment. Alpha-band activity (7-13 Hz) is the most prominent component in resting electroencephalogram (EEG), which is also thought to be a potential biomarker. Recent studies have shown the existence of multiple sub-oscillations within the alpha band, with distinct neural underpinnings. However, the specific contribution of these alpha sub-oscillations to the diagnosis and treatment of MDD remains unclear. MethodsIn this study, we recorded the resting-state EEG from MDD and HC populations in both open and closed-eye state conditions. We also assessed cognitive processing using the MATRICS Consensus Cognitive Battery (MCCB). ResultsWe found that the MDD group showed significantly higher power in the high alpha range (10.5–11.5 Hz) and lower power in the low alpha range (7–8.5 Hz) compared to the HC group. Notably, high alpha power in the MDD group is negatively correlated with working memory performance in MCCB, whereas no such correlation was found in the HC group. Furthermore, using five established classification algorithms, we discovered that combining alpha oscillations with MCCB scores as features yielded the highest classification accuracy compared to using EEG or MCCB scores alone. ConclusionsOur results demonstrate the potential of sub-oscillations within the alpha frequency band as a potential distinct biomarker. When combined with psychological scales, they may provide guidance relevant for the diagnosis and treatment of MDD.

Alterations in subcortical magnetic susceptibility and disease-specific relationship with brain volume in major depressive disorder and schizophrenia

Quantitative susceptibility mapping is a magnetic resonance imaging technique that measures brain tissues’ magnetic susceptibility, including iron deposition and myelination. This study examines the relationship between subcortical volume and magnetic susceptibility and determines specific differences in these measures among patients with major depressive disorder (MDD), patients with schizophrenia, and healthy controls (HCs). This was a cross-sectional study. Sex- and age- matched patients with MDD (n = 49), patients with schizophrenia (n = 24), and HCs (n = 50) were included. Magnetic resonance imaging was conducted using quantitative susceptibility mapping and T1-weighted imaging to measure subcortical susceptibility and volume. The acquired brain measurements were compared among groups using analyses of variance and post hoc comparisons. Finally, a general linear model examined the susceptibility–volume relationship. Significant group-level differences were found in the magnetic susceptibility of the nucleus accumbens and amygdala (p = 0.045). Post-hoc analyses indicated that the magnetic susceptibility of the nucleus accumbens and amygdala for the MDD group was significantly higher than that for the HC group (p = 0.0054, p = 0.0065, respectively). However, no significant differences in subcortical volume were found between the groups. The general linear model indicated a significant interaction between group and volume for the nucleus accumbens in MDD group but not schizophrenia or HC groups. This study showed susceptibility alterations in the nucleus accumbens and amygdala in MDD patients. A significant relationship was observed between subcortical susceptibility and volume in the MDD group’s nucleus accumbens, which indicated abnormalities in myelination and the dopaminergic system related to iron deposition.

Alterations in the white matter structure of major depressive disorder patients and their link to childhood trauma.

Major Depressive Disorder (MDD) is significantly influenced by childhood trauma (CT), affecting brain anatomy and functionality. Despite the unique disease trajectory in MDD patients with CT, the underlying neurobiological mechanisms remain unclear. Our objective is to investigate CT's impact on the white matter structure of the brain in patients with MDD. This research employed tract-based spatial statistics (TBSS) to detect variations between groups in Fractional Anisotropy (FA) throughout the whole brain in 71 medication-free MDD patients and 97 HCs. Participants filled out the Childhood Trauma Questionnaire (CTQ) and assessments for depression and anxiety symptoms. The relationship between FA and CTQ scores was explored with partial correlation analysis, adjusting for factors such as age, gender, educational background, and length of illness. Compared to HCs, the MDD group showed decreased FA values in the right posterior limb of the internal capsule (PLIC), the inferior fronto-occipital fasciculus (IFOF), and bilateral superior longitudinal fasciculus (SLF). Simple effects analysis revealed that compared to HC-CT, the MDD-CT group demonstrated decreased FA values in right PLIC, IFOF, and bilateral SLF. The MDD-nCT group showed decreased FA values in right PLIC and IFOF compared to HC-nCT. The total scores and subscale scores of CTQ were negatively correlated with the FA in the right SLF. The right SLF may potentially be influenced by CT during the brain development of individuals with MDD. These results enhance our knowledge of the role of the SLF in the pathophysiology of MDD and the neurobiological mechanisms by which CT influences MDD.