First-episode Major Depressive Disorder Research Articles

Add-On Intermittent Theta Burst Stimulation Improves the Efficacy of First-Episode and Recurrent Major Depressive Disorder: Real-World Clinical Practice.

Repetitive transcranial magnetic stimulation (rTMS) is an effective and evidence-based treatment for major depressive disorder (MDD). This retrospective study aimed to explore the efficacy of add-on iTBS treatment in MDD in real-world clinical practice. One hundred and fifty-nine inpatients with MDD in a general hospital were included in this study. These patients were treated with at least 8 sessions of iTBS, in addition to antidepressants and supportive psychotherapy. Symptoms of depression and anxiety were assessed with the Hamilton Depression Rating Scale (HDRS) and the Hamilton Rating Scale for Anxiety (HAMA) at baseline and after 2-4 weeks of treatment. The improvement degree of depressive and anxious symptoms was compared between the first-episode MDD (n=107) and recurrent MDD (n=52) groups. Depressive and anxious symptoms were reduced significantly after the add-on iTBS treatment; the response and remission rates in the first-episode MDD group were 55.14% and 28.97%, which were 63.46% and 28.85% for the recurrent MDD group, respectively (P>0.05). The response rate and remission rate of anxiety in the first-episode MDD group was 64.13% and 57.45% for HAMA, and 66.67% and 62.50% for the recurrent MDD group (P>0.05). Our findings indicated that antidepressant and anti-anxiety efficacy of add-on iTBS treatment remains equivocal in real-world clinical practice, regardless of a first-episode depression diagnosis or recurrent depression.

Disrupted effective connectivity of the default, salience and dorsal attention networks in major depressive disorder: a study using spectral dynamic causal modelling of resting-state fMRI

<h3>Background:</h3> Understanding the neural basis for major depressive disorder (MDD) is essential for its diagnosis and treatment. Aberrant activation and functional connectivity of the default mode network (DMN), salience network (SN) and dorsal attention network (DAN) have been found consistently in patients with MDD. However, whether effective connectivity within and between these networks is altered in MDD remains unknown. The primary objective of this study was to investigate the effective connectivity of the 3 networks in patients with MDD at rest. <h3>Methods:</h3> We included 63 patients with MDD (35 first-episode and 28 recurrent) and 74 healthy controls, and collected resting-state functional MRI data for all participants. We defined 15 regions of interest from the 3 functional brain networks of interest using group independent component analysis. We estimated the coupling parameters that reflected the causal interactions among these regions using spectral dynamic causal modelling. We used parametric empirical Bayes to determine commonalities across groups, differences between patients with MDD and healthy controls, and differences between patients with recurrent and first-episode MDD. <h3>Results:</h3> We found positive (excitatory) connections within each network, negative (inhibitory) connections from the SN and DAN to the DMN, and positive connections from the DAN to the SN across groups. Compared to healthy controls, patients with MDD showed increased positive connections within the DMN, a decreased absolute value of negative connectivity from the SN to the DMN, and increased positive connections from the SN to the DAN. We also found that patients with recurrent MDD showed remarkably different effective connections compared to patients with first-episode MDD, especially related to the DAN. <h3>Limitations:</h3> Because of the relatively small sample size and the unclear medication history of the MDD sample, the present findings are in need of replication. <h3>Conclusion:</h3> These findings suggest that effective connectivity among high-order brain functional networks during rest was disrupted in patients with MDD. Moreover, patients with recurrent MDD exhibited different effective connections compared to patients with first-episode MDD. These differences in effective connectivity might provide new insights into the neural substrates of MDD.

Altered fronto-central theta-gamma coupling in major depressive disorder during auditory steady-state responses

ObjectiveNeural oscillations during sensory and cognitive events interact at different frequencies. However, such evidence in major depressive disorder (MDD) remains scarce. We explored the possible abnormal neural oscillations in MDD by analyzing theta-phase/gamma-amplitude coupling (TGC). MethodsResting-state and auditory steady-state response (ASSR) electroencephalography recordings were obtained from 35 first-episode MDD and 35 healthy controls (HCs). TGC during rest, ASSR stimulation, and ASSR baseline between and within groups were analyzed to evaluate MDD alterations. Receiver operating characteristic (ROC), TGC comparison between MDD severity subgroups (mild, moderate, major), and correlations were investigated to determine the potential use of altered TGC for identifying MDD. ResultsIn MDD, left fronto-central TGC decreased during stimulation, while right fronto-central TGC increased during baseline. The area under ROC curve for altered TGC was 0.863. Furthermore, during stimulation, moderate and major MDD groups exhibited significantly lower TGC than mild group, and fronto-central TGC was negatively correlated with depression scale scores. ConclusionsOur results provided the first evidence for an abnormal TGC response of fronto-central regions in MDD during an ASSR task. Importantly, altered TGC may be promising biomarkers of MDD. SignificanceOur findings enhance the understanding of physiological mechanisms underlying MDD and aid in its clinical diagnosis.

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

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

Sex differences in the association of plasma cytokines and neurocognition in first-episode major depressive disorder

BackgroundPeripheral cytokines were found to be involved in the pathophysiology of neurocognition in individuals with major depressive disorder (MDD). However, whether there are sex differences in this association between cytokines and cognition in MDD remains unknown. Our aim is to examine sex differences in the relationship between plasma cytokines and cognition in MDD. MethodOne hundred and twenty-seven first episode drug naïve patients with MDD and sixty healthy controls (HCs) were recruited for present study. The MATRICS Consensus Cognitive Battery was administered to measure the cognition. Plasma concentrations of nineteen cytokines were measured using high sensitivity multiplex bead-based assays. ResultsBoth female and male patients with MDD had significant cognitive impairment in verbal learning and visual learning and had higher levels of a range of cytokines than HCs (all p < 0.05). Female patients performed worse in trail making (F = 4.442, p = 0.018) and had higher concentration of interleukin (IL)-4 (F = 7.775, p = 0.006) than males. In female MDD, a significant positive association between category frequency and level of IL-4 was observed (B = 8.040, p = 0.031). However, this association was not present in male MDD or HCs (p > 0.05). LimitationPresent study used a cross-sectional design. ConclusionFemale MDD patients had worse trail making performance and higher level of IL-4 than males. The elevated IL-4 in female MDD was positively associated with category fluency, suggesting that IL-4 may be involved in the pathophysiology related to specific cognitive domain in female MDD patients.

Correlation between Aβ1-42, Dnmt3a2, urinary AD7c-NTP and cognitive dysfunction in first-episode and recurrent MDD: A case-control study.

Major depressive disorder (MDD) is one of the most prevalent mental illnesses worldwide and involves cognitive dysfunction that may negatively impact clinical and social outcomes. Previous studies have suggested that beta-amyloid peptide (Aβ1-42), DNA methyltransferase (Dnmt3a2), and urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) are associated with cognitive impairment. However, there are no relevant studies in MDD. The aim of this study was to assess the correlation between serum Aβ1-42, Dnmt3a2, and urinary AD7c-NTP and cognitive dysfunction in MDD. A total of 59 eligible patients were included in the study, including 29 patients with first-episode MDD (FEDs) and 30 patients with recurrent MDD (RMDDs), and 30 matched healthy controls (HCs) were selected. Participants' cognitive functioning was evaluated using the MATRICS consensus cognitive battery (MCCB). The enzyme-linked immunosorbent assay (ELISA) method was used to measure the concentrations of the three proteins. Statistical analysis was completed using Statistical Package for the Social Sciences (SPSS) 20.0. The statistical significance was set as P < 0.05. Serum Dnmt3a2 and urinary AD7c-NTP showed significant differences among the three groups (both P < 0.001), but there were no significant differences in Aβ1-42 levels. Upon examining the results of cognitive testing, we found that serum Aβ1-42 was negatively associated with working memory scores in RMDDs (P = 0.020), but Dnmt3a2 was positively associated with working memory and verbal learning scores in the same cohort (P = 0.012 and P = 0.037, respectively). In contrast, urinary AD7c-NTP was negatively correlated with verbal learning scores in FEDs (P = 0.013). Serum Dnmt3a2 and Aβ1-42 levels may be associated with cognitive impairment in RMDDs and may act as potential biomarkers of cognitive impairment. Although urinary AD7c-NTP was closely related to cognitive dysfunction in FEDs, this relationship did not hold in RMDDs.

Aberrant frontolimbic circuit in female depressed adolescents with and without suicidal attempts: A resting-state functional magnetic resonance imaging study.

The neurobiological basis of suicidal behaviors among female adolescents with major depressive disorder (MDD) remains largely unclear. Fifty-eight drug-naïve, first-episode female adolescent MDD [including 31 patients with suicidal attempt (SA group) and 27 patients without SA (non-SA group)], and 36 matched healthy controls (HCs) participated in the present study. Resting-state functional magnetic resonance imaging (MRI) was performed on each subject. The metrics of the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were compared among the three groups. Then seed-based functional connectivity (FC) was conducted based on the ALFF/fALFF and ReHo results, which were then correlated to clinical variables. Compared with the non-SA group, the SA group exhibited increased fALFF in the bilateral insula and right precentral gyrus, and enhanced ReHo in the left superior temporal gyrus, left middle cingulate cortex, right insula, and right precentral gyrus. Relative to the HCs, the SA group demonstrated additionally reduced fALFF and ReHo in the left middle frontal gyrus. Moreover, the SA group showed increased FC between the right precentral gyrus and the left middle frontal gyrus and left insula, and between the right insula and anterior/middle cingulate cortex compared to the non-SA and HC groups. In addition, the fALFF in the left middle frontal gyrus was positively correlated with the 17-item Hamilton Depression Rating Scale scores, and the values in the fALFF/ReHo in the right insula were positively correlated with the duration of MDD within the patient group. These findings highlight the multiple abnormalities of the frontolimbic circuit, which may enhance our understanding of the neurobiological basis underlying female MDD with SA during adolescence.

Altered functional connectivity in emotional subregions of the anterior cingulate cortex in young and middle-aged patients with major depressive disorder: A resting-state fMRI study

BackgroundIt has been demonstrated that the anterior cingulate cortex (ACC) has three subregions, involved in behavior, cognition, and emotion. However, the intrinsic connectivity of the ACC subregions in patients with major depressive disorder (MDD) is still unclear. In this study, functional magnetic resonance imaging (fMRI) data was used to detect the functional connectivity (FC) of ACC subregions and the correlation with the disease severity in young and middle-aged patients with MDD. MethodsA total of 36 young and middle-aged patients with first-episode MDD and 36 healthy controls (HCs) were enrolled in this study. FC was applied to investigate altered connectivity of the ACC subregion in MDD patients compared to HCs. Correlation analysis was then used to assess possible relationship between the neuroimaging findings and clinical symptoms in the patient group. ResultsCompared to HCs, young and middle-aged patients had significantly decreased FC between the emotional subregion of the ACC and the hippocampus, thalamus, insula, angular gyrus, and posterior cingulate cortex. The FC between the ACC emotional subregion and the insula, the AG, the RPHG was negatively correlated with depression index. The FC between the ACC emotional subregion and the putamen was positively correlated with depression index. ConclusionThe present findings indicate that abnormal ACC subregions-seeded FC may be implicated in the MDD-related abnormalities of emotion regulation and information processing. And there is a correlation between the above FC changes and the clinical symptoms of young and middle-aged MDD patients. This study may provide preliminary evidence for the ACC-related neural mechanism in young and middle-aged MDD patients and enhance the understanding of the pathophysiology of MDD.

The role of reelin in the pathological mechanism of depression from clinical to rodents

Major depressive disorder (MDD) is a devastating mental illness and the leading cause of disability worldwide. Previous studies have suggested that synaptic plasticity in the hippocampus plays an important role in depression pathogenesis. Reelin is expressed mainly in the frontal lobe and hippocampus, and is closely associated with neurodevelopment and synaptic plasticity. However, few studies have investigated its role in MDD combining clinical trials and animal experiments. We show that in a clinical trial, plasma reelin levels decreased in patients with first-episode drug-naïve MDD and increased after treatment; further, plasma reelin levels allowed to distinguish drug-naïve patients with first-episode MDD from healthy individuals. In rats, chronic mild and unpredictable stress led to a decrease in both reelin mRNA and protein levels in the hippocampus, which could be reversed by vortioxetine. Subsequent experiments confirmed that the reelin-ApoER2-NR2A /NR2B pathway regulates hippocampal synaptic plasticity and may be involved in depression or antidepressant responses. Our work contributes to a deeper understanding of MDD pathogenesis and provides new evidence that reelin should be considered a potential therapeutic target for MDD.

Altered gamma oscillations and beta–gamma coupling in drug-naive first-episode major depressive disorder: Association with sleep and cognitive disturbance

ObjectiveGamma oscillations contribute to the pathogenesis mechanisms of major depressive disorder (MDD) have been proposed, but gamma activity is not well characterized. This study is the first attempt to investigate the altered gamma oscillations in first-episode MDD, particularly the beta–gamma coupling, and to determine the potential symptomatic relationship with the identified gamma dysregulation. MethodsResting electroencephalography was recorded for 43 drug-naive first-episode MDD and 57 healthy control (HC) subjects. Integrated analysis of relative spectral power, weighted phase lag index, and phase–amplitude coupling (PAC) were utilized to reveal the alterations of gamma activities. Pearson's correlation was implemented to identify the relationship between altered gamma activities and the clinical depressive symptoms, which were categorized into four factors: anxiety somatization, retardation, cognitive disturbance, and sleep disturbance. ResultsCompared with HC subjects, MDD patients showed not only significantly decreased gamma powers in the left temporal and the bilateral occipital regions but also weakened gamma connectivity between the left hemisphere and the right frontal region. Furthermore, attenuated beta–gamma PAC of MDD patients was observed in the left temporal regions. Importantly, the suppression of left occipital mid- and high gamma oscillations were negatively correlated with sleep disturbance, while the deficits in left temporal beta–mid-gamma PAC and beta–high gamma PAC showed negative correlations with cognitive disturbance. LimitationsImportant limitations are the small sample size and the possible inclusion of bipolar depression in the MDD group. ConclusionsOur findings provide the first evidence that in first-episode MDD, aberrant gamma powers and beta–gamma coupling are associated with sleep and cognitive impairments, respectively, deepening our understanding of the physiological mechanisms underlying sleep and cognitive symptoms in first-episode MDD. Altered gamma oscillations emerge as promising biomarkers for diagnosing MDD.

Association between baseline cognitive symptoms and the subsequent presenteeism and global function in patients with major depressive disorder

Cognitive symptoms in major depressive disorder (MDD) contribute to impaired functional abilities and work productivity, particularly presenteeism. We investigated the association between baseline cognitive symptoms and subsequent presenteeism, and global functional impairment in Japanese patients with MDD from PERFORM-J (Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder in Japan) – a 6-month, multicenter, epidemiological study data. A total of 518 patients initiating antidepressant monotherapy (first-line or switched from another drug) were enrolled. Assessments include Perceived Deficits Questionnaire – Depression (PDQ-D) for cognitive complaints, Sheehan Disability Scale (SDS) for global function (analysed n = 318), and Work Productivity and Activity Impairment Questionnaire for presenteeism (analysed n = 122). A strong association between changes in presenteeism and changes in SDS scores (r: total = 0.636; work/school = 0.686) was observed. After adjusting for sociodemographic and MDD-related factors, patients without cognitive complaints at baseline showed lower odds of impaired presenteeism at 6 months versus patients with cognitive complaints (0.243, 95% CI: 0.079 to 0.747, p = 0.014) and also in patients with first episode of MDD against with recurrent MDD (0.327 (95% CI: 0.136 to 0.787). Similarly, patients without cognitive complaints had healthier global functioning (lower mean SDS total score) than patients with cognitive complaints (8.3 vs 11.2; 95% CI, −5.189 to −0.578; p = 0.014). First depressive episode (lower risk of presenteeism), being male, and low baseline SDS total score (better global functioning) were also associated with improved outcomes. These results highlight the potential value of baseline PDQ-D scores in predicting subsequent workplace and global functioning in patients undergoing treatment for MDD.

Cerebral blood flow in adolescents with drug-naive, first-episode major depressive disorder: An arterial spin labeling study based on voxel-level whole-brain analysis.

PurposeThe major depressive disorder (MDD) can be a threat to the health of people all over the world. Although governments have developed and implemented evidence-based interventions and prevention programs to prevent MDD and maintain mental health in adolescents, the number of adolescents with this condition has been on the rise for the past 10 years.MethodsA total of 60 adolescents were recruited, including 32 drug-naive adolescents with first-episode MDD and 28 healthy controls (HCs). Alterations in the intrinsic cerebral activity of the adolescents with MDD were explored using arterial spin labeling (ASL) while differences in the regional cerebral blood flow (rCBF) of the two groups were assessed based on voxel-based whole-brain analysis. Finally, correlations between the regional functional abnormalities and clinical variables were investigated for adolescents with MDD.ResultsCompared with HCs, MDD patients had a lower rCBF in the left triangular part of the inferior frontal gyrus (IFGtriang) but a higher one in the right Precental gyrus (PreCG). Negative correlations were also noted between the CBF in the left IFGtriang and the Hamilton depression scale (HAMD) scores of MDD patients.ConclusionElucidating the neurobiological features of adolescent patients with MDD is important to adequately develop methods that can assist in early diagnosis, precaution and intervention.

Resting-state functional magnetic resonance imaging-based identification of altered brain the fractional amplitude of low frequency fluctuation in adolescent major depressive disorder patients undergoing electroconvulsive therapy.

PurposeWhile electroconvulsive therapy (ECT) has been repeatedly been shown to effectively and efficiently treat the major depressive disorder (MDD), the mechanistic basis for such therapeutic efficacy remains to be firmly established. As such, further research exploring the ECT-based treatment of MDD in an adolescent population is warranted.MethodsThis study included 30 treatment-naïve first-episode MDD patients and 30 healthy control (HC) individuals (aged 12–17 years). All participants were scanned using rs-fMRI, and the 30 MDD patients were scanned again after 2 weeks of the ECT treatment period. Intrinsic local activity in each voxel was assessed based on the fractional amplitude of low frequency fluctuation (fALFF) parameter, with all fALFF analyses being completed using the REST application. Correlations between ECT-related changes in fALFF and clinical parameters were additionally examined.ResultsRelative to HCs, MDD patients exhibited increased fALFF values in the right inferior frontal gyrus (ORBinf), inferior occipital gyrus (IOG), and the left middle frontal gyrus (MFG) at baseline. Following ECT, these patients exhibited significant increases in fALFF values in the right medial superior frontal gyrus (SFGmed), dorsolateral superior frontal gyrus (SFGdor), anterior cingulate, and paracingulate gyrus (ACG), median cingulate and paracingulate gyrus (DCG), and left MFG. MDD patient HAMD scores were negatively correlated with fALFF values when analyzing pre-ECT vs. post-HCT ΔHAMD and fALFF values in the right SFGmed, SFGdor, and the left MFG.ConclusionThese data suggest that ECT induced altered fALFF in some regions of the brain, suggesting that these alterations may serve as a neurobiological indicator of ECT effectiveness in MDD adolescents.

Early Effects of Repetitive Transcranial Magnetic Stimulation Combined With Sertraline in Adolescents With First-Episode Major Depressive Disorder.

BackgroundAdolescence is a period of high incidence for depression. However, there is a limited treatment option for the adolescent depression. For treatment-resistant major depressive disorder, HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) appears therapeutically effective. The aim of the study is to explore the early effects of repetitive transcranial magnetic stimulation in combination with sertraline in adolescents with first-episode major depressive disorder.MethodsA total of 100 teenage patients with first-episode depression were randomly divided into the study groups. Both groups were treated with sertraline. In addition, the study group was treated with ten sessions of add-on rTMS. The control group was given sertraline only. The depressive symptom and cognitive function were assessed by the Hamilton depression rating scale 17 version (HAMD-17), Children’s Depression Rating Scale-Revised (CDRS-R), Integrated visual and auditory continuous performance test (IVA-CPT), and THINC-it.ResultsThe number of early improvers after 2 weeks of treatment in the study group was statistically significant higher compared to the control group (95.83% vs 73.47%, χ2 = 9.277, P = 0.002). There was significant difference observed in responder rates (62.50% vs. 28.57%, χ2 = 11.262, P = 0.001) or in remission rates (31.25% vs. 6.12%, χ2 = 10.130, P = 0.001) between the two groups at 4 weeks. The score of HAMD-17 and CDRS-R in the study group were significantly lower than the control group (Fgroup = 12.91 vs 10.21, P < 0.05). Attention Quotient (listening, visual and full-scale) attention quotient of IVA-CPT in the study group were higher than those in the control group after treatment, and the differences were statistically significant(P < 0.05). The study group showed higher score in Spotter than the control group after treatment (P < 0.05).DiscussionThis is the most extensive blinded, randomized clinical study to date examining the efficacy of 10-Hz add-on rTMS for first-onset adolescent depression. Our results support that add-on rTMS accelerates the efficacy of the antidepressants, improving the depressive symptoms and cold cognitive function in first-episode adolescent depression.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ChiCTR2100048534].

Abnormal Reginal Homogeneity in Left Anterior Cingulum Cortex and Precentral Gyrus as a Potential Neuroimaging Biomarker for First-Episode Major Depressive Disorder.

ObjectiveThere is no objective method to diagnose major depressive disorder (MDD). This study explored the neuroimaging biomarkers using the support vector machine (SVM) method for the diagnosis of MDD.Methods52 MDD patients and 45 healthy controls (HCs) were involved in resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Imaging data were analyzed with the regional homogeneity (ReHo) and SVM methods.ResultsCompared with HCs, MDD patients showed increased ReHo in the left anterior cingulum cortex (ACC) and decreased ReHo in the left precentral gyrus (PG). No correlations were detected between the ReHo values and the Hamilton Rating Scale for Depression (HRSD) scores. The SVM results showed a diagnostic accuracy of 98.96% (96/97). Increased ReHo in the left ACC, and decreased ReHo in the left PG were illustrated, along with a sensitivity of 98.07%(51/52) and a specificity of100% (45/45).ConclusionOur results suggest that abnormal regional neural activity in the left ACC and PG may play a key role in the pathophysiological process of first-episode MDD. Moreover, the combination of ReHo values in the left ACC and precentral gyrusmay serve as a neuroimaging biomarker for first-episode MDD.

Combinatorial panel with endophenotypes from multilevel information of diffusion tensor imaging and lipid profile as predictors for depression.

Clinical heterogeneity in major depressive disorder likely reflects the range of etiology and contributing factors in the disorder, such as genetic risk. Identification of more refined subgroups based on biomarkers such as white matter integrity and lipid-related metabolites could facilitate precision medicine in major depressive disorder. A total of 148 participants (15 genetic high-risk participants, 57 patients with first-episode major depressive disorder and 76 healthy controls) underwent diffusion tensor imaging and plasma lipid profiling. Alterations in white matter integrity and lipid metabolites were identified in genetic high-risk participants and patients with first-episode major depressive disorder. Then, shared alterations between genetic high-risk and first-episode major depressive disorder were used to develop an imaging x metabolite diagnostic panel for genetically based major depressive disorder via factor analysis and logistic regression. A fivefold cross-validation test was performed to evaluate the diagnostic panel. Alterations of white matter integrity in corona radiata, superior longitudinal fasciculus and the body of corpus callosum and dysregulated unsaturated fatty acid metabolism were identified in both genetic high-risk participants and patients with first-episode major depressive disorder. An imaging x metabolite diagnostic panel, consisting of measures for white matter integrity and unsaturated fatty acid metabolism, was identified that achieved an area under the receiver operating characteristic curve of 0.86 and had a significantly higher diagnostic performance than that using either measure alone. And cross-validation confirmed the adequate reliability and accuracy of the diagnostic panel. Combining white matter integrity in corpus callosum, superior longitudinal fasciculus and corona radiata, and unsaturated fatty acid profile may improve the identification of genetically based endophenotypes in major depressive disorder to advance precision medicine strategies.

Abnormal gut microbiota and bile acids in patients with first-episode major depressive disorder and correlation analysis.

Gut microbiota and its metabolite bile acids may play a significant role in the occurrence and development of major depressive disorder (MDD). Therefore, this study analyzes gut microbiota and bile acids, as well as their correlation in patients. Thirty-one patients with MDD and 29 healthy controls (HCs) were enrolled in this study. We collected their both blood and feces. Plasma bile acid content was determined by liquid chromatography-mass spectrometry and gut microbiota was detected by 16SrRNA gene sequencing and subsequently analyzed. We also analyzed the correlation between different gut microbiota, bile acids, and Hamilton Depression (HAMD) score. The α-diversity analysis found that Simpson and Pielou evenness index was much higher in HCs than in the patients with MDD. The β-diversity of the two groups were differences by nonmetric multidimensional scaling analysis. Linear discriminant analysis effect size analysis identified 16 different strains. Bile acids detection showed that 23-nordeoxycholic acid in patients with MDD was significantly higher than in HCs, whereas taurolithocholic acid (TLCA), glycolithocholic acid (GLCA), and lithocholic acid 3-sulfate were significantly lower. Spearman correlation analysis showed that Turicibacteraceae, Turicibacterales, and Turicibacter were positively related with TLCA, GLCA, glycodeoxycholic acid (GDCA), and taurodeoxycholic acid, and were negatively correlated with HAMD score. At the same time, TLCA, GLCA, and GDCA were negatively correlated with HAMD score. Gut microbiota and bile acids metabolism are disturbances in MDD, and there exists a correlation between gut microbiota and bile acids metabolism. Moreover, their interaction may be related to the pathophysiological mechanism of MDD.

Multimetric structural covariance in first-episode major depressive disorder: a graph theoretical analysis.

Background:Abnormalities of cortical morphology have been consistently reported in major depressive disorder (MDD), with widespread focal alterations in cortical thickness, surface area and gyrification. However, it is unclear whether these distributed focal changes disrupt the system-level architecture (topology) of brain morphology in MDD. If present, such a topological disruption might explain the mechanisms that underlie altered cortical morphology in MDD.Methods:Seventy-six patients with first-episode MDD (33 male, 43 female) and 66 healthy controls (32 male, 34 female) underwent structural MRI scans. We calculated cortical indices, including cortical thickness, surface area and local gyrification index, using FreeSurfer. We constructed morphological covariance networks using the 3 cortical indices separately, and we analyzed the topological properties of these group-level morphological covariance networks using graph theoretical approaches.Results:Topological differences between patients with first-episode MDD and healthy controls were restricted to the thickness-based network. We found a significant decrease in global efficiency but an increase in local efficiency of the left superior frontal gyrus and the right paracentral lobule in patients with first-episode MDD. When we simulated targeted lesions affecting the most highly connected nodes, the thickness-based networks in patients with first-episode MDD disintegrated more rapidly than those in healthy controls.Limitations:Our sample of patients with first-episode MDD has limited generalizability to patients with chronic and recurrent MDD.Conclusion:A systems-level disruption in cortical thickness (but not surface area or gyrification) occurs in patients with first-episode MDD.

State-independent and -dependent behavioral and neuroelectrophysiological characteristics during dynamic decision-making in patients with current and remitted depression

BackgroundIt is unclear whether the altered decision-making (DM) observed in patients with major depressive disorder (MDD) is neurophysiological and whether it improves with remission of depressive symptoms. The aim of this study was to identify developmental patterns of DM behavior, related cognitive characteristics, and electrophysiological abnormalities in patients with MDD across clinical stages. MethodsA sample of 48 first-episode MDD patients (FD group), 41 remitted MDD patients (RD group), and 43 healthy controls (HCs) completed psychometric assessments and performed the balloon analogue risk task (BART) while event-related potentials (ERPs) were recorded. ResultsThe RD group had lower depressiveness, self-blame, rumination, and catastrophizing tendencies, and higher mental resilience scores than the FD group, but retained significant differences from HCs. MDD patients showed a more conservative DM strategy than HCs, with no significant difference between the FD and RD groups. Compared to the FD group, the RD group had a smaller FRN for negative feedback and a trend toward a smaller P3 for positive feedback. Compared with HCs, the RD group had a smaller P3 during the positive feedback phase. FRN amplitude correlated positively with depression level and negatively with mental resilience. LimitationsBecause a comparative cross-section design was employed, longitudinal studies are needed to make causal inferences. ConclusionMDD patients presented a stable risk-avoidance bias in actively depressed and remission periods, consistent with a state-independent impairment pattern. Significantly reduced FRN amplitudes during remission indicated a state-dependent impairment pattern, and FRN amplitudes correlated with depression level. An abnormal feedback P3 component may be a state-independent characteristic that may become more pronounced with MDD progression.

Disorder- and cognitive demand-specific neurofunctional alterations during social emotional working memory in generalized anxiety disorder and major depressive disorder

BackgroundGeneralized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) are both characterized by cognitive and social impairments. Determining disorder-specific neurobiological alterations in GAD and MDD by means of functional magnetic resonance imaging (fMRI) may promote determination of precise diagnostic markers. MethodsThis study aimed to examine disorder-specific behavioral and neural alterations at the intersection of social and cognitive processing in treatment-naïve first-episode GAD (n = 35) and MDD (n = 37) patients compared to healthy controls (n = 35) by employing a social-emotional n-back fMRI paradigm. ResultsNo behavioral differences between patients and healthy controls were observed. However, GAD patients exhibited decreased bilateral dorsomedial prefrontal cortex (dmPFC) engagement during the 0-back condition yet increased dmPFC engagement during the 1-back condition compared to MDD and healthy participants. In contrast, MDD patients exhibited increased dmPFC-insula coupling during 0-back, yet decreased coupling during 1-back, compared to GAD and healthy participants. Dimensional symptom-load analysis confirmed that increased dmPFC-insula connectivity during 0-back was positively associated with depressive symptom load. LimitationsThe moderate sample size in the present study did not allow us to further explore gender differences. In addition, some patients exhibited GAD and MDD comorbidity according to the M.I.N.I. interview. Finally, the paradigm we used did not allow to further disentangle emotion-specific effects on working memory. ConclusionsThese findings suggest that the dmPFC engaged in integrating affective and cognitive components and self-other processing exhibits GAD-specific neurofunctional dysregulations whereas functional dmPFC communication with the insula, a region involved in salience processing, may represent an MDD-specific neurofunctional deficit.