Effect of childhood trauma on cognitive function in individuals with major depressive disorder and healthy controls.

BACKGROUND: Individuals with major depressive disorder (MDD) exhibit cognitive impairment, while childhood trauma (CT) is associated with an elevated risk of both MDD and cognitive dysfunction. The effect of CT on cognitive function in MDD patients and healthy controls (HCs) is unclear. METHODS: MDD patients and HCs were enrolled between December 2013 and December 2016. The Childhood Trauma Questionnaire (CTQ) was used to assess CT. Depressive symptoms and cognitive function were assessed at baseline and after 8-week acute-phase treatment with selective serotonin reuptake inhibitors (SSRIs) in MDD patients. RESULTS: A total of 909 people were included in the analysis. The interaction between MDD and CT had a main effect on Digit Symbol-Coding Test (DSCT), Stroop Color Test (SCT), and Stroop Color-Word Test (SCWT) scores. The effect of CT on cognitive function disappeared after adjusting for MDD diagnosis and years of education. Neglect could predict poor performance on SCT and SCWT in the HC group. After acute-phase treatment with SSRIs, CT did not significantly predict changes in cognitive function or depressive symptoms. LIMITATIONS: The CTQ assessment might cause recall bias, and the cross-sectional design could not establish the causal link between CT and cognitive function. CONCLUSION: The effect of CT on cognitive function was modulated by MDD diagnosis and years of education. CT did not predict changes in depressive symptoms or cognitive function after acute-phase treatment with SSRIs. The direct influence of CT on cognitive function in MDD patients may be over-estimated. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02023567; registration date: December 2013.

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

BACKGROUND: While 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. METHODS: Sixty-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. RESULTS: The 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. CONCLUSIONS: Cortical 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.

Immunoregulatory role of the gut microbiota in inflammatory depression.

Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.

Characteristics of gut microbiota and its correlation with hs-CRP and somatic symptoms in first-episode treatment-naive major depressive disorder.

OBJECTIVE: Most patients with major depressive disorder (MDD) have somatic symptoms, but little studies pay attention in the microbial-inflammatory mechanisms of these somatic symptoms. Our study aimed to investigate alterations in gut microbiota and its correlation with inflammatory marker levels and somatic symptoms in first-episode treatment-naive MDD. METHODS: Subjects contained 160 MDD patients and 101 healthy controls (HCs). MDD patients were divided into MDD with somatic symptoms group (MDDS) and MDD without somatic symptoms group (MDDN) based on Somatic Self-rating Scale (SSS). 16S ribosomal RNA sequencing were performed to analyze the composition of the fecal microbiota. The inflammatory factors were measured using enzyme linked immunosorbent assay (ELISA). Correlation among the altered gut microbiota, inflammatory factor and severity of clinical symptoms were analysized. RESULTS: Relative to HCs, MDD patients had higher levels of high-sensitivity C-reactive protein (hs-CRP) as well as disordered α-diversity and ß-diversity of gut microbiota. Linear discriminant effect size (LEfSe) analysis showed that MDD patients had higher proportions of Bifidobacterium, Blautia, Haemophilus and lower proportions of Bacteroides, Faecalibacterium, Roseburia, Dialister, Sutterella, Parabacteroides, Bordetella, and Phascolarctobacterium from the genus aspect. Furthermore, correlation analysis showed Bacteroides and Roseburia had negative correlations with the hs-CRP, HAMD-24, the total and factor scores of SSS in all participants. Further, compared with MDDN, the Pielous evenness was higher in MDDS. Random Forest (RF) analysis showed 20 most important genera discriminating MDD-S and MDDN, HCs. The ROC analysis showed that the AUC was 0.90 and 0.81 combining these genera respectively. CONCLUSION: Our study manifested MDD patients showed disordered gut microbiota and elevated hs-CRP levels, and altered gut microbiota was closely associated with hs-CRP, depressive symptoms, and somatic symptoms.

Latent classes of symptom trajectories among major depressive disorder patients in China.

OBJECTIVE: This study aimed to understand the long-term symptom trajectories of Chinese patients with major depressive disorder (MDD) using piecewise latent growth modeling and growth mixture modeling. The investigation also aimed to identify the baseline characteristics indicative of poorer treatment outcomes. METHODS: A total of 558 outpatients with MDD were assessed using a sequence of surveys. The Hamilton Rating Scale for Depression (HRSD), Hamilton Anxiety Rating Scale (HAMA), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to evaluate baseline depression, anxiety, and cognitive function. Depression symptom severity was subsequently measured at the 1-month, 2-month, 6-month, 1-year, and 2-year follow-ups. RESULTS: Results indicated three depressive symptomology trajectories, including (a) severe, improving class (12.72 %), (b) partially responding, later deteriorating class (6.09 %), and (c) moderate, improving class (81.18 %). Logistic regression analyses showed that a history of cardiovascular disease (CVD) increased the odds of belonging to the partially responding, later deteriorating class, whereas higher baseline depression increased the odds of belonging to the severe, improving class compared to the moderate, improving class. Patients who experienced less depression relief during the first month of treatment had a lower probability of belonging to the moderate, improving class. LIMITATIONS: Participant attrition in this study may have inflated the estimated rate of treatment-resistant patients. CONCLUSIONS: The burden of CVD and poorer initial treatment response are plausible risk factors for poorer treatment outcomes, highlighting targets for intervention in Chinese MDD patients.

Gut microbiota composition in depressive disorder: a systematic review, meta-analysis, and meta-regression.

Studies investigating gut microbiota composition in depressive disorder have yielded mixed results. The aim of our study was to compare gut microbiome between people with depressive disorder and healthy controls. We did a meta-analysis and meta-regression of studies by searching PubMed, Web of Science, Embase, Scopus, Ovid, Cochrane Library, ProQuest, and PsycINFO for articles published from database inception to March 07, 2022. Search strategies were then re-run on 12 March 2023 for an update. We undertook meta-analyses whenever values of alpha diversity and Firmicutes, Bacteroidetes (relative abundance) were available in two or more studies. A random-effects model with restricted maximum-likelihood estimator was used to synthesize the effect size (assessed by standardized mean difference [SMD]) across studies. We identified 44 studies representing 2091 patients and 2792 controls. Our study found that there were no significant differences in patients with depressive disorder on alpha diversity indices, Firmicutes and Bacteroidetes compared with healthy controls. In subgroup analyses with regional variations(east/west) as a predictor, patients who were in the West had a lower Chao1 level (SMD -0.42[-0.74 to -0.10]). Subgroup meta-analysis showed Firmicutes level was decreased in patients with depressive disorder who were medication-free (SMD -1.54[-2.36 to -0.72]), but Bacteroidetes level was increased (SMD -0.90[0.07 to 1.72]). In the meta-regression analysis, six variables cannot explain the 100% heterogeneity of the studies assessing by Chao1, Shannon index, Firmicutes, and Bacteroidetes. Depleted levels of Butyricicoccus, Coprococcus, Faecalibacterium, Fusicatenibacter, Romboutsia, and enriched levels of Eggerthella, Enterococcus, Flavonifractor, Holdemania, Streptococcus were consistently shared in depressive disorder. This systematic review and meta-analysis found that psychotropic medication and dietary habit may influence microbiota. There is reliable evidence for differences in the phylogenetic relationship in depressive disorder compared with controls, however, method of measurement and method of patient classification (symptom vs diagnosis based) may affect findings. Depressive disorder is characterized by an increase of pro-inflammatory bacteria, while anti-inflammatory butyrate-producing genera are depleted.

Psychological characteristics and emotional difficulties underlying school refusal in adolescents using functional near-infrared spectroscopy.

BACKGROUND: This study aims to explore the psychological characteristics, related emotional problems and potential NIR brain function mechanism of adolescents who refuse to attend school. METHODS: The study included 38 adolescents (12-18 years old) who were not attending school and 35 healthy controls (12-18 years old) who are attending school regularly. Participants completed (1) general demographics, (2) Eysenck Personality Questionnaire (EPQ), (3) Zung Self-Rating Depression Scale (SDS), (4) Zung Self-Rating Anxiety Scale (SAS), and (5) Symptom Checklist-90 (SCL-90). In addition to the clinical tests, participants completed functional near-infrared spectroscopy (fNIRS). Mental health, personality, and emotional state were evaluated in both groups to explore the differences and to understand the underlying mechanisms of school refusal during adolescence. RESULTS: Adolescents who did not attend school had higher neuroticism scores on the Eysenck Personality Questionnaire than healthy controls (p(FDR) < 0.001), introversion and concealment scores were lower than those of healthy controls (p(FDR) < 0.001), there was no significant difference in psychoticism scores between groups. SDS, SAS, SCL-90 scores and factor scores were higher than those of healthy control group (p(FDR) < 0.001), NIR functional brain imaging was different from healthy control group in the 12 and 27 channels (p(FDR) = 0.030, p(FDR) = 0.018), and no difference was found in the remaining channels (p(FDR) > 0.05). There were statistically significant differences in age and gender between the adolescents who refused school and the control group (p(FDR) < 0.001). CONCLUSION: School refusal adolescents are relatively introverted and sensitive and need more attention in daily life. Although the adolescents' emotional problems did not reach the diagnostic criteria of depressive disorder and anxiety disorder, their scores were still higher than those of the control group, suggesting that we should pay more attention to their emotional problems in order to better help them return to school. Using fNIRS, it was found that abnormalities in frontal lobe regions in adolescents with school refusal behaviors, which would contribute to early diagnosis and timely intervention of school refusal behaviors.

Proinflammatory phenotype in major depressive disorder with adulthood adversity: In line with social signal transduction theory of depression.

BACKGROUND: The social signal transduction theory of depression proposes that life stress can be transformed into inflammatory signals, and ultimately lead to the development of major depressive disorder (MDD). The hypotheses of this study were: (1) The pro-inflammatory effect of life stress was only seen in patients with MDD, but not in healthy controls (HCs); (2) Inflammation can mediate the relationship between life stress and depressive symptoms. METHODS: This study included 170 MDD patients and 196 HCs, and 13 immune-inflammatory biomarkers closely related to MDD were measured, principal component analysis (PCA) was adopted to extract the inflammatory index. Life stress was assessed by Life Event Scale (LES), a total score of >32 points on the LES was considered as adulthood adversity (AA). Path analyses were used to explore the relationship among adulthood stress, inflammatory index, and severity of depression. RESULTS: Among MDD patients, α2M, CXCL-1, IL-1ß, and TLR-1 levels were higher in patients with AA than non-AA group (all FDR-adjusted P values <0.05), meanwhile, the levels of CCL-2 and IL-18 were lower. Path analyses suggested that pro- and anti-inflammatory index could mediate the association between AA and severity of depression in MDD patients. CONCLUSION: This study found that inflammatory signals can mediate the relationship between adulthood adversity and depression, however, the causal relationship need to be further confirmed. These findings shed light on further understanding the theory of social signal transduction in MDD and provide clues for stress management and controlling inflammation strategies in depression. CLINICAL TRIALS: NCT02023567.

A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to verify the efficacy and safety of ansofaxine (LY03005) for major depressive disorder.

Major depressive disorder (MDD) is the most prevalent form of depression and is becoming a great challenge for public health and medical practice. Although first-line antidepressants offer therapeutic benefits, about 35% of depressed patients are not adequately treated, creating a substantial unmet medical need. A multicenter, double-blind, randomized, placebo-controlled phase 3 clinical trial was conducted in patients with MDD in China to assess the efficacy and safety of ansofaxine (LY03005), a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. Eligible 588 MDD patients were included and randomly assigned (1:1:1) to 8-week treatment with ansofaxine 80 mg/day(n = 187), ansofaxine 160 mg/day(n = 186), or placebo(n = 185). The primary efficacy endpoint was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to the end of the study. Safety indexes included adverse events, vital signs, physical examination, laboratory tests, 12-lead electrocardiogram (ECG), and evaluation of suicide tendency and sexual function. Significant differences were found in mean changes in MADRS total score at week 8 in the two ansofaxine groups (80 mg, -20.0; 160 mg, -19.9) vs. placebo (-14.6; p < 0.0001). All doses of ansofaxine were generally well-tolerated. Treatment-emergent adverse events (TEAEs) were reported by 137 (74.46%) patients in ansofaxine 80 mg group, 144 (78.26%) patients in ansofaxine 160 mg and 125 (67.93%) patients in the placebo group. The incidence of treatment-related adverse events (TRAEs) was 59.2% (109 patients), 65.22% (120 patients) in the 80, 160 mg ansofaxine groups, and 45.11% (83 patients) in the placebo group. The initial results of this trial indicate that ansofaxine at both the 80 mg/day and 160 mg/day was effective and safe in adult patients with MDD. ClinicalTrials.gov Identifier: NCT04853407.

Association analysis of gut microbiota and efficacy of SSRIs antidepressants in patients with major depressive disorder.

BACKGROUND: Relevant studies have shown that gut microbiome plays an important role in the occurrence, development and treatment of major depressive disorder (MDD). Many studies have also shown that, selective serotonin reuptake inhibitors (SSRIs) antidepressants can improve the symptoms of depression by changing the distribution of gut microbiome, Here we investigated whether a distinct gut microbiome was associated with Major depressive disorder (MDD), and how it was modulated by SSRIs antidepressants. METHOD: In this study, we analyzed the gut microbiome composition of 62 patients with first-episode MDD and 41 matched healthy controls, before SSRIs antidepressants treatment, using 16S rRNA gene sequencing. MDD patients characterized as treatment-resistant (TR) or responders (R) to antidepressants by score reduction rate were ≥50 % after SSRIs antidepressants treatment for eight weeks. RESULTS: LDA effect size (LEfSe) analysis found that there were 50 different bacterial groups among the three groups, of which 19 genera were mainly at the genus level. The relative abundance of 12 genera increased in the HCs group, 5 genera in the R group increased in relative abundance, and 2 genera in the TR group increased in relative abundance. The correlation analysis of 19 bacterial genera and the score reduction rate showed that Blautia, Bifidobacterium and Coprococcus with higher relative abundance in the treatment effective group were related to the efficacy of SSRIs antidepressants. CONCLUSIONS: Patients with MDD have a distinct gut microbiome that changes after SSRIs antidepressants treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients with MDD.

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

Objective: 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. Methods: 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. Results: 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). Conclusion: 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.

Distinguishing between bipolar depression and unipolar depression based on the reward circuit activities and clinical characteristics: A machine learning analysis.

BACKGROUND: Differentiating bipolar depression (BD) from unipolar depression (UD) is a major clinical challenge. Identifying the potential classifying biomarkers between these two diseases is vital to optimize personalized management of depressed individuals. METHODS: Here, we aimed to integrate neuroimaging and clinical data with machine learning method to classify BD and UD at the individual level. Data were collected from 31 healthy controls (HC group) and 80 depressive patients with an average follow-up period of 7.51 years. Of these patients, 32 got diagnosis conversion from major depressive disorder (MDD) to BD (BD group) and 48 remain persistent diagnosis of MDD (MDD group). Using graph theory and functional connectivity (FC) analysis, we investigated the differences in reward circuit properties among three groups. Then we applied a support vector machine and leave-one-out cross-validation methods to classify BD and UD patients based on neuroimaging and clinical data. RESULTS: Compared with MDD and HC, BD showed decreased degree centrality of right mediodorsal thalamus (MD) and nodal efficiency (NE) of left ventral pallidum. Compared with BD and HC, MDD showed decreased NE of right MD and increased FC between right MD and bilateral dorsolateral prefrontal cortex and left ventromedial prefrontal cortex. Notably, the classifier obtained high classification accuracies (87.50 %) distinguishing BD and UD patients based on reward circuit properties and clinical features. LIMITATIONS: The classifying model requires out-of-sample replication analysis. CONCLUSION: The reward circuit dysfunction can not only provide additional information to assist clinical differential diagnosis, but also in turn informed treatment decision of depressive patients.

Abnormal cortical-striatal-thalamic-cortical circuit centered on the thalamus in MDD patients with somatic symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: Somatic symptoms are common comorbidities of major depressive disorder (MDD), and negatively impact the course and severity of the disease. In order to enrich the understanding of the pathological mechanism and clarify the neurobiological basis of somatic symptoms in depression, we attempted to explore the changes of brain structure and function in a large sample between depression with and without somatic symptoms. METHODS: Structure magnetic resonance imaging (MRI) data were collected from 342 patients with somatic symptoms (SD), 208 patients without somatic symptoms (NSD), and 510 healthy controls (HCs) based on the REST-meta-MDD project. We analyzed the whole brain VBM maps of the three groups, and combined with weight degree centrality (DC) index, we investigated whether the brain regions with gray matter volume (GMV) and gray matter density (GMD) abnormalities in MDD patients with somatic symptoms had corresponding brain functional abnormalities. RESULTS: Between depression with and without somatic symptoms, we found that there are extensive GMV and GMD differences involving cortical regions such as the temporal lobe, occipital lobe, and insula, as well as subcortical brain regions such as thalamus and striatum. The comparison results of weight DC signals of GMV and GMD abnormal clusters between the SD and NSD groups were basically consistent with the GMV and GMD abnormal clusters. CONCLUSION: The results indicate that the structure and function of cortical-striatal-thalamic-cortical (CSTC) circuit centered on the thalamus were abnormal in MDD patients with somatic symptoms. This may be the neurobiological basis of somatic symptoms in MDD.

Analysis of Whole Blood and Urine Trace Elements in Children with Autism Spectrum Disorders and Autistic Behaviors.

The relationship between trace elements and neurological development is an emerging research focus. We performed a case-control study to explore (1) the differences of 13 trace elements chromium (Cr), manganese (Mn), cobalt (Co), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), stannum (Sn), stibium (Sb), mercury (Hg), titanium (TI), and plumbum (Pb) concentration in whole blood and urine between autism spectrum disorder (ASD) children and their typical development peers, and (2) the association between the 13 trace elements and core behaviors of ASD. Thirty ASD subjects (cases) and 30 age-sex-matched healthy subjects from Baise City, Guangxi Zhuang Autonomous Region, China, were recruited. Element analysis was carried out by inductively coupled plasma-optical emission spectrometry. Autistic behaviors were assessed using Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Children Neuropsychological and Behavior Scale (CNBS). The whole blood concentrations of Mo (p = 0.004), Cd (0.007), Sn (p = 0.003), and Pb (p = 0.037) were significantly higher in the ASD cases than in the controls. Moreover, Se (0.393), Hg (0.408), and Mn (- 0.373) concentrations were significantly correlated between whole blood and urine levels in ASD case subjects. There were significant correlations between whole blood Sb (0.406), Tl (0.365), Mo (- 0.4237), Mn (- 0.389), Zn (0.476), and Se (0.375) levels and core behaviors of ASD. Although the mechanism of trace element imbalance in ASD is unclear, these data demonstrate that core behaviors of ASD may be affected by certain trace elements. Further studies are recommended for exploring the mechanism of element imbalance and providing corresponding clinical treatment measures.

Theta oscillations: A rhythm difference comparison between major depressive disorder and anxiety disorder.

Background: Due to substantial comorbidities of major depressive disorder (MDD) and anxiety disorder (AN), these two disorders must be distinguished. Accurate identification and diagnosis facilitate effective and prompt treatment. EEG biomarkers are a potential research hotspot for neuropsychiatric diseases. The purpose of this study was to investigate the differences in EEG power spectrum at theta oscillations between patients with MDD and patients with AN. Methods: Spectral analysis was used to study 66 patients with MDD and 43 patients with AN. Participants wore 16-lead EEG caps to measure resting EEG signals. The EEG power spectrum was measured using the fast Fourier transform. Independent samples t-test was used to analyze the EEG power values of the two groups, and p < 0.05 was statistically significant. Results: EEG power spectrum of the MDD group significantly differed from the AN group in the theta oscillation on 4-7 Hz at eight electrode points at F3, O2, T3, P3, P4, FP1, FP2, and F8. Conclusion: Participants with anxiety demonstrated reduced power in the prefrontal cortex, left temporal lobe, and right occipital regions. Confirmed by further studies, theta oscillations could be another biomarker that distinguishes MDD from AN.

A resting state fMRI study of major depressive disorder with and without anxiety.

BACKGROUND: The neurobiology of the Major depressive disorder (MDD) with anxiety is still unclear. The present study aimed to explore the brain correlates of MDD with and without anxiety in men and women during resting-state fMRI. METHODS: Two hundred and fifty-four patients with MDD (MDD with anxiety, N = 152) and MDD without anxiety, N = 102) and 228 healthy controls (HCs) participated in this study. We compared the fALFF(fractional amplitude of low-frequency fluctuations) and ReHo(regional homogeneity) of ACC(anterior cingulate cortex) and insula among these three groups. We also compared gender difference between MDD with anxiety and MDD without anxiety. RESULTS: We found that the fALFF values within the ACC and insula were significantly lower in MDD with anxiety compared to without anxiety and HCs. However, we did not find differences in ReHo values among the three groups. In women, we found significant differences in fALFF values between MDD with and without anxiety. These differences were not observed in men. CONCLUSIONS: It is possible that MDD with anxiety show less spontaneous BOLD-fMRI signal intensity within the ACC and insula compared to MDD without anxiety, especially in women. The fALFF within the ACC and insula can be a potential biomarker for severe MDD phenotype.

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

AIM: 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. METHODS: 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. RESULTS: The α-diversity analysis found that Simpson and Pielou evenness index was much higher in HCs than in the patients with MDD. The ß-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. CONCLUSIONS: 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.

Altered Cingulum Functioning in Major Depressive Disorder Patient With Suicide Attempts: A Resting-State Functional Magnetic Resonance Imaging Study.

Background: Major depressive disorder (MDD) with suicide attempts (SA) poses a significant public health issue. This study aims to identify neurobiological markers for MDD with SA on resting-state brain functional magnetic resonance imaging (rs-fMRI). Methods: Fifty-one unmedicated adult MDD participants, 27 with SA on the Beck Scale for Suicidal Ideation and 24 without SA, underwent rs-fMRI scanning. A group of 30 healthy controls (HC) matched for age, gender, and education-level with MDD were chosen. A whole brain analysis of regional homogeneity (ReHo) was performed on subjects to identify regions where brain activity was associated with SA. Multiple comparison analysis was performed for ReHo. Pearson's correlation analysis was performed between HAMD-SA scores and ReHo. The statistical significance level was set at p < 0.05. Results: We examined whether there were significant differences among the three groups in whole brain ReHo during resting state. Subjects with SA showed significant increase of ReHo in the right Cingulum Post in comparison with those without SA. Subjects with SA showed significant decrease of ReHo in the right Cingulate Gyrus/Precuneus in comparison with HC. The mean ReHo from the significant brain region was associated with HAMD-SA (item 3 of the HAMD) scores (r = 0.349, P = 0.012) but was not associated with HAMD-24 scores. Conclusion: These results indicate that SA is associated with altered resting-state brain activity. The pattern of elevated activity in the cingulum functioning may be related to SA. Identifying cingulum activity associated with SA may help to elucidate its pathogenesis and etiology.

Co-Expression Network Modeling Identifies Specific Inflammation and Neurological Disease-Related Genes mRNA Modules in Mood Disorder.

Objectives: Mood disorders are a kind of serious mental illness, although their molecular factors involved in the pathophysiology remain unknown. One approach to examine the molecular basis of mood disorders is co-expression network analysis (WGCNA), which is expected to further divide the set of differentially expressed genes into subgroups (i.e., modules) in a more (biologically) meaningful way, fascinating the downstream enrichment analysis. The aim of our study was to identify hub genes in modules in mood disorders by using WGCNA. Methods: Microarray data for expression values of 4,311,721 mRNA in peripheral blood mononuclear cells drawn from 21 MDD, 8 BD, and 24 HC individuals were obtained from GEO (GSE39653); data for genes with expression in the bottom third for 80% or more of the samples were removed. Then, the top 70% most variable genes/probs were selected for WGCNA: 27,884 probes representing 21,840 genes; correlation between module genes and mood disorder (MDD+BD vs. HC) was evaluated. Results: About 52% of 27,765 genes were found to form 50 co-expression modules with sizes 42-3070. Among the 50 modules, the eigengenes of two modules were significantly correlated with mood disorder (p < 0.05). The saddlebrown module was found in one of the meta-modules in the network of the 50 eigengenes along with mood disorder, 6 (IER5, NFKBIZ, CITED2, TNF, SERTAD1, ADM) out of 12 differentially expressed genes identified in Savitz et al. were found in the saddlebrown module. Conclusions: We found a significant overlap for 6 hub genes (ADM, CITED2, IER5, NFKBIZ, SERTAD1, TNF) with similar co-expression and dysregulation patterns associated with mood disorder. Overall, our findings support other reports on molecular-level immune dysfunction in mood disorder and provide novel insights into the pathophysiology of mood disorder.

Resting-State fMRI in Predicting Response to Treatment With SSRIs in First-Episode, Drug-Naive Patients With Major Depressive Disorder.

OBJECTIVE: For major depressive disorder (MDD), there has been a lack of neuroimaging markers of efficacy of pharmacological treatment. In this study, we aimed to explore the neuroimaging mechanisms in patients with first-episode MDD and identify markers that predict the efficacy of 5-hydroxytryptamine reuptake inhibitors (SSRIs) with the use of resting-state brain imaging technology. METHODS: A total of 101 patients with first-episode MDD and 53 normal controls were finally included in this study. Based on the reduction rate of the score of Hamilton Depression Rating Scale (HAMD-17) during the 2-week SSRI treatment, 31 patients were assigned into the unresponsive group and 32 were assigned into the responsive group. The brain function was compared between patients with MDD and normal controls, and the diagnostic value of brain function was analyzed. With brain regions showing differences between patients with MDD and normal controls as a mask, and the brain function between the responsive and unresponsive groups were compared. Correlations between brain function the HAMD-17 score reduction rate during the 2-week SSRI treatment were analyzed. RESULTS: Compared to normal controls, patients with MDD showed increased ReHo in the left parahippocampal gyrus and right parahippocampal gyrus, decreased ReHo in the right middle occipital gyrus, and decreased functional connectivity between the right and left parahippocampal gyri, right middle occipital gyrus and middle temporal gyrus. Receiver operator characteristic (ROC) curve analysis showed that the area under the curve (AUC) was 0.544 (95% CI: 0.445-0.644) for ReHo and 0.822 (95% CI: 0.734-0.909) for functional connectivity. Logistic regression pooling of the differences in ReHo mean time series with the functional connectivity mean time series was performed for the ROC curve analysis, which showed an AUC of 0.832 (95% CI: 0.752-0.911). Compared to the responsive group, the unresponsive group showed elevated ReHo in the right parahippocampal gyrus and lower functional connectivity in the middle temporal gyrus. We also found that the ReHo value was negatively correlated with the HAMD-17 score reduction after 2 weeks of SSRI treatment. CONCLUSION: Altered resting-state brain function in some regions might be a neurobiological marker for the diagnosis of MDD, and ReHo values are expected to be predictors of patient response to treatment with SSRIs. CLINICAL TRIAL REGISTRATION: [http://www.chictr.org.cn/], identifier [ChiCTR1900028722].