Identifying latent subtypes of symptom trajectories in major depressive disorder patients and their predictors.

This study aimed to identify different symptom trajectories based on the severity of depression symptoms within a 2-month follow-up, and to explore predictive factors for different symptom trajectories. Three hundred and ninety-two adults diagnosed with major depressive disorder (MDD) were recruited from two longitudinal cohorts. Patients received antidepressant treatment as usual, and the depression symptoms were evaluated by the 17-item Hamilton depression rating scale (HAMD-17) at baseline, two weeks, and eight weeks. Based on the HAMD-17 scores, different trajectories of symptom change were distinguished by applying Growth Mixture Modeling (GMM). Furthermore, the baseline sociodemographic, clinical, and cognitive characteristics were compared to identify potential predictors for different trajectories. Through GMM, three unique depressive symptom trajectories of MDD patients were identified: (1) mild-severity class with significant improvement (Mild, n = 255); (2) high-severity class with significant improvement (High, n = 39); (3) moderate-severity class with limited improvement (Limited, n = 98). Among the three trajectories, the Mild class had a relatively low level of anxiety symptoms at baseline, whereas the High class had the lowest education level and the worst cognitive performance. Additionally, participants in the Limited class exhibited an early age of onset and experienced a higher level of emotional abuse. MDD patients could be categorised into three distinct latent subtypes through different symptom trajectories in this study, and the characteristics of these subtype patients may inform identifications for trajectory-specific intervention targets.

5-Methoxytryptophan Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting the Intestinal Epithelial Damage and Inflammatory Response.

Background: Colitis is a refractory intestinal inflammatory disease significantly affecting the quality of a patient's life and increasing the risk of exacerbation. The primary factors leading to colitis encompass infections, insufficient blood flow, and the buildup of collagen as well as white blood cells. Among various available therapeutics, 5-methoxytryptophan (5-MTP) has emerged as one of the protectants by inhibiting inflammatory damage. Nonetheless, there is no report on the role of 5-MTP in the treatment of colitis. Materials and Methods: To verify the anti-inflammatory effect of 5-MTP in vivo, we first constructed mouse model with dextran sulfate sodium-induced colitis. Furthermore, the macrophage infiltration and release of inflammatory factors through western blot (WB) and hematoxylin-eosin staining analyses were examined. Intestinal epithelial cell tight junction damage and apoptosis were investigated by WB analysis, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Finally, we examined the generation of cellular inflammation and analyzed the influence of 5-MTP on M1 polarization at the cellular level. Results: This study initially confirmed that 5-MTP possessed an excellent therapeutic effect on colitis. 5-MTP inhibits macrophage infiltration and the generation of inflammatory factors. In addition to its effects on immune cells, 5-MTP significantly inhibits intestinal epithelial cell tight junction damage and apoptosis in vivo. Moreover, it inhibits inflammation and M1 polarization response in vitro. Conclusion: 5-MTP counteracts excessive inflammation, thereby preventing intestinal epithelial tight junction damage. In addition, inhibition of apoptosis suggests that 5-MTP may be a potential therapeutic agent for colitis.

The relationship between personality traits and dysfunctional attitudes in individuals with or without major depressive disorder: a case control study.

BACKGROUND: Dysfunctional attitudes, which are characterized by distorted self-cognitions, were considered to be linked to personality traits. It was found that certain personality traits may predict dysfunctional attitudes in patients with major depressive disorder (MDD). Nonetheless, the relationship between personality traits and dysfunctional attitudes remains under-researched. AIMS: The aim of this study is to examine the relationship between specific domains of Sixteen Personality Factor (16PF) and dysfunctional attitudes in Chinese participants with or without MDD. In addition, the present study explores the associations between 16PF and eight subtypes of dysfunctional attitudes, based on the proposed eight-factor structure of the Chinese version of the Dysfunctional Attitude Scale-Form A (C-DAS-A). METHODS: One hundred and sixty-eight participants with MDD and 130 healthy participants were included in the study (Trial Registration Number: ChiCTR1800014591). Personality was assessed using the 16PF Questionnaire. Dysfunctional attitudes were measured through the C-DAS-A. RESULTS: The 16PF dimensions associated with dysfunctional attitudes and the eight subtypes were mainly concentrated in the four anxiety facets including factors C, L, O, and Q4, in both MDD and HC groups. There were significant differences in the 16 PF dimensions that would explain dysfunctional attitudes between the two groups, which were as follows: factors C, G, and O in the MDD group, and factors L and Q4 in the HC group. CONCLUSIONS: Personality traits, especially the anxiety-related personality traits, were distinctly associated with the development of dysfunctional attitudes in people with or without MDD.

Impact of childhood maltreatment on adult resilience.

BACKGROUND: Previous studies suggested that childhood maltreatment is associated with poor health outcomes. While not everyone who experiences abuse as a child goes on to experience poor mental health, some traumatized people are grown to be more resilient than others. Few studies have examined the association between childhood maltreatment and adult resilience. This study aimed to determine different relationships between specific types and features of childhood maltreatment with adult resilience among Chinese with Major Depressive Disorder (MDD) and healthy controls (HCs). METHODS: A total of 101 patients with MDD and 116 participants in the healthy control (HC) group from Zhumadian Psychiatric Hospital and its nearby communities were included in this analysis. Childhood maltreatment was assessed retrospectively using Childhood Trauma Questionnaire (CTQ). Adults' resilience was assessed by the Connor-Davidson Resilience Scale (CD-RISC). Generalized linear models were applied between childhood maltreatment (specific types and features) and resilience adjusting for covariates. RESULTS: The total score of CD-RISC and factor scores of strength, optimism, and tenacity in the HC group were higher than those in the MDD group. CTQ total score had a negative association with optimism score among participants in MDD (ß=-0.087, P < 0.001) and HC (ß=-0.074, P = 0.023) groups. Higher emotional neglect (EN) score (ß=-0.169, P = 0.001) and physical neglect (PN) score (ß=-0.153, P = 0.043) were related to a worse optimism score in MDD group. Emotional abuse (EA) score was associated with a worse tenacity score (ß=-0.674, P = 0.031) in MDD group. For participants in HC group, higher EN and PN scores were related to worse resilience scores (tenacity, strength, and optimism). CONCLUSIONS: Patients with MDD showed lower optimism than HCs. Childhood maltreatment, especially childhood negect, independently contributed to optimism, with more severe childhood maltreatment predictive of worse performance of optimism. EA in childhood was also linked to worse tenacity in adult patients with MDD.

The longitudinal change pattern of cognitive subtypes in medication-free patients with major depressive disorder: a cluster analysis.

This study aimed to investigate whether there are different cognitive subtypes in patients with major depressive disorder (MDD) and the change pattern of cognitive clusters across the course of MDD. A battery of comprehensive cognitive tests was used to assess the executive function, processing speed, attention, and memory of 153 medication-free patients and 142 healthy controls (HCs). After 6 months of treatment with antidepressants, 87 patients completed cognitive tests again. K-means cluster analysis was performed to determine the cognitive subtypes. A preserved cognition cluster and an impaired cognition cluster were identified in the acute episode phase and the 6-month follow-up phase. 80.5% of the patients remained in their original subgroup after 6 months of treatment. The impaired cognition cluster during the 6-month follow-up period could be predicted by impaired cognition during the episode phase, disease state (remission or non-remission), current illness duration, and education level. This study supporting the heterogeneity of cognitive performance across the course of disease in patients with MDD using cluster analysis. It was found that cognitive impairment during depressive episodes was predictive of poorer cognitive performance even after treatment with antidepressants. Therefore, interventions targeting cognitive function from the early stages of MDD is essential.

Dexamethasone Liposomes Alleviate Osteoarthritis in miR-204/-211-Deficient Mice by Repolarizing Synovial Macrophages to M2 Phenotypes.

We undertook this study to investigate the effects and mechanisms of dexamethasone liposome (Dex-Lips) on alleviating destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) in miR-204/-211-deficient mice. Dex-Lips was prepared by the thin-film hydration method. The characterization of Dex-Lips was identified by the mean size, zeta potential, drug loading, and encapsulation efficiencies. Experimental OA was established by DMM surgery in miR-204/-211-deficient mice, and then Dex-Lips was treated once a week for 3 months. Von Frey filaments was used to perform the pain test. The inflammation level was evaluated with quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Polarization of macrophages was evaluated by immunofluorescent staining. X-ray, micro-CT scanning, and histological observations were conducted in vivo on DMM mice to describe the OA phenotype. We found that miR-204/-211-deficient mice displayed more severe OA symptoms than WT mice after DMM surgery. Dex-Lips ameliorated DMM-induced OA phenotype and suppressed pain and inflammatory cytokine expressions. Dex-Lips could attenuate pain by regulating PGE2. Dex-Lips treatments reduced the expression of TNF-α, IL-1ß, and IL-6 in DRG. Moreover, Dex-Lips could reduce inflammation in the cartilage and serum. Additionally, Dex-Lips repolarize synovial macrophages to M2 phenotypes in miR-204/-211-deficient mice. In conclusion, Dex-Lips inhibited the inflammatory response and alleviated the pain symptoms of OA by affecting the polarization of macrophages.

Aberrant Resting-State Functional Connectivity in MDD and the Antidepressant Treatment Effect-A 6-Month Follow-Up Study.

BACKGROUND: The mechanism by which antidepressants normalizing aberrant resting-state functional connectivity (rsFC) in patients with major depressive disorder (MDD) is still a matter of debate. The current study aimed to investigate aberrant rsFC and whether antidepressants would restore the aberrant rsFC in patients with MDD. METHODS: A total of 196 patients with MDD and 143 healthy controls (HCs) received the resting-state functional magnetic resonance imaging and clinical assessments at baseline. Patients with MDD received antidepressant treatment after baseline assessment and were re-scanned at the 6-month follow-up. Network-based statistics were employed to identify aberrant rsFC and rsFC changes in patients with MDD and to compare the rsFC differences between remitters and non-remitters. RESULTS: We identified a significantly decreased sub-network and a significantly increased sub-network in MDD at baseline. Approximately half of the aberrant rsFC remained significantly different from HCs after 6-month treatment. Significant overlaps were found between baseline reduced sub-network and follow-up increased sub-network, and between baseline increased sub-network and follow-up decreased sub-network. Besides, rsFC at baseline and rsFC changes between baseline and follow-up in remitters were not different from non-remitters. CONCLUSIONS: Most aberrant rsFC in patients with MDD showed state-independence. Although antidepressants may modulate aberrant rsFC, they may not specifically target these aberrations to achieve therapeutic effects, with only a few having been directly linked to treatment efficacy.

The percentage of cognitive impairment in patients with major depressive disorder over the course of the depression: A longitudinal study.

BACKGROUND: Cognitive impairments (CI) are prevalent and persistent in patients with major depressive disorder (MDD). There is a lack of longitudinal studies exploring the changes of the percentage of CI among MDD patients before and after a long-term antidepressant treatment and the risk factors that predict the residual CI. METHODS: A neurocognitive battery was performed to assess four domains of cognitive function, including executive function, processing speed, attention, and memory. CI was set as cognitive performance scoring 1.5 SDs lower than the mean scores of healthy controls (HCs). Logistic regression models were conducted to examine the risk factors for the after-treatment residual CI. RESULTS: Over 50 % of patients showed at least one kind of CI. After the antidepressant treatment, the overall cognitive performance among remitted MDD patients was identical to HCs, however, there were still 24 % of the remitted MDD patients had at least one type of CI, especially in executive function and attention. Additionally, the percentage of CI among non-remitted MDD patients was still significantly different from HCs. Our regression analysis further identified that except for the non-remission of MDD, CI at baseline could also predict the residual CI in MDD patients. LIMITATIONS: A relatively high drop-out rate at follow-ups. CONCLUSIONS: Cognitive impairment in executive function and attention is persistent even in remitted patients with MDD, and baseline cognitive performance can predict the post-treatment cognitive performance. Our findings emphasize the integral role of early cognitive intervention in MDD treatment.

Modulation of resting-state functional connectivity in default mode network is associated with the long-term treatment outcome in major depressive disorder.

BACKGROUND: Treatment non-response and recurrence are the main sources of disease burden in major depressive disorder (MDD). However, little is known about its neurobiological mechanism concerning the brain network changes accompanying pharmacotherapy. The present study investigated the changes in the intrinsic brain networks during 6-month antidepressant treatment phase associated with the treatment response and recurrence in MDD. METHODS: Resting-state functional magnetic resonance imaging was acquired from untreated patients with MDD and healthy controls at baseline. The patients' depressive symptoms were monitored by using the Hamilton Rating Scale for Depression (HAMD). After 6 months of antidepressant treatment, patients were re-scanned and followed up every 6 months over 2 years. Traditional statistical analysis as well as machine learning approaches were conducted to investigate the longitudinal changes in macro-scale resting-state functional network connectivity (rsFNC) strength and micro-scale resting-state functional connectivity (rsFC) associated with long-term treatment outcome in MDD. RESULTS: Repeated measures of the general linear model demonstrated a significant difference in the default mode network (DMN) rsFNC change before and after the 6-month antidepressant treatment between remitters and non-remitters. The difference in the rsFNC change over the 6-month antidepressant treatment between recurring and stable MDD was also specific to DMN. Machine learning analysis results revealed that only the DMN rsFC change successfully distinguished non-remitters from the remitters at 6 months and recurring from stable MDD during the 2-year follow-up. CONCLUSION: Our findings demonstrated that the intrinsic DMN connectivity could be a unique and important target for treatment and recurrence prevention in MDD.

Relationship between childhood maltreatment and cognitive function in medication-free patients with major depressive disorder.

This study aimed to elucidate the contribution of childhood maltreatment (CM) and the disease of major depressive disorder (MDD) on cognitive function in medication-free patients in a current depressive episode, and to examine the effect of CM on the improvement of cognitive function after treatment with antidepressants. One hundred and fifty-three unmedicated patients with MDD and 142 healthy controls (HCs) underwent clinical interviews. CM assessment was performed using the Childhood Trauma Questionnaire (CTQ), and a battery of comprehensive neurocognitive tests was used to assess the participants' executive function, processing speed, attention, and memory. After 6 months of treatment with antidepressants, the neurocognitive tests were reperformed in patients with MDD and HCs. There was a significant main effect of MDD on all four cognitive domains, while the main effect of CM was only significant on memory. No significant interactive effect was found between MDD and CM on any of the cognitive domains. In the MDD group, higher CTQ total score was predictive of poorer memory performance. After treatment, significant main effects of treatment and MDD were found on all four cognitive domains in remitted patients with MDD. No significant main effect of CM or three-way interaction effect of treatment × MDD × CM was found on any of the cognitive domains. The disease of MDD contributed to impairments in all four cognitive domains. CM independently contributed to memory impairment in patients in a current depressive episode, with higher severity of CM predictive of poorer memory performance.

Aryl hydrocarbon receptor activation drives polymorphonuclear myeloid-derived suppressor cell response and efficiently attenuates experimental Sjögren's syndrome.

Myeloid-derived suppressor cells (MDSCs) comprise heterogeneous myeloid cell populations with immunosuppressive capacity that contribute to immune regulation and tolerance induction. We previously reported impaired MDSC function in patients with primary Sjögren's syndrome (pSS) and mice with experimental SS (ESS). However, the molecular mechanisms underlying MDSC dysfunction remain largely unclear. In this study, we first found that aryl hydrocarbon receptor (AhR) was highly expressed by human and murine polymorphonuclear MDSCs (PMN-MDSCs). Indole-3-propionic acid (IPA), a natural AhR ligand produced from dietary tryptophan, significantly promoted PMN-MDSC differentiation and suppressive function on CD4+ T cells. In contrast, feeding a tryptophan-free diet resulted in a decreased PMN-MDSC response, a phenotype that could be reversed by IPA supplementation. The functional importance of PMN-MDSCs was demonstrated in ESS mice by using a cell-depletion approach. Notably, AhR expression was reduced in PMN-MDSCs during ESS development, while AhR antagonism resulted in exacerbated ESS pathology and dysregulated T effector cells, which could be phenocopied by a tryptophan-free diet. Interferon regulatory factor 4 (IRF4), a repressive transcription factor, was upregulated in PMN-MDSCs during ESS progression. Chromatin immunoprecipitation analysis revealed that IRF4 could bind to the promoter region of AhR, while IRF4 deficiency markedly enhanced AhR-mediated PMN-MDSC responses. Furthermore, dietary supplementation with IPA markedly ameliorated salivary glandular pathology in ESS mice with restored MDSC immunosuppressive function. Together, our results identify a novel function of AhR in modulating the PMN-MDSC response and demonstrate the therapeutic potential of targeting AhR for the treatment of pSS.

Olfactory Ecto-mesenchymal Stem Cell-derived Exosomes Ameliorate Murine Sjögren's Syndrome via Suppressing Tfh Cell Response.

Objectives: To investigate the effect of olfactory ecto-mesenchymal stem cell-derived exosomes (OE-MSC-Exos) on T follicular helper (Tfh) cell response and their implication in treating experimental Sjögrens syndrome (ESS). Methods: C57BL/6 mice were immunized with salivary glands (SG) proteins to induce ESS mouse model. OE-MSC-Exos were added to the Tfh cell polarization condition, and the proportion of Tfh cells was detected by FCM. The PD-L1 of OE-MSCs was silenced with small interfering RNA to extract siPD-L1-OE-MSC-Exos. Results: We found that transfer of OE-MSC-Exos markedly attenuated disease progression and reduced Tfh cell response in mice with ESS. In culture, OE-MSC-Exos potently inhibited the differentiation of Tfh cells from naïve T cells. Moreover, OE-MSC-Exos expressed high level of the ligand for the programmed cell death protein 1 (PD-L1), knocking down PD-L1 expression in OE-MSC-Exos significantly decreased their capacity to suppress Tfh cell differentiation in vitro. Consistently, transfer of OE-MSC-Exos with PD-L1 knockdown exhibited profoundly diminished therapeutic effect in ESS mice, accompanied with sustained Tfh cell response and high levels of autoantibody production. Conclusion: Our results suggest that OE-MSC-Exos may exert their therapeutic effect in ameliorating ESS progression via suppressing Tfh cell response in a PD-L1-dependent manner.

Childhood Emotional Neglect Is Associated With Low Social Support in Chinese Patients With Major Depressive Disorder.

Background: Previous studies have shown that childhood maltreatment (CM) is closely associated with social support in the general population. However, little is known about the associations of different types of CM with social support in Chinese patients with major depressive disorder (MDD), which was the goal of the current study. Methods: One hundred and sixty-six patients with moderate-to-severe MDD were enrolled. Participants were assessed by the Childhood Trauma Questionnaire-28 item Short Form, Social Support Rating Scale (SSRS), the 24-item Hamilton rating scale for depression, and the 14-item Hamilton Anxiety Rating Scale. Correlation analysis and Hierarchical multiple linear regression analysis were adopted to investigate associations of types of CM with social support. Results: (1) Physical neglect (PN) and emotional neglect (EN) were the most commonly reported types of CM in patients with MDD. (2) EN was the only type of CM significant in the regression models of the SSRS total score, the score of subjective support, and the score of utilization of support. Limitations: The data of CM was collected retrospectively and recall bias may be introduced. Assessment of CM and social support were self-reported and could be influenced by the depression status. Conclusion: In Chinese patients with MDD, PN and EN are the most prevalent types of CM. EN is the only type of CM associated with low social support in regression models, calling for special attention in the assessment and intervention of EN.

Childhood Maltreatment Predicts Specific Types of Dysfunctional Attitudes in Participants With and Without Depression.

Background: Studies have shown a strong association between childhood maltreatment (CM) and major depressive disorder (MDD). Dysfunctional attitudes (DAs) play a crucial role in the development of MDD. In this study, we aimed to investigate whether (1) DAs are associated with CM, (2) specific CM types predict specific types of DAs, and (3) higher childhood trauma counts (CTCs) predict more DAs. Methods: One hundred seventy-one MDD participants and 156 healthy controls (HCs) were enrolled for the study. CM was assessed retrospectively with the Childhood Trauma Questionnaire. DAs were evaluated using the Chinese version of the Dysfunctional Attitude Scale-Form A (C-DAS-A). A series of analyses, including multiple analyses of covariance and hierarchical regression analyses, were used in this study to examine the hypotheses. Results: The proportion of CM was 60.2% in the MDD group and 44.2% in the HC group. The 2 × 2 analysis of covariance results showed no interaction effect between CM and MDD on C-DAS-A total score. When the factor scores replaced the C-DAS-A total score, a similar trend was observed. Within the MDD group, emotional abuse (EA) predicted two forms of DAs: self-determination type and overall DAs; physical neglect (PN) was predictive of attraction and repulsion-type DAs. Higher childhood trauma counts significantly predicted more types of DAs in the MDD group. Conclusion: DAs are a trait feature of CM. EA and PN predict specific types of DAs in MDD patients. Higher CTCs predict more DAs in MDD patients.

Epidemiology of Takayasu arteritis in Shanghai: A hospital-based study and systematic review.

BACKGROUND: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. METHODS: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. RESULTS: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. CONCLUSIONS: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

Functional connectivity evidence for state-independent executive function deficits in patients with major depressive disorder.

BACKGROUND: Persistent neurocognitive deficits are often associated with poor outcomes of major depressive disorder (MDD). Executive dysfunction is the most common cognitive deficit in MDD. However, it remains unclear which subcomponent of executive dysfunction is state-independent with distinct neural substrates. METHODS: A comprehensive neurocognitive test battery was used to assess four subcomponents of executive function (working memory, inhibition, shifting, and verbal fluency) in 95 MDD patients and 111 matched healthy controls (HCs). After 6 months of paroxetine treatment, 56 patients achieved clinical remission (rMDD) and completed the second-time neurocognitive test. Network-based statistics analysis was utilized to explore the changes in functional connectivity (FC). RESULTS: Compared with the HCs, all the four subcomponents of MDD patients were significantly impaired. After treatment, there was a significant improvement in working memory, inhibition, and verbal fluency in the rMDD group. And shifting and verbal fluency of the rMDD group remained impaired compared with the HCs. Fifteen functional connections were interrupted in the MDD group, and 11 connections remained in a disrupted state after treatment. Importantly, verbal fluency was negatively correlated with the disrupted FC between the right dorsal prefrontal cortex and the left inferior parietal lobule in patients with MDD and remitted MDD. LIMITATIONS: The correlation analysis of the association between cognitive impairment and connectivity alterations precluded us from making causal inferences. CONCLUSIONS: Verbal fluency is the potential state-independent cognitive deficit with distinct neural basis in patients with MDD.

Evidence for Progressive Cognitive Deficits in Patients With Major Depressive Disorder.

Background: Cognitive deficits have shown progressive feature in major depressive disorder (MDD). However, it remains unknown which component of cognitive function is progressively impaired across episodes of MDD. Here we aim to identify the progressively impaired cognitive components in patients with MDD. Methods: A comprehensive neurocognitive test battery was used to assess the cognitive components (executive function, attention, processing speed, memory, working memory, inhibition, shifting, and verbal fluency) in 35 patients with first-episode MDD (FED), 60 patients with recurrent MDD (RD) and 111 matched healthy controls (HCs). After 6 months of treatment with antidepressant, 20 FED and 36 RD patients achieved clinical remission and completed their second-time neurocognitive tests. Statistical analyses were conducted to identify the impaired cognitive components in the FED and RD groups before and after treatment, and to assess the relationship between the cognitive components and the number of episodes and total illness duration in the MDD patient group. Results: At baseline, both the FED and RD groups showed impairments in all of the cognitive components; the FED and RD groups showed no significant difference in all of the components except for shifting. After remission, only shifting in the RD group showed no significant improvement and remained in an impaired status. Furthermore, shifting was the only component negatively correlated with the number of episodes as well as the total illness duration. Conclusions: Shifting may serve as the progressive cognitive deficit across episodes of MDD. Clinical Trials Registration: Registry name: HPA function and MRI study of trauma-related depression; Registration number: ChiCTR1800014591; URL: http://www.chictr.org.cn/edit.aspx?pid=24669&htm=4.

Corrigendum: Gender Differences in Dysfunctional Attitudes in Major Depressive Disorder.

[This corrects the article DOI: 10.3389/fpsyt.2020.00086.].

The effects of childhood trauma on the onset, severity and improvement of depression: The role of dysfunctional attitudes and cortisol levels.

BACKGROUND: Childhood trauma is an important early social risk factor for the development of the major depressive disorder (MDD). Both childhood trauma and depression are associated with dysfunctional attitudes and dysregulation in stress hormones. We aimed to clarify the path from childhood trauma to depression and identify potential predictors of antidepressant treatment outcomes. OBJECTIVES: One hundred and thirty-nine MDD patients and 112 healthy controls were included at baseline. Depressive symptoms were assessed with both self-reported and expert-rated scales. Childhood trauma and dysfunctional attitudes were evaluated and blood cortisol levels were assayed. Patients received an open-label antidepressant trial with paroxetine and their depressive symptoms were monitored by the Hamilton Depression Rating Scale (HAMD) during 6 months of treatment. After 6 months, 94 patients received the same assessments as the baseline. RESULTS: At baseline, the influence of childhood trauma on depression diagnosis was mediated by dysfunctional attitudes. In patients with MDD, the influence of childhood trauma on depression severity was mediated by both dysfunctional attitudes and cortisol levels. Baseline childhood trauma predicted the antidepressant treatment outcome during early treatment phase and baseline cortisol levels predicted the antidepressant treatment outcome at later treatment phase. After 6-month antidepressant treatment, a significant remission by time effect was found on dysfunctional attitudes and depression severity but not on cortisol levels. CONCLUSION: Effect of childhood trauma on depression onset was mediated by dysfunctional attitudes. The relationship between childhood trauma and depressive symptoms was mediated by dysfunctional attitudes and cortisol levels in MDD patients. Baseline childhood trauma and cortisol levels may be moderators for antidepressant treatment response at different treatment phase.