Drug-naive Major Depressive Disorder Patients Research Articles

Prevalence and associated factors of obesity in patients with major depressive disorder at different ages of onset.

Major depressive disorder (MDD) and obesity are two serious public health problems. Although there have been some research on both, there have few studies on differences in obesity among MDD patients at different ages of onset. The study aims to evaluate the prevalence and factors associated with obesity in MDD patients at different ages of onset. This study totally recruited 1718 first-episode drug-naive MDD patients aged from 18 to 60years. All subjects were divided into two subgroups: early adulthood onset (EAO, 18-45years) and mid-adulthood onset (MAO, 45-60years). Clinical symptoms of patients were evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) positive subscale. Baseline parameters including body mass index (BMI), blood pressure, and hematological biochemical parameters were assessed to investigate the association between these parameters and weight gain risk. The percentages of overweight and obesity patients with MDD in EAO group were 54.4% and 4.1%, respectively, and the percentages of overweight and obesity patients with MDD in MAO group were 60.4% and 2.8%, respectively. MDD patients in the MAO group had a longer duration of illness and higher scores in HAMD, HAMA, and PANSS positive subscale. They also had higher levels of thyroid stimulating hormone (TSH), anti-thyroglobulin (TgAb), fasting blood glucose (FBG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), systolic and diastolic blood pressures (SBP and DBP) levels. BMI did not differ significantly between the two groups. In the EAO group, statistically significant differences were found among normal weight, overweight and obese group in duration of illness, age of onset, TSH, TgAb, thyroid peroxidase antibody (TPOAb), free thyroxine (FT4), TC, triglycerides (TG), SBP and DBP. The TSH, TgTb and SBP were identified as risk factors for weight gain. In the MAO group, statistically significant differences were found among normal weight, overweight and obese group in TSH and FBG. The two indicators were identified as risk factors for weight gain. There were no significant differences in the weight of MDD patients at different ages of onset, while the factors that could potentially lead to obesity did show some differences.

Ghrelin and depressive symptoms in patients with first-episode drug-naïve major depressive disorder: The mediating role of hypothalamic-pituitary-adrenal axis.

Major depressive disorder (MDD) is one of the global burdens of disease, and its pathogenesis remains unclear. An increasing amount of research indicates that ghrelin regulates mood in patients with MDD. Still, current results are inconsistent, and the mechanisms underlying how ghrelin modulates depressive symptoms are inconclusive, especially in first-episode drug-naïve MDD patients. Therefore, this study aims to investigate the relationship and potential mechanism between ghrelin and first-episode drug-naïve MDD. Ninety first-episode drug-naïve MDD patients and 65 healthy controls (HCs) were included. Hamilton Depression Scale (HAMD-17) as a measure of depressive symptoms. Plasma levels of ghrelin and hypothalamic-pituitary-adrenal axis (HPA-axis) hormones were measured in all participants. Compared to HCs, the ghrelin levels were higher in the MDD (p < .001) and still showed significance after covarying for sex, age, and Body Mass Index (BMI). Ghrelin was positively related to corticotropin-releasing-hormone (CRH) levels (r = .867, p < .001), adrenocorticotropic hormone (ACTH) levels (r = .830, p < .001), and cortisol levels (r = .902, p < .001) in partial correlation analysis. In addition, there was a positive correlation between HAMD total score and ghrelin levels (r = .240, p = .026). Other than that, the HAMD total score also had a positive correlation with the CRH (r = .333, p = .002) and cortisol (r = .307, p = .004) levels. Further mediation analysis demonstrated that the relationship between ghrelin and HAMD total score was mediated by CRH (ab-path; β = .4457, 95% CI = 0.0780-1.0253, c-path; β = .2447, p = .0260, c'-path; β = -.2009, p = .3427). These findings revealed that plasma ghrelin provides a pivotal link to depressive symptoms in first-episode drug-naive MDD patients. CRH mediated the relationship between ghrelin and HAMD total score. It might provide new insights into understanding the pathogenesis of MDD, contributing to intervention and treatment from this approach.

The potential predictors for treatment-resistance depression after selective serotonin reuptake inhibitors therapy in Han Chinese: A resting-state functional magnetic resonance imaging study.

Selective serotonin reuptake inhibitors (SSRIs) are among the most important antidepressants. However, there is limited research on predicting the occurrence of treatment-resistant depression (TRD) after 5 years. Examining the predictive effect of TRD occurrence using resting-state fMRI in patients initiating SSRIs treatment at the onset of major depressive disorder (MDD) could potentially enhance TRD management. A total of 60 first-episode drug-naive MDD patients who met the criteria, along with 41 healthy controls of Han Chinese ethnicity, were recruited. All MDD patients received SSRIs as the initial treatment for relieving depressive symptoms. Resting-state fMRI scans were conducted for all subjects. Follow-up assessments were conducted over a period of five years, during which MDD patients were categorized into treatment-resistant depression (TRD) and non-treatment-resistant depression (NRD) groups based on disease progression. Amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and Regional Homogeneity (ReHo) values were calculated and compared among the three groups. Additionally, receiver operating characteristic (ROC) curves were employed to identify potential predictors. After 5 years of follow-up, it was found that 43 MDD patients were classified as NRD, while 17 were classified as TRD. In comparison to TRD, NRD exhibited decreased ALFF in the left middle cingulum gyrus (MCG.L) and in the right middle frontal gyrus (MFG.R), as well as decreased ReHo in MCG.L. Furthermore, NRD showed increased fALFF in the left precuneus (PCUN.L). The area under the curve (AUC) values were as follows: 0.724 (MCG.L by ALFF), 0.732 (MFG.R), 0.767 (PCUN.L), 0.774 (MCG.L by ReHo), 0.878 (combined), 0.547 (HAMD), and 0.408 (HAMA) respectively. The findings suggest that PCUN.L, MFG.R, MCG.L, and the combined measures may indicate the possibility of developing TRD after 5 years when SSRIs are used as the initial therapy for relieving depressive symptoms in MDD patients.

Plasma oxidative stress marker levels related to functional brain abnormalities in first-episode drug-naive major depressive disorder

Major Depressive Disorder (MDD) is marked by abnormal brain function and elevated plasma oxidative stress markers. The specific relationship between these factors in MDD remains unclear. In this study, we conducted resting-state fMRI scans on fifty-seven first-episode, drug-naive MDD patients and sixty healthy controls. Plasma levels of oxidative stress markers (superoxide dismutase (SOD) and glutathione reductase (GSR)) were assessed using ELISA. Our results revealed a positive correlation between plasma SOD and GSR levels in MDD patients and the amplitude of low-frequency fluctuation (ALFF) values in key brain regions—thalamus, anterior cingulate gyrus, and superior frontal gyrus. Further analysis indicated positive correlations between plasma SOD and GSR levels and specific ALFF values in MDD patients without suicidal ideation, with these correlations not significant in MDD patients with suicidal ideation. Additionally, seed-based whole-brain functional connectivity analysis demonstrated a negative correlation between plasma GSR levels and connectivity between the thalamus and insula, while plasma SOD levels showed a positive correlation with connectivity between the thalamus and precuneus. These findings contribute to our understanding of MDD's pathophysiology and heterogeneity, highlighting the association between plasma oxidative stress markers and functional abnormalities in diverse brain regions.

Prevalence and risk factors for abnormal glucose metabolism in first-episode and drug-naïve major depressive disorder outpatients with comorbid anxiety: A cross-sectional study from a large sample of the Chinese Han population

BackgroundBoth abnormal glucose metabolism and anxiety have been reported to be common in major depressive disorder (MDD). However, few studies have explored glucose disturbances in first-episode and drug-naive (FEDN) MDD patients with anxiety. The purpose of this study was to examine the prevalence and risk factors of glucose disturbance in FEND MDD patients comorbid with anxiety. Methods1718 FEDN MDD patients were included in this study. The positive subscale of the Positive and Negative Syndrome Scale (PANSS), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD) were used to measure psychotic, anxiety and depressive symptoms respectively. Sociodemographic and biochemical indicators were also collected. ResultsThe prevalence of glucose disorders in MDD patients combined with anxiety was 15.7 %, significantly higher than in MDD patients without anxiety symptoms (7.1 %). Glucose disturbances were associated with HAMD score, HAMA score, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), anti-thyroglobulin (TGAb), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C), fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), suicide attempts, and psychotic symptoms. Further logistic regression showed that illness duration, TSH, TGAb, and TPOAb levels were correlates of glucose disturbances in MDD patients with anxiety. LimitationsNo causal relationship could be drawn due to the cross-sectional design. ConclusionsOur findings suggest that TSH, TGAb and TPOAb may be promising biomarkers of glucose disturbances in MDD comorbid with anxiety, suggesting the importance of regular assessment of thyroid function parameters for abnormal glucose metabolism prevention.

Prevalence of sexual dysfunction and its association with psychological symptoms in drug-naive major depressive disorder patients in West China.

Sexual dysfunction is commonly observed in individuals with Major Depressive Disorder (MDD), along with various psychological symptoms such as anxiety, somatic complaints, interpersonal sensitivity, and obsessive-compulsive tendencies. However, there is a research gap in understanding the impact of these psychological symptoms on sexual functioning in MDD. Furthermore, there is limited data on the incidence of sexual dysfunction among drug-naive MDD patients in West China. This study aims to determine the prevalence of sexual dysfunction in this patient population and explore its association with other psychological indicators. We conducted a retrospective analysis of patient data from October 2020 to September 2022 using propensity score matching. A focused group of 165 males and 490 females was selected from a total of 1941 MDD patients. This allowed for a comparative analysis of demographic data, as well as scores from the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Symptom Checklist-90 (SCL-90), the Arizona Sexual Experience Scale (ASEX). Our findings reveal that 46.2% of drug-naive MDD patients experienced sexual dysfunction. Notably, there was a higher prevalence of sexual dysfunction among female patients (50.3%) compared to males (37.5%). MDD patients without sexual dysfunction consistently exhibited higher SDS scores than those with sexual dysfunction (p < 0.01), There were no statistically significant differences between male and female MDD patients with or without concomitant sexual dysfunction in terms of Somatic complaints, Obsessive-compulsive, Interpersonal sensitivity, Anxiety, Phobic anxiety, Paranoid ideation, Psychoticism and Diet/sleep difficulties (p > 0.05). In addition, male MDD patients with sexual dysfunction showed a emerging trend towards elevated Hostility scores on the SCL-90 (p = 0.058), male MDD patients with sexual dysfunction showed an increasing trend in hostility scores on the SCL-90, whereas female MDD patients with sexual dysfunction did not show such a trend. The study highlights a significant gender difference in the prevalence of sexual dysfunction among MDD patients, with females being more susceptible than males. There is a positive correlation between the severity of depression and sexual dysfunction in both genders. Interestingly, male MDD patients demonstrated a potential protective effect of hostility against sexual dysfunction, which was not observed in female patients.

Prevalence and clinical profile of comorbid anxiety in young adult patients with first-episode and drug-naive major depressive disorder.

Patients with major depressive disorder (MDD) frequently have coexisting anxiety disorders. However, few studies have focused on the prevalence and risk factors of comorbid anxiety symptoms in young adult first-episode and drug-naive (FEDN) MDD patients. We recruited 520 FEDN MDD patients and collected their demographic and clinical data. The Hamilton Depression Rating Scale (HAMD), the Hamilton Anxiety Rating Scale (HAMA) and the positive scale of the Positive and Negative Syndrome Scale (PANSS) were used to measure depressive symptoms, anxiety symptoms and psychotic symptoms, respectively. Anxiety symptoms were found in 79.6% of young adult patients. Besides, anxiety group patients had a higher prevalence of psychotic symptoms than the non-anxiety group. Anxiety symptoms were substantially related to suicide attempts in young adult patients. Logistic analysis shows that suicide attempts and total HAMD scores were significantly associated with anxiety symptoms. The findings show that anxiety symptoms are common in Chinese young adult MDD patients. The anxiety group was more likely to have psychotic symptoms, suicide attempts, and more severe depressive symptoms than the non-anxiety group. Suicide attempts were associated with anxiety symptoms in young adult MDD patients, suggesting the importance of reducing anxiety symptoms in this population to prevent suicides.

Uncovering the Neural Correlates of Anhedonia Subtypes in Major Depressive Disorder: Implications for Intervention Strategies.

Major depressive disorder (MDD) represents a serious public health concern, negatively affecting individuals' quality of life and making a substantial contribution to the global burden of disease. Anhedonia is a core symptom of MDD and is associated with poor treatment outcomes. Variability in anhedonia components within MDD has been observed, suggesting heterogeneity in psychopathology across subgroups. However, little is known about anhedonia subgroups in MDD and their underlying neural correlates across subgroups. To address this question, we employed a hierarchical cluster analysis based on Temporal Experience of Pleasure Scale subscales in 60 first-episode, drug-naive MDD patients and 32 healthy controls. Then we conducted a connectome-wide association study and whole-brain voxel-wise functional analyses for identified subgroups. There were three main findings: (1) three subgroups with different anhedonia profiles were identified using a data mining approach; (2) several parts of the reward network (especially pallidum and dorsal striatum) were associated with anticipatory and consummatory pleasure; (3) different patterns of within- and between-network connectivity contributed to the disparities of anhedonia profiles across three MDD subgroups. Here, we show that anhedonia in MDD is not uniform and can be categorized into distinct subgroups, and our research contributes to the understanding of neural underpinnings, offering potential treatment directions. This work emphasizes the need for tailored approaches in the complex landscape of MDD. The identification of homogeneous, stable, and neurobiologically valid MDD subtypes could significantly enhance our comprehension and management of this multifaceted condition.

Gender differences in the association between anxiety symptoms and thyroid hormones in young patients with first-episode and drug naïve major depressive disorder.

Gender differences are prevalent in major depressive disorder (MDD), but the gender differences in the relationship between comorbid anxiety and thyroid hormones in young first-episode and drug-naive (FEND) MDD patients are unknown. A total of 1,289 young outpatients with FEDN MDD were recruited. Demographic and clinical data were collected for each patient. The patient's blood glucose, blood pressure, thyroid hormone, and thyroid antibody levels were measured. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) were used to assess patients' depression, anxiety, and positive symptoms, respectively. The prevalence of comorbid anxiety disorders was 80.4 and 79.4% in male and female MDD patients, respectively. Patients with anxiety had higher HAMD and PANSS scores, higher serum thyroid stimulating hormone (TSH), anti-thyroglobulin antibody (A-TG), and thyroid peroxidase antibody (A-TPO) levels, higher blood glucose and blood pressure levels, and more patients with psychotic symptoms and suicide attempts. Male patients were younger and had a younger age of onset. Logistic regression analysis showed that HAMD score and comorbid suicide attempts were significant predictors of anxiety symptoms in both males and females, whereas A-TG predicted anxiety symptoms in female patients only. Limitations: No causal relationship could be drawn due to the cross-sectional design. This study showed gender differences in factors associated with anxiety symptoms in patients with MDD. Some factors were associated with anxiety symptoms in both male and female patients, while A-TG was only associated with anxiety symptoms in female patients.

Changes of cortical thickness in the first episode, drug-naive depression patients with and without melancholic features

Melancholic depression (MD) is a more severe type of major depressive disorder (MDD) with a core feature of anhedonia. However, its pathophysiology remains unclear. The current study aims to investigate whether there is a significant difference in cortical thickness (CT) that can be used to differentiate MD patients from non-melancholic depression (NMD) patients. We recruited 137 first-episode drug-naive MDD patients and 75 healthy controls (HCs) for structural magnetic resonance imaging, analyzed using the Surface-based morphometry approach. Meanwhile, the MDD patients were divided into the MD and NMD subgroups according to their scores on the Montgomery-Asberg Depression Rating Scale and Hamilton Depression Rating Scale. No significant CT differences among the three groups were found. We also did not find significant CT changes between the NMD and the HCs groups or between the MD and NMD groups. However, the CT of the left postcentral gyrus and right precuneus among MD patients were larger than HCs. Moreover, the CT of the left postcentral gyrus and right precuneus were not correlated with the severity of the disease and illness duration. The findings suggest that the CT alterations of the left postcentral gyrus and the right precuneus are distinct pathological mechanisms for MD.

Depression severity partially mediates the association between thyroid function and psychotic symptoms in first-episode, drug-naive major depressive disorder patients with comorbid anxiety at different ages of onset

BackgroundAnxiety and psychotic symptoms are common in patients with major depressive disorder (MDD), with a strong association with thyroid function. Age of onset contributes to the heterogeneity of MDD patients. This study aimed to assess the prevalence of psychotic symptoms in MDD patients with comorbid anxiety and to explore the relationship between thyroid function and psychotic symptoms by ages of onset. MethodsA total of 894 first-episode, drug-naïve Chinese Han MDD patients with comorbid anxiety were recruited. Thyroid function and psychometric measures including Hamilton Anxiety Scale, Hamilton Depression Scale, and Positive and Negative Syndrome Scale were evaluated. Patients were divided into early adulthood onset (EAO, < 45 years old) and mid-adulthood onset (MAO, ≥ 45 years old) groups. ResultsThe MAO subgroup had a higher prevalence of psychotic symptoms compared to EAO subgroup. TSH and TPOAb levels were positively correlated with psychotic symptoms severity, with a more pronounced effect in MAO subgroup. Furthermore, MDD severity partially mediated the effects of TPOAb and TSH levels on psychotic symptoms in both subgroups. LimitationsA causal relationship could not be demonstrated with this cross-sectional study, and the results should be limited to first-episode, drug-naïve MDD patients without considering more potential confounders. Moreover, the male-to-female ratio imbalance is present. ConclusionsOur results indicated that age of onset moderated the association between thyroid function and psychotic symptom, and depression severity partially mediated the effects of thyroid function on psychotic symptoms, suggesting thyroid function may serve as a biomarker of psychotic symptoms in MDD patients with anxiety.

Thyroid dysfunction in young, first-episode and drug-naïve patients with major depressive disorder: prevalence and associated clinical factors.

The incidence of thyroid dysfunction (TD) and major depressive disorder (MDD) is increasing year by year in the general population. However, the prevalence and correlates of TD in first-episode drug-naive (FEDN) MDD patients have not been explored. This study sought to fill this gap and examine the association between TD and MDD. We recruited 1,289 FEDN MDD patients aged 18 ~ 45 years. A total of 1,289 FEDN MDD outpatients were recruited. Demographical and suicide data were collected for each patient, and lipid profiles, thyroid function, and fasting blood glucose (FBG) levels were measured. The Hamilton Depression Scale 17 (HAMD-17) was assessed for depression. The prevalence of TD in young FEDN MDD patients was 64.86%. Compared with those without TD, patients with TD had longer duration of illness, greater HAMD score, higher BMI, TG, TC, and LDL-C levels, and higher suicide attempt rates, but lower HDL-C and FBG levels. Further logistic regression indicated that duration of illness, HAMD score, TC, HDL-C, BMI, and FBG levels were significantly associated with TD. No causal relationship can be drawn due to the cross-sectional design. TD is common in young FEDN MDD patients. So clinicians should monitor thyroid function in patients with MDD.

LRFN5 and OLFM4 as novel potential biomarkers for major depressive disorder: a pilot study

Evidences have shown that both LRFN5 and OLFM4 can regulate neural development and synaptic function. Recent genome-wide association studies on major depressive disorder (MDD) have implicated LRFN5 and OLFM4, but their expressions and roles in MDD are still completely unclear. Here, we examined serum concentrations of LRFN5 and OLFM4 in 99 drug-naive MDD patients, 90 drug-treatment MDD patients, and 81 healthy controls (HCs) using ELISA methods. The results showed that both LRFN5 and OLFM4 levels were considerably higher in MDD patients compared to HCs, and were significantly lower in drug-treatment MDD patients than in drug-naive MDD patients. However, there were no significant differences between MDD patients who received a single antidepressant and a combination of antidepressants. Pearson correlation analysis showed that they were associated with the clinical data, including Hamilton Depression Scale score, age, duration of illness, fasting blood glucose, serum lipids, and hepatic, renal, or thyroid function. Moreover, these two molecules both yielded fairly excellent diagnostic performance in diagnosing MDD. In addition, a combination of LRFN5 and OLFM4 demonstrated a better diagnostic effectiveness, with an area under curve of 0.974 in the training set and 0.975 in the testing set. Taken together, our data suggest that LRFN5 and OLFM4 may be implicated in the pathophysiology of MDD and the combination of LRFN5 and OLFM4 may offer a diagnostic biomarker panel for MDD.

Association between thyroid autoimmunity and clinical characteristics in first-episode and drug-naive depressed patients with suicide attempts

BackgroundPrevious reports had linked depression to thyroid function. However, the relationship between thyroid function and clinical characteristics in major depressive disorder (MDD) patients with suicidal attempts (SA) is still unclear. AimsThis study aims to reveal the association between thyroid autoimmunity and clinical characteristics in depressed patients with SA. MethodsWe divided 1718 first-episode and drug-naive MDD patients into groups with suicide attempt (MDD-SA) and without suicide attempt (MDD-NSA). Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the positive subscale of the Positive and Negative Syndrome Scale (PANSS) were assessed; thyroid function and autoantibodies were detected. ResultsThe total scores of HAMD, HAMA and psychotic positive symptoms were significantly higher in patients with MDD-SA, accompanied by higher levels of TSH, TG-Ab and TPO-Ab, than in patients with MDD-NSA, without gender differences. Total scores of positive symptoms (TSPS) in MDD-SA patients with increased TSH or TG-Ab was significantly higher than in MDD-NSA patients and in MDD-SA patients with normal TSH and TG-Ab. The proportion of elevated-TSPS in MDD-SA patients was >4 times that in MDD-NSA patients. The proportion of MDD-SA patients with elevated-TSPS was >3 times that with not-elevated TSPS patients. ConclusionsThyroid autoimmune abnormalities and psychotic positive symptoms may be the clinical features of MDD-SA patients. Psychiatrists should be more alert to the possibility of suicidal behaviors when they first encounter such a patient.

Co-expression network of mRNA and DNA methylation in first-episode and drug-naive adolescents with major depressive disorder.

We explored the DNA methylation and messenger RNA (mRNA) co-expression network and hub genes in first-episode, drug-naive adolescents with major depressive disorder (MDD). To preliminarily explore whether adolescent MDD has unique mechanisms compared with adult MDD. We compared DNA methylation and mRNA profiles of peripheral blood mononuclear cells from four first-episode and drug-naive adolescents with MDD and five healthy adolescent controls (HCs). We performed differential expression analysis, constructed co-expression network, and screened the hub genes. And enrichment analysis was performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We also downloaded DNA methylation and mRNA datasets of adults with MDD (GSE113725/GSE38206) from the GEO database, and performed differential expression and enrichment analysis. Our clinical data showed that 3034 methylation sites and 4190 mRNAs were differentially expressed in first-episode, drug-naive adolescents MDD patients compared with HCs. 19 hub genes were screened out according to the high degree value in the co-expression network. The results from the GEO database showed that compared with adult HCs, there were 290 methylation sites and 127 mRNAs were differentially expressed in adult MDD patients. Compared with adolescent HCs and adult MDD patients, the DNA methylation and mRNA expression patterns of first-episode, drug-naive adolescent MDD patients were different. The co-expression network of DNA methylation and mRNA and the screened hub genes may play an important role in the pathogenesis of MDD in first-episode, drug-naive adolescents. Compared with adult MDD, adolescent MDD is more enriched in metabolism in terms of function and pathways.

Desynchronized white matter function and structure in drug-naive first-episode major depressive disorder patients.

Major depressive disorder (MDD) is a highly prevalent mental disease. Using magnetic resonance imaging (MRI), although numerous studies have revealed the alterations in structure and function of grey matter (GM), few studies focused on the synchronization of white matter (WM) structure and function in MDD. The aim of this study was to investigate whether functional and structural abnormalities of WM play an essential role in the neurobiological mechanisms of MDD. Gradient-echo imaging sequences at 3.0T were used to gather resting state functional MRI (rsfMRI) data, which were performed on 33 drug-naive first-episode MDD patients and 34 healthy controls (HCs). After data preprocessed, amplitude of low frequency fluctuation (ALFF) of WM was calculated. ALFF values in different frequency bands were analyzed, including typical (0.01-0.15 Hz) band, slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) bands. In addition, the fractional anisotropy (FA) values in WM in 23 patients and 26 HCs were examined using tract-based spatial statistics (TBSS) and tractography based on diffusion tensor imaging (DTI). Pearson correlation analysis was applied to analyze the relationships between ALFF values and Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA). Compared with the HCs, MDD patients showed decreased ALFF values in posterior thalamic radiation (PTR) and superior longitudinal fasciculus (SLF) in slow-5 frequency band, no significant differences of ALFF values were found in typical and slow-4 frequency bands. In addition, there were no significant differences in FA values with TBSS analysis as well as the number of fibers in PTR and SLF with tractography analysis between two groups. Further correlation analysis showed that the ALFF value in SLF was negatively correlated with HAMA-2 score (r = -0.548, p FDR = 0.037) in patients. Our results indicated that WM dysfunction may be associated with the pathophysiological mechanism of depression. Our study also suggested that the functional damage of the WM may precedes the structural damage in first-episode MDD patients. Furthermore, for mental disorders, slow-5 frequency band may be a more sensitive functional indicator for early detection of abnormal spontaneous brain activity in WM.

Altered spatio-temporal state patterns for functional dynamics estimation in first-episode drug-naive major depression.

Patients with major depressive disorder (MDD) display affective and cognitive impairments. Although MDD-associated abnormalities of brain function and structure have been explored in depth, the relationships between MDD and spatio-temporal large-scale functional networks have not been evaluated in large-sample datasets. We employed data from International Big-Data Center for Depression Research (IBCDR), and comparable 543 healthy controls (HC) and 314 first-episode drug-naive (FEDN) MDD patients were included. We used a multivariate pattern classification method to learn informative spatio-temporal functional states. Brain states of each participant were extracted for functional dynamic estimation using an independent component analysis. Then, a multi-kernel pattern classification method was developed to identify discriminative spatio-temporal states associated with FEDN MDD. Finally, statistical analysis was applied to intrinsic and clinical brain characteristics. Compared with HC, FEDN MDD patients exhibited altered spatio-temporal functional states of the default mode network (DMN), the salience network, a hub network (centered on the dorsolateral prefrontal cortex), and a relatively complex coupling network (visual, DMN, motor-somatosensory and subcortical networks). Multi-kernel classification models to distinguish patients from HC obtained areas under the receiver operating characteristic curves up to 0.80. Classification scores correlated with Hamilton Depression Rating Scale scores and age at MDD onset. FEDN MDD patients had multiple abnormal spatio-temporal functional states. Classification scores derived from these states were related to symptom severity. The assessment of spatio-temporal states may represent a powerful clinical and research tool to distinguish between neuropsychiatric patients and controls.

Gut Microbiome Composition Linked to Inflammatory Factors and Cognitive Functions in First-Episode, Drug-Naive Major Depressive Disorder Patients.

ObjectiveThe microbiota–gut–brain axis, especially the inflammatory pathway, may play a critical role in the pathogenesis of cognitive impairment in major depressive disorder (MDD). However, studies on the microbiota-inflammatory-cognitive function axis in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and explore the correlation between gut microbiota and inflammatory factors, cognitive function in MDD patients.MethodStudy participants included 66 first-episode, drug naïve MDD patients as well as 43 healthy subjects (HCs). The composition of fecal microbiota was evaluated using16S rRNA sequencing and bioinformatics analysis. The cytokines such as hs-CRP, IL-1β, IL-6, IL-10, and TNF-α in peripheral blood were detected via enzyme linked immunosorbent assay (ELISA); assessment of cognitive functions was performed using the Color Trail Test (CTT), The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (SCWT).ResultsWe found that compared with HCs, MDD patients had cognitive impairments and showed different α-diversity and β-diversity of gut microbiota composition. LDA effect size (LEfSe) analysis found MDD have higher Deinococcaceae and lower Bacteroidaceae, Turicibacteraceae, Clostridiaceae and Barnesiellaceae at family level. Deinococcus and Odoribacter was higher in the MDD group, however, Bacteroides, Alistipes, Turicibacter, Clostridium, Roseburia, and Enterobacter were lower at genus level. Furthermore, In MDD patients, the Bacteroidaceae and Bacteroides were both positively correlated with hsCRP, CCT1, CCT2. Alistipes was positively correlated with IL-6, Word time, Color time, Word-Color time, Color-Word time and negatively correlated with Delayed Memory, Total score and Standardized score. Turicibacteraceae and Turicibacter were both negatively correlated with IL-1β and IL-6.ConclusionThe present findings confirm that the gut microbiota in MDD patients have altered gut microbes that are closely associated with inflammatory factors and cognitive function in MDD patients.

Oxidative and Nitrosative Stress in Major Depressive Disorder: A Case Control Study.

Introduction: The role of increased oxidative stress and alterations to the nitric oxide (NO) pathway have been implicated in major depressive disorder (MDD). The two pathways interact closely with each other but have not been studied simultaneously in MDD. This study aimed to assess and compare the levels of oxidative and nitrosative stress in the neutrophils (PMNs) of drug-naive MDD patients and their first-degree relatives. Methods: 29 drug-naive MDD patients and 27 healthy first-degree relatives and healthy controls aged 18–45 years were included in this study. An assessment of the levels of reactive oxygen species (ROS), nitrites, neuronal NO synthase (nNOS), and myeloperoxidase in PMNs, and cortisol in serum was carried out. Results: Compared to healthy controls, the generation of free radicals, myeloperoxidase activity, and nNOS mRNA expression in PMNs, and cortisol level in serum were significantly higher in drug-naive depression patients. Indeed, increased levels of myeloperoxidase and serum cortisol were also noted in first-degree relatives. The total nitrite content in the PMNs and plasma however was significantly lower in both patients and first-degree relatives. Interestingly, a positive correlation was established in the ROS levels in the PMNs, plasma and neutrophil nitrite, and the serum cortisol level between MDD patients and their first-degree relatives. Conclusion: The results of this study contribute towards a better understanding of the familial association of depressive disorder, and demonstrate for the first time that neutrophil ROS/RNS, plasma nitrite, and serum cortisol levels are positively correlated between MDD patients and their first-degree relatives. However, further studies in larger, more diverse samples are needed to extend these pathways as potential biomarkers to identify persons at high risk for psychopathology at an early stage.

Dynamic Altered Amplitude of Low-Frequency Fluctuations in Patients With Major Depressive Disorder.

Background: Major depressive disorder (MDD) has demonstrated abnormalities of static intrinsic brain activity measured by amplitude of low-frequency fluctuation (ALFF). Recent studies regarding the resting-state functional magnetic resonance imaging (rs-fMRI) have found the brain activity is inherently dynamic over time. Little is known, however, regarding the temporal dynamics of local neural activity in MDD. Here, we investigated whether temporal dynamic changes in spontaneous neural activity are influenced by MDD.Methods: We recruited 81 first-episode, drug-naive MDD patients and 64 age-, gender-, and education-matched healthy controls who underwent rs-fMRI. A sliding-window approach was then adopted for the estimation of dynamic ALFF (dALFF), which was used to measure time-varying brain activity and then compared between the two groups. The relationship between altered dALFF variability and clinical variables in MDD patients was also analyzed.Results: MDD patients showed increased temporal variability (dALFF) mainly focused on the bilateral thalamus, the bilateral superior frontal gyrus, the right middle frontal gyrus, the bilateral cerebellum posterior lobe, and the vermis. Furthermore, increased dALFF variability values in the right thalamus and right cerebellum posterior lobe were positively correlated with MDD symptom severity.Conclusions: The overall results suggest that altered temporal variability in corticocerebellar–thalamic–cortical circuit (CCTCC), involved in emotional, executive, and cognitive, is associated with drug-naive, first-episode MDD patients. Moreover, our study highlights the vital role of abnormal dynamic brain activity in the cerebellar hemisphere associated with CCTCC in MDD patients. These findings may provide novel insights into the pathophysiological mechanisms of MDD.