First-episode Major Depressive Disorder Patients Research Articles

Altered functional brain activity in first-episode major depressive disorder treated with electro-acupuncture: A resting-state functional magnetic resonance imaging study

BackgroundPrevious studies have found electroacupuncture could improve the clinical symptoms of first-episode major depressive disorder (MDD), but the exact neural mechanism of action needs to be further elucidated. MethodsTwenty-eight first-episode MDD patients were randomly divided into 14 electro-acupuncture stimulation (EAS) groups and 14 sham-acupuncture stimulation (SAS) groups, and clinical symptoms were assessed and functional magnetic resonance imaging (fMRI) scans were done in both groups. Amplitude of low-frequency fluctuations (ALFF) was used to observe the changes between the pre-treatment and post-treatment in the two groups, and the altered brain areas were selected as region of interest (ROI) to observe the FC changes. Meanwhile, the correlation between the altered clinical symptoms and the altered ALFF and FC of brain regions in the two groups was analyzed. ResultsThe EAS significantly decreased the HAMD-24 and HAMA-14 scores of MDD than SAS group. The imaging results revealed that both groups were able to increase the ALFF of the left middle temporal gyrus and the left cerebellar posterior lobe. When using the left middle temporal gyrus and the left posterior cerebellar lobe as ROIs, EAS group increased the FC between the left middle temporal gyrus with the left superior frontal gyrus, the left middle frontal gyrus, and the left hippocampus, and decreased the FC between the left posterior cerebellar lobe and the left calcarine gyrus, while SAS group only increased the FC between the left middle temporal gyrus with the left superior frontal gyrus. The alternations in clinical symptoms after EAS treatment were positively correlated with the altered ALFF values in the left middle temporal gyrus and the altered FC values in the left middle temporal gyrus and the left middle frontal gyrus. ConclusionEA demonstrates modulation of functional activity in the default mode network (DMN), sensorimotor network (SMN), cognitive control network (CCN), limbic system, and visual network (VN) for the treatment of the first-episode MDD. Our findings contribute to the neuroimaging evidence for the efficacy of EAS.

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.

Reduced gray matter volume of the hippocampal tail in melancholic depression: evidence from an MRI study

BackgroundMelancholic depression (MD) is one of the most prevalent and severe subtypes of major depressive disorder (MDD). Previous studies have revealed inconsistent results regarding alterations in grey matter volume (GMV) of the hippocampus and amygdala of MD patients, possibly due to overlooking the complexity of their internal structure. The hippocampus and amygdala consist of multiple and functionally distinct subregions, and these subregions may play different roles in MD. This study aims to investigate the volumetric alterations of each subregion of the hippocampus and amygdala in patients with MD and non-melancholic depression (NMD).MethodsA total of 146 drug-naïve, first-episode MDD patients (72 with MD and 74 with NMD) and 81 gender-, age-, and education-matched healthy controls (HCs) were included in the study. All participants underwent magnetic resonance imaging (MRI) scans. The subregional segmentation of hippocampus and amygdala was performed using the FreeSurfer 6.0 software. The multivariate analysis of covariance (MANCOVA) was used to detect GMV differences of the hippocampal and amygdala subregions between three groups. Partial correlation analysis was conducted to explore the relationship between hippocampus or amygdala subfields and clinical characteristics in the MD group. Age, gender, years of education and intracranial volume (ICV) were included as covariates in both MANCOVA and partial correlation analyses.ResultsPatients with MD exhibited a significantly lower GMV of the right hippocampal tail compared to HCs, which was uncorrelated with clinical characteristics of MD. No significant differences were observed among the three groups in overall and subregional GMV of amygdala.ConclusionsOur findings suggest that specific hippocampal subregions in MD patients are more susceptible to volumetric alterations than the entire hippocampus. The reduced right hippocampal tail may underlie the unique neuropathology of MD. Future longitudinal studies are required to better investigate the associations between reduced right hippocampal tail and the onset and progression of MD.

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 Neuroimaging Role of Modified Electroconvulsive Therapy in the Major Depressive Disorder: Effectiveness in First-Episode Antipsychotic-Naive Major Depressive Disorder Patients

Objectives. It is a high risk for adolescents with first-episode major depressive disorder (MDD) to commit suicide. However, few studies reported the effect of modified electroconvulsive therapy (MECT) in first-episode antipsychotic-naive MDD adolescents. Methods. The study explores the alternations of regional homogeneity of modified electroconvulsive therapy to treat the first-episode antipsychotic-naive major depressive disorder. 72 first-episode MDD patients were recruited from Tianyou Hospital Affiliated to Wuhan University of Science and Technology from October 2017 to May 2020, and 65 of 72 completed the trial. Results. Before MECT treatment, ReHo values of the bilateral cerebellum and left cuneus were higher, and ReHo value of left postcentral and supramarginal gyrus was lower in MDD patients compared to healthy subjects (HS). After treatment, the MDD patients have higher ReHo values of the right insula and postcentral gyrus, while left fusiform gyrus were lower than the pretreatment. Compared to the HS, the ReHo values of left lingual gyrus, right calcarine cortex, and right mid occipital thalamus were higher in the posttreatment. In the posttreatment, left calcarine cortex and right cerebrum were lower than in healthy subjects. Conclusions. The study confirmed that MECT improves psychotic symptoms in patients with first-episode antipsychotic-naive MDD. These results further contributed to a more tailored treatment approach to MDD from the pathophysiological and neuroimaging views.

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 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.

Abnormal voxel-mirrored homotopic connectivity in first-episode major depressive disorder using fMRI: a machine learning approach.

To explore the interhemispheric information synergy ability of the brain in major depressive disorder (MDD) patients by applying the voxel-mirrored homotopic connectivity (VMHC) method and further explore the potential clinical diagnostic value of VMHC metric by a machine learning approach. 52 healthy controls and 48 first-episode MDD patients were recruited in the study. We performed neuropsychological tests and resting-state fMRI scanning on all subjects. The VMHC values of the symmetrical interhemispheric voxels in the whole brain were calculated. The VMHC alterations were compared between two groups, and the relationship between VMHC values and clinical variables was analyzed. Then, abnormal brain regions were selected as features to conduct the classification model by using the support vector machine (SVM) approach. Compared to the healthy controls, MDD patients exhibited decreased VMHC values in the bilateral middle frontal gyrus, fusiform gyrus, medial superior frontal gyrus and precentral gyrus. Furthermore, the VMHC value of the bilateral fusiform gyrus was positively correlated with the total Hamilton Depression Scale (HAMD). Moreover, SVM analysis displayed that a combination of all clusters demonstrated the highest area under the curve (AUC) of 0.87 with accuracy, sensitivity, and specificity values of 86.17%, 76.74%, and 94.12%, respectively. MDD patients had reduced functional connectivity in the bilateral middle frontal gyrus, fusiform gyrus, medial superior frontal gyrus and precentral gyrus, which may be related to depressive symptoms. The abnormality in these brain regions could represent potential imaging markers to distinguish MDD patients from healthy controls.

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.

Correlation of event-related potentials N170 with dysfunctional attitudes in patients with major depressive disorder

BackgroundCognitive impairment frequently accompanies first-episode major depressive disorder (MDD) in patients. Early detection and intervention for cognitive impairment can enhance the quality of life for individuals with depressive disorders. Impaired emotion recognition may serve as an initial manifestation of cognitive impairment in these patients. This study examines the characteristics of event-related potentials N170 and dysfunctional attitudinal questionnaire total scores, as well as each factor and their correlation, revealing characteristic electroencephalogram (EEG) changes associated with cognitive impairment in first-episode MDD patients. MethodA total of 88 patients experiencing first-episode MDD and 29 healthy volunteers from the same period participated in the study. They underwent event-related potential N170 measures to assess mood recognition function, the 17-item Hamilton depression scale (HAMD-17) to evaluate the severity of depressive disorder, and the Dysfunctional Attitudes Scales(DAS) to appraise cognitive function. ResultThe dysfunctional attitude questionnaire's total score and each factor score were higher in the MDD group compared to the healthy control (HC) group. The MDD group exhibited lower amplitudes than the HC group at CZ, PZ, POZ, P7, PO7, P8, and PO8 electrode points. A correlation was identified between the P7 and PO7 electrode points of the event-related potential N170 and cognitive function. LimitationThis study solely considered neutral face emotional stimuli and did not account for depressive disorder subtypes. ConclusionDifferences were observed between the MDD and HC groups in cognitive function and N170 amplitude in the central brain region (CZ, PZ, POZ), left posterior temporal region (P7), left occipitotemporal region (PO7), right posterior temporal region (P8), and right occipitotemporal region (PO8). Additionally, a correlation was found between N170 latency in the left posterior temporal region of the brain (P7) and the left occipitotemporal region (PO7) with cognitive function.

Normative modeling analysis reveals corpus callosum volume changes in early and mid-to-late first episode major depression

BackgroundIt has been widely accepted that major depressive disorder (MDD) impacts brain structures including the Corpus Callosum (CC). However, this assumption is based on scarce literature data involving small sample sizes. Furthermore, it is still unclear whether such CC volume changes may already be present at a first depressive episode. MethodsTo further investigate this question, we compared 369 first-episode MDD patients (mean age = 35 years (sd = 12), 249 females; 283 early onset, 86 mid-to-late onset) from the open-source REST meta-MDD database closely matched for age and gender to 490 never-depressed individuals (mean age = 37 years (sd = 14); 309 females) using Z-scores obtained from normative neuroanatomical modeling to assess individual variability in CC (sub)volumes. ResultsRelative to the norms established by the healthy controls, first-episode MDD patients displayed CC volume (z-score) reductions in the entire CC (including the body), as did mid-to-late-onset first-episode MDD patients (age ≥ 45 y). In early-onset first-episode MDD patients (age ≤ 44 y), depression severity symptoms were related to volume increases in the entire CC, as well as the body and splenium. LimitationsNo data on depressive episode duration. Relatively small sample size for mid-to-late first-episode MDD patients. ConclusionsOur data revealed CC (sub)volume differences in early versus mid-to-late onset first episode MDD. Especially at early onset, depression severity may result in neural white matter activity as potential reaction to stress influences. Our results underline the importance of prompt clinical interventions at early onset MDD.

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.

Abnormal dynamic functional connectivity of thalamic subregions in patients with first-episode, drug-naïve major depressive disorder.

Recent studies have shown that major depressive disorder (MDD) is associated with altered intrinsic functional connectivity (FC) of the thalamus; however, investigations of these alterations at a finer time scale and the level of thalamic subregions are still lacking. We collected resting-state functional MRI data from 100 treatment-naïve, first-episode MDD patients and 99 age-, gender- and education-matched healthy controls (HCs). Seed-based whole-brain sliding window-based dFC analyses were performed for 16 thalamic subregions. Between-group differences in the mean and variance of dFC were determined using threshold-free cluster enhancement algorithm. For significant alterations, there relationships with clinical and neuropsychological variables were further examined via bivariate and multivariate correlation analyses. Of all thalamic subregions, only the left sensory thalamus (Stha) showed altered variance of dFC in the patients characterized by increases with the left inferior parietal lobule, left superior frontal gyrus, left inferior temporal gyrus, and left precuneus, and decreases with multiple frontal, temporal, parietal, and subcortical regions. These alterations accounted for, to a great extent, clinical, and neuropsychological characteristics of the patients as revealed by the multivariate correlation analysis. In addition, the bivariate correlation analysis revealed a positive correlation between the variance of dFC between the left Stha and right inferior temporal gurus/fusiform and childhood trauma questionnaires scores (r = 0.562, P < 0.001). These findings suggest that the left Stha is the most vulnerable thalamic subregion to MDD, whose dFC alterations may serve as potential biomarkers for the diagnosis of the disease.

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.

Decreased dorsal attention network homogeneity as a potential neuroimaging biomarker for major depressive disorder

BackgroundGaining insight into abnormal functional brain network homogeneity (NH) has the potential to aid efforts to target or otherwise study major depressive disorder (MDD). The NH of the dorsal attention network (DAN) in first-episode treatment-naive MDD patients, however, has yet to be studied. As such, the present study was developed to explore the NH of the DAN in order to determine the ability of this parameter to differentiate between MDD patients and healthy control (HC) individuals. MethodsThis study included 73 patients with first-episode treatment-naive MDD and 73 age-, gender-, and educational level-matched healthy controls. All participants completed the attentional network test (ANT), Hamilton Rating Scale for Depression (HRSD), and resting-state functional magnetic resonance imaging (rs-fMRI) analyses. A group independent component analysis (ICA) was used to identify the DAN and to compute the NH of the DAN in patients with MDD. Spearman's rank correlation analyses were used to explore relationships between significant NH abnormalities in MDD patients, clinical parameters, and executive control reaction time. ResultsRelative to HCs, patients exhibited reduced NH in the left supramarginal gyrus (SMG). Support vector machine (SVM) analyses and receiver operating characteristic curves indicated that the NH of the left SMG could be used to differentiate between HCs and MDD patients with respective accuracy, specificity, sensitivity, and AUC values of 92.47 %, 91.78 %, 93.15 %, and 65.39 %. A significant positive correlation was observed between the left SMG NH values and HRSD scores among MDD patients. ConclusionsThese results suggest that NH changes in the DAN may offer value as a neuroimaging biomarker capable of differentiating between MDD patients and healthy individuals.

Volumetric assessment of individual thalamic nuclei in patients with drug-naïve, first-episode major depressive disorder.

Despite the previous inconsistent findings of structural and functional abnormalities of the thalamus in patients with major depressive disorder (MDD), the disruption of the thalamic nuclei in the pathophysiology of this disorder has not yet been adequately studied. Therefore, we investigated the volumetric changes of thalamic subregions and their nuclei in drug-naïve, first-episode MDD patients. We also investigated the association between HAM-D scores, a clinical scale frequently used to evaluate the severity of depression and thalamic nuclei volumes in MDD patients. This study included 76 drug-naïve MDD patients and an equal number of healthy subjects. Magnetic resonance imaging (MRI) data were obtained using a 3T MR system and thalamic nuclei volumes were evaluated using FreeSurfer ver.7.11. The volumetric differences were compared by one-way analysis of covariance (ANCOVA) and to ensure that effects were not accounted for by other factors, age, sex, and ETICV variables were included as covariates. We observed significant volume reductions of the left whole thalamus (p < 0.003) and several thalamic nuclei mostly on the left side in the MDD group compared with healthy controls (HCs). Furthermore, we have revealed weak negative correlations between several thalamic nuclei volumes and HAM-D total and subscale scores. This is the first research study to investigate alterations of the various thalamic nuclei volumes in MDD patients compared with HCs. Moreover, we first analyzed the association between individual thalamic nuclei volumes and HAM-D subscale scores. Though our study may be restricted at certain levels, especially by the demographic difference between the two groups, they possibly contribute at a preliminary level to understanding the thalamic structural changes at its subregions in patients with drug-naïve, first-episode MDD.

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.

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state fMRI study.

Seed-based analysis find that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). The voxel-based neuro-psychological mechanism of taVNS on patients with first-episode MDD is poorly understood. Twenty-two first-episode MDD patients accepted 8-week taVNS treatment. Resting-state fMRI were scanned before and after the treatment. Voxel-based analyses were performed to characterize the spontaneous brain activity. Health controls (n = 23) were recruited to minimize the test-retest effects. The analysis of covariance (ANCOVA) was performed to determine the treatment-related changes. Then the correlations between the changes of the brain activity and the Hamilton Depression Rating Scale (HAMD) / Hamilton Anxiety Scale remission rate were estimated. Significant group-by-time interactions on voxel-based analyses were observed in inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited the higher brain activity in the VSi, while upregulated the precuneus. The functional connectivity (FC) between VSi and precuneus decreased. Positive correlations were found between the HAMD remission rate and the alterant brain activity in the VSi. TaVNS reduced the functional connectivity between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Relationship between lipid profile and suicide attempts in first-episode major depressive disorder patients

Abstract Introduction: Cholesterol is considered a core component of the central nervous system, essential for cell membrane stability and the correct functioning of neurotransmitters. Cholesterol plays a vital role in the brain’s second messenger system related to the mechanism of action of antidepressant drugs and mood stabilizers. It may be involved in the etiology and pathogenesis of mood disorders. Aim: This study aims to explicate facts and views about the role of cholesterol levels in depressive disorder and suicidality. Materials and Methods: This was a cross-sectional comparative study where the patients were divided into two groups, i.e., subjects with first-episode major depressive disorder (MDD) with a recent suicide attempt and without suicide attempt. A detailed psychiatric interview, their sociodemographic characteristics, and clinical details were noted on a structured pro forma. MDD diagnosis in the patients was made using the Diagnostic and Statistical Manual of Mental Disorders V. Hamilton Depression Rating Scale was used on subjects to determine the patient’s level of depression. After the overnight fast, blood samples are collected between 6 am and 7 am. Total cholesterol (TC), triglyceride, high-density lipid levels, and low-density lipid levels were measured on the Cobas c311 machine. Results: In the current study, a positive correlation was noted in TC (r = 0.488) and low-density lipid (LDL) levels (r = 0.549) in subjects with depression and suicide attempts. Conclusion: The present study results add to the other studies that support an association between serum cholesterol with depression and suicide. Understanding the significance of lower cholesterol levels is central for future treatments of depressive disorder.

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

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