Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment

Objective

This study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method.

Methods

Twenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later.

Results

There was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups.

Conclusion

These results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA.     

S100B蛋白与心境障碍的相关性研究进展

心境障碍是由各种原因引起的以显著而持久的心境或情感改变为主要特征的一组疾病,包括重性抑郁障碍和双相障碍两个主要疾病亚型.随着现代生活节奏的加快,其患病率正逐年上升.世界卫生组织(WHO)有关全球疾病总负担的统计显示,1990年重性抑郁障碍和双相障碍分别排在第5位和第18位,预计到2020年,重性抑郁障碍的疾病负担将上升至第二位.目前心境障碍的病因及发病机制仍不明,近来国外学者开始提出心境障碍就是胶质细胞的功能障碍,而S100B蛋白作为一种胶质细胞源性的蛋白质,可能与心境障碍有着密切的联系[1].本文总结国内外相关研究,对S100B蛋白与心境障碍的关系作如下综述.     

Abnormal Dynamic Functional Connectivity of the Left Rostral Hippocampus in Predicting Antidepressant Efficacy in Major Depressive Disorder

Objective Some pharmacological treatments are ineffective in parts of patients with major depressive disorder (MDD), hence this needs prediction of effective treatment responses. The study aims to examine the relationship between dynamic functional connectivity (dFC) of the hippocampal subregion and antidepressant improvement of MDD patients and to estimate the capability of dFC to predict antidepressant efficacy. Methods The data were from 70 MDD patients and 43 healthy controls (HC); the dFC of hippocampal subregions was estimated by sliding-window approach based on resting-state functional magnetic resonance imaging (R-fMRI). After 3 months treatment, 36 patients underwent second R-fMRI scan and were then divided into the response group and non-response group according to clinical responses. Results The result manifested that MDD patients exhibited lower mean dFC of the left rostral hippocampus (rHipp.l) compared with HC. After 3 months therapy, the response group showed lower dFC of rHipp.l compared with the non-response group. The dFC of rHipp.l was also negatively correlated with the reduction rate of Hamilton Depression Rating Scale. Conclusion These findings highlighted the importance of rHipp in MDD from the dFC perspective. Detection and estimation of these changes might demonstrate helpful for comprehending the pathophysiological mechanism and for assessment of treatment reaction of MDD.     

Serum S100B Protein Levels in Patients with Panic Disorder: Effect of Treatment with Selective Serotonine Reuptake Inhibitors

ObjectiveAltered serum S100B protein levels have been shown in several psychiatric disorders. Our aim was to investigate whether plasma S100B is different in patients with panic disorder (PD) when compared with controls. Our second aim was to investigate whether treatment with SSRIs have an effect on S100B levels in patients with PD.MethodsThe sample included 32 patients diagnosed with PD (21 women, 11 men) per DSM-IV criteria and 21 healthy controls (11 women, 10 men). S100B levels were measured with BioVendor Human S100B ELISA (Enzyme Linked Immunosorbent Assay) kit.Results14 patients were not on drug treatment (43.8%) while 18 patients were taking various SSRIs. Median S100B value was 151.7 pg/mL (minimum-maximum: 120.4-164.7 pg/mL) in the control group, 147.4 pg/mL (minimum-maximum: 138.8-154.1 pg/mL) in the drug free group and 153.0 pg/mL (minimum-maximum: 137.9-164.7 pg/mL) in the treatment group. Kruskal-Wallis analysis showed a significant diffrerence among the three groups (z=9.9, df=2, p=0.007). Follow up Mann-Whitney-U tests indicated that while the control and the patients with treatment were not significantly different (z=-0.05, p=0.96), there were significant differences between the control group and untreated patients (z=-2.6, p=0.009) and treated and untreated patients (z=-3.0, p=0.003).ConclusionOur results suggested that, serum S100B protein level might be decreased in untreated PD patients and that patients who were treated with SSRIs had similar S100B level to healthy controls.     

Plasma Levels of IL-23 and IL-17 before and after Antidepressant Treatment in Patients with Major Depressive Disorder

Objective

Cytokines are believed to have a role in the pathophysiology of major depression. The alteration in levels of pro-inflammatory cytokines [interleukin 1β (IL-1β), IL-2, IL-6, IL-12, interferon γ, and tumor necrosis factor α] in major depression supports the cytokine hypothesis of this illness. IL-23 and IL-17 are also pro-inflammatory cytokines, but few studies have focused on their role in major depression. This study investigated the potential role of the IL-23 and IL-17 axis in major depression.

Methods

Plasma IL-23 and IL-17 levels were measured in 26 major depressive disorder (MDD) patients before and after 6-week treatment with antidepressants; these levels were measured in 28 age- and sex-matched normal controls. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS). IL-23 and IL-17 plasma levels were estimated using quantitative enzyme-linked immunosorbent assay.

Results

Pre-treatment plasma levels of IL-23 and IL-17 in MDD patients were not significantly different from those of normal controls. In MDD patients, IL-23 and IL-17 levels after 6 weeks of antidepressant treatment were not different from the baseline levels. There was no significant correlation between changes in the cytokine levels and changes in the HDRS scores representing the severity of depression.

Conclusion

The present study does not support a potential involvement of IL-23 and IL-17 axis in major depression. Replication and extension using a larger sample are required.     

Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications

Major depressive disorder (MDD), also referred to as depression, is one of the most common psychiatric disorders with a high economic burden. The etiology of depression is still not clear, but it is generally believed that MDD is a multifactorial disease caused by the interaction of social, psychological, and biological aspects. Therefore, there is no exact pathological theory that can independently explain its pathogenesis, involving genetics, neurobiology, and neuroimaging. At present, there are many treatment measures for patients with depression, including drug therapy, psychotherapy, and neuromodulation technology. In recent years, great progress has been made in the development of new antidepressants, some of which have been applied in the clinic. This article mainly reviews the research progress, pathogenesis, and treatment of MDD.     

Proteomic Analysis of Serum from Patients with Major Depressive Disorder to Compare Their Depressive and Remission Statuses

ObjectiveCurrently, there are a few biological markers to aid in the diagnosis and treatment of depression. However, it is not sufficient for diagnosis. We attempted to identify differentially expressed proteins during depressive moods as putative diagnostic biomarkers by using quantitative proteomic analysis of serum.MethodsBlood samples were collected twice from five patients with major depressive disorder (MDD) at depressive status before treatment and at remission status during treatment. Samples were individually analyzed by liquid chromatography-tandem mass spectrometry for protein profiling. Differentially expressed proteins were analyzed by label-free quantification. Enzyme-linked immunosorbent assay (ELISA) results and receiver-operating characteristic (ROC) curves were used to validate the differentially expressed proteins. For validation, 8 patients with MDD including 3 additional patients and 8 matched normal controls were analyzed.ResultsThe quantitative proteomic studies identified 10 proteins that were consistently upregulated or downregulated in 5 MDD patients. ELISA yielded results consistent with the proteomic analysis for 3 proteins. Expression levels were significantly different between normal controls and MDD patients. The 3 proteins were ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 and complement component 1qC, which were upregulated during the depressive status. The depressive status could be distinguished from the euthymic status from the ROC curves for these proteins, and this discrimination was enhanced when all 3 proteins were analyzed together.ConclusionThis is the first proteomic study in MDD patients to compare intra-individual differences dependent on mood. This technique could be a useful approach to identify MDD biomarkers, but requires additional proteomic studies for validation.     

Neural Network Based Response Prediction of rTMS in Major Depressive Disorder Using QEEG Cordance

Objective

The combination of repetitive transcranial magnetic stimulation (rTMS), a non-pharmacological form of therapy for treating major depressive disorder (MDD), and electroencephalogram (EEG) is a valuable tool for investigating the functional connectivity in the brain. This study aims to explore whether pre-treating frontal quantitative EEG (QEEG) cordance is associated with response to rTMS treatment among MDD patients by using an artificial intelligence approach, artificial neural network (ANN).

Methods

The artificial neural network using pre-treatment cordance of frontal QEEG classification was carried out to identify responder or non-responder to rTMS treatment among 55 MDD subjects. The classification performance was evaluated using k-fold cross-validation.

Results

The ANN classification identified responders to rTMS treatment with a sensitivity of 93.33%, and its overall accuracy reached to 89.09%. Area under Receiver Operating Characteristic (ROC) curve (AUC) value for responder detection using 6, 8 and 10 fold cross validation were 0.917, 0.823 and 0.894 respectively.

Conclusion

Potential utility of ANN approach method can be used as a clinical tool in administering rTMS therapy to a targeted group of subjects suffering from MDD. This methodology is more potentially useful to the clinician as prediction is possible using EEG data collected before this treatment process is initiated. It is worth using feature selection algorithms to raise the sensitivity and accuracy values.     

Hypothalamic-Pituitary-End-Organ Axes: Hormone Function in Female Patients with Major Depressive Disorder

Classic hypothalamic-pituitary-end-organ feedback loops – the hypothalamic-pituitary-adrenal axis (HPAA), hypothalamic-pituitary-thyroidal axis (HPTA), and hypothalamic-pituitary-gonadal axis (HPGA) – are associated with the neuroendocrine and immune systems in major depressive disorder (MDD). Female patients with MDD present with evident neuroendocrine and immunological changes. Glucocorticoid, thyroid hormone, and reproductive steroid levels fluctuate with menstrual cycles, which might lead to glucocorticoid receptor resistance, impairment of triiodothyronine conversion, and sex hormone secretion disorders. In this review, we summarize the independent and interactive functions of these three axes in female MDD patients. The similar molecular structure of steroids implies an interrelationship between the hypothalamic-pituitary-end-organ axes and the competitive inhibitory effects at the receptor level, especially when considering the HPAA and HPGA.     

Distinguishing Quantitative Electroencephalogram Findings between Adjustment Disorder and Major Depressive Disorder

Objective

Adjustment disorder (ADJ) is a common diagnosis. However, it is difficult to distinguish ADJ from other major Axis I disorders, such as major depressive disorder (MDD). The aim of this study was to determine the distinguishing neurophysiological characteristics between ADJ and MDD using quantitative analysis of an electroencephalogram (QEEG).

Methods

The study included 30 patients with ADJ and 51 patients with MDD. Resting (eye closed) vigilance controlled EEG recordings were assessed at 19 electrode sites according to the international 10/20 system. QEEG absolute power and coherence were calculated for the delta, theta, alpha and beta bandwidths.

Results

Absolute powers of alpha and high beta bands, particularly at the frontocentral area, differed between MDD and ADJ group (p<0.05). Interhemispheric coherence values for the delta and beta bands were lower in the ADJ group than in the MDD group (p<0.05). Intrahemispheric coherence values for the alpha band were also lower in the ADJ group (p<0.05).

Conclusion

The differences in QEEG power and coherence in our investigation suggest that underlying pathophysiologic mechanisms may be different between ADJ and MDD.     

The Korean Medication Algorithm for Major Depressive Disorder (KMA-MDD): Report of the Korean Society of Depressive and Bipolar Disorders

Objective. There are many differences in biological characteristics, clinical situations, and medical insurance systems with ethnic groups or countries. The Korean Society of Depressive and Bipolar Disorders decided to develop a Korean treatment algorithm for major depressive disorder. Methods. The Korean Medication Algorithm Project for Major Depressive Disorder (KMAP-MDD) was designed with the following principles: (1) to be an ideal algorithm, (2) to be a Korean algorithm, (3) to be a medication algorithm, (4) to be an evidence-based and formal consensus algorithm. After collecting and reviewing many literature citations and reports by evidence-based rule, we constructed a survey questionnaire for formal consensus of Korean experts. By employing panels of experts to review the evidence and survey results thoroughly, we used evidence-based algorithm development as a component of a formal consensus development process. Results. We developed two algorithms for the KMA-MDD: one for major depressive disorder without psychotic feature and the other for major depressive disorder with psychotic features. Clinical guidelines for the implementation of KMA-MDD were also developed. The KMA-MDD provides specific treatment strategies for each stage. Conclusions. The KMA-MDD is the first Korean algorithm for treatment of major depressive disorder. It is based on evidence which supports the efficacy of each treatment, and it has obtained the consensus of Korean experts. We hope that the KMA-MDD will be good practical tool for clinicians who treat major depressive disorder in Korea.     

Antidepressant Effects on Emotional Temperament: Toward a Biobehavioral Research Paradigm for Major Depressive Disorder

Background: Given the limited efficacy of current pharmacotherapy for major depressive disorder (MDD) and the historical decline in antidepressant development, there is increasing clinical urgency to develop more effective treatments. Objectives: To synthesize findings from clinical psychology and affective neuroscience related to the construct of emotional temperament; to examine the effects of antidepressants on the temperament dimensions of positive (PA) and negative affectivity (NA); and to propose a biobehavioral research paradigm for the treatment of MDD. Methods: We begin with an introduction to PA and NA, which emphasizes their construct development, historical context, and relevance to psychopathology. We then review studies of antidepressant effects on PA and NA, and explore two related hypotheses: (1) Cause‐correction: The antidepressant response may fundamentally occur through changes in emotional temperament, with subsequent spread to syndrome or symptom changes; (2) preferential effects: Antidepressants with different mechanisms of action may have preferential effects on PA or NA. Results: Preliminary findings appear to support the cause‐correction hypothesis; there is insufficient clinical evidence to support the preferential effects hypothesis. Conclusions: PA and NA are biologically based temperament dimensions, which modulate emotional, motivational, and behavioral responses to positive and negative incentives. They can be altered by antidepressants, and may independently contribute to depression improvement. In addition, the distinct biobehavioral features of PA and NA suggest that combined pharmacological and cognitive–behavioral treatments targeting these dimensions may have specific, and perhaps, synergistic antidepressant effects.     

Circulating Plasma Micro RNAs in Patients with Major Depressive Disorder Treated with Antidepressants: A Pilot Study

ObjectiveSignificant progress was made in the understanding etiopathogenic factors related to MDD, including through research on the role of micro RNAs (miRs). We investigated plasma miRs as potential markers for MDD in patients treated with antidepressants.MethodsAt the initiation and at the end of twelve weeks of treatment, blood samples were collected and a structured diagnostic interview and a standardized depression rating scale for the presence and severity of major depression were done. The average decrease in HAMD score was 76.89%. Plasma miR expression profiling was performed by real time PCR. The lists of up-regulated (cut-off=2) and down-regulated miRs were imported into the miRWalk2.0 algorithm and used for target predictions. KEGG database pathways analysis was used to retrieve the pathways significantly targeted by at least two of the miRs.ResultsOf the 222 miRs detected in plasma samples of MDD patients, 40 were differentially expressed after treatment. Twenty-three miRs were significantly overexpressed with fold changes between 1.85 and 25.42, and 17 miRs were significantly downregulated with fold changes from 0.28 to 0.68. Pathway analysis revealed a list of 29 pathways for up-regulated miRs, and 20 pathways for down-regulated miRs. Six dysregulated miRs are common to all the top five pathways (Wnt signaling, Cancer, Endocytosis, Axon guidance, MAPK signaling): miR-146a-5p, miR-146b-5p, miR-221-3p, miR-24-3p, miR-26a-5p.ConclusionOverall, our miRWalk analysis of changes in plasma microRNAs after treatment of patients with major depression might open a new avenue for the understanding of Escitalopram mode of action and for its side effects.     

Type-D Personality Can Predict Suicidality in Patients with Major Depressive Disorder

Objective

This study investigated the putative association between type-D personality and suicidality, including the history of suicide attempt and suicidal ideation in patients with major depressive disorder (MDD).

Methods

Eighty-six outpatients aged between 18 and 65 years with MDD were recruited for this study from Ilsan Paik Hospital. The cohort was stratified into two subgroups according to the presence of type-D personality and history of suicide attempt (yes vs. no). Depression severity was evaluated using the Hamilton Depression Rating Scale. The type-D Personality Scale-14 (DS-14), the Beck Hopelessness Scale (BHS), the Barratt Impulsiveness Scale (BIS), the Hamilton Anxiety Scale, and the Beck Scale for Suicidal Ideation (BSS) were also applied.

Results

The total BSS, BHS, and BIS scores were higher for the group with type-D personality than for the group without this personality (p=0.004, 0.01, and 0.003, respectively). In addition, the total scores for the BSS, BHS, and social inhibition (SI; subscale of DS-14) were higher for the group with a history of suicide attempt than for the group without this history (p=0.0000004, 0.003, and 0.033, respectively). There were positive correlations between the total DS-14 score and the total BSS, BHS, and BIS scores (r=0.413 and p=0.000077, r=0.404 and p=0.00012, and r=0.245 and p=0.024, respectively).

Conclusion

Depressed patients with type-D personality are more vulnerable to suicidality than those without type-D personality, even when the MDD severity is identical. In addition, the SI score was higher in patients with a history of suicide attempt than in those without this history.     

Serum S100B and antioxidant enzymes in bipolar patients

Bipolar disorder (BD) is a chronic, severe, and highly disabling psychiatric disorder; peripheral markers have been used to assess biochemical alterations associated with BD and/or possibly involved in its pathophysiology. Beyond neuronal commitment, many groups have proposed the involvement of glial activity in psychiatric disorders. Other biochemical markers, particularly associated with oxidative stress, have been studied in BD. In the present study, we evaluated glial involvement and oxidative stress in patients with BD. Glial activity was assessed by measuring serum S100B content; oxidative stress was assessed using serum thiobarbituric acid reactive substances (TBARS) and activities of antioxidant enzymes in BD patients during different episodes of disease. We found a significant increment of serum S100B during episodes of mania and depression, but not in euthymic patients. Superoxide dismutase (SOD) activity, as well the SOD/glutathione peroxidase plus catalase ratio, was also increased in manic and depressed patients. On the other hand, TBARS levels were increased in BD patients regardless of the phase of the disorder. These findings suggest a potential oxidative damage in BD patients. This peripheral oxidative imbalance indicates that systemic changes are taking place during the active phases of the illness. Such changes appear to relate to astrocyte function, as indicated by serum S100B elevation.     

Relevance of Norepinephrine–Dopamine Interactions in the Treatment of Major Depressive Disorder

Central dopaminergic and noradrenergic systems play essential roles in controlling several forebrain functions. Consequently, perturbations of these neurotransmissions may contribute to the pathophysiology of neuropsychiatric disorders. For many years, there was a focus on the serotonin (5‐HT) system because of the efficacy of selective serotonin reuptake inhibitors (SSRIs), the most prescribed antidepressants in the treatment of major depressive disorder (MDD). Given the interconnectivity within the monoaminergic network, any action on one system may reverberate in the other systems. Analysis of this network and its dysfunctions suggests that drugs with selective or multiple modes of action on dopamine (DA) and norepinephrine (NE) may have robust therapeutic effects. This review focuses on NE‐DA interactions as demonstrated in electrophysiological and neurochemical studies, as well as on the mechanisms of action of agents with either selective or dual actions on DA and NE. Understanding the mode of action of drugs targeting these catecholaminergic neurotransmitters can improve their utilization in monotherapy and in combination with other compounds particularly the SSRIs. The elucidation of such relationships can help design new treatment strategies for MDD, especially treatment‐resistant depression.     

The effects of gender and numbers of depressive episodes on serum S100B levels in patients with major depression

S100B protein is a calcium-binding protein mostly derived from glial cells, which exerts trophic or toxic effects on neural cell depending on its concentration. It has been reported that S100B played an important role as a potential marker in psychiatric disorders. Thus, we will explore the clinical implication of S100B in major depression, especially the effect of gender and numbers of depressive episodes on S100B. The levels of serum S100B were measured with enzyme-linked immunosorbent assay (ELISA) in 54 patients with major depression and 35 age-matched healthy controls. The S100B levels in major depressed patients were significantly higher than those in controls. The serum S100B levels in female patients were significantly higher than those in male patients. Patients with recurrent depressive episodes had significantly higher S100B levels than those in first-episode depression. Serum S100B levels were significantly positive related with the numbers of depressive episode, family history and cognitive disturbance scores. These findings confirmed an increase in serum S100B levels in major depressive patients and presence of a sexual dimorphism. Moreover, numbers of depressive episodes in depression seemed to have an additional increasing effect on S100B levels.