Major Depressive Episode Patients Research Articles

How changes in depression severity and borderline personality disorder intensity are linked – a cohort study of depressed patients with and without borderline personality disorder

BackgroundBorderline personality disorder (BPD) is often complicated by comorbid major depressive episodes (MDEs), which can occur as part of major depressive disorder (MDD) or bipolar disorder (BD). Such comorbidity is related to worse outcomes in both disorders. Subsyndromal features of BPD are also common in depression. However, studies of simultaneous changes in BPD and depression severities are scarce, and their interactions are poorly understood.AimsStudying the associations between changes in BPD and depression symptoms over the course of an MDE.MethodsIn a 6-month naturalistic cohort study of MDE/BPD, MDE/MDD, and MDE/BD patients (N = 95), we measured change in BPD features between baseline and six months with the Borderline Personality Disorder Severity Index (BPDSI), an interviewer-rated instrument quantifying recent temporal frequency of BPD symptoms. We examined changes in BPD severity and their correlation with depression severity and other clinical measures and compared these across patient groups.ResultsThere were significant reductions in BPD severity, both in number of positive BPD criteria (-0.35, sd 1.38, p = 0.01672) and in BPDSI scores (-4.23, SD 6.74, p < 0.001), reflecting mainly a reduction in temporal frequency of symptoms. These were similar in all diagnostic groups. In multivariate regression models, changes in depression severity independently associated with changes in symptoms in the BDSI. This relationship was strongest in MDE/BPD patients but was not found in MDD patients without BPD.ConclusionsIn the six-month follow-up, BPD features in MDE patients alleviated mainly by decreasing temporal symptom frequency and intensity. In BPD patients with comorbid MDE, changes in both conditions are strongly correlated.

Predictors of cognitive behavioral therapy for insomnia (CBT-I) effects in insomnia with major depressive episode

Insomnia plays a critical role in the onset and maintenance of Major Depressive Episode (MDE). Cognitive behavioral therapy for insomnia (CBT-I) can successfully improve the sleep of patients with insomnia and MDE. Nonetheless, the factors influencing CBT-I's effects in MDE remain uncertain. This study aimed to identify predictors of insomnia improvement following CBT-I, as well as predictors of insomnia response, remission in patients with MDE and specific insomnia subtypes. Initially, we compared a 4-session weekly CBT-I treatment to baseline sleep education (SE) in a control group. This confirmed CBT-I's positive effects and the need to explore predictive factors. Notably, treatment-resistant depression (TRD) predicted reduced insomnia severity with CBT-I. Patients exhibiting seasonal fluctuations in depressive symptoms and sleep patterns throughout the year, or having daytime dysfunction, experienced enhanced CBT-I efficacy, especially for early awakenings insomnia. Conversely, shorter sleep duration predicted a less favorable response to CBT-I, less improvement in daytime dysfunction and sleep disturbance worries. Additionally, MDE with suicide attempts predicted a poorer improvement of daytime dysfunction. Further research is essential to comprehensively grasp the mechanisms behind CBT-I's heightened effectiveness in MDE patients with TRD and seasonal fluctuations.

Partial Response to Antidepressant Treatment: The Role of Nutraceutical Compounds.

Depression represents one of the most severe psychiatric disorders, characterized by low mood episodes, as well as loss of interest. Major Depressive Episodes (MDE) treatment relies primarily on monoaminergic prescriptions. However, although the presence of many antidepressant medications, their efficacy is still partial. A promising intervention to improve antidepressant treatment may be the use of adjunctive nutraceuticals. Aim of the present study was to assess the efficacy of a N-Acetyl-cysteine, S-Adenosyl-L-Methionine and Folic acid's combination for the treatment of depressive symptoms in a sample of MDE patients. Fifty outpatients with a MDE diagnosis in the context of different psychiatric disorders such as Major Depression, Bipolar Disorder, Anxiety disorders, and Personality disorders were recruited. The sample was divided into different groups based on the nutraceutical administration: a) concurrently with an AD (starter group); b) add-on to an already prescribed treatment; c) single treatment. A significant reduction of CGI-Severity and Improvement scores from baseline to the end of treatment was found. Moreover, the starter group showed a significantly greater CGI-Improvement score compared to the other groups. Ninety-four percent of patients did not show any side effects. The present study showed promising results for the use of nutraceuticals in the add-on treatment of MDE. Those compounds may be considered a versatile, tolerable, and effective add-on treatment for the reduction of depressive symptoms impact and for improving the functioning of patients affected by MDE.

Serum claudin-5 levels among patients with unipolar and bipolar depression in relation to the pro-inflammatory cytokine tumor necrosis factor-alpha levels

Accumulating evidence indicates that inflammation and neurovascular unit (NVU) dysfunction contribute to depression via disrupted blood–brain barrier (BBB) integrity. Claudin-5, an endothelial tight-junction protein expressed in the NVU and contributing to BBB integrity, has been implicated in psychiatric disorders, including major depressive disorder (MDD) and schizophrenia. In an animal model of depressive-like behavior, the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) was found to affect BBB permeability and claudin-5 expression of NVU endothelial cells. To the best of the authors’ knowledge, this study is the first to assess the relationship between serum claudin-5 and TNF-α levels, during major depressive episodes (MDEs). Serum levels of claudin-5 and TNF-α of 40 patients diagnosed with current MDE [19 with MDD and 21 with bipolar disorder (BD)] and 28 matched healthy controls (HCs) were analyzed. Claudin-5 and TNF-α serum levels in the MDE group were significantly higher than in the HC one. Discrete analysis according to MDE type indicated significantly increased claudin-5 serum levels in BD but not in MDD patients, compared to HCs, even after controlling for confounders. In the MDE group, a significant positive correlation was found between claudin-5 and TNF-α serum levels. In complementary analysis, serum levels of the pro-inflammatory cytokine interleukin-6 were significantly higher among MDE patients compared to HCs, however, no significant correlation was found with claudin-5 levels. In conclusion, as indicated by preclinical studies, our clinical study suggests a possible specific interaction between the NVU/BBB marker claudin-5 and the inflammatory marker TNF-α in the pathogenesis of depression.

Resting-State Functional Connectivity Impairment in Patients with Major Depressive Episode.

This study aims to develop new approaches to characterize brain networks to potentially contribute to a better understanding of mechanisms involved in depression. We recruited 90 subjects: 49 healthy controls (HC) and 41 patients with a major depressive episode (MDE). All subjects underwent clinical evaluation and functional resting-state MRI. The data were processed investigating functional connectivity network measures across the two groups using Brain Connectivity Toolbox. The statistical inferences were developed at a functional network level, using a false discovery rate method. Linear discriminant analysis was used to differentiate between the two groups. Significant differences in functional connectivity (FC) between depressed patients vs. healthy controls was demonstrated, with brain regions including the lingual gyrus, cerebellum, midcingulate cortex and thalamus more prominent in healthy subjects as compared to depression where the orbitofrontal cortex emerged as a key node. Linear discriminant analysis demonstrated that full-connectivity matrices were the most precise in differentiating between depression vs. health subjects. The study provides supportive evidence for impaired functional connectivity networks in MDE patients.

Affective temperament and mood spectrum symptoms in workers suffering from work-related stress disorders

IntroductionAdjustment Disorders (AD) which develop in response to work-related stressors represent a model of psychiatric occupational disease. Major Depressive Episodes (MDE) although often associated to work-related stressors are unlikely recognized by insurance institutes as occupational diseases. Affective temperament and mood spectrum symptoms are possible factors of vulnerability to stress. The aim of this study was to investigate if temperaments and mood spectrum symptoms had a different distribution among workers exposed to occupational stress and suffering from different psychiatric disorders (AD, MDE). Methods156 AD and 97 MDE patients were recruited and evaluated with scales for perceived stress (PSM) and work-related stress (JCQ), for psychopathological symptoms (BDI-II, SAS), for affective temperament (TEMPS-A[P]) and for lifetime mood spectrum symptoms (MOODS-SR). Group comparisons and correlation analyses between variables were performed by parametric or non-parametric statistical tests according to variables distribution. ResultsThe diagnostic groups did not differ for perceived and occupational stress levels. MDE patients reported significantly higher BDI-II score and MOODS-SR scores than AD ones. The hyperthymic temperament was significantly more frequent in AD than in MDE group. The hyperthymic score, differently from other dimensions of temperament and from mood spectrum components, negatively correlated or did not correlate with psychopathological symptoms severity and perceived stress levels. LimitationsPredictive limitation because of cross-sectional design. ConclusionsThe hyperthymic temperament as opposed to lifetime subtreshold mood symptoms appears to be more represented in patients suffering from occupational AD than in MDE ones. Acknowledging vulnerability factors to job stress could support clinicians in occupational diseases prevention and management.

Treatment Patterns During Major Depressive Episodes Among Patients with Major Depressive Disorder: A Retrospective Database Analysis.

BackgroundMajor depressive disorder, a highly prevalent mental health condition, can be challenging to treat.ObjectiveWe aimed to characterize treatment patterns within and across multiple major depressive episodes in patients receiving treatment for major depressive disorder.MethodsAdults with newly diagnosed major depressive disorder and one or more major depressive episodes were identified using the IBM® MarketScan® Commercial database. Eligible patients had 12 months of continuous enrollment before and after diagnosis. Lines of therapy were periods of continuous treatment with one or more antidepressant claims. Antidepressant, atypical antipsychotic, or mood stabilizer regimens as monotherapy or adjunctive therapy were characterized by lines of therapy and major depressive episodes. Descriptive analyses were performed.ResultsA total of 455,082 patients were included in the analysis. The majority of treatment regimens were monotherapy, which decreased with subsequent lines of therapy, while adjunctive treatments increased with subsequent lines of therapy. There were 1860 unique adjunctive regimens identified. Of the 40,315 patients (9%) who received adjunctive therapy, 8024 (20%; 2% of all patients) received atypical antipsychotic-adjunctive regimens. Only 19% of patients treated with atypical antipsychotic-adjunctive therapy discontinued treatment versus 42% of monotherapy-treated patients. On average, patients who received an adjunctive atypical antipsychotic received it as their third line of therapy and approximately 400 days after the initial antidepressant treatment.ConclusionsIn this study, many patients continued monotherapy major depressive disorder regimens and experienced multiple treatment changes. Few patients were treated with adjunctive therapy. These results suggest underutilization of potentially effective treatments, which represents an opportunity to optimize the treatment of patients with major depressive disorder.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-022-00316-4.

Comparison of cognitive impairments with lipid profiles and inflammatory biomarkers in unipolar and bipolar depression

Cognitive impairments is one of important accompanied symptom in Unipolar depressive disorder (UD) and bipolar disorder (BD) that was hard to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. In this study, we could highlight the difference of cognitive ability in UD and BD by testing lipid profiles and inflammatory biomarkers in major depressive episodes (MDE). 207 subjects (96 unipolar and 111 bipolar depressed patients) were included in this study. We applied Montreal Cognitive Assessment (MoCA) to test cognitive ability. The 24-item Hamilton Depression Rating Scale was used for assessment at the beginning of treatment. A series of clinical variables and lipid profiles were collected from clinic record. We detected pro-inflammatory biomarkers Interleukin-1β (IL-1β), Interleukin-6 (IL-6), C-reaction protein (CRP) levels and brain-derived neurotrophic factor (BDNF) by enzyme linked immunosorbent assay. From the results, cognitive impairments were more popular in BD than UD, most obviously in severe cognitive impairments (MoCA score<23). And UD showed better cognitive ability than BD in MoCA, particularly in language domain. Compared lipid profiles like total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB) and lipoprotein α (Lpα), we found that ApoB was higher in BD than UD that maybe a risk factor in cognition. There was no obviously difference in TC, TG, HDL-C, LDL-C, ApoA1, or Lpα. Also, we found CRP level in BD was higher than UD, and showed no significant difference in IL-1β and IL-6 levels. Furthermore, BDNF level which was neurotrophic biomarker for cognition and mood was significantly declined in BD compared with UD. Correlation analysis showed that ApoB and CRP was negative closed associated with MoCA scores. And BDNF level was positive related with cognitive ability in MDE patients. From our results mentioned that quantitative lipid profiles and inflammatory biomarkers analysis might help to objectively identify between these disorders and up our understanding of their pathophysiology. And ApoB, CRP and BDNF could be as potential peripheral candidates in cognitive evaluation to distinguish UD and BD.

The GG genotype of the serotonin 4 receptor genetic polymorphism, rs1345697, is associated with lower remission rates after antidepressant treatment: Findings from the METADAP cohort

BackgroundPharmacological studies have yielded valuable insights into the role of the serotonin 4 receptor (HTR4) in major depressive episodes (MDE) and response to antidepressant drugs (AD). A genetic association has been shown between HTR4 and susceptibility to mood disorders. Our study aims at assessing the association between the HTR4 genetic polymorphism, rs1345697, and improvement in depressive symptoms and remission after antidepressant treatment in MDE patients. Methods492 depressed patients from the METADAP cohort were treated prospectively for 6 months with ADs. The clinical outcomes according to HTR4 rs1345697 were compared after 1 (M1), 3 (M3), and 6 (M6) months of treatment. Mixed-effects logistic regression and adjusted linear models assessed the association between rs1345697 and 17-item Hamilton Depression Rating Scale (HDRS) score improvement and response/remission. ResultsOver the 6 months of treatment, mixed-effects regressions showed lower improvements in HDRS scores (Coefficient=1.52; Confident Interval (CI) 95% [0.37–2.67]; p = 0.009) and lower remission rates (Odds Ratio=2.0; CI95% [1.0–4.1]; p = 0.05) in GG homozygous patients as compared to allele A carriers. LimitationsThe major limitations of our study are the uncertainty of the rs1345697 effect on HTR4 function, the substantial drop-out rate, and the fact that analysis is not based on randomization between polymorphism groups. ConclusionsIn our study, patients who were homozygous carriers of the variant G of the HTR4 rs1345697 had lower depressive symptoms improvement and 2-fold lower remission rates after antidepressant treatment as compared to allele A carriers. Randomization study should be done to confirm these results.

Reliability and validity of the Chinese version of the CUDOS-M in patients with mood disorders: A multicenter study across China

Background: A useful scale for identification of mixed features in major depressive episodes (MDE) patients is urgent in China. This study aimed to evaluate the reliability and validity of the Chinese version of the Clinically Useful Depression Outcome Scale supplemented with questions for the DSM-5 mixed features specifier (Chinese-CUDOS-M) in MDE patients. Methods: A total of 152 MDE patients were recruited and assessed using Chinese-CUDOS-M, Patient Health Questionnaire-9 (PHQ-9) and 32-item Hypomania Checklist (HCL-32). Principal component analysis (PCA) and exploratory factor analysis (EFA) were conducted. The predictive validity was calculated by the area under the receiver operating characteristic curve (AUROC). Results: The Cronbach's alpha of Chinese-CUDOS-M was 0.85. PCA showed three common factors with eigenvalue greater than 1; the eigenvalue of factor I was 4.96, with 38.1% of variance explanation. Chinese-CUDOS-M depression subscale was associated with PHQ-9 (r = 0.83, p<0.01), and manic subscale was associated with HCL-32 (r = 0.73, p< 0.01). AUROC of the Chinese-CUDOS-M for patients with mixed depression was 0.90 (95%CI: 0.85–0.95), with a cut-off value of 7, sensitivity of 0.95, and specificity of 0.73. Furthermore, AUROC was 0.88 in patients with major depressive disorder (MDD), with a cut-off value of 7, sensitivity of 0.96, and specificity of 0.71. AUROC was 0.92 in bipolar disorder (BD) depression patients, with a cut-off value of 9, sensitivity of 0.89, and specificity of 0.87. Conclusion: Our study shows that the Chinese-CUDOS-M can identify mixed features in both MDD and BD depression with satisfactory reliability and validity.

Comorbid major depression in first-episode drug-naïve patients with schizophrenia: Analysis of the Depression in Schizophrenia in China (DISC) study

BackgroundDepression is very common in patients with schizophrenia, but few studies have investigated the diagnosed major depressive episode (MDE) in first episode and drug naive (FEDN) schizophrenia. To our best knowledge, this is the first large sample study to examine the prevalence, clinical correlates and associated factors of diagnosed MDE in FEDN schizophrenia, as well as the relationship between depressive symptoms and psychopathological symptoms in these schizophrenia patients. MethodsA total of 996 FEDN schizophrenia patients were recruited. The 17-item Hamilton Depression Rating Scale (HAMD17) and Positive and Negative Syndrome Scale (PANSS) were used to assess the severity of depression and psychopathology, respectively. ResultsOur results demonstrated that MDE coexisted in nearly half (49.30%) of FEDN schizophrenia patients. Male gender, smoking, PANSS general psychopathology and early age of onset were associated with MDE in patients with FEDN schizophrenia (all p<0.05). In schizophrenia patients with MDE, oridinal logistic regression showed that men (OR=6.65, 95%CI: 4.12-10.45, p<0.001) and smoking (OR=1.94, 95%CI: 1.25-3.01, p=0.003) were positively associated with severity category of depression (all p<0.05), while multivariate regression showed that HAMD17 total score was significantly associated with the PANSS general psychopathology (B=0.06, t=2.72, p=0.007) and total scores (B=0.04, t=2.57, p=0.01). ConclusionOur study shows that the prevalence of comorbid MDE is high in FEDN schizophrenia patients. Some demographic and clinical variables are associated with the severity of depression in these schizophrenia patients.

Peripheral tryptophan and serotonin and kynurenine pathways in major depression: A case-control study

IntroductionThe tryptophan pathway along with its two branches of metabolism to serotonin and kynurenine seems to be affected in major depression. In depressed patients, peripheral levels of tryptophan, serotonin, kynurenine and their metabolite remain unclear.ObjectivesTherefore, peripheral tryptophan and metabolites of serotonin and kynurenine were investigated extensively in 173 patients suffering from a current major depressive episode (MDE) and compared to 214 healthy controls (HC).MethodsFasting plasma levels of 11 peripheral metabolites were quantified: tryptophan, serotonin pathway (serotonin, its precursor 5-hydroxy-tryptophan and its metabolite the 5-hydroxy-indole acetic acid), and kynurenine pathway (kynurenine and six of its metabolites including anthranilic acid, kynurenic acid, nicotinamide, picolinic acid, xanthurenic acid and 3-hydroxy-anthranilic acid).Results60 (34.7%) patients were antidepressant drug free. Tryptophan levels did not differ between MDE patients and HC. Serotonin and its precursor (5-hydroxy-tryptophan) levels were lower in MDE patients than HC. Whereas, its metabolite (5-hydroxy-indole acetic acid) levels were within the standard range. Kynurenine and four of its metabolites (kynurenic acid, nicotinamide, picolinic acid and xanthurenic acid) were lower in MDE patients.ConclusionsThis study uses the largest ever sample of MDE patients, with an extensive assessment of peripheral tryptophan metabolism in plasma. These findings provide new insights into the peripheral signature of MDE. The reasons for these changes should be further investigated. These results might suggest a better stratification of patients and different therapeutic strategies therapeutic strategies.

Treatment-Resistant Depression in a Real-World Setting: First Interim Analysis of Characteristics, Healthcare Resource Use, and Utility Values of the FondaMental Cohort.

Background: Major depressive disorder (MDD) is among the most common psychiatric disorders. One-third of patients are usually unresponsive to several lines of treatment. This study aimed to describe the FondaMental French cohort of patients with treatment-resistant depression (TRD) and to estimate utility and healthcare resource use outcomes. Methods: Patients with TRD were evaluated prospectively over four years (baseline, 6, 12, 18, 24, 36 and 48 months) in a real-world clinical setting. Interim analyses focused on the first two consecutive years. Four MDD-related states (major depressive episode (MDE), response, remission, recovery) were defined based on the MADRS (Montgomery–Åsberg depression rating scale) and other clinical events. Health status was assessed with the EuroQol 5 Dimensions 5 Level (EQ-5D-5L) questionnaire. Utility values were estimated as preference measures that the patients assigned to their overall health status. Results: This study was based on 252 patients with TRD. The mean utility value by health state was 0.41, 0.63, 0.80, and 0.90, for MDE, response, remission, and recovery, respectively. At baseline, 59% of patients had an MADRS score of at least 28. Their baseline average utility value was lower compared to the other patients (0.43 versus 0.58, p < 0.001). This significant difference persisted at the following visits. The rate of patients in MDEs having at least one hospitalisation for depression or other reasons than depression was generally higher than that in the other health states. Conclusion: This study documented patterns in healthcare resource consumption, quality of life, and other characteristics in patients with TRD, both globally and by health state and depression severity.

Diagnosis and Treatment of Depression in Patients with Schizophrenia

Depression is the third most common illness among patients with schizophrenia which negatively affects the course of the disease and significantly contributes to the mortality rate, due to increased suicide. Depression, along with negative symptoms and cognitive deficits, is one of the main factors that significantly decreases the quality of life and the disease prognosis in patients with schizophrenia. In addition, depression increases the frequency of exacerbations and readmissions, decreases the quality and duration of remissions and is associated with more frequent substance abuse and an increased economic burden. Data on the prevalence of depression among patients with schizophrenia are contradictory and are associated with a low detection rate of depression in such patients, a lack of clear diagnostic criteria and difficulties in differentiation between extrapyramidal and negative symptoms. The average prevalence of depression that meets the diagnostic criteria of major depressive episodes in patients with schizophrenia is 25% at a specific point, and 60% over the course of a lifetime; the frequency of subsyndromal depression is much higher. It is essential to distinguish between primary (axial syndrome) and secondary depressive symptoms (extrapyramidal symptoms, psychogenic or nosogenic reactions, social factors, etc.) to determine treatment strategies.&#x0D; The published data relating to randomized clinical trials for the development of evidence-based guidelines are limited. Current recommendations are based mainly on the results of small-scale trials and reviews. Certain atypical antipsychotics (quetiapine, lurasidone, amisulpride, aripiprazole, olanzapine, clozapine) are superior to typical antipsychotics in the reduction of depressive symptoms. Clozapine is effective in the management of patients at risk from suicide. The additional prescription of antidepressants, transcranial magnetic stimulation and electroconvulsive therapy are not always effective and are only possible following the management of acute psychosis in cases when antipsychotic monotherapy proved to be ineffective.

Corticotropin releasing hormone receptor CRHR1 gene is associated with tianeptine antidepressant response in a large sample of outpatients from real-life settings

Polymorphisms of genes involved in the hypothalamic–pituitary–adrenocortical (HPA) axis have been associated with response to several antidepressant treatments in patients suffering of depression. These pharmacogenetics findings have been reported from independent cohorts of patients mostly treated with selective serotonin reuptake inhibitors, tricyclic antidepressant, and mirtazapine. Tianeptine, an atypical antidepressant, recently identified as a mu opioid receptor agonist, which prevents and reverses the stress induced by glucocorticoids, has been investigated in this present pharmacogenetics study. More than 3200 Caucasian outpatients with a major depressive episode (MDE) from real-life settings were herein analyzed for clinical response to tianeptine, a treatment initiated from 79.5% of the subjects, during 6–8 weeks follow-up, assessing polymorphisms targeting four genes involved in the HPA axis (NR3C1, FKPB5, CRHR1, and AVPR1B). We found a significant association (p < 0.001) between CRHR1 gene variants rs878886 and rs16940665, or haplotype rs878886*C–rs16940665*T, and tianeptine antidepressant response and remission according to the hospital anxiety and depression scale. Analyses, including a structural equation model with simple mediation, suggest a moderate effect of sociodemographic characteristics and depressive disorder features on treatment response in individuals carrying the antidepressant responder allele rs8788861 (allele C). These findings suggest direct pharmacological consequences of CRHR1 polymorphisms in the antidepressant tianeptine response and remission, in MDE patients. This study replicates the association of the CRHR1 gene, involved in the HPA axis, with (1) a specificity attributed to treatment response, (2) a lower risk of chance finding, and in (3) an ecological situation.

Transcranial Direct Current Stimulation as an Add-on Treatment to Cognitive-Behavior Therapy in First Episode Drug-Naïve Major Depression Patients: The ESAP Study Protocol.

Background: Major Depressive Disorder (MDD) affects more than 264 million people worldwide. Current treatments include the use of psychotherapy and/or drugs, however ~30% of patients either do not respond to these treatments, or do not tolerate the side effects associated to the use of pharmacological interventions. Thus, it is important to study non-pharmacological interventions targeting mechanisms not directly involved with the regulation of neurotransmitters. Several studies demonstrated that transcranial Direct Current Stimulation (tDCS) can be effective for symptoms relief in MDD. However, tDCS seems to have a better effect when used as an add-on treatment to other interventions.Methods/Design: This is a study protocol for a parallel, randomized, triple-blind, sham-controlled clinical trial in which a total of 90 drug-naïve, first-episode MDD patients (45 per arm) will be randomized to one of two groups to receive a 6-weeks of CBT combined with either active or sham tDCS to the dorsolateral prefrontal cortex (DLPFC). The primary outcome will depressive symptoms improvement as assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) at 6-weeks. The secondary aim is to test whether CBT combined with tDCS can engage the proposed mechanistic target of restoring the prefrontal imbalance and connectivity through the bilateral modulation of the DLPFC, as assessed by changes over resting-state and emotional task eliciting EEG.Discussion: This study evaluates the synergetic clinical effects of CBT and tDCS in the first episode, drug-naïve, patients with MDD. First episode MDD patients provide an interesting opportunity, as their brains were not changed by the pharmacological treatments, by the time course, or by the recurrence of MDD episodes (and other comorbidities).Trial Registration: This study is registered with the United States National Library of Medicine Clinical Trials Registry (NCT03548545). Registered June 7, 2018, clinicaltrials.gov/ct2/show/NCT03548545. Protocol Version 1.

Characterization of rapid cycling bipolar patients presenting with major depressive episode within the BRIDGE-II-MIX study.

The "Bipolar Disorders: Improving Diagnosis, Guidance, and Education" (BRIDGE-II-Mix) study aimed to estimate the frequency of mixed states in patients with a major depressive episode (MDE) according to different definitions and to compare their clinical validity, looking into specific features such as rapid cycling (RC). Psychiatric symptoms, socio-demographic, and clinical variables were collected from a sample of 2811 MDE patients, of which 726 (25.8%) were diagnosed with bipolar disorder (BD). The characteristics of bipolar patients with RC (BD-RC) and without (BD-NRC) RC were compared. Of 726 BD patients, 159 (21.9%) met DSM-5 criteria for RC. BD-RC group presented a higher number of lifetime depressive episodes (p<0.001) with shorter duration of depressive episodes, and more psychiatric comorbidities, as well as higher rates of atypical features (p=0.016) and concomitant (hypo)manic symptoms (irritable mood (p=0.001); risky behavior (p=0.005); impulsivity (p=0.006); and psychomotor agitation (p=0.029)). Patients with RC had a worse functioning (p=0.033), more obesity (p=0.003), and were significantly more likely to be treated with three or more drugs (p=0.007). Important clinical differences between bipolar patients with and without a RC include more depressive morbidity, higher incidence of anxiety disorders, addiction, bulimia, and borderline personality disorder, as well as atypical features during depression and symptoms such as irritability, risky behavior, impulsivity, and agitation. RC patients had poorer functioning than patients without RC, more obesity, and had to be treated with more drugs.

Sex-dependent grades of haematopoietic modulation in patients with major depressive episodes are associated with suicide attempts

Suicide is the leading cause of non-natural death worldwide, and major depressive disorder (MDD) is the mood disorder with the highest prevalence among individuals with suicidal behaviour (SB). The role of inflammation and immunomodulation in mood disorders has raised interest in recent years, as inflammation biomarkers have been reported to be increased in mood disorder patients, suggesting a role of inflammation in their pathogenesis. The influence of inflammation on the haematopoietic production is well known; however, a comprehensive study of the haematopoietic production in patients with major depressive episodes (MDE) is lacking. We examined global haematopoietic parameters from complete blood counts (CBC) of patients with MDE, in search of prognostic patterns. MDE patients presented differences in several CBC parameters, differences that were clearly pronounced and/or significant in concurrence with suicide attempts (SA). Red and white blood cell lineage parameters were affected, suggesting general haematopoietic modulation or imbalance. We observed distinct haematological parameter changes in women versus men, with men presenting milder alterations than women. Interestingly, we found that the List of Threatening Experiences (LTE) score, but not the Childhood Trauma Questionnaire (CTQ), was associated with the haematopoietic alterations observed exclusively in women and, more importantly, served as a parameter to stratify female MDE patients based on concurrence or non-concurrence with SA. In conclusion, grades of haematopoietic modulation in MDE patients are associated with absence or presence of SA. Haematopoietic manifestations differ between men and women and, in the latter, are markedly influenced by late, and not early, traumatic events.

Neuroendocrine abnormalities associated with untreated first episode patients of major depressive disorder with comorbid obstructive sleep apnea

There are few studies that explore the relationship of neuroendocrine hormones of the HPA, HPT and HPG axes with major depressive disorder (MDD) with comorbid obstructive sleep apnea (OSA). The aim of this study is to examine neuroendocrine abnormalities and the relationship in untreated first episode patients of MDD comorbided with OSA. Polysomnography, neuroendocrine hormones were determined for 111 patients. After excluding the influences of age and BMI, phase I in non-REM sleep (N1)% increased significantly in MDD with OSA when compared with non-OSA. In the OSA group, cortisol increased and exceeded the normal standard, and for the numbers of patients exceeding the normal range, there were significant difference between two groups. In MDD with OSA, adrenocorticotropic hormone was significantly negatively correlated with slow wave sleep (SWS)%, while thyroxine was significantly correlated with phase II in non-REM sleep (N2)%, and prolactin was significantly negatively correlated with N1%. This study revealed that for untreated first episode MDD patients with OSA, the HPA axis was hyperfunctional. Cortisol and adrenocorticotropic hormone may be increased along with disturbed sleep structure and less slow-wave sleep time. Concurrently prolactin was decreased and thyroxine increased during the N1 and N2 phase of sleep.

Lack of association between unipolar or bipolar depression and serum aquaporin-4 autoantibodies

Aquaporin-4 (AQP4), an astrocyte water channel protein, is the target antigen of serum immunoglobulin G (IgG) autoantibody in neuromyelitis optica spectrum disorders (NMOsd), a group of inflammatory, demyelinating diseases of the central nervous system. Recently, a reduction in blood vessels coverage by AQP4-immunoreactive astrocytes was demonstrated in depressed patients, indicating a role for AQP4 in mood disorders. Moreover, a possible association between depression and serum AQP4-IgG was suggested in a case report of a treatment resistant depression (TRD) patient diagnosed with NMOsd with positive serum AQP4 autoantibodies. We investigated, for the first time, the presence of serum AQP4-IgG in patients with unipolar and bipolar depression and healthy controls (HCs). In this multicenter study, 25 major depressive disorder (MDD) and 25 bipolar disorder (BD) patients, during an acute major depressive episode (MDE), and 30 matched HCs were screened for the presence of serum AQP4-IgG, using a cell-based assay. The MDE patients underwent a repeated AQP4-IgG assessment at a 3-month follow-up visit. The MDE group (N = 50) had illness duration of 12.7 years (SD = 10.5), 12% of them were psychotropic medication-free and 26% were defined as TRD. All MDE patients and HCs, including three BD patients who experienced a manic switch, were seronegative for AQP4-IgG at baseline and follow-up assessments. In conclusion, contrary to our hypothesis, AQP4 autoantibodies were not detected in serum of unipolar and bipolar depressed patients. However, AQP4 may still play a role in the pathogenesis of mood disorders through different mechanisms of action such as altered brain AQP4 expression.