Diagnosis Of Major Depressive Disorder Research Articles

Long-Term Treatment with Trazodone Once-A-Day (TzOAD) in Patients with MDD: An Observational, Prospective Study.

This was an observational, prospective, single-group, multicentre, international study aimed to describe the clinical response, functional impairment, and quality of life (QoL) of patients suffering from major depressive disorder (MDD) and in treatment with Trazodone Once-A-Day (TzOAD) monotherapy, over a 24-week period. A total of 200 patients with a diagnosis of MDD who had been treated with TzOAD monotherapy were enrolled from 26 sites across 3 European countries (Bulgaria, Czech Republic, and Poland), including psychiatric private practices, and outpatient departments from general and psychiatric hospitals. Study assessments were completed by physicians and patients during routine visits within the normal practice of care. Clinical response was assessed by Clinical Global Impressions - Improvement (CGI-I) responders' percentage at 24 (±4) weeks. The majority of patients (86.5%) reported an improvement on the CGI-I compared to baseline. Results of the study confirm the well-known safety and tolerability of TzOAD, as well as its effectiveness on depressive symptoms, such as improvement in QoL, sleep quality, and overall functioning accompanied by favourable adherence and low drop-out rate. To our knowledge, this is the first observational, long-term study in patients suffering from MDD, conducted with TzOAD. The improvement observed in clinical response, overall functioning, depressive symptoms, and QoL along the 24 weeks (+4) maintenance period and the very good retention rate, suggest that TzOAD may represent an effective and well tolerated treatment option for patients suffering from MDD.

Diagnoses and new therapeutic strategy focused on physiological alteration of tryptophan metabolism

The monoamine hypothesis has been common hypotheses for the pathophysiology of major depressive disorder (MDD). Since mainstream antidepressants are selective serotonin (5-HT) reuptake inhibitors, hypo-serotonergic function has been implicated in the MDD. However, one-third of patients are refractory to the treatment with antidepressants. Tryptophan (TRP) is metabolized via the kynurenine (KYN) and 5-HT pathways. Indoleamine 2,3-dioxygenase 1 (IDO1) is the first metabolizing enzyme in the TRP-KYN pathway which is inducible by pro-inflammatory cytokines, involved depression-like behavior via 5-HT depletion due to decreased level of TRP in the 5-HT pathway. Kynurenine 3-monooxygenase (KMO) is the enzyme in the metabolism of KYN to 3-hydroxykynurenine. KMO deficiency increases level of kynurenic acid (KA), a KYN metabolite by kynurenine aminotransferases (KATs) and induces depression-like behavior. Interestingly, Chronic unpredictable mild stress (CUMS) is associated with a disruption of the hypothalamus-pituitary-adrenocortical (HPA) system and increases KA level with decreased KMO expression in the prefrontal cortex. The decrease of KMO may be related to the reduction in expression of microglia, since KMO is mainly found in microglia in the nervous system. CUMS increases KA level via alternation of enzymes from KMO to KAT. KA is α7 nicotinic acetylcholine receptor (α7nAChR) antagonist. Activation of α7nAChR by nicotine or galantamine attenuates CUMS-induced depression-like behaviors. Taken together, depletion of 5-HT by induction of IDO1 and α7nAChR antagonism by KA via decreased KMO expression cause depression-like behavior, suggesting that metabolic alterations in TRP-KYN pathway are highly involved in the pathophysiology of MDD. Therefore, TRP-KYN pathway is expected to be an attractive target for the development of novel diagnosis of MDD and antidepressants.

Epidemiology and Burden of Treatment-Resistant Depression in Colombia: Analysis of the TRAL Study

ObjectivesTo estimate the prevalence of treatment-resistant depression (TRD) in Colombia, and characterize hospitalized major depressive disorder (MDD) patients for disability, health-related quality of life (HRQoL) and work-impairment. Materials and methodsAdult MDD patients (n=162) from 4 centers in Colombia, with a clinical diagnosis of MDD based on DSM-5 and MINI, were consecutively included. Patients with psychosis, schizophrenia, bipolar disorder, schizoaffective disorder, dementia, with severe chemical dependence or currently participating in another clinical trial were excluded. Patient reported outcomes and clinical assessment scales were used as outcomes with WPAI:D (work impairment), EQ-5D (QoL) and Sheehan Disability Scale, as well as healthcare resource utilization. ResultsPrevalence of TRD in Colombia among patients treated at psychiatric reference sites was 32.1% [24.9%; 39.3%], higher in private institutions. Most patients were females and single. 55% reported having moderate to severe problems with usual activities at the beginning of the study. Mean percent of working time missed due to depression was around 53%, and work impairment was roughly 67%. A mean of 2.85 days in the last seven were marked by lost school/work, with higher losses in TRD patients compared to non-TRD. Overall results for HRQoL were lower in TRD patients, but disability and work impairment were higher in non-TRD. ConclusionsThere is a high prevalence of mental disorders in Colombia, including TRD, impacting significantly HRQoL. The burden associated with them may be reduced by a most comprehensive and customized usage of therapies, including the innovations, and implementation of national mental health programs.

The Burden of Attention-Deficit/Hyperactivity Disorder Traits in Adult Patients with Major Depressive Disorder in Japan.

Symptoms of attention-deficit/hyperactivity disorder (ADHD) often overlap with and are hidden by those of mood disorders, including major depressive disorder (MDD), resulting in adult ADHD patients being misdiagnosed as MDD. This study aims to examine if diagnosed MDD patients are more likely to exhibit ADHD traits and if the presence of ADHD traits increases the humanistic burden, including the impairment of health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), and health-care resource utilization (HRU), on MDD patients in Japan. This study utilized existing National Health and Wellness Survey (NHWS) data. The 2016 Japan NHWS is an internet-based survey comprising a total of 39,000 respondents, including those with MDD and/or ADHD. A randomly selected subset of the respondents responded to the Japanese-version Adult ADHD self-report scale (ASRS-v1.1; ASRS-J) symptom checklist. Respondents were considered ASRS-J-positive if the total score was ≥36. The HRQoL, WPAI, and HRU were assessed. Among MDD patients (n = 267), 19.9% were screened ASRS-J-positive, while 4.0% of non-MDD respondents (n = 8885) were ASRS-J-positive. There was a significant association between MDD status and ASRS-J status (crude odds-ratio [OR]: 5.9) as well as between MDD status and ADHD-diagnosis status (crude OR: 22.6). MDD patients who were ASRS-J positive experienced significantly lower HRQoL and higher WPAI than those who were ASRS-J negative. Limitations of this study include potential recall bias owing to the self-report nature of the survey and lack of objective confirmation of MDD diagnosis through review of medical records. This study demonstrated a significant association between MDD status and exhibiting ADHD traits. Adult MDD patients screened ASRS-J-positive experienced significantly higher humanistic burden than patients screened ASRS-J-negative. Our results emphasize the importance of ensuring appropriate screening of ADHD and looking out for potentially hidden ADHD symptoms when diagnosing and treating MDD in adulthood.

Serum cytokines-based biomarkers in the diagnosis and monitoring of therapeutic response in patients with major depressive disorder

Several lines of evidence have suggested that cytokines are implicated in the pathophysiology of depression and antidepressant treatment outcome. However, the results are not always congruent and partly contradictory. We therefore examined the serum levels of multiple cytokines in patients with major depressive disorder (MDD), with the aim to identify serum cytokines-based biomarkers for MDD diagnosis and antidepressant response. Fifty-nine patients with MDD and 61 healthy controls were included. The baseline levels of serum cytokines between MDD group and control group were compared, and the discriminative ability of different cytokines in predicting MDD patients from healthy controls was investigated using the receiver operating characteristic (ROC) curve method. The baseline levels of serum cytokines between antidepressant nonresponders and responders were compared, and the discriminative ability of different cytokines in predicting nonresponders from responders was evaluated using the ROC curve method. Compared to controls, 15 of the 37 serum cytokines were increased, while 8 cytokines were decreased in MDD patients (all P<0.05). The results of ROC curve showed that the Area Under Curve (AUC) values of 15 cytokines including IL-2, IL-5, IL-6, IL-8, IL-12, IL-13, IL-16, CCL3, CCL4, CCL17, CXCL10, TNF-α, TNF-β, VEGF-C, and FGF basic were greater than 0.7 in discriminating MDD patients from healthy control. Moreover, after 4-week treatment, levels of the 2 cytokines (IL-12 and TSLP) elevated at baseline significantly down-regulated, and levels of the 6 cytokines (IL-5, IL-16, CCL17, CXCL10, TNF-β, and PIGF) decreased at baseline significantly up-regulated (all P<0.05). Furthermore, a positive relationship was found between TNF-α levels and Hamilton Depression Rating Scale-24 (HAMD-24) scores in patients with MDD at baseline (r=0.302, P=0.019). Additionally, compared to responders, nonresponders exhibited decreased levels of IL-1α, IL-5, IL-13, IL-15, VEGF, and ICAM-1 (all P<0.05). The ROC curve analysis demonstrated that a combined panel of IL-1α, IL-5, and ICAM-1 achieved a high accuracy in discriminating antidepressant nonresponders from responders (AUC=0.850, sensitivity=83.3%, specificity=81.8%). These results suggested that alterations in peripheral cytokines levels hold significant promise as biomarkers for MDD diagnosis and antidepressant response.

Evaluation of expressed self-contempt in psychotherapy: an exploratory study

ABSTRACT Self-contempt may be a frequent but overlooked clinical phenomenon, associated with a number of psychological problems such as increased sadness and shame. It was shown that self-contempt interferes with productive emotional processing and the quality of therapeutic alliance. This study aims to develop a reliable measure of expressed self-contempt given that a previous three-point assessment may be too restrictive in range, resulting in non-significant results. Thus, the present study applied an extended observer-rated scale to different participant groups in different contexts. This explorative phase focuses on a sample of N = 61 participants divided into three groups, including n = 20 controls, n = 21 patients with a diagnosis of borderline personality disorderand n = 20 patients with a diagnosis of major depressive disorder. Levels of self-contempt are compared between the groups and are associated with symptom indicators. Reliability of the instrument is analysed using inter-rater reliability and internal consistency, which are sufficient. The level of expressed self-contempt is not related to symptom intensity. Patients with borderline personality disorder do not express more self-contempt than the other groups. While further research should establish full validity of the scale, reliability is satisfactory and the use of the scale can be recommended.

Serum Angiotensin-Converting Enzyme Methylation Level and Its Significance in Patients With Comorbid Major Depressive Disorder and Hypertension.

Major depressive disorder (MDD) often coexists with hypertension (HYT). DNA methylation has elicited vital functionality in their development. Angiotensin-converting enzyme (ACE) is a vital enzyme in blood pressure. This study investigated the effect of ACE methylation on depression and HYT severity in patients with comorbid MDD and HYT (MDD + HYT). A total of 119 patients (41 men, 78 women, average age: 56.8 ± 9.1 years) with MDD + HYT were enrolled, with 89 healthy subjects (29 men, 60 women, average age: 57.4 ± 9.7 years) were enrolled. The Hamilton Depression Rating Scale-17 and self-rating depression scale scoring scales were used to assess the depression degree of patients, serum ACE methylation level in MDD + HYT patients was measured by means of bisulfite sequencing polymerase chain reaction, with subsequent analysis of the diagnostic efficacy of ACE methylation for MDD + HYT. The independent risk factors for sMDD + HYT were explored. Serum ACE methylation levels were significantly increased in MDD + HYT patients. The area under the curve of serum ACE methylation level for accurate diagnosis of MDD + HYT was 0.8471, and the cut-off value was 26.9 (sensitivity 83.19%, specificity 73.03%). ACE methylation was an independent risk factor for sMDD + HYT (P = 0.014; odds ratio, 1.071; 95% confidence interval = 1.014-1.131). The elevated serum ACE methylation level (P < 0.001) in patients with MDD + HYT elicited definite diagnostic values for MDD + HYT, and ACE methylation level was independently correlated with sMDD + HYT (P < 0.05).

Automated Detection of Central-positive Complexes &amp; Postictal Generalized EEG Suppression in ECT-induced Seizures – An Illustrative Case Report (P10-1.009)

<h3>Objective:</h3> We present a case of using automated algorithms to analyze central-positive complexes (CPCs) and postictal generalized electroencephalographic suppression (PGES) in the context of ECT-induced seizures. Our goal is to characterize peri-ictal EEG changes in ECT-induced seizures to define their unique features as generalized seizures. <h3>Background:</h3> Generalized seizures induced by electroconvulsive therapy (ECT) have been proposed as a model to study epileptic seizures in humans. We recently described generalized, high-amplitude waveforms with maximum positive voltage over the vertex (CPCs) during ECT-induced seizures. Furthermore, we developed an automated algorithm for detecting postictal PGES, defined as electroencephalographic (EEG) activity of ≤10 mV following a generalized seizure. <h3>Design/Methods:</h3> This investigation is a secondary analysis of data collected from Reconstructing Consciousness and Cognition Phase 2 study (ClinicalTrials.gov NCT02761330). A 53-year-old female with a diagnosis of major depressive disorder underwent 5 sessions of right unilateral ECT during concurrent 64-channel EEG recordings. Quantitative EEG analysis allowed for assessment of spatiotemporal properties and spectral content during the peri-ictal period. CPC and PGES durations, quantified by automated algorithms, were compared to those derived through visual interpretation by expert epileptologists. <h3>Results:</h3> CPCs occurred during Phase III of all recorded seizures, with a median duration of 41 seconds. CPC evolved from 4.1 to 3.2 Hz as the seizures progressed. Peak-amplitude CPC scalp topology was consistent across patient’s seizures, showing maximal positive polarity over the vertex and surrounding regions and maximal negative polarity over the subocular electrodes. PGES duration lasted 5–45 seconds (median of 22 seconds) following the seizure and the median time to responsiveness after the seizure was 18.3 minutes. The findings using the automated algorithm were comparable to manual visual interpretation. <h3>Conclusions:</h3> This case presents the utility of automated algorithms to analyze CPCs and PGES characteristics, many of which were comparable to those evaluated through visual EEG interpretation. <b>Disclosure:</b> Dr. Nayak has nothing to disclose. Dr. Kafashan has nothing to disclose. Dr. Nascimento has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zogenix. The institution of Dr. Nascimento has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biocodex. Dr. Nascimento has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Nascimento has received research support from Zogenix. The institution of Dr. Nascimento has received research support from Biocodex. The institution of Dr. Nascimento has received research support from Greenwich. Dr. Nascimento has received publishing royalties from a publication relating to health care. Dr. Nascimento has a non-compensated relationship as a Editorial Team Member with Neurology RFS that is relevant to AAN interests or activities. Dr. Nascimento has a non-compensated relationship as a Production Team with Neurology Podcast that is relevant to AAN interests or activities. The institution of Dr. Palanca has received research support from National Institutes of Health. The institution of Dr. Palanca has received research support from McDonnell Center for Systems Neuroscience. The institution of Dr. Palanca has received research support from American Federation for Suicide Prevention. Dr. Palanca has received intellectual property interests from a discovery or technology relating to health care. Dr. Palanca has received personal compensation in the range of $100,000-$499,999 for serving as a Employee with Washington University School of Medicine in St. Louis. Dr. Hogan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. The institution of Dr. Hogan has received research support from Biogen Inc. The institution of Dr. Hogan has received research support from Engage Therapeutics. The institution of Dr. Hogan has received research support from Otsuka Pharmaceuticals. The institution of Dr. Hogan has received research support from Cerevel Therapeutics.

Suicide in Veterans with Post-Traumatic Headache: An Analysis of Health Systems Data (P14-12.001)

Suicide in Veterans with Post-Traumatic Headache: An Analysis of Health Systems Data (P14-12.001)

Evaluation of burning mouth syndrome and salivary chromogranin A in major depressive disorder patients

Major depressive disorder represents a growing concern as its prevalence keeps rising worldwide; with this rising, there is also an increased demand in the field of oral medicine in developed countries, and since many disorders and orofacial pain have been linked to be associated with psychiatric disorders and conditions, this study was aimed to evaluate burning mouth syndrome and salivary chromogranin A in major depressive disorder patients. The study sample included 49 patients who received a diagnosis of major depressive disorder, being under treatment for at least two weeks. The control group consists of 34 healthy subjects with no signs & symptoms of systemic disease. The study group received the diagnosis according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM5), in Najaf city. The results showed that for the study sample, 23 (46.9%) patients had Burning Mouth Syndrome (BMS), while 26 (53.1%) patients did not have BMS for the study group. As for the control group, 5 (14.7%) individuals reported having BMS, and 29 (85.3%) didn’t. The findings of the present study revealed a significant difference in salivary chromogranin A levels between the study and control groups (p < 0.05) using a t-test. We found salivary chromogranin A is an excellent salivary biomarker for MDD., and MDD patients have much higher incidents of reporting BMS, indicating the importance of psychological factors in this condition.

Research and Diagnostic Algorithmic Rules (RADAR) and RADAR Plots for the First Episode of Major Depressive Disorder: Effects of Childhood and Recent Adverse Experiences on Suicidal Behaviors, Neurocognition and Phenome Features.

Recent studies have proposed valid precision models and valid Research and Diagnostic Algorithmic Rules (RADAR) for recurrent major depressive disorder (MDD). The aim of the current study was to construct precision models and RADAR scores in patients experiencing first-episode MDD and to examine whether adverse childhood experiences (ACE) and negative life events (NLE) are associated with suicidal behaviors (SB), cognitive impairment, and phenome RADAR scores. This study recruited 90 patients with major depressive disorder (MDD) in an acute phase, of whom 71 showed a first-episode MDD (FEM), and 40 controls. We constructed RADAR scores for ACE; NLE encountered in the last year; SB; and severity of depression, anxiety, chronic fatigue, and physiosomatic symptoms using the Hamilton Depression and Anxiety Rating Scales and the FibroFatigue scale. The partial least squares analysis showed that in FEM, one latent vector (labeled the phenome of FEM) could be extracted from depressive, anxiety, fatigue, physiosomatic, melancholia, and insomnia symptoms, SB, and cognitive impairments. The latter were conceptualized as a latent vector extracted from the Verbal Fluency Test, the Mini-Mental State Examination, and ratings of memory and judgement, indicating a generalized cognitive decline (G-CoDe). We found that 60.8% of the variance in the FEM phenome was explained by the cumulative effects of NLE and ACE, in particular emotional neglect and, to a lesser extent, physical abuse. In conclusion, the RADAR scores and plots constructed here should be used in research and clinical settings, rather than the binary diagnosis of MDD based on the DSM-5 or ICD.

Neuropsychiatric and cognitive features of major depressive disorder in aging, based on the data from the US National Alzheimer's Coordinating Center (NACC)

ObjectiveThe diagnosis of Major Depressive Disorder (MDD) is based on the DSM-V criteria and is established by a clinician. This allows quantifying depression based on clinical criteria. As such, MDD differs from other types of depressions that are measured by subjective scales. Here, we evaluated the MDD risk factor on other neuropsychiatric symptoms (NPS) as well as MDD association with cognitive performance in Alzheimer's disease (AD), Mild Cognitive Impairment (MCI) and Healthy Controls (HC). MethodsData of 208 patients with AD, 291 patients with MCI and 647 HC were extracted from the National Alzheimer's Coordinating Center database. All participants included in this study were assessed by a physician for the MDD criteria, underwent an NPS evaluation using the NeuroPsychiatric Inventory, and a comprehensive cognitive assessment. Participants were classified as being with and without MDD. We performed logistic regression and MANCOVA models respectively with NPS and cognitive performance as variables of interest and MDD as fixed factors within each group. The MANCOVA was controlled for the effects of age, sex, and education. ResultsMDD increased the risk for psychotic, affective and behavioral NPS in MCI, as well as affective and behavioral NPS in HC and AD. Also, MCI with MDD had lower performance on selective attention and mental flexibility. ConclusionsMDD seems to increase the probability of a prevalence of NPS in all groups (HC, MCI and AD). Longitudinal data processing would help to understand the neuropsychiatric evolution of elderly subjects with MDD.

The impact of adverse childhood experiences on adult depression severity and treatment outcomes

BackgroundPast research has established that adverse childhood experiences (ACE) are correlated with depression severity. The purpose of the present study was to examine how the number and nature of ACE exposure is associated with symptomatology and treatment outcomes in adult patients with treatment resistant depression (TRD). MethodsParticipants include 454 patients with a diagnosis of major depression or persistent depressive disorder. A one-way analysis of variance (ANOVA) was used to assess whether number of ACEs was associated with certain outcomes. Linear regression analyses were performed to model the associations between the five ACE subtypes (e.g., sexual abuse, physical violence, injury/illness, childhood grief, and parental upheaval) and symptom severity. Logistic regression analyses were then used to model the association between ACE subtypes and history of lifetime suicide attempt(s) and inpatient admission(s). ResultsGreater ACE exposure was associated with more severe symptomatology and treatment outcomes, but these differences were only seen between patients reporting no ACEs versus 3+ ACEs. Only the subtypes of violence and illness/injury were significant predictors of more severe symptomatology. The ACE subtypes of sexual trauma and violence uniquely predicted a lifetime suicide attempt(s), and only the subtype of sexual trauma predicted lifetime inpatient admission(s). LimitationsLimitations of the present study include retrospective adult assessments of childhood trauma, lack of data on ACE severity and timing, and the cross-sectional reporting of multiple study measures. ConclusionsExposure to multiple ACE subtypes, particularly sexual and physical trauma, is associated with depression symptom severity, and history of suicidality, and inpatient admission(s).

Preliminary findings on the effect of childhood trauma on the functional connectivity of the anterior cingulate cortex subregions in major depressive disorder.

Childhood trauma (CT) is a known risk factor for major depressive disorder (MDD), but the mechanisms linking CT and MDD remain unknown. The purpose of this study was to examine the influence of CT and depression diagnosis on the subregions of the anterior cingulate cortex (ACC) in MDD patients. The functional connectivity (FC) of ACC subregions was evaluated in 60 first-episode, drug-naïve MDD patients (40 with moderate-to-severe and 20 with no or low CT), and 78 healthy controls (HC) (19 with moderate-to-severe and 59 with no or low CT). The correlations between the anomalous FC of ACC subregions and the severity of depressive symptoms and CT were investigated. Individuals with moderate-to severe CT exhibited increased FC between the caudal ACC and the middle frontal gyrus (MFG) than individuals with no or low CT, regardless of MDD diagnosis. MDD patients showed lower FC between the dorsal ACC and the superior frontal gyrus (SFG) and MFG. They also showed lower FC between the subgenual/perigenual ACC and the middle temporal gyrus (MTG) and angular gyrus (ANG) than the HCs, regardless of CT severity. The FC between the left caudal ACC and the left MFG mediated the correlation between the Childhood Trauma Questionnaire (CTQ) total score and HAMD-cognitive factor score in MDD patients. Functional changes of caudal ACC mediated the correlation between CT and MDD. These findings contribute to our understanding of the neuroimaging mechanisms of CT in MDD.

Agreement between survey- and register-based measures of depression in Denmark.

Register-based studies of major depressive disorder (MDD) do not capture all prevalent cases, as untreated cases and diagnoses made by general practitioners are not recorded in the registers. We examined the prevalence and agreement of survey- and register-based measures of depression, and explored sociodemographic and health-related factors that may have influenced this agreement. All 32,407 participants in the 2017 Central Denmark Region How are you? survey were linked to hospital and prescription records. A checklist for depressive symptoms within the last 14 days (Major Depression Inventory; MDI) from the survey was compared with register-based assessment of hospital-diagnosed MDD and/or prescriptions for antidepressants. We estimated agreement between survey-based and register-based measures for depression and used logistic regression models to explore selected associated factors. In total, 5.9% of How are you? survey participants screened positive for current depression on the MDI. Of these, 51.3% (95% confidence interval (CI): 49.0-53.6) filled a prescription for an antidepressant medication during the 10 years prior or 2 years following the administration of the survey, and 14.5% (95% CI: 12.9-16.2) were treated for MDD in a psychiatric hospital-based setting. When using a higher threshold of the MDI indicating more severe current depression, 22.8% (95% CI: 19.6-26.1) of those who screened positive also received an MDD diagnosis and 63.4% (95% CI: 59.7-67.2) were prescribed antidepressants during this 12-year period. Among those with current depression, female sex, older age, chronic diseases, hospital-treated self-harm, and being permanently outside the workforce were associated with having a register-based MDD diagnosis or antidepressant prescription. Among those with a register-based depression record, female sex, younger age, hospital-treated self-harm, stress, and severe loneliness were associated with current depression. We found that as few as 15% of individuals with current depression in the general Danish population were captured by the psychiatric hospital register, while 51% of these individuals were identifiable in the prescription register. These findings demonstrate that register-based measures significantly underestimate the true prevalence of depression by identifying only the cases that are most severe.

Gut-brain axis volatile organic compounds derived from breath distinguish between schizophrenia and major depressive disorder.

Signatures from the metabolome and microbiome have already been introduced as candidates for diagnostic and treatment support. The aim of this study was to investigate the utility of volatile organic compounds (VOCs) from the breath for detection of schizophrenia and depression. Patients with a diagnosis of major depressive disorder (MDD) or schizophrenia, as well as healthy controls, were recruited to participate. After being clinically assessed and receiving instruction, each participant independently collected breath samples for subsequent examination by proton transfer-reaction mass spectrometry. The sample consisted of 104 participants: 36 patients with MDD, 34 patients with schizophrenia and 34 healthy controls. Through mixed-model and deep learning analyses, 5 VOCs contained in the participants' breath samples were detected that significantly differentiated between diagnostic groups and healthy controls, namely VOCs with mass-to-charge ratios (m/z) 60, 69, 74, 88 and 90, which had classification accuracy of 76.8% to distinguish participants with MDD from healthy controls, 83.6% to distinguish participants with schizophrenia from healthy controls and 80.9% to distinguish participants with MDD from those with schizophrenia. No significant associations with medication, illness duration, age of onset or time in hospital were detected for these VOCs. The sample size did not allow generalization, and confounders such as nutrition and medication need to be tested. This study established promising results for the use of human breath gas for detection of schizophrenia and MDD. Two VOCs, 1 with m/z 60 (identified as trimethylamine) and 1 with m/z 90 (identified as butyric acid) could then be further connected to the interworking of the microbiota-gut-brain axis.

Vitamin D-binding protein in plasma microglia-derived extracellular vesicles as a potential biomarker for major depressive disorder

No well-established biomarkers are available for the clinical diagnosis of major depressive disorder (MDD). Vitamin D-binding protein (VDBP) is altered in plasma and postmortem dorsolateral prefrontal cortex (DLPFC) tissues of MDD patients. Thereby, the role of VDBP as a potential biomarker of MDD diagnosis was further assessed. Total extracellular vesicles (EVs) and brain cell-derived EVs (BCDEVs) were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls (HCs) in discovery (20 MDD patients and 20 HCs) and validation cohorts (88 MDD patients and 38 HCs). VDBP level in the cerebrospinal fluid (CSF) from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide (LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles (MDEVs). VDBP was significantly decreased in MDD plasma MDEVs compared to HCs, and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among BCDEVs. VDBP in plasma MDEVs was decreased both in depressed rhesus macaques and mice. A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus macaques. VDBP levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed mice. The main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.

The effect of depression on prosthesis prescription in men and women who have undergone a lower limb amputation

Purpose To determine gender disparities and potential factors that modify prosthesis prescription practices in veteran patients who have undergone their first major unilateral amputation due to diabetes or peripheral arterial disease. Materials and Methods A retrospective cohort study using the VA Corporate Data Warehouse to compare prosthesis prescription rates and time to prescription between men and women veterans. The primary exposure was gender. The primary outcome was a qualifying prosthesis prescription within 12 months of the incident amputation. The secondary outcome was time to prosthesis prescription. Multiple logistic and linear regression was used to control for potential confounders and identify potential effect modification. Results 2,862 individuals met study criteria, with 1690 (60%) prescribed a qualifying prosthesis. Men were more likely to receive a prosthesis prescription than women (59% versus 45%, respectively; p = 0.03). This difference was observed primarily among those with a diagnosis of major depressive disorder. In this subgroup, the odds of men receiving a prosthesis over women was over 3 times (adjusted odds ratio = 3.3; 95% Confidence Interval, 1.5, 7.4). Men had a mean shorter time to prescription compared to women (112 ± 72 versus 136 ± 79 days, respectively, p = 0.08). Conclusions Depression in women negatively impacts their prosthesis prescription rates and time to prescription compared to men. This disparity may have significant impacts on future function and quality of life. Implications for Rehabilitation This study found that men more commonly received a prosthesis prescription and received it earlier than women. This disparity was most extreme among women who had been diagnosed with major depressive disorder. Providers should identify at risk patients early and consider targeted interventions to address depression during the preoperative and immediate postoperative phases. Future research should continue to work to identify gender-specific needs that exacerbate disparity.

Two-channel EEG based diagnosis of panic disorder and major depressive disorder using machine learning and non-linear dynamical methods

The current study aimed to investigate the possibility of rapid and accurate diagnoses of Panic disorder (PD) and Major depressive disorder (MDD) using machine learning. The support vector machine method was applied to 2-channel EEG signals from the frontal lobes (Fp1 and Fp2) of 149 participants to classify PD and MDD patients from healthy individuals using non-linear measures as features. We found significantly lower correlation dimension and Lempel-Ziv complexity in PD patients and MDD patients in the left hemisphere compared to healthy subjects at rest. Most importantly, we obtained a 90% accuracy in classifying MDD patients vs. healthy individuals, a 68% accuracy in classifying PD patients vs. controls, and a 59% classification accuracy between PD and MDD patients. In addition to demonstrating classification performance in a simplified setting, the observed differences in EEG complexity between subject groups suggest altered cortical processing present in the frontal lobes of PD patients that can be captured through non-linear measures. Overall, this study suggests that machine learning and non-linear measures using only 2-channel frontal EEGs are useful for aiding the rapid diagnosis of panic disorder and major depressive disorder.

Perceived parenting styles and incidence of major depressive disorder: results from a 6985 freshmen cohort study

BackgroundEven though a fair amount of studies focus on depression among college students, the effect of perceived parenting styles on the incidence of major depressive disorder (MDD) among representative freshmen in Chinese context is scarcely studied. The aim of this study is to investigate the effect of parenting styles on MDD in Chinese freshmen.MethodsA total of 9,928 Chinese freshmen were recruited in 2018. 6985 valid questionnaires were collected at one-year follow-up. Composite International Diagnostic Interview 3.0 (CIDI-3.0) was used for the diagnosis of MDD. Egna Minnen Beträffande Uppfostran (EMBU) questionnaire and Beck Depression Inventory-II (BDI-II) were used to assess parenting styles and baseline depressive symptoms, respectively. The associations between parenting styles and MDD incidence was analyzed with logistic regression.ResultsThe incidence of MDD in freshmen was 2.23% (95%CI: 1.91-2.60%). Maternal overprotection (OR = 1.03, 95%CI: 1.01–1.05) and disharmony relationship between parents (OR = 2.35, 95% CI: 1.42–3.89) increased the risk of new-onset MDD in freshmen, respectively. Mild depressive symptoms (OR = 2.06, 95%CI: 1.06–4.02), moderate (OR = 4.64, 95%CI: 2.55–8.44) and severe depressive symptoms (OR = 7.46, 95%CI: 2.71–20.52) at baseline increased the risk of new-onset MDD.ConclusionsMaternal overprotection, disharmony relationship between parents and baseline depressive symptoms are risk factors for new-onset MDD in Chinese freshmen.