MDD In Patients Research Articles

Spatiotemporal discoordination of brain spontaneous activity in major depressive disorder

BackgroundMajor depressive disorder (MDD) is a widespread mental health issue, impacting spatial and temporal aspects of brain activity. The neural mechanisms behind MDD remain unclear. To address this gap, we introduce a novel measure, spatiotemporal topology (SPT), capturing both the hierarchy and dynamic attributes of brain activity in depressive disorder patients. MethodsWe analyzed fMRI data from 285 MDD inpatients and 141 healthy controls (HC). SPT was assessed by coupling brain gradient measurement and time delay estimation. A nested machine learning process distinguished between MDD and HC using SPT. Person's correlation tested the link between SPT's and symptom severity, and another machine learning method predicted the gap between patients' chronological and brain age. ResultsSPT demonstrated significant differences between patients and healthy controls (F = 2.944, p < 0.001). Machine learning approaches revealed SPT's ability to discriminate between patients and healthy controls (Accuracy = 0.65, Sensitivity = 0.67, Specificity = 0.64). Moreover, SPT correlated with the severity of depression symptom (r = 0.32. pFDR = 0.045) and predicted the gap between patients' chronological age and brain age (r = 0.756, p < 0.001). LimitationsEvaluation of brain dynamics was constrained by MRI temporal resolution. ConclusionsOur study introduces SPT as a promising metric to characterize the spatiotemporal signature of brain function, providing insights into deviant brain activity associated with depressive disorders and advancing our understanding of their psychopathological mechanisms.

Development and validation of a machine learning model for prediction of comorbid major depression disorder among narcolepsy type 1

BackgroundMajor depression disorder (MDD) forms a common psychiatric comorbidity among patients with narcolepsy type 1 (NT1), yet its impact on patients with NT1 is often overlooked by neurologists. Currently, there is a lack of effective methods for accurately predicting MDD in patients with NT1. ObjectiveThis study utilized machine learning (ML) algorithms to identify critical variables and developed the prediction model for predicting MDD in patients with NT1. MethodsThe study included 267 NT1 patients from four sleep centers. The diagnosis of comorbid MDD was based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5). ML models, including six full models and six compact models, were developed using a training set. The performance of these models was compared in the testing set, and the optimal model was evaluated in the testing set. Various evaluation metrics, such as Area under the receiver operating curve (AUC), precision-recall (PR) curve and calibration curve were employed to assess and compare the performance of the ML models. Model interpretability was demonstrated using SHAP. ResultIn the testing set, the logistic regression (LG) model demonstrated superior performance compared to other ML models based on evaluation metrics such as AUC, PR curve, and calibration curve. The top eight features used in the LG model, ranked by feature importance, included social impact scale (SIS) score, narcolepsy severity scale (NSS) score, total sleep time, body mass index (BMI), education years, age of onset, sleep efficiency, sleep latency. ConclusionThe study yielded a straightforward and practical ML model for the early identification of MDD in patients with NT1. A web-based tool for clinical applications was developed, which deserves further verification in diverse clinical settings.

Association between NTRK2 Polymorphisms, Hippocampal Volumes and Treatment Resistance in Major Depressive Disorder.

Despite the increasing availability of antidepressant drugs, a high rate of patients with major depression (MDD) does not respond to pharmacological treatments. Brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling is thought to influence antidepressant efficacy and hippocampal volumes, robust predictors of treatment resistance. We therefore hypothesized the possible role of BDNF and neurotrophic receptor tyrosine kinase 2 (NTRK2)-related polymorphisms in affecting both hippocampal volumes and treatment resistance in MDD. A total of 121 MDD inpatients underwent 3T structural MRI scanning and blood sampling to obtain genotype information. General linear models and binary logistic regressions were employed to test the effect of genetic variations related to BDNF and NTRK2 on bilateral hippocampal volumes and treatment resistance, respectively. Finally, the possible mediating role of hippocampal volumes on the relationship between genetic markers and treatment response was investigated. A significant association between one NTRK2 polymorphism with hippocampal volumes and antidepressant response was found, with significant indirect effects. Our results highlight a possible mechanistic explanation of antidepressant action, possibly contributing to the understanding of MDD pathophysiology.

Resting State Functional Connectivity is Associated With Treatment Response in Major Depression: A Real World Study

IntroductionMajor depressive disorder (MDD) is largely considered the most prevalent psychiatric disorder worldwide. Despite its domineering presence, effective treatment for many individuals remains elusive. Investigation into relevant biological markers, specifically neuroimaging correlates, of MDD and treatment response have gained traction in recent years; however, findings are still inconsistent.ObjectivesIn this study, we aimed to investigate the resting state functional connectivity patterns associated with treatment response in MDD inpatients in a real world setting.MethodsForty-three inpatients suffering from a major depressive episode were recruited from the psychiatric ward at IRCCS San Raffaele Hospital in Milan, Italy. Symptom severity was assessed via the 21-item Hamilton Depression Rating Scale (HDRS). The percentage of decrease in HDRS scores from admission to discharge was then calculated with the formula [(HDRS admission – HDRS discharge) * 100] / HDRS admission. All patients underwent a 3T MRI scan within one week of admission to acquire resting-state fMRI images, which included 200 sequential T2*-weighted volumes. Images were preprocessed using the CONN toolbox, running within Statistical Parametric Mapping (SPM 12). Preprocessing was performed according to a standard pipeline. A voxel-wise metric, intrinsic connectivity contrast (ICC), was implemented to explore the global resting state functional connectivity (rs-FC) patterns associated with treatment response. ICC-derived maps were then entered in the second-level analyses to examine the effect of the percentage of HDRS decrease, including age, sex, admission HDRS score, duration of hospitalization, and antidepressant dose equivalents as nuisance covariates.ResultsWe found that the percentage of HDRS decrease after treatment predicted rs-FC. ICC analysis identified 2 clusters where changes in HDRS scores were significantly associated with rs-FC, with increased connectivity in the supramarginal gyrus (pFDR = 0.002) and decreased connectivity in the amygdala and parahippocampal gyrus (pFDR = 0.047).ConclusionsOur results suggest that altered connectivity of the supramarginal gyrus, amygdala and parahippocampal gyrus is related to antidepressant treatment response. Given that these brain areas are implicated in emotional processing and mood, it is conceivable that a better integrity of brain connectivity may facilitate treatment response in major depression.Disclosure of InterestNone Declared

Effect of Neutrophil to Lymphocyte ratio on antidepressant treatment response: moderating effect of sex and mediating effect of Hippocampal volumes.

IntroductionIn recent years much focus has been put on the role of immune/inflammatory alterations in affecting Major Depression (MDD) development and antidepressant efficacy. Neutrophil-to-lymphocyte ratio (NLR) is an inexpensive inflammatory marker shown to be elevated in depressed patients, with large population studies reporting this effect only in women. However, its relation to treatment response is much less clear. Reduced hippocampal volumes (HV) are among the few consistent brain structural predictors of poor treatment response, and they have been shown to be influenced by inflammatory status.ObjectivesTo investigate the effect of NLR on treatment response in MDD patients, testing a possible moderating role of sex. To investigate the effect of NLR on HV and test a possible mediating role of the latter in the relation between NLR and treatment response.MethodsOur study was performed on a sample of 120 MDD inpatients suffering from a non psychotic depressive episode (F=78; M=42). Depression severity was assessed via the Hamilton Depression Rating Scale (HDRS), both at admission and discharge; as a measure of treatment response, delta HDRS was calculated subtracting the two scores. NLR was calculated for each subject. Patients underwent 3T MRI acquisition and bilateral HV were estimated.ResultsWe found a significant moderating effect of sex on the relationship between NLR and Delta HDRS (p &lt; 0.001): a negative relation was found in women (p &lt; 0.001) and a positive one in men (p = 0.042). NLR was found to negatively affect left HV in the whole sample (p = 0.027) and in women (p = 0.038). A positive effect on Delta HDRS was found for both left (p = 0.038) and right (p = 0.027) HV. Finally, we found a significant indirect effect of NLR values on Delta HDRS through left HV in women (95% BCa CI [- 0.948, -0.017]); the direct effect of NLR on Delta HDRS also remained significant (p = 0.002).ConclusionsSex was found to moderate the relation between NLR and treatment response. The detrimental effect in women is in line with previous reports linking inflammation to hampered antidepressant effect; the positive one in men is more surprising: however, the only studies to date on the effect of NLR on antidepressant efficacy report a positive effect in patients with psychotic depression. In women we found NLR to affect treatment response partially through its effect on left HV, providing a possible, albeit incomplete, mechanistic explanation of the effect of inflammatory status on antidepressant efficacy.Disclosure of InterestNone Declared

MicroRNAs as novel peripheral markers for suicidality in patients with major depressive disorder.

Major depressive disorder (MDD) constitutes a main risk factor for suicide. Suicide risk in psychiatric patients is primarily determined by often unreliable, self-reported information. We assessed serum levels of three microRNAs (miRNAs), previously demonstrated to be dysregulated in post-mortem brain samples of suicide victims, as potential peripheral biomarkers for suicidality. All study participants were diagnosed with MDD according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria. Suicidality, defined as acute suicide risk or suicide attempt within one week prior to study entry, was assessed by clinical interview. Relative serum levels of miR-30a, miR-30e, and miR-200a, normalized to U6, were measured by quantitative real-time PCR in MDD inpatients with (MDD/SI, N = 19) and without (MDD, N = 31) acute suicide risk. Median age and gender distribution were comparable in both groups. Levels of miR-30a, miR-30e, and miR-200a were significantly elevated in MDD/SI compared to MDD. Subgroup analysis of the MDD/SI group showed that levels of miR-30e and miR-200a were significantly higher and miR-30a was increased by trend in patients admitted following a suicide attempt (N = 7) compared to patients with acute suicide risk but without recent suicide attempt (N = 12). Additionally, use of two databases for in silico transcription factor-miRNA interaction prediction indicated early growth response protein (EGR) 1 as potential transcriptional regulator for all three miRNAs. This study demonstrates suicide risk in MDD patients to be associated with increased levels of miR-30a, miR-30e, and miR-200a. Thus, these miRNAs might constitute potential biomarkers to predict suicidal behavior in MDD patients.

Cortical Inhibition and Plasticity in Major Depressive Disorder.

BackgroundMajor depressive disorder (MDD) is a severe psychiatric disorder that is associated with various cognitive impairments, including learning and memory deficits. As synaptic plasticity is considered an important mechanism underlying learning and memory, deficits in cortical plasticity might play a role in the pathophysiology of patients with MDD. We used Transcranial Magnetic Stimulation (TMS) to assess inhibitory neurotransmission and cortical plasticity in the motor cortex of MDD patients and controls.MethodsWe measured the cortical silent period (CSP) and short interval cortical inhibition (SICI), as well as intermittent theta-burst stimulation (iTBS), in 9 drug-free MDD inpatients and 18 controls.ResultsThe overall response to the CSP, SICI, and iTBS paradigms was not significantly different between the patient and control groups. iTBS induction resulted in significant potentiation after 20 mins in the control group (t(17) = −2.8, p = 0.01), whereas no potentiation was observed in patients.ConclusionsPotentiation of MEP amplitudes was not observed within the MDD group. No evidence was found for medium-to-large effect size differences in CSP and SICI measures in severely depressed drug-free patients, suggesting that reduced cortical inhibition is unlikely to be a robust correlate of the pathophysiological mechanism in MDD. However, these findings should be interpreted with caution due to the high inter-subject variability and the small sample size.SignificanceThese findings advance our understanding of neurophysiological functioning in drug-free severely depressed inpatients.

Incremental burden of comorbid major depressive disorder in patients with type 2 diabetes or cardiovascular disease: a retrospective claims analysis

BackgroundThe estimated prevalence of comorbid major depressive disorder (.MDD) is 11% in patients with type 2 diabetes (T2D) and 15–20% in those with cardiovascular disease (CVD). Comorbid MDD continues to be a significant source of economic burden to the healthcare system.MethodsWe assessed the incremental healthcare burden of comorbid MDD in patients with T2D or CVD. This real-world, retrospective, administrative claims study analyzed commercially insured adults with T2D or CVD diagnosed on at least 2 separate claims within 12 months of each other (between January 1, 2011, and September 30, 2018). CVD included congestive heart failure, peripheral vascular disease, coronary heart disease, and cerebrovascular disease. The study compared patients with and without MDD with either T2D or CVD. Study assessments included all-cause healthcare resource utilization (proportion of patients with hospitalization, emergency department [ED] visits, and outpatient visits) and cost.ResultsPatients were matched by propensity score for demographics and baseline characteristics, resulting in similar baseline characteristics for the respective subcohorts. After matching, 22,892 patients with T2D (11,446 each with and without MDD) and 28,298 patients with CVD (14,149 each with and without MDD) were included.At follow-up, patients with T2D and MDD had significantly higher rates of hospitalization (26.1% vs 17.4%, P < 0.0001) and ED visits (55.3% vs 43.0%, P < 0.0001) than those observed in patients without MDD. The total cost for patients with T2D and MDD at follow-up was significantly higher than for those without MDD ($16,511 vs $11,550, P < 0.0001). Similarly, at follow-up, patients with CVD and MDD had significantly higher rates of hospitalization (45.4% vs 34.1%, P < 0.0001) and ED visits (66.5% vs 55.4%, P < 0.0001) than those observed in patients without MDD. Total cost at follow-up for patients with CVD and MDD was significantly higher than for those without MDD ($25,546 vs $18,041, P < 0.0001).ConclusionsPatients with either T2D or CVD and comorbid MDD have higher total all-cause healthcare utilization and cost than similar patients without MDD. Study findings reinforce the need for appropriate management of MDD in patients with these comorbid diseases, which in turn may result in cost reductions for payers.Trial registrationNot applicable.

Recovery of High Interference Memory in Spite of Lingering Cognitive Deficits in a Longitudinal Pilot Study of Hospitalized Depressed Patients.

BackgroundMajor depressive disorder has deleterious impacts on mood, cognition, and many functions of daily life. Even after remission of mood symptoms, patients frequently report persistent cognitive deficits. By contrast, the neurogenic theory of depression posits that recovery from depression is dependent upon a restoration of neurogenesis. The present study was designed to test this prediction by assessing performance in MDD in-patients on a broad battery of cognitive tasks including the Mnemonic Similarity Task, a high interference memory test that is a putative correlate of neurogenesis. We predicted that remitted patients should exhibit recovery of function on this task, even though they may show residual deficits on other cognitive tasks.Methods18 hospitalized patients diagnosed with MDD and 22 healthy control participants matched for age, sex, and education completed a battery of mood and cognitive tests at two time points. Patients completed their baseline assessments when first admitted to hospital and repeated the same assessments upon remission, typically 4–5 weeks later and just prior to their release from hospital. Control participants were tested at baseline and 4–5 weeks later on the same assessment battery, which included the BDI-II, BAI, Cohen’s PSS, Mnemonic Similarity Task, and several sub-tests adapted from the CANTAB.ResultsAt baseline, MDD patients were impaired relative to controls on the MST and many other cognitive tasks. Upon remission, patients’ MST scores did not differ from those of healthy controls, although patients were still impaired on Pattern Recognition Memory, Spatial Recognition Memory, Delayed Matching to Sample and Paired Associates Learning relative to healthy control participants.ConclusionThe lingering memory deficits observed in remitted patients with MDD observed here are broadly consistent with findings in the literature. Importantly, however, remitted patients showed recovery of cognitive function on the Mnemonic Similarity Task. This is the first study that we are aware of to report recovery of function on a high interference, putatively neurogenesis-dependent memory test in a longitudinal sample of hospitalized MDD patients from admission to remission. Our findings are consistent with the neurogenic theory of depression, which posits that a restoration of neurogenesis is linked to recovery from depression.

Vagus Nerve Stimulation (VNS) vs. Deep Brain Stimulation (DBS) Treatment for Major Depressive Disorder and Bipolar Depression: A Comparative Meta-analytic Review Article View

International Journal of Medicine and Public Health,2018,8,3,119-130.DOI:10.5530/ijmedph.2018.3.26Published:October 2018Type:Original ArticleVagus Nerve Stimulation (VNS) vs. Deep Brain Stimulation (DBS) Treatment for Major Depressive Disorder and Bipolar Depression: A Comparative Meta-analytic ReviewAli Mahmood Khan, Rizwan Ahmed, Vijaya Padma Kotapati, Sabrina K Dar, Iqra Qamar, Afshan Jafri, Maria Ibrahim, Pawan Kumar, and Gulshan Begum Ali Mahmood Khan1*, Rizwan Ahmed2, Vijaya Padma Kotapati3, Sabrina K Dar4, Iqra Qamar5, Afshan Jafri6, Maria Ibrahim7, Pawan Kumar8, Gulshan Begum9 1University of Texas Rio Grande Valley, Texas, USA. 2Liaquat College of Medicine and Dentistry, Karachi, PAKISTAN. 3Manhattan Psychiatric Center, New York, USA. 4Zucker Hillside Hospital, New York, USA. 5Beth Israel Deaconess Medical Center, Massachusetts, USA. 6Panjabrao Deshmukh Memorial Medical College, Amravathi, Maharashtra, INDIA. 7Massachusetts Institute of Technology, Boston, USA. 8Knapp Medical Center, Weslaco, Texas, USA. 9Jamaica Hospital Medical Center, 8900 Van Wyck Expy, Richmond Hill, NY 11418, USAAbstract:Background: Patients who suffer from major depressive episodes and bipolar disorder often exhibit pharmaco-resistance. Therefore, novel treatment methodologies are being proposed to treat the disease or provide symptomatic relief. VNS and DBS are two such techniques, both of which utilize neurostimulation to achieve therapeutic relief. However, it is necessary to establish the comparative efficacies of these methods in treating MDD in patients. Objective: To assess the relative difference in the efficacy of VNS versus DBS for treatment of Major Depressive Disorder and bipolar depression and to provide evidence for the superior technique. Methods: To compare the efficacy of VNS versus DBS for the reduction of depressive symptoms in patients who meet the criteria for a major depressive episode, we conducted a meta-analysis of studies of the subject. Twenty-six studies were selected, consisting of 1160 patients who were treated with either VNS (Mean age = 47.75 years old, mean duration of illness = 22.86 years) or DBS (Mean age = 33.11 years old, mean duration of illness = 9.9 years) treatment arms and analyzed them to determine the amount of improvement in mood. The primary outcome measures were evaluated in terms of change between pre-test and post-test scores over a period of three months, as measured by HDRS and MADRS rating scales. Results: A comparison of the summary effect size produced by VNS (HDRS = 1.247, MADRS = 1.110) to that produced by DBS (HDRS = 2.063, MADRS = 1.996) seems to demonstrate that DBS is the more effective treatment. The effect size for VNS was lower than that of DBS groups, indicating that DBS is more effective than VNS. The finding is corroborated by the tests of heterogeneity; while the VNS group of studies indicated a high level of heterogeneity Vs. DBS group indicated insignificant level of heterogeneity. Conclusion: Current meta-analysis demonstrates that Deep Brain Stimulation (DBS) is a better treatment modality for Major Depressive Disorder and Bipolar Depression than Vagus Nerve Stimulation (VNS). However, as the VNS and DBS groups differed concerning the clinical profiles of the patients (both in terms of age and regarding the duration of the illness. Research studies with larger, synchronous sample sizes and control groups are required for a meta-analysis to draw a steadfast conclusion. Keywords:Bipolar Depression, DBS, Major Depressive Disorder, Neuro-modulation, VNSView:PDF (766.78 KB)

Impact of early and recent stress on white matter microstructure in major depressive disorder

BackgroundMajor Depressive Disorder (MDD) is a worldwide-spread pathology, characterized by lifetime-recurrent episodes. Adverse childhood experiences (ACE) increase the lifetime risk of developing depression and affect the structure of the brain. Recent stressful events (RSE) can trigger the onset of depressive episodes, and affect grey matter volume. The aim of our study is to analyse the effect of both early and recent stress events on white matter microstructure in MDD patients and healthy volunteers. MethodsSixty-five MDD inpatients and fifty-nine healthy controls underwent MRI acquisition of diffusion tensor images with a 3.0T scanner. Severity of ACE and RSE was rated, respectively, on the Risky Families Questionnaire and on the Social Readjustment Rating Scale. ResultsA significant effect of diagnosis was observed, with MDD subjects showing reduced fractional anisotropy (FA) and axial diffusivity (AD) compared to healthy controls in all the major association, projection and commissural tracts. In patients with MDD, but not in healthy controls, both ACE and RSE correlated with measures of WM microstructure: ACE correlated negatively with AD and MD, whereas RSE correlated negatively with FA. LimitationsThe two diagnostic groups differed for age and education, previous and current medications, and treatment periods. Conclusions. Exposure to both early and recent stress exerts a widespread effect on WM microstructure of MDD patients, with a different impact possibly depending from the developmental period in which the stress has occurred.

The recovery index: A novel approach to measuring recovery and predicting remission in major depressive disorder

BackgroundClinicians view “recovery” as the reduction in severity of symptoms over time, whereas patients view it as the restoration of premorbid functioning level and quality of life (QOL). The main purpose of this study is to incorporate patient-reported measures of functioning and QOL into the assessment of patient outcomes in MDD and to use this data to define recovery. MethodUsing the STAR*D study of patients diagnosed with MDD, this present analysis grades patients' MDD severity, functioning level, and QOL at exit from each level of the study, as well as at follow-up. Using Item Response Theory, we combined patient data from functioning and QOL measures (WSAS, Q-LES-Q) in order to form a single latent dimension named the Recovery Index. ResultsRecovery Index – a latent measure assessing impact of illness on functioning and QOL – is able to predict remission of MDD in patients who participated in the STAR*D study. ConclusionsBy incorporating functioning and quality of life, the Recovery index creates a new dimension towards measuring restoration of health, in order to move beyond basic symptom measurement.

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.

Lower PHQ-9 cutpoint accurately diagnosed depression in people with long-term conditions attending the Accident and Emergency Department

BackgroundMajor Depressive Disorder (MDD) is frequent in the Accident and Emergency Department (AED) but is often unrecognized. We aimed to assess the prevalence of MDD and determine the psychometric properties of the PHQ-9 in diagnosing MDD in patients with long-term medical conditions attending an AED. MethodsThe PHQ-9 was administered to 349 patients with diabetes, COPD and chronic inflammatory rheumatic diseases, mainly rheumatoid arthritis and spondyloarthropathies, visiting an AED. The MINI interview was used as the criterion standard for MDD. Receiver operator characteristic (ROC) curve analysis was performed to determine the optimal PHQ-9 cutpoint for MDD. Construct validators included psychological distress (SCL-90-R), illness perceptions (B-IPQ) and Health-Related Quality of Life (WHOQOL-BREF). ResultsThe prevalence of MDD was 27.2%. At an optimal cutpoint of 8, PHQ-9 had a sensitivity of 90.5% and specificity of 89.4%. The area under the curve (0.96) was excellent. Convergent validity was established by the strong associations between PHQ-9 scores and functional status, SCL-90-R depression, illness perceptions and AED visits during the previous year. LimitationsThe sample consisted of multiple rather a single disease group, preventing us from accounting for illness severity using specific disease severity indices. ConclusionMDD is frequent in patients with long-term medical conditions attending the AED and the PHQ-9, at a cutpoint of 8, is an accurate, reliable and valid measure for MDD screening in this patient population.

Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder

In this study, we used new technology to investigate whether a coherent pattern of enhanced expression of inflammatory and other immune activation genes in circulating monocytes is found in patients with major depression. Since a high inflammatory state of monocytes might be related to glucocorticoid resistance, we also included the genes for the two isoforms of the glucocorticoid receptor. For this study, we aimed at finding a similar coherent pattern of inflammatory and immune activation genes in monocytes of patients with MDD and recruited 47 medication-free melancholic MDD inpatients and 42 healthy controls. A quantitative-polymerase chain reaction (Q-PCR) monocyte gene expression analysis was performed using a panel of inflammatory-related genes previously identified as abnormally regulated in mood disorder patients. Selected serum cytokines/chemokines were assessed using a cytometric bead array. Depressive symptoms were analysed using Hamilton depression scores (HAMD). Thirty-four of the 47 monocyte inflammatory-related genes were significantly upregulated and 2 were significantly downregulated as compared to controls, the latter including the gene for the active GRα in particular in those with a high HAMD score. The reduced GRα expression correlated strongly to the upregulation of the inflammatory genes in monocytes. Serum levels of IL6, IL8, CCL2 and VEGF were significantly increased in patients compared to controls. Our data show the deregulation of two interrelated homoeostatic systems, that is, the immune system and the glucocorticoid system, co-occurring in major depression.

Dimensions in major depressive disorder and their relevance for treatment outcome

BackgroundMajor depressive disorder (MDD) is a heterogeneous disease. More homogeneous psycho(patho)logical dimensions would facilitate MDD research as well as clinical practice. The first aim of this study was to find potential dimensions within a broad psychopathological assessment in depressed patients. Second, we aimed at examining how these dimensions predicted course in MDD. MethodsTen psychopathological variables were assessed in 75 MDD inpatients. Factor and regression analyses assessed putative relations between psychopathological factors and depression severity and outcome after 8 weeks of treatment. ResultsA 3-factor model (eigenvalue: 54.4%) was found, representing a psychomotor change, anhedonia and negative affect factor. Anhedonia and negative affect predicted depression severity (R2=0.37, F=20.86, p<0.0001). Anhedonia predicted non-response (OR 6.00, CI 1.46–24.59) and both negative affect (OR 5.69, CI 1.19–27.20) and anhedonia predicted non-remission (OR 9.28, CI 1.85–46.51). LimitationsThe sample size of the study was relatively modest, limiting the number of variables included in the analysis. ConclusionsResults confirm that psychomotor change, anhedonia and negative affect are key MDD dimensions, two of which are related to treatment outcome.

Acetylcholine and alpha 1-adrenergic sensitivity in the separation of depression and anxiety.

Three relatively clear-cut diagnostic groups, namely primary major depressive disorder-endogenous subtype (PRI MDD-E), primary anxiety disorder with no depression (PRI ANX), and normal controls as well as two additional patient groups with mixed or coexisting anxious/depressive diagnoses were studied. Clinical assessment was made by routine psychiatric interview, Schedule of Affective Disorder and Schizophrenia (SADS) research interview, and obtaining family history of MDD. Subjects underwent both routine 'baseline' sleep EEG polygraphic arecoline, a muscarinic, cholinergic agonist infused during sleep. Cholinergic sensitivity was assessed by measuring the time to induction of REM sleep after arecoline infusion. In addition, a subgroup of MDD patients underwent pupillographic testing. Peripheral alpha-adrenergic responsivity was measured by the magnitude of pupillary mydriatic response after local ocular instillation of phenylephrine. Successful separation (83% correct classification) of the 'pure' groups (PRI MDD-E, PRI ANX, and normal) was achieved by discriminant function analysis of sleep EEG variables. Compared to PRI ANX and normal groups, patients with PRI MDD-E had supersensitive cholinergic REM-induction response, shorter REM latency, increased first REM density and REM percent. Separation of the PRI ANX and normal groups was by intermittent awake time, delta sleep percent, and total REM density. Classification of the mixed anxious/depressive groups was next attempted using the discriminant coefficients derived from the above analysis of 'pure' groups. We found that the presence of absence of family history of MDD in patients with mixed diagnosis offered the best prediction of classification into PRI MDD-E and PRI ANX groups, respectively. MDD patients with coexisting panic disorder were significantly subsensitive to phenylephrine-induced mydriasis compared to MDD patients without anxiety.