Edgar Arrua Vares

Biological differences between melancholic and nonmelancholic depression subtyped by the CORE measure

Background The purpose of this study was to compare melancholic patients rated by the CORE measure of observable psychomotor disturbance with nonmelancholic and control subjects across a set of biomarkers. Methods Depressed patients were classified as melancholic or nonmelancholic by using the CORE measure. Both groups of patients, as well as control subjects, were compared for a set of clinical and laboratory measures. Serum levels of brain-derived neurotrophic factor, of two markers of oxidative stress (protein carbonyl content [PCC] and thiobarbituric acid reactive substances [TBARS]), and of several immunity markers (interleukin [IL]-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-alpha, and interferon-gamma) were analyzed. Results Thirty-three depressed patients and 54 healthy controls were studied. Depressive patients showed higher IL-4, IL-6, and PCC values than healthy controls. Thirteen (39%) of the depressed patients were assigned as melancholic by the CORE measure. They generated lower interferon-gamma (compared with nonmelancholic depressed patients) and TBARS (compared with both the nonmelancholic subset and controls) and returned higher IL-6 levels than controls. Both depressive groups generated higher PCC scores than controls, with no difference between melancholic and nonmelancholic subsets. Conclusion A sign-based measure to rate melancholia was able to replicate and extend biological findings discriminating melancholic depression. Signs of psychomotor disturbance may be a useful diagnostic measure of melancholia.

Depression Dimensions: Integrating Clinical Signs and Symptoms from the Perspectives of Clinicians and Patients.

Background Several studies have recognized that depression is a multidimensional construct, although the scales that are currently available have been shown to be limited in terms of the ability to investigate the multidimensionality of depression. The objective of this study is to integrate information from instruments that measure depression from different perspectives–a self-report symptomatic scale, a clinician-rated scale, and a clinician-rated scale of depressive signs–in order to investigate the multiple dimensions underlying the depressive construct. Methods A sample of 399 patients from a mood disorders outpatient unit was investigated with the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HDRS), and the Core Assessment of Psychomotor Change (CORE). Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were used to investigate underlying dimensions of depression, including item level analysis with factor loadings and item thresholds. Results A solution of six depression dimensions has shown good-fit to the data, with no cross-loading items, and good interpretability. Item-level analysis revealed that the multidimensional depressive construct might be organized into a continuum of severity in the following ascending order: sexual, cognitive, insomnia, appetite, non-interactiveness/motor retardation, and agitation. Conclusion An integration of both signs and symptoms, as well as the perspectives of clinicians and patients, might be a good clinical and research alternative for the investigation of multidimensional issues within the depressive syndrome. As predicted by theoretical models of depression, the melancholic aspects of depression (non-interactiveness/motor retardation and agitation) lie at the severe end of the depressive continuum.

Translation and cross-cultural adaptation of the Temperament & Personality Questionnaire into Brazilian Portuguese

INTRODUCTION The Temperament & Personality Questionnaire (T&P) is a self-report instrument designed to evaluate personality styles overrepresented in patients with depression. This report briefly describes the translation and adaptation of the T&P into Brazilian Portuguese. METHODS The procedures, which included 10 steps, followed guidelines for the adaptation of self-report instruments defined by the International Society For Pharmacoeconomics and Outcomes Research (ISPOR) Task Force for Translation and Cultural Adaptation. RESULTS The author of the original T&P questionnaire authorized and participated in the translation conducted by the authors and independent native speakers. Evaluation of the translated questionnaire indicated that only minor adjustments were required in the Portuguese version. CONCLUSIONS The Brazilian version of T&P, translated and adapted following a rigid standardized process, is available for use free of charge and may be especially useful in pursuing links between personality styles and depressive conditions.

Childhood trauma and dimensions of depression: a specific association with the cognitive domain.

Objective: To investigate associations between a history of childhood trauma and dimensions of depression in a sample of clinically depressed patients. Methods: A sample of 217 patients from a mood-disorder outpatient unit was investigated with the Beck Depression Inventory, the Hamilton Depression Rating Scale, the CORE Assessment of Psychomotor Change, and the Childhood Trauma Questionnaire. A previous latent model identifying six depressive dimensions was used for analysis. Path analysis and Multiple Indicators Multiple Causes (MIMIC) models were used to investigate associations between general childhood trauma and childhood maltreatment modalities (emotional, sexual, and physical abuse; emotional and physical neglect) with dimensions of depression (sexual, cognition, insomnia, appetite, non-interactiveness/retardation, and agitation). Results: The overall childhood trauma index was uniquely associated with cognitive aspects of depression, but not with any other depressive dimension. An investigation of childhood maltreatment modalities revealed that emotional abuse was consistently associated with depression severity in the cognitive dimension. Conclusion: Childhood trauma, and specifically emotional abuse, could be significant risk factors for the subsequent development of cognitive symptoms of major depression. These influences might be specific to this depressive dimension and not found in any other dimension, which might have conceptual and therapeutic implications for clinicians and researchers alike.

Association between core-assigned melancholia and the melancholia subscale of the HAM-D

BACKGROUND Clinical observation and research data suggest that major depression (MD) is a heterogeneous disorder, possibly representing a group of different clinical entities. The identification of more homogeneous subtypes of depression could enhance research and enable development of more specific treatments. A melancholic subtype of MD, defined by the presence of observable psychomotor disturbance (PMD), is proposed to be more homogeneous and associated with biological determinants. The aim of this study was to investigate the homogeneity of this melancholic subtype in terms of symptoms by searching for an association between melancholia and a unidimensional subscale of the Hamilton Depression Rating Scale (HAM-D) proposed to have biological validity (HAM-D6). METHODS A cross-sectional assessment of 385 outpatients presenting with a unipolar major depressive episode was carried out to evaluate depressive symptoms using the HAM-D and melancholic or nonmelancholic subtype, according to the CORE measure of PMD. RESULTS Melancholic patients exhibited more severe depressive symptoms, mainly associated with the HAM-D6. The items of this melancholia subscale represent 42.3% of the total HAM-D and were responsible for 59.4% of between-group differences. Correlation analysis showed similar results. LIMITATIONS Most patients received previous treatment, and some were not at the nadir of the episode when assessed. This could have lowered the CORE measure sensibility. CONCLUSION Melancholic depression, as assigned by the CORE measure, represents a more severe and homogeneous subtype of MD. This observation may allow identification of proper biomarkers and development of more specific treatments.

Val66Met polymorphism association with serum BDNF and inflammatory biomarkers in major depression

Abstract Objectives: Current evidence supports participation of neurotrophic and inflammatory factors in the pathogenesis of major depressive disorder (MDD). Some studies reported an association between the Val66Met polymorphism (rs6265) of brain-derived neurotrophic factor (BDNF) gene with MDD and peripheral BDNF levels. However, no previous studies have examined the association of this polymorphism with inflammation. The present study assessed the association of the Val66Met polymorphism with serum levels of BDNF and inflammatory markers among depressed outpatients. Methods: All participants (n = 73) met DSM-IV criteria for a unipolar depressive episode. The serum levels of BDNF and inflammatory biomarkers (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) were compared between individuals presenting with at least one Met allele (Met-carriers) and those homozygous for the Val allele. Results: In our sample (84.9% female, mean age 52.4 ± 10.3 years), 24.7% (n = 18) were Met-carriers. After Bonferroni correction, the Met allele was significantly associated with higher BDNF and lower TNF-α. These associations persisted after adjusting for potential confounders. Conclusions: The pattern of low BDNF and high inflammation in MDD may be influenced by the Val66Met polymorphism. The association of a polymorphism in the BDNF gene with inflammatory markers in addition to BDNF levels suggests an interaction between these systems.

Illness severity and biomarkers in depression: Using a unidimensional rating scale to examine BDNF

BACKGROUND Numerous studies have reported reduced peripheral brain-derived neurotrophic factor (BDNF) in major depression (MD). However, most of these studies used multidimensional depression rating scales, and failed to identify a relationship between BDNF levels and depression severity. Unidimensional scales are a more valid measure of syndrome severity. In these scales, items are ordered in increasing severity, so that as scores increase, syndrome severity increases; thus, each item adds unique information, and items can be totaled to a meaningful sum. The current study used the HAM-D6, a unidimensional measure of depression, to examine if it could identify a correlation between serum BDNF and depression severity. METHODS Serum BDNF levels and symptom severity were assessed in 163 depressed patients, including those with both unipolar (84.0%) and bipolar (16.0%) depression. The evaluation of depression severity included the total HAM-D17 and 3 subscales, including the HAM-D6. RESULTS On average, patients presented moderate to severe depression (HAM-D17=21.2±5.5). Overall BDNF levels were 60.4±22.6ng/mL. The correlation between serum BDNF and depression severity was modest and not different when assessed by the HAM-D6 subscale or the HAM-D17 as a whole (z=0.951; p=0.341), despite being statistically significant for the HAM-D6 (r=-0.185; p=0.019; 95% CI: -0.335 to -0.033), but not for the entire HAM-D17 (r=-0.127; p=0.108; 95% CI: -0.272 to 0.027). CONCLUSION We could not identify a strong relationship between serum BDNF levels and depression severity using the HAM-D6. This is in concordance with results of previous studies that reported no correlation between these variables, and indicates that the properties of the clinical measures used cannot explain the results these studies.