Lower levels of brain-derived neurotrophic factor are associated with melancholic psychomotor retardation among depressed inpatients.

OBJECTIVES: Melancholic depression is a type of depression which is closely related to biological variables than are other types of depression. Its clinical features can be assessed using six items on the Hamilton Depression Rating Scale (HAM-D6 ). Previous studies have shown, using item response theory, that the symptom depressed mood is the least severe melancholic feature; work and activities, somatic symptoms and psychic anxiety are of moderate severity; and feelings of guilt and psychomotor retardation are the most severe. We aimed to evaluate whether the more severe melancholic signs or symptoms were associated with decreases in brain-derived neurotrophic factor (BDNF) levels. METHODS: A total of 151 severely depressed inpatients had their BDNF levels analyzed by comparing those who presented with each HAM-D6 melancholic feature to those for whom the HAM-D6 feature was absent, using multiple linear regressions. The levels of BDNF of patients who presented with each melancholic feature were also compared with those of 100 healthy controls. RESULTS: Depressed patients' median BDNF level was 44.06 ng/mL (interquartile range [IQR]: 33.99-62.4 ng/mL), and controls' median BDNF level was 65.22 ng/mL (IQR: 49.87-76.08 ng/mL) (P < .001). The presence of depressed mood, work and activities, somatic symptoms, psychic anxiety, and guilty feelings was not associated with BDNF levels. However, the presence of psychomotor retardation was associated with reduced BDNF (median reduction -10.07 ng/mL; 95% confidence interval [CI]: -19.43 to -0.71; P = .03). CONCLUSIONS: To the best of our knowledge, this study is the first to associate BDNF levels with melancholic features in a sample of severely depressed inpatients. The main finding of this study was that severely depressed inpatients who presented the most severe melancholic feature, psychomotor retardation, had significantly reduced BDNF levels in the blood.

Pharmacological treatment of bipolar depression: qualitative systematic review of double-blind randomized clinical trials.

Randomized clinical trial (RCT) is the best study design for treatment-related issues, yet these studies may present a number of biases and limitations. The objective of this study is to carry out a qualitative analysis of RCT methodology in the treatment of bipolar depression (BD). A systematic review covering the last 20 years was performed on PubMed selecting double-blind RCTs for BD. The identification items of the articles, their design, methodology, outcome and grant-related issues were all analyzed. Thirty articles were included, all of which had been published in journals with an impact factor >3. While almost half studies (46.7%) used less than 50 patients as a sample, 70% did not describe or did not perform sample size calculation. The Last Observation Carried Forward (LOCF) method was used in 2/3 of the articles and 53.4% of the studies had high sample losses (>20%). Almost half the items were sponsored by the pharmaceutical industry and 33.3% were sponsored by institutions or research foundations. Articles on the pharmacological treatment of BD have several limitations which hinder the extrapolation of the data to clinical practice. Methodological errors and biases are common and statistical simplifications compromise the consistency of the findings.

Protective factors against depressive symptoms among Brazilian healthcare workers during the initial stages of the COVID-19 pandemic: a cross-sectional study.

OBJECTIVES: This study aims to assess the prevalence of depressive symptoms among healthcare workers and possible factors associated with this outcome (resilience, spirituality, social support, quality of life, among other individual variables). Our hypothesis is that some of these factors can have a protective effect on depressive symptoms. DESIGN: Web-based cross-sectional survey. SETTING: Participants were recruited online from 16 April to 23 April 2020. PARTICIPANTS: 1043 healthcare workers, predominantly Brazilians, aged 18 years or older. PRIMARY AND SECONDARY OUTCOME MEASURES: Depression was the primary outcome, measured using the Patient Health Questionnaire-9 (PHQ-9). Possible protective factors were measured in the following ways: social support was assessed by the modified Medical Outcomes Study Social Support Survey (mMOS-SS); spirituality, religiousness and personal beliefs (SRPB) were evaluated using the 9-item SRPB module of the brief WHO Quality of Life instrument (WHOQoL-SRPB-bref); quality of life was assessed using the brief EUROHIS instrument for Quality of Life (EUROHIS-QoL 8-item); resilience was assessed using the 10-item Connor-Davidson Resilience Scale (CD-RISC 10). RESULTS: 23% met the criteria for depression according to the PHQ-9 scale. Quality of life (B=-3.87 (-4.30 to -3.43), ß=-0.37, p<0.001), social support (B=-0.32 (-0.59 to -0.05), ß=-0.04, p=0.022), resilience (B=-0.19 (-0.23 to -0.15), ß=-0.20, p<0.001), SRPB (B=-0.03 (-0.05 to -0.02), ß=-0.01, p<0.001) and physical exercise (B=-0.95 (-1.40 to -0.51), ß=-0.08, p<0.001) demonstrated protective effects against depression. CONCLUSION: Healthcare workers have a high risk of developing depressive symptoms during the COVID-19 pandemic, especially those working in the front line. However, there are factors that seem to work as protective mechanisms against depression, notably perceived quality of life.

Different cytokine patterns associate with melancholia severity among inpatients with major depressive disorder.

BACKGROUND: Six melancholic features (MFs) of the Hamilton Depression Rating Scale (HAM-D6) represent the construct of melancholia along a continuum of severity (from least to most severe: depressed mood, work and activities, somatic symptoms, psychic anxiety, guilty feelings, psychomotor retardation). We aimed to evaluate the association between these MFs and inflammatory cytokines (IC) in the blood. METHODS: Each IC [interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2), IL-4, IL-6, IL-10, and IL-17] was associated with the HAM-D6 MFs of 139 severely depressed inpatients, using multiple linear regressions adjusted for covariates. Levels were compared with those of 100 healthy controls. RESULTS: Depressed mood was associated with higher levels of IL-4 (ß = 0.167; p = 0.041). Psychic anxiety: lower IL-17 levels (ß = -0.173; p = 0.039). Guilt feelings: lower IL-2 levels (ß = -0.168; p = 0.041) Psychomotor retardation: higher IL-6 levels (ß = 0.195; p = 0.017). Depressed patients' TNF-α, INF-γ, and IL-4 levels were not significantly different from controls. Depressed patients' IL-2, IL-6, IL-10, and IL-17 levels were higher than those of controls (p <0.001). CONCLUSION: Less severe MFs (depressed mood, psychic anxiety, and guilt feelings) were associated with an anti-inflammatory pattern (higher IL-4, lower IL-17 and lower IL-2, respectively). The presence of the most severe MF, psychomotor retardation, was associated with a higher pro-inflammatory response (higher IL-6).

The Major Depressive Disorder Hierarchy: Rasch Analysis of 6 items of the Hamilton Depression Scale Covering the Continuum of Depressive Syndrome.

OBJECTIVES: Melancholic features of depression (MFD) seem to be a unidimensional group of signs and symptoms. However, little importance has been given to the evaluation of what features are related to a more severe disorder. That is, what are the MFD that appear only in the most depressed patients. We aim to demonstrate how each MFD is related to the severity of the major depressive disorder. METHODS: We evaluated both the Hamilton depression rating scale (HDRS-17) and its 6-item melancholic subscale (HAM-D6) in 291 depressed inpatients using Rasch analysis, which computes the severity of each MFD. Overall measures of model fit were mean (±SD) of items and persons residual = 0 (±1); low χ2 value; p>0.01. RESULTS: For the HDRS-17 model fit, mean (±SD) of item residuals = 0.35 (±1.4); mean (±SD) of person residuals = -0.15 (±1.09); χ2 = 309.74; p<0.00001. For the HAM-D6 model fit, mean (±SD) of item residuals = 0.5 (±0.86); mean (±SD) of person residuals = 0.15 (±0.91); χ2 = 56.13; p = 0.196. MFD ordered by crescent severity were depressed mood, work and activities, somatic symptoms, psychic anxiety, guilt feelings, and psychomotor retardation. CONCLUSIONS: Depressed mood is less severe, while guilt feelings and psychomotor retardation are more severe MFD in a psychiatric hospitalization. Understanding depression as a continuum of symptoms can improve the understanding of the disorder and may improve its perspective of treatment.