Serum cytokine variations among inpatients with major depression, bipolar disorder, and schizophrenia versus healthy controls: a prospective 'true-to-life' study.

Background: There is increasing evidence of the association between chronic low-grade inflammation and severe mental illness (SMI). The objective of our study was to assess serum cytokine levels (SCLs) at admission and discharge in a true-to-life-setting population of inpatients with major depression (MD), bipolar disorder (BD), and schizophrenia (Sz), as well as of healthy controls. Methods: We considered MD, BD, and Sz to be SMIs. We evaluated 206 inpatients [MD, N = 92; BD, N = 26; mania (Ma), N = 44; Sz, N = 44). Generalized estimating equations were used to analyze variations in SCL [interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17] at hospital admission and discharge. Results of 100 healthy controls were compared with those of SMI patients at both time points. We evaluated patients' improvement during in-hospital treatment in terms of general psychiatric symptoms, global clinical impression, functionality, and manic and depressive symptoms with validated scales. Results: In all, 68.9% of patients completed the study. Overall, SMI inpatients had higher SCL when compared with controls regardless of diagnosis. There was a significant decrease in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity Scale (CGI-S) scores, and an increase in Global Assessment of Functioning (GAF) scores for all disorders evaluated (p < 0.001), as well as a significant decrease in HDRS-17 scores among MD inpatients (p < 0.001) and in YMRS scores among Ma inpatients (p < 0.001). IL-2 and IL-6 levels decreased significantly between admission and discharge only among MD inpatients (p = 0.002 and p = 0.03, respectively). We found no further statistically significant changes in SCL among the remaining disorders (BD, Ma, and Sz). There was no significant decrease in IFN-γ (p = 0.64), TNF-α (p = 0.87), IL-4 (p = 0.21), IL-10 (p = 0.88), and IL-17 (p = 0.71) levels in any of the evaluated diagnoses. Conclusion: MD inpatients had a decrease in IL-2 and IL-6 levels during hospitalization, which was accompanied by clinical improvement. No associations were found for the remaining SMIs (BD, Ma, and Sz).

Potential predictors of depressive symptoms during the initial stage of the COVID-19 outbreak among Brazilian adults.

BACKGROUND: In early 2020, Sars-Cov-2 was identified in China as a new coronavirus. Due to its transmission, Sars-Cov-2 has spread rapidly across the world. In the early stage of the disease outbreak, psychiatric symptoms have been reported, including depressive symptoms. In this study, we assessed the prevalence of depressive symptoms in quarantine and its association with sociodemographic variables and known protective factors for depression, such as spirituality, social support, resilience, and quality of life. METHODS: A cross-sectional web-based questionnaire was distributed via social media. The instruments consisted of the 8-item EUROHIS-QOL, PHQ-9, Social Support Questionnaire, WHOQoL-SRPB, and CD-RISC. RESULTS: A total of 3,274 participants were included in this study. 23.67% of the participants met the criteria for a depressive episode. Higher age, spirituality, social support, resiliency, and quality of life were associated with less depressive symptoms. Quarantine length; mental health treatment; chronic disease; age; sex; lower levels of spirituality, social support, resilience, quality of life, physical exercise, and education; and unpaid occupation were found to be predictors of depressive symptoms during COVID-19 quarantine. LIMITATIONS: The data are limited to the pandemic initial period, the sample isn't random and the use of self-reported questionnaires are some limitations of our study. CONCLUSIONS: During the initial phase of the COVID-19 outbreak in Brazil, quarantine time, treatment for mental health, chronic illness, lower levels of education, and unpaid occupation were positively associated with depressive symptoms. Age, sex, spirituality, social support, resilience, quality of life, and physical exercise showed a negative relationship with depressive symptoms.

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).

Psychotic depression in hospitalized patients: Longitudinal outcomes of psychotic vs. nonpsychotic depression among inpatients.

Even though psychotic depression is related to worse outcomes than nonpsychotic depression, there is increasing evidence that this greater severity is not solely explained by the depressive symptoms. We evaluated the socio-demographic and clinical characteristics, as well as the differences in clinical outcomes of psychiatric hospitalization between psychotic and non-psychotic depression. Two-hundred-eighty-eight depressive inpatients were assessed within 72 h after hospitalization and 24 h before discharge. We compared scores of Hamilton Depression Rating Scale 17-items (HDRS-17), Clinical Global Impression (CGI), Brief Psychiatric Rating Scale (BPRS), and Global Assessment of Functioning (GAF) between psychotic and nonpsychotic patients. Instruments were compared both cross-sectionally - on admission and discharge - and longitudinally. Longitudinal outcomes were corrected for potential confounders (sex, age, age at disease onset, years of study, previous history of mania/hypomania, electroconvulsive therapy in current hospitalization, history of attempted suicide, number of suicide attempts, and previous hospitalizations). One-hundred-thirty-one depressive inpatients (45.4%) presented psychotic features. Both groups showed similar HDRS-17 scores at admission and discharge. However, psychotic patients had worse scores on BPRS, CGI, and GAF at both timepoints. Both groups had similar improvement on HDRS-17 (P = 0.75), CGI (P = 0.5), and GAF (P = 0.84), but psychotic patients had greater improvement on BPRS (P < 0.001). Psychotic inpatients showed worse clinical and functional parameters. Nonetheless, the groups did not differ in depressive symptom severity. These findings reinforce the hypothesis that depressive episode with psychotic features is a more severe form of the disease irrespective of intensity of affective symptomatology.

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.

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.