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Lucas Spanemberg,1,2 Marco Antonio Caldieraro,1 Edgar Arrua Vares,1 Bianca Wollenhaupt-Aguiar,3,4 Márcia Kauer-Sant’Anna,3,4 Sheila Yuri Kawamoto,1 Emily Galvão,3–5 Gordon Parker,6,7 Marcelo P Fleck1,8 1Mood Disorders Program, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, 2Department of Psychiatry, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, 3INCT Translational Medicine, Hospital de Clínicas de Porto Alegre, 4Bipolar Disorders Program and Laboratory of Molecular Psychiatry, Universidade Federal do Rio Grande do Sul, 5Centro Universitário Metodista, Porto Alegre, Brazil; 6School of Psychiatry, University of New South Wales, 7Black Dog Institute, Sydney, NSW, Australia; 8Neuromodulation Research Clinic, Douglas Mental Health University Institute, Montréal, ON, Canada 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. Keywords: melancholic depression, oxidative stress, inflammatory cytokines, brain-derived neurotrophic factor

Background: There has been increasing interest in the measurement of quality of life in cross-sectional investigations and in the assessment of intervention outcomes in elderly adults. Several instruments used in this measurement have not yet been adequately tested.Objective: To describe the psychometric properties of the World Health Organization's Quality of Life Instrument-Short Version (WHOQOL-BREF) in a sample of Brazilian elderly.Method: A total of 424 elderly adults selected through convenience sampling completed the instruments WHOQOL-BREF, the Beck Depression Inventory (BDI), the Beck Hopelessness Scale (BHS) and a sociodemographic data form. Discriminant validity, concurrent validity, criterion validity and internal consistency were analyzed.Results: The sample comprised predominantly women (64.2%), community-dwelling subjects (84.4%) and subjects who consider themselves healthy (67.5%). All domains in the instrument showed the ability to discriminate levels of depressive symptoms and hopelessness, as well as different perceptions of health status. The correlation coefficients among the domains and the BDI and BHS scores were statistically significant. The reliability coefficients present scores ranging from 0.614 to 0.925.Conclusion: The WHOQOL-BREF instrument shows suitable psychometric performance in a sample of Brazilian older adults, becoming a useful alternative in the measurement of quality of life in this population. [ABSTRACT FROM AUTHOR]

Background: Chronic pain (CP) and thyroid hormones' (TH) abnormalities are associated with depression, but the impact of pain and TH fluctuation on the response to depression treatment is uncertain., Methods: Eighty-eight patients with major depression were evaluated before and after 6 months of specific treatment, through scales of symptoms' severity (HAM-D-17), psychomotor disturbance (CORE), and quality of life (WHOQOL-Bref). We reviewed psychiatric medications and measured TSH, T3 and T4. We used Generalized Estimating Equations to assess the interaction effect between CP and treatment time on depression severity and TH levels, and Bonferroni to compare means., Results: 47.7 % of the patients had CP. Patients with and without CP did not differ at baseline. At follow-up, those with CP experienced a more modest decrease in symptoms' severity and no improvement in any domain of psychomotor disturbance, contrasting with a decrease of over 40 % from the baseline values of CORE in patients without CP (non-CP). Initial and final scores were respectively: HAM-D CP 24.06 and 19.3, Δ = -4.75; HAM-D non-CP 22.92 and 14.7, Δ = -8.21; CORE CP 5.36 and 5.24, Δ = -0.12; CORE non-CP 5.8 and 3.22, Δ = -2.57. There was no interaction with TH or life quality. Model adjustments for psychotropic drugs received and sensitivity analysis excluding somatic symptoms from severity scales did not impact the results., Limitations: Findings may not replicate in mildly depressed patients from primary care. Pain scales were not applied., Conclusions: Individuals with chronic pain showed a suboptimal response to depression treatment, regardless of the medications used or TH levels., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Background: The definition of population-specific outcomes is an essential precondition for the implementation of value-based health care. We developed a minimum standard outcome set for overall adult health (OAH) to facilitate the implementation of value-based health care in tracking, comparing, and improving overall health care outcomes of adults across multiple conditions, which would be of particular relevance for primary care and public health populations., Methods: The International Consortium for Health Outcomes Measurement (ICHOM) convened an international panel (patients, clinicians, and topic experts). Following the development of a conceptual framework, a modified Delphi method (supported by public consultations) was implemented to identify, in sequence, the relevant domains, the best instruments for measuring them, the timing of measurement, and the relevant adjustment variables., Findings: Outcomes were identified in relation to overall health status and the domains of physical, mental, and social health. Three instruments covering these domains were identified: PROMIS Scale v1.2-Global Health (10 items), WHO Wellbeing Index (5 items), and the WHO Disability Assessment Schedule 2.0 (12 items). Case-mix variables included a range of sociodemographic and biometric measures. Yearly measurement was proposed for all outcomes and most case-mix variables., Interpretation: The ICHOM OAH Standard Set has been developed through consensus-based methods based on predefined criteria following high standards for the identification and selection of high-quality measures The involvements of a wide range of stakeholders supports the acceptability of the set, which is readily available for use and feasibility testing in clinical settings., (© 2021. The Author(s).)

Objectives: The COVID-19 pandemic has resulted in widespread morbidity and mortality with the consequences expected to be felt for many years. Significant variation exists in the care even of similar patients with COVID-19, including treatment practices within and between institutions. Outcome measures vary among clinical trials on the same therapies. Understanding which therapies are of most value is not possible unless consensus can be reached on which outcomes are most important to measure. Furthermore, consensus on the most important outcomes may enable patients to monitor and track their care, and may help providers to improve the care they offer through quality improvement. To develop a standardised minimum set of outcomes for clinical care, the International Consortium for Health Outcomes Measurement (ICHOM) assembled a working group (WG) of 28 volunteers, including health professionals, patients and patient representatives., Design: A list of outcomes important to patients and professionals was generated from a systematic review of the published literature using the MEDLINE database, from review of outcomes being measured in ongoing clinical trials, from a survey distributed to patients and patient networks, and from previously published ICHOM standard sets in other disease areas. Using an online-modified Delphi process, the WG selected outcomes of greatest importance., Results: The outcomes considered by the WG to be most important were selected and categorised into five domains: (1) functional status and quality of life, (2) mental functioning, (3) social functioning, (4) clinical outcomes and (5) symptoms. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, clinical factors and treatment-related factors., Conclusion: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of care to patients with COVID-19. Their consistent definition and collection could also broaden the implementation of more patient-centric clinical outcomes research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The Sydney Melancholia Prototype Index (SMPI) is a scale that uses a non-conventional strategy to assess melancholia status based on prototypic symptoms and illness course variables. This study aimed to evaluate the performance of the first translation of this instrument in a non-English-speaking population., Methods: A sample comprising 106 Brazilian outpatients with depression was evaluated simultaneously with the Brazilian version of the self-rated SMPI (SMPI-SR) and clinician-rated SMPI (SMPI-CR). The kappa coefficient and t test were used to evaluate concurrent validity vs. DSM-IV, CORE system, Hamilton Depression Rating Scale-6 item (HAM-D6), and HAM-D17 assignments to a melancholic or non-melancholic class. The prevalence of melancholia as well as sensitivity and specificity were calculated across instruments., Results: The prevalence of melancholia was highest using DSM-IV criteria (56.6%). The kappa agreement between SMPI-CR and DSM-IV melancholia assignment was moderate (kappa 0.44, p ≤ 0.001). SMPI-CR-assigned melancholic patients had significantly higher CORE, HAM-D17, and HAM-D6 scores. The test-retest consistency values for the SMPI were modest at best, and somewhat superior for the CR version., Conclusion: The Brazilian SMPI-CR presented satisfactory psychometric properties (which were superior to those of the SMPI-SR), and therefore appears to be a useful option for identifying melancholia and studying its causes and optimal treatments.

Background: Major depressive disorder (MDD) is heterogeneous, but official diagnostic classifications and widely used rating scales are based on the premise that MDD is a single disorder and that symptoms are equally important to assess severity. Also, patients and clinicians frequently diverge in how they evaluate MDD severity. In order to better understand the differences between MDD scales used by clinicians and patients in the context of MDD heterogeneity, we performed a network analysis from an approach that focuses on the interaction of symptoms rather than total score., Methods: The Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory with 21 items (BDI) scored by the clinician or patient, respectively, were used to estimate the networks based on 794 MDD patients. The networks were estimated using software R 4.0.2 and Graphical Lasso, identifying communities of symptoms by the clique percolation method, and the mixed graphical models were used to evaluate the explained variance of each symptom., Results: The networks presented different communities of symptoms and connection structure (M = 0.177, p = 0.0028). The guilt connection strength and its association with suicidal ideation was greater in the BDI network., Limitations: Transversal data from severe, chronic, or treatment resistant depression patients., Conclusions: The present study suggests that the self-rated scale may perform better when assessing association between guilt and other symptoms, especially suicidal ideation. Communities of symptoms and edges between symptoms suggest that insomnia may be an independent symptom, thus requiring specific interventions. Some similar items are strongly connected and could be collapsed., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: The recognition of the Brazilian Sign Language (Libras) as the official language of the Brazilian deaf, in 2002, reaffirms the linguistic and cultural particularities of the deaf population. Therefore, there is a lack of a validated instrument for assessing the Quality of Life of deaf people using Libras. With authorization from the World Health Organization (WHO), a version of the WHOQOL-Bref in Libras was developed, called WHOQOL-Bref/Libras. However, its psychometric properties have not been examined as yet. Therefore, the purpose of this work is to perform the psychometric validation of the WHOQOL-Bref/Libras., Methods: WHOQOL-Bref/Libras and a sociodemographic questionnaire were applied to 311 deaf people from the five Brazilian regions. To assess temporal stability, the questionnaire was readministered to 52 deaf people, over an interval of 2 weeks., Results: WHOQOL-Bref/Libras demonstrated satisfactory psychometric values for reliability, discriminant and construct validity, temporal stability, and internal consistency. Cronbach's alpha coefficient showed satisfactory values for each of the WHOQOL-Bref domains: Physical health (0.641), Psychological (0.705), Environment (0.710), and Overall-Bref domains (0.873). The WHOQOL-Bref/Libras is the appropriate option to assess the quality of life of deaf people who communicate through Libras., Conclusion: WHOQOL-Bref/Libras had a satisfactory psychometric performance; therefore, it is a valid option that will provide autonomous participation for the deaf in quality of life investigations.

Patient-reported outcome measures (PROMs) are self-rated scales and indices developed to improve the detection of the patients' subjective experience. Given that a considerable number of PROMs are available, it is important to evaluate their validity and usefulness in a specific research or clinical setting. Published guidelines, based on psychometric criteria, do not fit in with the complexity of clinical challenges, because of their quest for homogeneity of components and inadequate attention to sensitivity. Psychometric theory has stifled the field and led to the routine use of scales widely accepted yet with a history of poor performance. Clinimetrics, the science of clinical measurements, may provide a more suitable conceptual and methodological framework. The aims of this paper are to outline the major limitations of the psychometric model and to provide criteria for clinimetric patient-reported outcome measures (CLIPROMs). The characteristics related to reliability, sensitivity, validity, and clinical utility of instruments are critically reviewed, with particular reference to the differences between clinimetric and psychometric approaches. Of note is the fact that PROMs, rating scales, and indices developed according to psychometric criteria may display relevant clinimetric properties. The present paper underpins the importance of the clini-metric methodology in choosing the appropriate PROMs. CLIPROM criteria may also guide the development of new indices and the validation of existing PROMs to be employed in clinical settings., (© 2021 S. Karger AG, Basel.)

Introduction: Depression is possibly not a single syndrome but rather comprises several subtypes. DSM-5 proposes a melancholia specifier with phenotypic characteristics that could be associated with clinical progression, biological markers or therapeutic response. The Sydney Melancholia Prototype Index (SMPI) is a prototypic scale aimed to improve the diagnosis of melancholia. So far, there is only an English version of the instrument available. The aim of this study is to describe the translation and adaptation of the English version of the SMPI into Brazilian Portuguese., Methods: Translation and cross-cultural adaptation of the self-report (SMPI-SR) and clinician-rated (SMPI-CR) versions into Brazilian Portuguese were done following recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). This guideline includes the following steps: preparation, forward translation, reconciliation, back translation, back translation review, harmonization, cognitive debriefing, debriefing results review, proofreading and final report., Results: The Brazilian Portuguese versions of the SMPI were well-accepted by respondents. Changes in about two-thirds of the items were considered necessary to obtain the final Brazilian Portuguese version of the SMPI., Conclusions: Both versions of the SMPI are now available in Brazilian Portuguese. The instrument could become an important option to enhance studies on melancholia in Portuguese-speaking samples.

Objective: This study used machine learning techniques combined with peripheral biomarker measurements to build signatures to help differentiating (1) patients with bipolar depression from patients with unipolar depression, and (2) patients with bipolar depression or unipolar depression from healthy controls., Methods: We assessed serum levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumor necrosis factor-α, interferon-γ, interleukin-17A, brain-derived neurotrophic factor, lipid peroxidation and oxidative protein damage in 54 outpatients with bipolar depression, 54 outpatients with unipolar depression and 54 healthy controls, matched by sex and age. Depressive symptoms were assessed using the Hamilton Depression Rating Scale. Variable selection was performed with recursive feature elimination with a linear support vector machine kernel, and the leave-one-out cross-validation method was used to test and validate our model., Results: Bipolar vs unipolar depression classification achieved an area under the receiver operating characteristics (ROC) curve (AUC) of 0.69, with 0.62 sensitivity and 0.66 specificity using three selected biomarkers (interleukin-4, thiobarbituric acid reactive substances and interleukin-10). For the comparison of bipolar depression vs healthy controls, the model retained five variables (interleukin-6, interleukin-4, thiobarbituric acid reactive substances, carbonyl and interleukin-17A), with an AUC of 0.70, 0.62 sensitivity and 0.7 specificity. Finally, unipolar depression vs healthy controls comparison retained seven variables (interleukin-6, Carbonyl, brain-derived neurotrophic factor, interleukin-10, interleukin-17A, interleukin-4 and tumor necrosis factor-α), with an AUC of 0.74, a sensitivity of 0.68 and 0.70 specificity., Conclusion: Our findings show the potential of machine learning models to aid in clinical practice, leading to more objective assessment. Future studies will examine the possibility of combining peripheral blood biomarker data with other biological data to develop more accurate signatures.

Recognition of the importance of religion and spirituality in psychiatry is increasing, and several studies have shown a predominantly inverse relationship between religiosity and depression. Brain-derived neurotrophic factor (BDNF) is a widely studied brain neurotrophin responsible for synaptic plasticity, dendritic and neuronal fiber growth, and neuronal survival. The objective of the present study was to evaluate BDNF levels across high and low intrinsic religiosity (IR) in depressed inpatients. Serum BDNF levels were evaluated from 101 depressed inpatients at hospital admission and 91 inpatients at discharge. Religiosity was assessed using a validated version of the Duke University Religion Index. High IR patients had significantly higher serum BDNF at discharge than do low IR (52.0 vs. 41.3 ng/mL, P = 0.02), with a Cohen's d effect size difference of 0.56. High IR patients had a statistically significant increase in BDNF levels from admission to discharge (43.6 ± 22.4 vs. 53.8 ± 20.6 ng/mL, -1.950 (paired t-statistic), P = 0.05). The relationship between IR and BDNF levels (F = 6.199, P = 0.00) was controlled for the effects of depressive symptoms (  β = 2.73, P = 0.00) and psychiatric treatments, including selective serotonin reuptake inhibitors (SSRIs) ( β = 0.17, P = 0.08), serotonin and norepinephrine reuptake inhibitors (SNRIs) (  β = -0.23, P = 0.02), tricyclic antidepressants (TCAs) (  β = -0.17, P = 0.10), lithium (  β = 0.29, P = 0.00), anticonvulsants (  β = 0.22, P = 0.03), antipsychotics (  β = -0.05, P = 0.61), and electroconvulsive therapy (  β = 0.00, P = 0.98). The current findings suggest a potential pathway to help understand the protective effect of religiosity in depressive disorders., (Copyright © 2019 Mosqueiro, Fleck and Rocha.)

Objective: To test the reliability and the discriminant and convergent validity of the abbreviated Brazilian Portuguese World Health Organization's Quality of Life Instrument - Spirituality, Religion, and Personal Beliefs module (WHOQOL-SRPB BREF)., Methods: In a sample of 404 individuals, we applied a general questionnaire, the WHOQOL-BREF, the long-form SRPB, the Brief Religious-Spiritual Coping Scale (RCOPE), and the Beck Depression Inventory (BDI). Priority was given to the 9-item SRPB assessment: its unidimensionality was tested through confirmatory factor analysis and Rasch analysis., Results: Confirmatory factor analysis of the 9-item SRPB assessment indicated an adjusted model with acceptable fit to data. In the Rasch analysis, general fit measures showed adequate performance. The 9-item SRPB assessment showed good internal consistency (alpha = 0.85), and could differentiate (discriminant validity) between religious and atheist/agnostic respondents (mean = 74.7±14.1 and 56.8±15.5, respectively; t = 6.37; degrees of freedom [df] = 402; p < 0.01) and between non-depressed and depressed respondents (mean = 76.5±12.9 and 67.1±16.5; t = 5.57; df = 190.5; p < 0.01). Correlations (convergent validity) were significant with the positive-RCOPE subscale (r = 0.58, p < 0.01) and the WHOQOL-BREF domains (Pearson coefficient ranging between 0.24 and 0.49; p < 0.01), but were in the negative direction with the negative-RCOPE subscale (r = -0.10, p < 0.05). Correlation with the long-form SRPB domain (r = 0.934) was almost perfect., Conclusion: The Brazilian Portuguese 9-item SRPB has good psychometric properties and confirmed the findings of the long-form Brazilian Portuguese version and the abbreviated English version.

Background: This is a qualitative study that aims to investigate the effect of depressive status on responses to items on the WHO quality of life assessment instrument (WHOQOL-Bref), comparing which aspects of the individual's life he or she takes into account in responding to the items related to quality of life when depressed and when euthymic., Results: Six adult women were interviewed prior to initiating treatment for a depressive episode and were then interviewed again six months later when in remission from the episode. The 'think aloud' method of cognitive interviewing was used. Based on the Wilcoxon test, the seven items that exhibited a significant change with the improvement of the depressive condition were examined in depth, and the think aloud method was used to reveal the subjects' cognitive processes. Depressive symptoms were associated with different interpretations of some items and the response scale. Also, for some items, patients chose the same response for the item both times but justified their choice differently during the depressive episode and in euthymia., Conclusions: We found that, in addition to the impact caused by depression on quality of life, there are peculiarities in the way the depressed individual makes subjective assessments. We believe that qualitative studies such as the present one may provide important support in the interpretation of quantitative results.

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.

Objective: The authors examined the prospective relationship between physical activity and incident depression and explored potential moderators., Method: Prospective cohort studies evaluating incident depression were searched from database inception through Oct. 18, 2017, on PubMed, PsycINFO, Embase, and SPORTDiscus. Demographic and clinical data, data on physical activity and depression assessments, and odds ratios, relative risks, and hazard ratios with 95% confidence intervals were extracted. Random-effects meta-analyses were conducted, and the potential sources of heterogeneity were explored. Methodological quality was assessed using the Newcastle-Ottawa Scale., Results: A total of 49 unique prospective studies (N=266,939; median proportion of males across studies, 47%) were followed up for 1,837,794 person-years. Compared with people with low levels of physical activity, those with high levels had lower odds of developing depression (adjusted odds ratio=0.83, 95% CI=0.79, 0.88; I 2 =0.00). Furthermore, physical activity had a protective effect against the emergence of depression in youths (adjusted odds ratio=0.90, 95% CI=0.83, 0.98), in adults (adjusted odds ratio=0.78, 95% CI=0.70, 0.87), and in elderly persons (adjusted odds ratio=0.79, 95% CI=0.72, 0.86). Protective effects against depression were found across geographical regions, with adjusted odds ratios ranging from 0.65 to 0.84 in Asia, Europe, North America, and Oceania, and against increased incidence of positive screen for depressive symptoms (adjusted odds ratio=0.84, 95% CI=0.79, 0.89) or major depression diagnosis (adjusted odds ratio=0.86, 95% CI=0.75, 0.98). No moderators were identified. Results were consistent for unadjusted odds ratios and for adjusted and unadjusted relative risks/hazard ratios. Overall study quality was moderate to high (Newcastle-Ottawa Scale score, 6.3). Although significant publication bias was found, adjusting for this did not change the magnitude of the associations., Conclusions: Available evidence supports the notion that physical activity can confer protection against the emergence of depression regardless of age and geographical region.

Few studies have investigated the relationship between spiritual/religious coping (S/R coping) and panic disorder (PD). This Brazilian longitudinal study evaluated if S/R coping and depressive symptoms can predict PD remission and improved quality of life (QoL). There were 101 outpatients with PD who were followed up for 12 to 16 weeks. The prevalence ratio (PR) between positive S/R coping and negative S/R coping and PD remission was assessed, as well as the association between positive S/R coping and negative S/R coping and QoL. After adjusting for confounding factors, positive S/R coping presented an inverse PR with PD remission, which was not statistically significant (0.88; p = 0.075). There was no association between S/R coping and QoL. Depressive symptoms were negatively associated with PD remission (PR = 0.97; p < 0.01) and were not predictive of a better QoL.

Objective: To test the psychometric properties of the EUROHIS-QOL 8-item index in a Brazilian sample., Methods: The sample consisted of 151 patients and 174 healthy controls (n=325). Several psychometric properties were tested., Results: Reliability showed good internal consistency (Cronbach's alpha = 0.81). The measure showed good discriminant validity between patients and healthy controls (mean1 = 3.32, SD1 = 0.70; mean2 = 3.77, SD2 = 0.63, t = 6.12, p < 0.001). Convergent validity showed significant correlations (p < 0.001) between the EUROHIS-QOL 8-item index and all domains of the WHOQOL-Bref (overall r = 0.47; general health r = 0.54; physical r = 0.69; psychological r = 0.62; social relationship r = 0.55; environment r = 0.55) and between the EUROHIS-QOL 8-item index and the domains of the SF-36, except for the social domain (p = 0.38). On Rasch analysis of unidimensionality, general fit measures showed adequate performance. The EUROHIS-QOL 8-item index also showed good fit on confirmatory factor analysis (CFA) (chi-square = 18.46, degrees of freedom [df] = 15; comparative fit index [CFI] = 0.99; root mean square error of approximation [RMSEA] = 0.03; goodness of fit index [gfi] = 0.99; root mean square residual [RMR] = 0.03; p = 24)., Conclusion: The EUROHIS-QOL 8-item index showed good psychometric properties. It is a reliable quality of life measure that can be used in Brazilian populations.

Objective: There have been significant reductions in numbers of psychiatric beds and length of stay (LOS) worldwide, making LOS in psychiatric beds an interesting outcome. The objective of this study was to find factors measurable on admission that would predict LOS in the acute psychiatric setting., Methods: This was a prospective, observational study., Results: Overall, 385 subjects were included. The median LOS was 25 days. In the final model, six variables explained 14.6% of the variation in LOS: not having own income, psychiatric admissions in the preceding 2 years, high Clinical Global Impression and Brief Psychiatric Rating Scale scores, diagnosis of schizophrenia, and history of attempted suicide. All variables were associated with longer LOS, apart from history of attempted suicide., Conclusions: Identifying patients who will need to stay longer in psychiatric beds remains a challenge. Improving knowledge about determinants of LOS could lead to improvements in the quality of care in hospital psychiatry.

Objective: To assess the effectiveness of three mood disorder treatment algorithms in a sample of patients seeking care in the Brazilian public healthcare system., Methods: A randomized pragmatic trial was conducted with an algorithm developed for treating episodes of major depressive disorder (MDD), bipolar depressive episodes and mixed episodes of bipolar disorder (BD)., Results: The sample consisted of 259 subjects diagnosed with BD or MDD (DSM-IV-TR). After the onset of symptoms, the first treatment occurred ∼6 years and the use of mood stabilizers began ∼12 years. All proposed algorithms were effective, with response rates around 80%. The majority of the subjects took 20 weeks to obtain a therapeutic response., Conclusions: The algorithms were effective with the medications available through the Brazilian Unified Health System. Because therapeutic response was achieved in most subjects by 20 weeks, a follow-up period longer than 12 weeks may be required to confirm adequate response to treatment. Remission of symptoms is still the main desired outcome. Subjects who achieved remission recovered more rapidly and remained more stable over time., Clinical Trial Registration: NCT02901249, NCT02870283, NCT02918097.

Spirituality has been identified as an important dimension of quality-of-life. The objective of this study was to review the literature on quality-of-life and spirituality, their association, and assessment tools. A search was conducted of the keyterms 'quality-of-life' and 'spirituality' in abstract or title in the databases PsycINFO and PubMed/Medline between 1979-2005, complemented by a new search at PUBMED from 2006-2016. Quality-of-life is a new concept, which encompasses and transcends the concept of health, being composed of multiple domains: physical, psychological, environmental, among others. The missing measure in health has been defined as the individual's perception of their position in life in the context of culture and value system in which they live and in relation to their goals, expectations, standards, and concerns. There is consistent evidence of an association between quality-of-life and religiosity/spirituality (R/S), through studies with reasonable methodological rigour, using several variables to assess R/S (e.g. religious affiliation, religious coping, and prayer/spirituality). There are also several valid and reliable instruments to evaluate quality-of-life and spirituality. Further studies are needed, however, especially in Brazil. Such studies will provide empirical data to be used in planning health interventions based on spirituality, seeking a better quality-of-life. In the last 10 years, research is consistently growing about quality-of-life and spirituality in many countries, and also in many areas of health research.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Meta-analytical evidence suggests that brain-derived neurotrophic factor (BDNF) is altered in various psychiatric disorders. However, meta-analyses may be hampered by the heterogeneity of BDNF assays, lack of BDNF standard values and heterogeneity among the populations included in the studies. To address these issues, our study aimed to test, in a 'true-to-life' setting, the hypothesis that the serum BDNF level is nonspecifically reduced in acute severe mental illness (SMI) patients and increases during inpatient treatment. Consecutive samples of 236 inpatients with SMI and 100 healthy controls were recruited. SMI includes schizophrenia and severe mood disorders, and is characterized in the sample by the presence of at least 2 years of psychiatric treatment and disability. Generalized estimating equations were used to analyze BDNF serum levels at admission and upon discharge controlled by confounding factors. BDNF levels increased significantly between admission and discharge in SMI patients. BDNF levels showed significant reductions compared with controls both at admission and upon discharge. In addition, BDNF levels showed no difference among SMI patient diagnostic subgroups (unipolar depression, bipolar depression, schizophrenia and manic episode). The increase but non-restoration of BDNF levels, even with the general acute improvement of clinical scores, may reflect the progression of the disorder characteristically seen in these patients. BDNF levels could be considered as a marker for the presence of a nonspecific psychiatric disorder and possibly a transdiagnostic and nonspecific marker of disease activity.

Background: Naturalistic studies can be useful tools to understand how an intervention works in the real clinical practice. This study aims to investigate the outcomes in a naturalistically treated depressed inpatients cohort, who were referred, or not, to unilateral ECT., Methods: Depressed adults according to MINI admitted in a psychiatric unit were divided in unilateral ECT treated and non-ECT treated. Main outcomes were: depression improvement in Hamilton Rating Scale for Depression (HDRS-17) scores; response (HDRS-17 improvement ≥50 %); remission (HDRS-17 score ≤7); length of hospitalization., Results: Forty-three patients were included in unilateral ECT group and 104 in non-ECT group. No differences of psychotic symptoms, melancholic features or past maniac episode were found between groups. Unilateral ECT group had a mean HDRS-17 score higher than non-ECT group at admission (ECT: 25.05 ± 1.03; non-ECT: 21.61 ± 0.69; p = 0.001), but no significant difference was found at discharge (ECT: 7.70 ± 0.81; non-ECT: 7.40 ± 0.51; p = 0.75). Unilateral ECT group had a larger HDRS-17 score reduction during treatment (ECT: 18.24 ± 1.18; non-ECT:14.20 ± 0.76; p = 0.004). There were no significant differences in response and remission rates between groups. Unilateral ECT group had longer mean duration of hospitalization in days (ECT: 35.48 ± 2.48; non-ECT: 24.57 ± 1.50; p < 0.001), but there were no difference in mean time of treatment (ECT group:27.66 ± 1.95; non-ECT: 24.57 ± 1.50; p = 0.25)., Conclusions: Unilateral high-dose ECT is still a useful treatment option, in the real world clinical practice, to reduce the intensity of depressive symptoms in highly depressed inpatients.

Background: Spirituality may influence how patients cope with their illness., Objectives: We assessed whether spirituality may influence adherence to management of outpatients with heart failure., Methods: Cross sectional study enrolling consecutive ambulatory heart failure patients in whom adherence to multidisciplinary treatment was evaluated. Patients were assessed for quality of life, depression, religiosity and spirituality utilizing validated questionnaires. Correlations between adherence and psychosocial variables of interest were obtained. Logistic regression models explored independent predictors of adherence., Results: One hundred and thirty patients (age 60 ± 13 years; 67% male) were interviewed. Adequate adherence score was observed in 38.5% of the patients. Neither depression nor religiosity was correlated to adherence, when assessed separately. Interestingly, spirituality, when assessed by both total score sum (r = 0.26; p = 0.003) and by all specific domains, was positively correlated to adherence. Finally, the combination of spirituality, religiosity and personal beliefs was an independent predictor of adherence when adjusted for demographics, clinical characteristics and psychosocial instruments., Conclusion: Spirituality, religiosity and personal beliefs were the only variables consistently associated with compliance to medication in a cohort of outpatients with heart failure. Our data suggest that adequately addressing these aspects on patient's care may lead to an improvement in adherence patterns in the complex heart failure management.

Introduction: Exercise have antidepressant effects in people with Major Depressive Disorder (MDD). However, about to half of patients do not respond to exercise. The identification of factors that moderates the antidepressant effects of exercise in people with MDD may help researchers and health professionals to identify sub-groups of patients that would benefit more from exercise., Methods: A systematic review was carried out using Medline(PubMed), EMBASE and psycINFO up to April 2015. Individual and composite moderators were summarized and the strength of the evidence was assessed., Results: Eleven studies were included for review resulting in the identification of potential individual (two biological, three clinical, two psychological and two social individual) and two potential composite moderators (the interaction between BDNF and Body Mass Index (BMI) and between family history of mental illness and gender). Only the two biological features and the BDNF x BMI interaction provided confirmatory evidence., Limitations: Due the different statistical approaches used in the studies, it was not possible to perform meta-analyses. The small number of studies and the exploratory nature of the evidence limits a wider generalization of the findings., Conclusion: Potential clinical, psychological, social or biological moderators were identified. However, the small number of studies and the limited strength of the evidence requires further studies before drawn definitive results. Further trials should consider the inclusion of moderators analysis using an a-priori, theoretical/evidence based hypothesis in order to provide high quality evidence for the use of personalized medicine in exercise for depression., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: BDNF blood levels are reduced in MDD. They can be increased with pharmacologic treatment and ECT, but it is not clear whether the combination of treatments promotes an additional increase. The present study aims to evaluate whether combined treatment promotes an increase in BDNF, restoring the level to that of non-depressed controls., Methods: Ninety-nine adult inpatients were invited to participate in this naturalistic prospective cohort study between May 2011 and April 2013. Diagnosis was made by MINI, and the symptoms were evaluated at admission and at discharge by HDRS-17. Those inpatients with a diagnosis of depression were included and divided into two groups: those who underwent combined ECT and medication (31 subjects) and those who used only pharmacotherapy (68 subjects). Serum BDNF was measured in blood samples collected at admission and discharge. One hundred healthy blood donors without any psychiatric diagnosis were included as a control group., Results: There were no significant differences in serum BDNF levels between the combined and pharmacological groups at admission and at discharge, and no significant variation in BDNF occurred in any group during the treatment. There were no interactions between time and treatment groups nor significant time effects or treatment group effects for BDNF in the Generalized Estimating Equation Model (GEE). The control group had significantly higher serum BDNF levels in comparison with each of the treatment groups at admission and discharge (p = 0.00)., Conclusion: Combination of ECT with pharmacological treatment did not result in increased serum BDNF levels and did not restore levels to that of controls., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To describe and evaluate the response and predictors of remission during inpatient treatment in a psychiatric unit in a general hospital based on symptomatology, functionality, and quality of life (QoL)., Methods: Patients were admitted to a psychiatric unit in a tertiary general hospital in Brazil from June 2011 to December 2013 and included in the study if they met two of the severe mental illness (SMI) criteria: Global Assessment of Functioning (GAF) ≤ 50 and duration of service contact ≥ 2 years. Patients were assessed by the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI) Severity Scale , GAF, the World Health Organization Quality of Life Instrument - Abbreviated version (WHOQOL-Bref), and specific diagnostic scales., Results: A total of 239 patients were included. BPRS mean scores were 25.54±11.37 at admission and 10.96±8.11 at discharge (p < 0.001). Patients with manic episodes (odds ratio: 4.03; 95% confidence interval: 1.14-14.30; p = 0.03) were more likely to achieve remission (CGI ≤ 2 at discharge) than those with depressive episodes. Mean length of stay was 28.95±19.86 days. All QoL domains improved significantly in the whole sample., Conclusion: SMI patients had marked improvements in symptomatic and functional measures during psychiatric hospitalization. Patients with manic episodes had higher chance of remission according to the CGI.

Background: Treatment-resistant depression (TRD) is an extremely prevalent clinical condition. Although Interpersonal Psychotherapy (IPT) is an established treatment for uncomplicated depression, its effectiveness has never before been studied in patients with TRD in real-world settings. We investigate IPT as an adjunct strategy to treatment as usual (TAU) for TRD patients in a pragmatic, randomized, controlled trial., Methods: A total of 40 adult patients with TRD (satisfying the criteria for major depressive disorder despite adequate antidepressant treatment) were recruited from a tertiary care facility for this pragmatic trial and blinded to the evaluator. Patients were randomized to one of two treatment conditions: (1) TAU - pharmacotherapy freely chosen by the clinician (n=23) and (2) TAU+IPT (n=17). Assessments were performed at weeks 8, 12, 19 and 24. Changes in the estimated means of the Hamilton Depression Rating Scale score were the primary outcome measure. Secondary outcomes included patient-rated scales and quality of life scales. We used a linear mixed model to compare changes over time between the two groups., Results: Both treatments lead to improvements in depressive symptoms from baseline to week 24 with no significant between group differences in either primary: TAU (mean difference: 4.57; CI95%: 0.59-8.55; d=0.73) vs. IPT+TAU (mean difference: 5.86, CI95%: 1.50-10.22; d=0.93) or secondary outcomes., Limitations: Our relatively small sample limits our ability to detect differences between treatments., Conclusions: Both treatments lead to equal improvements in depressive symptoms. We found no evidence to support adding IPT to pharmacotherapy in patients with TRD., Trial Registration: ClinicalTrials.gov-NCT01896349., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Research on the association between electroconvulsive therapy (ECT) and increased brain derived neurotrophic factor (BDNF) levels has produced conflicting result. There have been few studies which have evaluated BDNF levels in clinical contexts where there was remission following treatment. The objective of this study was to investigate whether remission of depression following ECT is associated with changes in BDNF levels., Methods: Adult inpatients in a psychiatric unit were invited to participate in this naturalistic study. Diagnoses were made using the Mini-International Neuropsychiatric Interview (MINI) and symptoms were evaluated at admission and discharge using the Hamilton Rating Scale for Depression (HDRS-17). Thirty-one patients who received a diagnosis of depression and were subjected to ECT were included retrospectively. Clinical remission was defined as a score of less than eight on the HDRS-17 at discharge. Serum BDNF levels were measured in blood samples collected at admission and discharge with a commercial kit used in accordance with the manufacturer's instructions., Results: Subjects HDRS-17 scores improved following ECT (t = 13.29; p = 0.00). A generalized estimating equation (GEE) model revealed a remission × time interaction with BDNF levels as a dependent variable in a Wald chi-square test [Wald χ(2) = 5.98; p = 0.01]. A post hoc Bonferroni test revealed that non-remitters had lower BDNF levels at admission than remitters (p = 0.03), but there was no difference at discharge (p = 0.16)., Conclusion: ECT remitters had higher serum BDNF levels at admission and the level did not vary during treatment. ECT non-remitters had lower serum BDNF levels at admission, but levels increased during treatment and were similar to those of ECT remitters at discharge., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Exercise displays promise as an efficacious treatment for people with depression. However, no systematic review has evaluated the neurobiological effects of exercise among people with major depressive disorder (MDD). The aim of this article was to systematically review the acute and chronic biological responses to exercise in people with MDD. Two authors conducted searches using Medline (PubMed), EMBASE and PsycINFO. From the searches, twenty studies were included within the review, representing 1353 people with MDD. The results demonstrate that a single bout of exercise increases atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), copepetin and growth hormone among people with MDD. Exercise also potentially promotes long-term adaptations of copeptin, thiobarbituric acid reactive species (TBARS) and total mean frequency (TMF). However, there is limited evidence that exercise promotes adaptations on neurogenesis, inflammation biomarkers and brain structure. Associations between depressive symptoms improvement and hippocampus volume and IL-1β were found. Nevertheless, the paucity of studies and limitations presented within, precludes a more definitive conclusion of the underlying neurobiological explanation for the antidepressant effect of exercise in people with MDD. Further trials should utilize appropriate assessments of neurobiological markers in order to build upon the results of our review and further clarify the potential mechanisms associated with the antidepressant effects of exercise., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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.

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.

Background: Religiosity is inversely related to depression and is directly associated with positive psychological outcomes. Nonetheless, there is no consensus on whether or how religiosity could impact and protect against depression. The present study evaluated the association between intrinsic religiosity and resilient psychological characteristics in depressed inpatients., Methods: A sample of 143 depressed patients was prospectively evaluated in an inpatient psychiatric treatment in South Brazil. High Intrinsic Religiosity (HIR) and Low Intrinsic Religiosity (LIR) patients were compared across socio-demographic information, clinical measures, religiosity, resilience and quality of life. A linear regression model was used to evaluate the association between intrinsic religiosity and resilience, and the Cohen d test was utilized to assess effect sizes., Results: At admission, HIR patients showed higher HAM-D (p=0.05), BPRS (p=0.02), GAF (p=0.02), and CGI (p=0.03) scores, lower educational levels (p=0.04), higher social support (p=0.05), and fewer previous suicide attempts (p=0.05). At discharge, HIR patients showed higher quality of life (p=0.001) and higher resilience (p=0.000), with a large effect size difference between groups (1.02). Based on a linear regression model (adjusted r=0.19, p=0.000), intrinsic religiosity was associated with resilience, controlling for covariates., Conclusion: In a sample of depressed inpatients, intrinsic religiosity was found to be associated with resilience, quality of life, and fewer previous suicide attempts. These findings support the relevance of religiosity assessments in mental health practice and support the hypothesis that resilient psychological characteristics may mediate the positive effects of intrinsic religiosity in depression., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Major depressive disorder (MDD) is a significant cause of worldwide disability and treatment resistance is common. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has emerged as a treatment for MDD, and while efficacious, the daily commitment for typical 4-6 weeks of treatment poses a significant challenge. We aimed to determine the effectiveness and acceptability of an accelerated rTMS protocol for MDD., Methods: In this naturalistic trial, 27 patients with moderate to severe chronic and treatment-resistant MDD were treated with twice-daily HF-rTMS (10 Hz) applied over the left dorsolateral prefrontal cortex for 2 consecutive weeks (60,000 pulses). The primary outcomes were rates of clinical remission and response (16-item Quick Inventory of Depressive Symptomatology post-treatment score ≤ 6, and ≥ 50% reduction, respectively). Secondary outcomes were self-reported anxious symptoms, depressive symptoms and quality of life, and dropout rates as a proxy for acceptability., Results: Ten (37.0%) patients met criteria for clinical remission and 15 (55.6%) were classified as responders, with comparable outcomes for both moderate and severe MDD. Clinician-rated improvements in depressive symptoms were paralleled in self-reported depressive and anxious symptoms, as well as quality of life. No patient discontinued treatment., Limitations: This study is limited by short treatment duration that might be lengthened with corresponding improvements in effectiveness, limited duration of follow-up, small sample size, and an open-label design requiring randomized controlled replication., Conclusion: An accelerated protocol involving twice-daily sessions of HF-rTMS over the left DLPFC for 2 weeks was effective in treatment-resistant MDD, and had excellent acceptability. Additional research is required to optimize accelerated rTMS treatment protocols and determine efficacy using sham-controlled trials., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: There is growing interest in glutamatergic agents in depression, particularly ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. We aimed to assess the efficacy of ketamine in major depressive episodes., Method: We searched EMBASE, PsycINFO, CENTRAL, and Medline from 1962 to January 2014 to identify double-blind, randomized controlled trials with allocation concealment evaluating ketamine in major depressive episodes. Clinical remission, response and depressive symptoms were extracted by two independent raters. The primary outcome measure was clinical remission at 24 h, 3 days and 7 days post-treatment. Analyses employed a random-effects model., Results: Data were synthesized from seven RCTs employing an intravenous infusion and one RCT employing intranasal ketamine, representing 73 subjects in parallel arms and 110 subjects in cross-over designs [n = 34 with bipolar disorder (BD), n = 149 with major depressive disorder (MDD)]. Ketamine was associated with higher rates of clinical remission relative to comparator (saline or midazolam) at 24 h [OR 7.06, number needed to treat (NNT) = 5], 3 days (OR 3.86, NNT = 6), and 7 days (OR 4.00, NNT = 6), as well as higher rates of clinical response at 24 h (OR 9.10, NNT = 3), 3 days (OR 6.77, NNT = 3), and 7 days (OR 4.87, NNT = 4). A standardized mean difference of 0.90 in favor of ketamine was observed at 24 h based on depression rating scale scores, with group comparisons revealing greater efficacy in unipolar depression compared to bipolar depression (1.07 v. 0.68). Ketamine was associated with transient psychotomimetic effects, but no persistent psychosis or affective switches., Conclusion: Our meta-analysis suggests that single administrations ketamine are efficacious in the rapid treatment of unipolar and bipolar depression. Additional research is required to determine optimal dosing schedules, route, treatment schedules, and the potential efficacy of other glutamatergic agents.

Background: Exercise is a potential treatment for depression. However, few studies have evaluated the role of adjunct exercise in the treatment of severely major depressed inpatients. The goal of this study was to evaluate the effects of add-on exercise on the usual treatment of severely depressed inpatients., Methods: Fifty participants were randomized to an exercise (exercise + usual treatment) or a control (usual treatment) group. Twenty-five patients were randomly allocated to each group. The participants in the exercise group performed three sessions per week throughout the hospitalization period, with a goal dose of 16.5 kcal/kg/week plus the usual pharmacological treatment. Depressive symptoms and the Quality of Life (QoL) of the participants were assessed at the baseline, the second week, and discharge., Results: A significant group × time interaction was found for depressive symptoms and the physical and psychological domains of QoL. Differences between groups occurred at the second week and discharge with respect to depressive symptoms and the physical and psychological domains of QoL. There was no difference in the remission rate at discharge (48% and 32% for the exercise and control group, respectively). An NNT of 6.25 was found. No significant baseline characteristics predict remission at discharge., Conclusion: Add-on exercise is an efficacious treatment for severely depressed inpatients, improving their depressive symptoms and QoL. Initial acceptance of exercise remains a challenge., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)