Early growth response 1 (EGR1) is downregulated in peripheral blood from patients with major psychiatric disorders.

OBJECTIVES: To evaluate relative expression of genes with the potential to translate environmental stimuli into long-term alterations in the brain - namely Early Growth Response (EGR)1, EGR3, and Cryptochrome Circadian Regulator 2 (CRY2) - in peripheral blood from patients with Bipolar Disorder (BD), Schizophrenia (SZ), Major Depressive Disorder (MDD) and healthy controls (HC). METHODS: Thirty individuals ranging from 18 to 60 years were recruited for each group (BD, SZ, MDD or HC) from a Brazilian public hospital. Therefore, individuals' peripheral blood was collected and EGR1, EGR3 and CRY2 gene expression analyzed by PCR Real Time. RESULTS: EGR1 mRNA levels are significantly lower in psychiatric patients when compared to HC, but there is no difference for EGR3 and CRY2. Exploring the findings for each diagnosis, there is a significant difference between each diagnosis group only for EGR1, which was lower in BD, MDD and SZ as compared to HC. No significant correlations were found between gene expression and clinical features. CONCLUSIONS: EGR1 is downregulated in psychiatric patients, regardless of the diagnosis and may be a potential common target in major psychiatric disorders. EGR1, as a transcription factor, modulates many other genes and participates in crucial neuronal and synaptic processes, such as plasticity, neurotransmitters metabolism, vesicular transport and signaling pathways. The study of EGR1 and its upstream regulators in psychiatry might lead to potential new therapeutic targets.

Diagnosis of bipolar and major depressive disorders: The appropriateness of MINI compared to the clinical interview in a sample of patients with mood disorders in tertiary mental health care.

OBJECTIVE: The Mini International Neuropsychiatric Interview (MINI) is one of the most used instruments for the assessment of Mental Disorders, playing an essential role in psychiatric research and in clinical and hospital practice. Despite this, the accuracy of the MINI, when used by a psychiatrist, is poorly studied, particularly in relation to Bipolar Disorder (BD). The early diagnosis of BD and Major Depressive Disorder (MDD) is extremely important, as it provides an opportunity for intervention that can reduce the impact on the patient's daily life and functionality. As such, this study assesses the suitability of MINI for diagnosing BD or MDD in a sample of patients with mood disorders. METHOD: Agreement between the MINI and the clinical interview was assessed in a sample of 347 outpatients by calculating Cohen's kappa, sensitivity, specificity, positive predictive value, negative predictive value, and the area under the curve (AUC). RESULTS: The sample consisted of 347 patients with mood disorders. 279 were women (80.40%), 105 (30.3%) were diagnosed with MDD and 242 (69.7%) with BD from the assessment performed in the clinical interview. In the MINI assessment, 97 individuals (28%) were classified with a diagnosis of MDD and 250 (72%) with BD. We found a sensitivity of 87.2% and specificity of 62.8% for the MINI in the diagnosis of BD and a Cohen's kappa between the MINI and the clinical interview of 0.51. The AUC was 0.75. CONCLUSIONS: MINI has greater sensitivity (87.2%) for the diagnosis of BD and greater specificity (87.2%) for the diagnosis of MDD. In addition, the moderate Cohen kappa (0.51) and AUC (0.75) values between the MINI and the clinical interview are acceptable when considering most available psychiatric diagnostic tools.

Chronic pain predicts a worse response to depression treatment, regardless of thyroid function or psychotropics prescribed.

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.

Earlier age of onset is associated with a pro-inflammatory state in major depressive disorder.

Major depressive disorder (MDD) is a common condition that affects the general population over a wide range of ages, regardless of gender and social background. Early-onset of MDD in adulthood, between ages of 18 and 30 years, is associated with worse outcomes and increased years of disability. Stress load and physical health have been associated with age of onset in MDD. We aim to investigate whether early onset MDD might be associated with changes in systemic inflammatory markers. We examined levels of following cytokines: IL-1ß, IL-6, IL-10 and TNFα in 234 patients with MDD. Higher serum levels of TNFα and IL-1ß are associated with the early onset of the disorder in patients with MDD. IL-6 levels were also higher in the early onset group and IL-10 levels were higher in the late onset group, but with no significant difference. Changes in the anti-inflammatory/pro-inflammatory balance have been described in mood disorders and may be implicated in its severity and pattern of progression. Our findings reinforce that higher serum levels of IL-1ß and TNFα may be associated with the earlier onset subgroup of MDD patients. Future research that target inflammatory markers of immune modulation may be, key in the search for novel preventative therapeutics.

Implementation of Group Interpersonal Psychotherapy in primary care.

OBJECTIVE: To show the implementation process of IPT-G in primary care, including facilitating and obstructing factors, implementation strategies, and training and supervision of primary care professionals. METHODS: Quantitative (cross-sectional and longitudinal) analysis of pre and post-knowledge tests; qualitative analyses of the training courses; patient recruitment; conduction of IPT-G sessions; supervision of IPT-G therapists; application of a semi-structured questionnaire to assess, investigate, and develop strategies against the identified barriers. RESULTS: About 120 clinicians answered the pre-test; 84 completed the post-test. Pre- and post-test scores of IPT-G knowledge were significantly different. Twenty initially trained clinicians completed additional supervision in IPT-G. Qualitative analysis identified twelve barriers and six facilitators to IPT-G implementation in individual, organizational, and systemic contexts. CONCLUSIONS: Implementation of IPT-G in primary care is a complex process with several steps. In the first step, health professionals were successfully trained in IPT-G. However, subsequent steps were more complex. Therefore, careful planning of IPT-G implementation is essential to maximize the success of this innovation.

A Standard Set of Value-Based Patient-Centered Outcomes and Measures of Overall Health in Adults.

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.

Quality of life of family primary caregivers of individuals with bipolar disorder and schizophrenia in south of Brazil.

BACKGROUND: The process of deinstitutionalization of individuals with mental disorders (MD) brought greater family responsibility in terms of patient care. AIMS: Evaluate the Quality of Life (QoL) and its associated factors of primary caregivers of bipolar and schizophrenic subjects. METHODS: A cross-sectional survey was conducted from 2012 to 2015 with 125 caregivers at an outpatient service of a teaching hospital in the South of Brazil. QoL instruments (WHOQOL-Bref, SF-36), questionnaires regarding socio-demographic, clinical data and depressive symptoms (BDI) were applied. RESULTS: Caregivers of schizophrenic individuals presented lower QoL scores than caregivers of bipolar individuals, with moderate effect in physical, and social domains of WHOQOL-Bref, and in physical functioning, role-physical, and role-emotional domains of SF-36. QoL scores of caregivers were lower when compared with the normative data of the Brazilian population. The factors associated with lower QoL scores were: patient diagnosis of schizophrenia, female gender, presence of clinical disease and presence of depressive symptoms in the caregiver. CONCLUSIONS: Caregivers of patients with schizophrenia or bipolar disorder present a significant impairment in their QoL when compared with the general population, highlighting the relevance of developing support programs in the mental health services that include these caregivers.

Latent structure and factor reliability of the National Health Service Community Mental Health Service User Questionnaire.

BACKGROUND: National Health Service use the Community Mental Health Service User Questionnaire (NHS-CMH) to assess care quality. However, its reliability and internal validity is uncertain. AIMS: To test the NHS-CMH structure, reliability and item-level characteristics. METHODS: We used data from 11,373 participants who answered the 2017 NHS-CMH survey. First, we estimated the NHS-CMH structure using Exploratory Factor Analysis (EFA) in half of the dataset. Second, we tested the best EFA-derived model with Confirmatory Factor Analysis (CFA). We tested the internal validity, construct reliability (omega - ω), explained common variance of each factor (ECV), and item thresholds. RESULTS: EFA suggested a 4-factor solution. The structure derived from the EFA was confirmed, demonstrating good reliability for the four correlated dimensions: "Relationship with Staff" (ω = 0.952, ECV = 40.1%), "Organizing Care" (ω = 0.855, ECV = 21.4%), "Medication and Treatments" (ω = 0.837, ECV = 13.3%), and "Support and Well-being" (ω = 0.928, ECV = 25.3%). A second-order model with a high-order domain of "Quality of Care" is also supported. CONCLUSIONS: The NHS-CMH can be used to reliably assess four user-informed dimensions of mental health care quality. This model offers an alternative for its current use (item-level and untested sum scores analysis).

Implementation of Group Interpersonal Psychotherapy in primary care

ABSTRACT OBJECTIVE To show the implementation process of IPT-G in primary care, including facilitating and obstructing factors, implementation strategies, and training and supervision of primary care professionals. METHODS Quantitative (cross-sectional and longitudinal) analysis of pre and post-knowledge tests; qualitative analyses of the training courses; patient recruitment; conduction of IPT-G sessions; supervision of IPT-G therapists; application of a semi-structured questionnaire to assess, investigate, and develop strategies against the identified barriers. RESULTS About 120 clinicians answered the pre-test; 84 completed the post-test. Pre- and post-test scores of IPT-G knowledge were significantly different. Twenty initially trained clinicians completed additional supervision in IPT-G. Qualitative analysis identified twelve barriers and six facilitators to IPT-G implementation in individual, organizational, and systemic contexts. CONCLUSIONS Implementation of IPT-G in primary care is a complex process with several steps. In the first step, health professionals were successfully trained in IPT-G. However, subsequent steps were more complex. Therefore, careful planning of IPT-G implementation is essential to maximize the success of this innovation.

Which outcomes are most important to measure in patients with COVID-19 and how and when should these be measured? Development of an international standard set of outcomes measures for clinical use in patients with COVID-19: a report of the International Consortium for Health Outcomes Measurement (ICHOM) COVID-19 Working Group.

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.

Evaluation of major depression symptom networks using clinician-rated and patient-rated data.

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.

Factors associated with adherence to sports and exercise among outpatients with major depressive disorder.

INTRODUCTION: Individuals with major depressive disorder (MDD) face more barriers to engagement in sports and exercise interventions. Evaluating clinical and demographic factors associated with adherence to sports and exercise among MDD outpatients could support development of new options and strategies to increase their participation. METHODS: In a cross-sectional study, 268 depressed outpatients were evaluated (83.51% females; mean age = 50.74 [standard deviation {SD} = 10.39]). Sports and exercise participation were assessed using a question about participation frequency during the previous month. Clinical and demographic factors were evaluated. Linear regression was used to identify predictors of participation in sports and exercise. RESULTS: MDD patients with mild symptoms of depression (odds ratio [OR] = 2.42; 95% confidence interval [95%CI] 1.00, 5.88; p = 0.04) and patients with mild to moderate symptoms (OR = 3.96; 95%CI 1.41, 11.15; p = 0.009) were more likely to engage regularly in sports and exercise than patients with more severe depression. Moreover, smoking (OR = 0.23; 95%CI 0.67, 0.80; p = 0.007) and being divorced (OR = 0.22; 95%CI 0.57, 0.86; p = 0.03) were associated with lower rates of engagement in sports and exercise. CONCLUSION: Our findings indicate a significant association between clinical and demographic factors and participation in sports and exercise among MDD outpatients.

Psychotropic medication use among women seeking assisted reproductive technology (ART) therapy: A cross-sectional study.

Background Infertility is associated with increased anxiety, depressive symptoms and mood disorders. Unfortunately, mental health is not often addressed in infertility treatment and infertile patients could be at higher risk of self-administration of not prescribed drugs or/and be exposed to alternative emotional treatments. Therefore, the aim of the present study is to investigate the use of psychotropic medication and to evaluate the frequency of psychiatric diagnosis among infertile women seeking assisted reproductive technology (ART) therapy. Methods All infertile women starting treatment at an ART clinic who agreed to participate in the study were included. Patients were submitted to a structured psychiatric interview, the Mini International Neuropsychiatric Interview (M.I.N.I.). Current and lifetime use of psychotropic medication were assessed. Results Ninety patients who agreed to participate completed the research protocol.  A total of 12/90  were on current use of psychotropic medication.Thirty-six out of ninety patients  had at least one psychiatric disorder. Mood disorders were detected in 19 of the 90. Anxiety disorders were highly frequent, reaching 27/90 of the patients, as agoraphobia the most common diagnosis (12/90). Limitations The study has several limitations, such as the absence of a control group of fertile patients and strict inclusion criteria, in which only subjects that spontaneously agreed to participate were enrolled. Conclusion Women suffering from infertility seeking ART treatment are at high risk for depression and anxiety disorders and a considerable number of them are in use of medication. Its implications on infertility treatments and offspring are uncertain.

Factors associated with adherence to sports and exercise among outpatients with major depressive disorder

Abstract Introduction Individuals with major depressive disorder (MDD) face more barriers to engagement in sports and exercise interventions. Evaluating clinical and demographic factors associated with adherence to sports and exercise among MDD outpatients could support development of new options and strategies to increase their participation. Methods In a cross-sectional study, 268 depressed outpatients were evaluated (83.51% females; mean age = 50.74 [standard deviation {SD} = 10.39]). Sports and exercise participation were assessed using a question about participation frequency during the previous month. Clinical and demographic factors were evaluated. Linear regression was used to identify predictors of participation in sports and exercise. Results MDD patients with mild symptoms of depression (odds ratio [OR] = 2.42; 95% confidence interval [95%CI] 1.00, 5.88; p = 0.04) and patients with mild to moderate symptoms (OR = 3.96; 95%CI 1.41, 11.15; p = 0.009) were more likely to engage regularly in sports and exercise than patients with more severe depression. Moreover, smoking (OR = 0.23; 95%CI 0.67, 0.80; p = 0.007) and being divorced (OR = 0.22; 95%CI 0.57, 0.86; p = 0.03) were associated with lower rates of engagement in sports and exercise. Conclusion Our findings indicate a significant association between clinical and demographic factors and participation in sports and exercise among MDD outpatients.

Clinimetric Criteria for Patient-Reported Outcome Measures.

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.

First-time administration of the Sydney Melancholia Prototype Index (SMPI) to non-English-speaking patients: a study from Brazil.

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.