Trajectories of positive attributes from childhood to young adulthood and its associations with threat and deprivation.

OBJECTIVE: The aims of this study are to investigate the trajectory of positive attributes from childhood to early adulthood and to explore how those trajectories can be modified by two domains of childhood adversity - threat and deprivation. METHODS: A large prospective school-based community cohort of youths (n=2,511, 6-14 years of age, 45% female) was assessed and followed up for 3 years (80% retention) and 6 years (71% retention). Positive attributes were assessed by the Youth Strength Inventory (YSI). Childhood exposure to threat and deprivation were assessed by a composite measure using multiple indicators. RESULTS: Trajectories of YSI scores were non-linear and distinct for boys and girls. While boys presented a more stable trajectory; girls showed higher levels of positive attributes early in life that decrease over time around adolescence. Both exposure to threat and deprivation presented negative linear association with YSI over time. Furthermore, we found interactions between developmental stage and both adversity domains meaning that the effects of exposure to adversity were stronger at earlier developmental stages and almost non-significant closer to early adulthood. CONCLUSION: Our findings provide new evidence on trajectories of positive attributes in youth and reveal and how experiences of adversity in early life impact not only mental disorder but also positive aspects of mental health.

Perinatal and neonatal factors and mental disorders in children and adolescents: looking for the contributions of the early environment to common and dissociable aspects of psychopathology.

High rates of co-occurrence of mental disorders have been hypothesized to represent a result of common susceptibility to overall psychopathology. The purpose of this study is to test the hypothesis that commonalities among psychiatric disorders might be partially driven by sharable perinatal and neonatal environmental factors for mental disorders. Participants were 6-14 years of age children and their parents. Primary caregivers provided data on perinatal and neonatal information assessed retrospectively (n = 2231). Psychiatric disorders diagnoses were assessed using the Development and Well Being Behavior Assessment (DAWBA). We used bifactor models to disentangle common from dissociable aspects of psychopathology. These models allow modeling psychiatric disorders as the result of a common domain of psychopathology (p-factor) and three dissociable domains (fear, distress, and externalizing symptoms). Associations were tested using linear and tobit regression models. The p-factor was associated with male sex, low socioeconomic status, gestational smoking, gestational drinking, low levels of maternal education and presence of mental disorder in the mother. Associations with specific factors also emerged suggesting some risk factors might also have some role for fear, distress and externalizing factors. Our study supports the hypothesis that overall susceptibility to psychopathology might be partially driven by sharable perinatal and neonatal factors.

Post-COVID-19 condition: systemic inflammation and low functional exercise capacity.

Introduction: Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported. Methods: In this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6-12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group (n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment. Results: SRPF presented lower IL-4 concentration compared with Control (q = 0.0018) and with SR (q = 0.030), and lower IFN-α2 serum content compared with Control (q = 0.007). In addition, SRPF presented higher MIP-1ß serum concentration compared with SR (q = 0.029). SR presented lower CCL11 (q = 0.012 and q = 0.001, respectively) and MCP-1 levels (q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control (q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF (q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group (q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.

Intermittent Fasting as a Potential Therapeutic Instrument for Major Depression Disorder: A Systematic Review of Clinical and Preclinical Studies.

Recent studies have reported positive effects of Intermittent Fasting (IF) on metabolic parameters, cognition, and mood. However, regarding depressive symptoms, the effect of IF is not clear. The purpose of this review was to assess the available evidence on IF interventions for depression in both clinical and preclinical studies. Of the 23 included studies, 15 were performed on humans and 8 on animal models. The studies on rodents suggested that IF acts as a circadian regulator, improving neurotransmitter availability and increasing the levels of neurotrophic factors in the brain. However, the investigations on humans mainly evaluated healthy volunteers and showed a great heterogeneity regarding both the IF regimen studied and the observed effects on mood. Most available clinical trials have specific limitations, such as small sample sizes and uncontrolled designs. A comprehensive systematic review was conducted on five databases, PubMed, Cochrane, the Central Register of Controlled Trials, Web of Science databases, BVS and Scopus, identifying 23 relevant studies up to 6 October 2022. IF has potentially relevant physiological effects for the treatment of mood disorders, but better designed studies and controlled evaluations are needed to evaluate its efficiency in the treatment of major depression.

Translating measurement into practice: Brazilian norms for depressive symptom assessment with the Patient Health Questionnaire (PHQ-9)

Objectives: To provide practical norms for measuring depressive symptoms with the Patient Health Questionnaire 9 (PHQ-9) in Brazil through a state-of-the-art psychometrics analysis. Methods: We used a large representative dataset from the 2019 Brazilian National Health Survey (Pesquisa Nacional de Saúde - 2019), which included 90,846 Brazilian citizens. To assess scale structure, we assessed a unidimensional model using confirmatory factor analysis. Item response theory was used to characterize the distribution of depressive symptoms. Summed- and mean-based PHQ-9 scores were then linked using item response theory-based scores in generalized additive models. Finally, percentiles, T scores, and a newly developed score, called the decimal score (D score), were generated to describe PHQ-9 norms for the Brazilian population. Results: Confirmatory factor analysis revealed a good fit to the unidimensional model, being invariant to age and sex. Item response theory captured item-level information about the latent trait (reliable from 1 to 3 SDs above the mean). Brazilian norms were presented using summed scores, T scores, and D scores. Conclusion: This is the first study to determine Brazilian norms for the PHQ-9 among a large representative sample using robust psychometric tools. More precise PHQ-9 scores are now available and may be widely used in primary and specialized clinical care settings.

Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers.

Objective: To analyze the potential impact of sociodemographic, clinical and biological factors on the long-term cognitive outcome of patients who survived moderate and severe forms of COVID-19. Methods: We assessed 710 adult participants (Mean age = 55 ± 14; 48.3% were female) 6 to 11 months after hospital discharge with a complete cognitive battery, as well as a psychiatric, clinical and laboratory evaluation. A large set of inferential statistical methods was used to predict potential variables associated with any long-term cognitive impairment, with a focus on a panel of 28 cytokines and other blood inflammatory and disease severity markers. Results: Concerning the subjective assessment of cognitive performance, 36.1% reported a slightly poorer overall cognitive performance, and 14.6% reported being severely impacted, compared to their pre-COVID-19 status. Multivariate analysis found sex, age, ethnicity, education, comorbidity, frailty and physical activity associated with general cognition. A bivariate analysis found that G-CSF, IFN-alfa2, IL13, IL15, IL1.RA, EL1.alfa, IL45, IL5, IL6, IL7, TNF-Beta, VEGF, Follow-up C-Reactive Protein, and Follow-up D-Dimer were significantly (p<.05) associated with general cognition. However, a LASSO regression that included all follow-up variables, inflammatory markers and cytokines did not support these findings. Conclusion: Though we identified several sociodemographic characteristics that might protect against cognitive impairment following SARS-CoV-2 infection, our data do not support a prominent role for clinical status (both during acute and long-stage of COVID-19) or inflammatory background (also during acute and long-stage of COVID-19) to explain the cognitive deficits that can follow COVID-19 infection.

Translating measurement into practice: Brazilian norms for the Patient Health Questionnaire (PHQ-9) for assessing depressive symptoms.

OBJECTIVE: To provide practical norms for measuring depressive symptoms using the Patient Health Questionnaire 9 (PHQ-9) in Brazil using a state-of-art psychometrics analysis. METHODS: We used a large and representative Brazilian dataset from the 'Pesquisa Nacional de Saúde - 2019'(PNS-2019), which includes 90,846 Brazilian citizens. First, to assess the scale structure, we assessed the unidimensional model using Confirmatory Factor Analysis (CFA). Second, we used Item Response Theory (IRT) to characterize depressive symptoms´ distribution. Then, we linked summed- and meanbased PHQ-9 scores with the IRT-based score by using generalized additive models. Finally, we generated percentiles, T scores, and a newly developed score, called D scores (decimal scores), to describe the PHQ-9 norms for Brazilian population. RESULTS: CFA revealed a good fit to the unidimensional model, showing to be invariant to age and sex. IRT captured item-level information of the latent trait (reliable from 1 to 3 standard deviations above the mean). Brazilian norms were presented using summed-, T-scores, and D-scores. CONCLUSIONS: This is the first study to define Brazilian´s norms for the PHQ-9 among a large representative sample, using robust psychometric tools. More precise PHQ-9 scores are now available and may be widely used in primary and specialized clinical care settings.

Post-acute sequelae of SARS-CoV-2 associates with physical inactivity in a cohort of COVID-19 survivors.

The aim of this study was to determine whether Post-acute Sequelae of SARS-CoV-2 Infection (PASC) are associated with physical inactivity in COVID-19 survivors. This is a cohort study of COVID-19 survivors discharged from a tertiary hospital in Sao Paulo, Brazil. Patients admitted as inpatients due to laboratory-confirmed COVID-19 between March and August 2020 were consecutively invited for a follow-up in-person visit 6 to 11 months after hospitalization. Ten symptoms of PASC were assessed using standardized scales. Physical activity was assessed by questionnaire and participants were classified according to WHO Guidelines. 614 patients were analyzed (age: 56 ± 13 years; 53% male). Frequency of physical inactivity in patients exhibiting none, at least 1, 1-4, and 5 or more symptoms of PASC was 51%, 62%, 58%, and 71%, respectively. Adjusted models showed that patients with one or more persistent PASC symptoms have greater odds of being physically inactive than those without any persistent symptoms (OR: 1.57 [95% CI 1.04-2.39], P = 0.032). Dyspnea (OR: 2.22 [1.50-3.33], P < 0.001), fatigue (OR: 2.01 [1.40-2.90], P < 0.001), insomnia (OR: 1.69 [1.16-2.49], P = 0.007), post-traumatic stress (OR: 1.53 [1.05-2.23], P = 0.028), and severe muscle/joint pain (OR: 1.53 [95% CI 1.08-2.17], P = 0.011) were associated with greater odds of being physically inactive. This study suggests that PASC is associated with physical inactivity, which itself may be considered as a persistent symptom among COVID-19 survivors. This may help in the early identification of patients who could benefit from additional interventions tailored to combat inactivity (even after treatment of PASC), with potential beneficial impacts on overall morbidity/mortality and health systems worldwide.

Revisiting global cognitive and functional state 13 years after a clinical trial of lithium for mild cognitive impairment

Objectives: To re-evaluate a sample of older adults enrolled in a randomized controlled trial of lithium for amnestic mild cognitive impairment (MCI) after 11 to 15 years, re-assessing their current (or last available) global cognitive and functional state. Methods: We recalled all former participants of the Lithium-MCI trial conducted by our group between 2009 and 2012 to perform a single-blinded, cross-sectional evaluation of their global clinical state to compare the long-term outcome of those who received lithium vs. those who received placebo. Results: Of the original sample (n=61), we were able to reach 36 participants (59% of retention), of whom 22 had previously received lithium (61% of the recall sample) and 14 (39%) had received placebo. Since 30.5% of the recalled sample was deceased, psychometric data were collected only for 69.5% of the participants. We found statistically significant differences in current mean Mini Mental State Examination score according to previous treatment group (25.5 [SD, 5.3] vs. 18.3 [SD, 10.9], p = 0.04). The lithium group also had better performance in the phonemic Verbal Fluency Test than the control group (34.4 [SD, 14.4] vs. 11.6 [SD, 10.10], p < 0.001). Differences in these measures also had large effect sizes, as shown by Cohen's d values of 0.92 and 1.78, respectively. Conclusion: This data set suggests that older adults with amnestic MCI who had been treated with lithium during a previous randomized controlled trial had a better long-term global cognitive outcome than those from a matched sample who did not receive the intervention.

Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study.

Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample. This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures). Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006). We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.

Revisiting global cognitive and functional state 13 years after a clinical trial of lithium for mild cognitive impairment.

OBJECTIVES: To re-evaluate a sample of older adults enrolled in a randomized controlled trial of lithium for amnestic mild cognitive impairment (MCI) after 11 to 15 years, re-assessing their current (or last available) global cognitive and functional state. METHODS: We recalled all former participants of the Lithium-MCI trial conducted by our group between 2009 and 2012 to perform a single-blinded, cross-sectional evaluation of their global clinical state to compare the long-term outcome of those who received lithium vs. those who received placebo. RESULTS: Of the original sample (n=61), we were able to reach 36 participants (59% of retention), of whom 22 had previously received lithium (61% of the recall sample) and 14 (39%) had received placebo. Since 30.5% of the recalled sample was deceased, psychometric data were collected only for 69.5% of the participants. We found statistically significant differences in current mean Mini Mental State Examination score according to previous treatment group (25.5 [SD, 5.3] vs. 18.3 [SD, 10.9], p = 0.04). The lithium group also had better performance in the phonemic Verbal Fluency Test than the control group (34.4 [SD, 14.4] vs. 11.6 [SD, 10.10], p < 0.001). Differences in these measures also had large effect sizes, as shown by Cohen's d values of 0.92 and 1.78, respectively. CONCLUSION: This data set suggests that older adults with amnestic MCI who had been treated with lithium during a previous randomized controlled trial had a better long-term global cognitive outcome than those from a matched sample who did not receive the intervention.

Love, compassion and attachment in psychiatric care: perspectives for research and clinical practice.

Love, compassion and related constructs have drawn to much attention from the general public due to the increased need of a better and more humanistic medical care. However, those constructs have been constantly neglected in academic benches and high impact research journals due to the 'abstract' and 'non-measurable' nature of these constructs. At the same time, medicine is claiming for a more patient-oriented and empathetic care, as care has been more disease-oriented and less life- and health-oriented, as initially proposed. This piece tries to discuss and claim for a more compassionate and altruistic care, despite technical pressure from most healthcare systems. We aim, thus, to incentive more research and clinical practice toward this very important subject.

It is time to think about refugees' mental health: The case of Dzaleka Refugee Camp - Malawi.

Refugees are individuals who live outside of their country and are at increased risk of mental health problems. Even though many papers assessed Refugees' mental health, few intended to evaluate in remote areas, such as refugee camps. On this study we assessed 102 individuals who lives in the Dzaleka Refugee Camp - Malawi. We found 78% of individuals with probable depression, 53% with thoughts about death, 25.5% with suicidal plans, and 15% reporting having attempted suicide in the 12 months prior to the assessment. This data points out to an urgent political mobilization to promote mental health to this vulnerable population.

Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.

BACKGROUND: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce. METHODS: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment. RESULTS: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities. CONCLUSIONS: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.