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.

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.

Translation, cultural adaptation, and validation of the Brazilian Portuguese version of the Higher Education Stress Inventory (HESI-Br)

Abstract Objectives There are no validated instruments to measure education-related stress in Brazilian university students. Thus, we aimed to translate and test the internal reliability, convergent/discriminant validity, and measurement equivalence of the Higher Education Stress Inventory (HESI). Methods The translation protocol was carried out by two independent translators. The instrument was culturally adapted after a pilot version was administered to 36 university students. The final version (HESI-Br) was administered to 1,021 university students (mean age = 28.3, standard deviation [SD] = 9.6, 76.7% female) via an online survey that lasted from September 1 to October 15, 2020. The factor structure was estimated using exploratory factor analysis (EFA) on the first half of the dataset. We tested the best EFA-derived model with confirmatory factor analysis (CFA) on the second half. Convergent/discriminant validity was tested using the Depression, Anxiety and Stress Scale (DASS-21). Sex, age groups, period of study, family income and area of study were used to test measurement equivalence. Results EFA suggested five factors: career dissatisfaction; faculty shortcomings; high workload; financial concerns; and toxic learning environment. CFA supported the five-factor model (15 items), but not a higher order factor, suggesting multidimensionality. All five factors presented acceptable internal reliabilities, with Cronbach's α ≥ 0.72 and McDonald's ω ≥ 0.64. CFA models indicated that the HESI-Br and DASS-21 assess different but correlated underlying latent constructs, supporting discriminant validity. Equivalence was ascertained for all tested groups. Conclusion The 15-item HESI-Br is a reliable and invariant multidimensional instrument for assessing relevant stressors among university students in Brazil.

The impact of child psychiatric conditions on future educational outcomes among a community cohort in Brazil.

AIMS: Mental health problems early in life can negatively impact educational attainment, which in turn have negative long-term effects on health, social and economic opportunities. Our aims were to: (i) estimate the impacts of different types of psychiatric conditions on educational outcomes and (ii) to estimate the proportion of adverse educational outcomes which can be attributed to psychiatric conditions. METHODS: Participants (N = 2511) were from a school-based community cohort of Brazilian children and adolescents aged 6-14 years enriched for high family risk of psychiatric conditions. We examined the impact of fear- (panic, separation and social anxiety disorder, specific phobia, agoraphobia and anxiety conditions not otherwise specified), distress- (generalised anxiety disorder, major depressive disorder and depressive disorder not otherwise specified, bipolar, obsessive-compulsive, tic, eating and post-traumatic stress disorder) and externalising-related conditions (attention deficit and hyperactivity disorder, conduct and oppositional-defiant conditions) on grade repetition, dropout, age-grade distortion, literacy performance and bullying perpetration, 3 years later. Psychiatric conditions were ascertained by psychiatrists, using the Development and Well-Being Behaviour Assessment. Propensity score and inverse probability weighting were used to adjust for potential confounders, including comorbidity, and sample attrition. We calculated the population attributable risk percentages to estimate the proportion of adverse educational outcomes in the population which could be attributed to psychiatric conditions. Analyses were conducted separately for males and females. RESULTS: Fear and distress conditions in males were associated with school dropout (odds ratio (OR) = 2.76; 95% confidence interval (CI) = 1.06, 7.22; p < 0.05) and grade repetition (OR = 2.76; 95% CI = 1.32, 5.78; p < 0.01), respectively. Externalising conditions were associated with grade repetition in males (OR = 1.66; 95% CI = 1.05, 2.64; p < 0.05) and females (OR = 2.03; 95% CI = 1.15, 3.58; p < 0.05), as well as age-grade distortion in males (OR = 1.66; 95% CI = 1.05, 2.62; p < 0.05) and females (OR = 2.88; 95% CI = 1.61, 5.14; p < 0.001). Externalising conditions were also associated with lower literacy levels (ß = -0.23; 95% CI = -0.34, -0.12; p < 0.001) and bullying perpetration (OR = 3.12; 95% CI = 1.50, 6.51; p < 0.001) in females. If all externalising conditions were prevented or treated, we estimate that 5.0 and 4.8% of grade repetition would not have occurred in females and males, respectively, as well as 10.2 (females) and 5.3% (males) of age-grade distortion cases and 11.4% of female bullying perpetration. CONCLUSIONS: The study provides evidence of the negative impact of psychiatric conditions on educational outcomes in a large Brazilian cohort. Externalising conditions had the broadest and most robust negative impacts on education and these were particularly harmful to females which are likely to limit future socio-economic opportunities.

Heat stroke during long-term clozapine treatment: should we be concerned about hot weather?

OBJECTIVE: To describe the case of a patient with schizophrenia on clozapine treatment who had an episode of heat stroke. CASE DESCRIPTION: During a heat wave in January and February 2014, a patient with schizophrenia who was on treatment with clozapine was initially referred for differential diagnose between systemic infection and neuroleptic malignant syndrome, but was finally diagnosed with heat stroke and treated with control of body temperature and hydration. COMMENTS: This report aims to alert clinicians take this condition into consideration among other differential diagnoses, especially nowadays with the rise in global temperatures, and to highlight the need for accurate diagnosis of clinical events during pharmacological intervention, in order to improve treatment decisions and outcomes.

Heat stroke during long-term clozapine treatment: should we be concerned about hot weather? / Heat stroke durante tratamento de longo prazo com clozapina: devemos nos preocupar com o tempo quente?

Objective To describe the case of a patient with schizophrenia on clozapine treatment who had an episode of heat stroke. Case description During a heat wave in January and February 2014, a patient with schizophrenia who was on treatment with clozapine was initially referred for differential diagnose between systemic infection and neuroleptic malignant syndrome, but was finally diagnosed with heat stroke and treated with control of body temperature and hydration. Comments This report aims to alert clinicians take this condition into consideration among other differential diagnoses, especially nowadays with the rise in global temperatures, and to highlight the need for accurate diagnosis of clinical events during pharmacological intervention, in order to improve treatment decisions and outcomes.

Objetivo Descrever o caso de um paciente com esquizofrenia em tratamento com clozapina acometido por um episódio de heat stroke. Descrição do caso Durante uma onda de calor em janeiro e fevereiro de 2014, um paciente com esquizofrenia em tratamento com clozapina foi inicialmente encaminhado para diagnóstico diferencial de infecção sistêmica e síndrome neuroléptica maligna, tendo obtido o diagnóstico final de heat stroke, tratado com controle de temperatura corporal e hidratação. Comentários Este relato de caso tem como objetivo alertar os clínicos para este diagnóstico diferencial, que pode surgir com mais frequência à medida que as temperaturas globais continuarem a aumentar, e também destacar a importância da realização de um diagnóstico mais acurado, que possa melhorar as decisões de tratamento e os desfechos clínicos para os pacientes.

Treadmill exercise protects against pentylenetetrazol-induced seizures and oxidative stress after traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of acquired epilepsy, and significant resources are required to develop a better understanding of the pathologic mechanism as targets for potential therapies. Thus, we decided to investigate whether physical exercise after fluid percussion injury (FPI) protects from oxidative and neurochemical alterations as well as from behavioral electroencephalographic (EEG) seizures induced by subeffective convulsive doses of pentylenetetrazol (PTZ; 35 mg/kg). Behavioral and EEG recordings revealed that treadmill physical training increased latency to first clonic and tonic-clonic seizures, attenuated the duration of generalized seizures, and protected against the increase of PTZ-induced Racine scale 5 weeks after neuronal injury. EEG recordings also revealed that physical exercise prevented PTZ-induced amplitude increase in TBI animals. Neurochemical analysis showed that exercise training increased glutathione/oxidized glutathione ratio and glutathione levels per se. Exercise training was also effective against alterations in the redox status, herein characterized by lipid peroxidation (thiobarbituric acid reactive substances), protein carbonyl increase, as well as the inhibition of superoxide dismutase and Na⁺,K⁺-ATPase activities after FPI. On the other hand, histologic analysis with hematoxylin and eosin revealed that FPI induced moderate neuronal damage in cerebral cortex 4 weeks after injury and that physical exercise did not protect against neuronal injury. These data suggest that the ability of physical exercise to reduce FPI-induced seizures is not related to its protection against neuronal damage; however, the effective protection of selected targets, such as Na⁺/K⁺-ATPase elicited by physical exercise, may represent a new line of treatment for post-traumatic seizure susceptibility.

Resultados de dois esquemas de tratamento da pielonefrite durante a gravidez e correlação com o desfecho da gestação / Results of two treatment regimens for pyelonephritis during pregnancy and correlation with pregnancy outcome

OBJETIVO: Determinar o perfil epidemiológico das gestantes internadas por infecção do trato urinário, bem como verificar os agentes mais prevalentes e a resposta à antibioticoterapia. MÉTODOS: Estudo retrospectivo, que incluiu 106 gestantes internadas para tratamento de infecção do trato urinário no período entre janeiro de 2007 a dezembro de 2010. A avaliação constituiu-se de análise de prontuários dessas gestantes, observando-se informações sobre a internação e a gestação, bem como seu desfecho. Foi realizada a análise estatística por meio do programa Statistical Package for the Social Science, versão 15.0. Foram utilizados, para análise dos dados, o teste bilateral exato de Fisher e o teste t de Student, bem como métodos de estatística descritiva. RESULTADOS: Uroculturas positivas foram encontradas em 60,5% das gestantes internadas por infecção do trato urinário. O agente infeccioso mais frequente foi Escherichia coli e não houve diferença quanto à resistência, à recorrência ou a complicações entre os agentes etiológicos mais frequentes. Gestantes com infecção do trato urinário prévia tiveram maior risco de recorrência (OR=10,8; p<0,05). Os antibióticos mais frequentemente utilizados na internação foram ampicilina e cefazolina. Troca de esquema terapêutico por resistência bacteriana ocorreu em 11,9% das pacientes que usaram cefazolina e em 20% das que usaram ampicilina (OR=5,5; p<0,05). O índice de complicações gestacionais foi igual nos dois tratamentos. Não houve diferença entre as médias do número de dias de internação para os dois tratamentos. CONCLUSÃO: A ampicilina esteve associada a maior índice de resistência bacteriana que a cefazolina, necessitando de maior número de trocas do esquema terapêutico, sem resultar em diferença nos desfechos clínicos e tempo de internação.

PURPOSE: To determine the epidemiological profile of women admitted for urinary tract infection as well as to verify the most prevalent agents and response to antibiotic therapy. METHODS: A retrospective study of 106 pregnant women admitted to a university hospital for urinary tract infection treatment during the period between January 2007 to December 2010. The evaluation was based on analysis of the medical records of these pregnant women, with the observation of hospitalization and pregnancy data, as well as its outcome. Statistical analysis was performed using Statistical Package for the Social Science, version 15.0. The bilateral Fisher exact test and Student's t test were used for data analysis, as well as descriptive statistical methods. RESULTS: Positive urine cultures were observed in 60.5% of pregnant women admitted due to urinary tract infection. The most frequent infectious agent was Escherichia coli and no difference in resistance, recurrence or complications was observed between the most frequent etiologic agents. Pregnant women with previous UTI had a higher recurrence risk (OR=10.8; p<0.05). The antibiotics most commonly used during hospitalization were ampicillin and cefazolin. Change of therapeutic agent due to bacterial resistance occurred in 11.9% of patients who took cefazolin and in 20% of patients who took ampicillin (OR=5.5; p<0.05). The rate of gestational complications was the same for both treatments. There was no difference in mean number of days of hospitalization between the treatments. CONCLUSION: In the studied population ampicillin showed a higher rate of bacterial resistance than cefazolin, requiring a larger number of treatment regimen exchanges, without resulting in differences in clinical outcome or time of hospitalization.

Creatine reduces oxidative stress markers but does not protect against seizure susceptibility after severe traumatic brain injury.

Achievements made over the last years have highlighted the important role of creatine in health and disease. However, its effects on hyperexcitable circuit and oxidative damage induced by traumatic brain injury (TBI) are not well understood. In the present study we revealed that severe TBI elicited by fluid percussion brain injury induced oxidative damage characterized by protein carbonylation, thiobarbituric acid reactive species (TBARS) increase and Na(+),K(+)-ATPase activity inhibition 4 and 8 days after neuronal injury. Statistical analysis showed that after TBI creatine supplementation (300 mg/kg, p.o.) decreased the levels of protein carbonyl and TBARS but did not protect against TBI-induced Na(+),K(+)-ATPase activity inhibition. Electroencephalography (EEG) analysis revealed that the injection of a subconvulsant dose of PTZ (35 mg/kg, i.p.), 4 but not 8 days after neuronal injury, decreased latency for the first clonic seizures and increased the time of spent generalized tonic-clonic seizures compared with the sham group. In addition, creatine supplementation had no effect on convulsive parameters induced by a subconvulsant dose of PTZ. Current experiments provide evidence that lipid and protein oxidation represents a separate pathway in the early post-traumatic seizures susceptibility. Furthermore, the lack of consistent anticonvulsant effect exerted by creatine in this early phase suggests that its apparent antioxidant effect does not protect against excitatory input generation induced by TBI.

The involvement of Na+, K+-ATPase activity and free radical generation in the susceptibility to pentylenetetrazol-induced seizures after experimental traumatic brain injury.

Although the importance of brain trauma as risk factor for the development of epilepsy is well established, the mechanisms of epileptogenesis are not well understood. In the present study, we revealed that the injection of a subthreshold dose of PTZ (30 mg/Kg, i.p.) after 5 weeks of injury induced by Fluid Percussion Brain Injury (FPI) decreased latency for first clonic seizures, increased the time of spent generalized tonic-clonic seizures and electrocorticographic (EEG) wave amplitude. In addition, statistical analysis revealed that N-acetylcysteine (NAC) (100mg/kg) supplementation during 5 weeks after neuronal injury protected against behavioral and electrographical seizure activity elicited by subthreshold dose of PTZ. The supplementation of this antioxidant compound also protected against the Na(+),K(+)-ATPase activity inhibition and concomitant increase in the levels of oxidative stress markers (protein carbonylation and thiobarbituric acid-reactive substances-TBARS) in site and peri-contusional cortical tissue. In summary, the current experiments clearly showed that FPI model induces early posttraumatic seizures and suggest that an alteration in the lipid/protein oxidation, membrane fluidity, and Na(+),K(+)-ATPase activity may be correlated with neuronal excitability, a significant component of the secondary injury cascade that accompanies TBI.

Adaptation to oxidative challenge induced by chronic physical exercise prevents Na+,K+-ATPase activity inhibition after traumatic brain injury.

Physical exercise is likely to alter brain function and to afford neuroprotection in several neurological diseases. Although the favorable effects of physical exercise on traumatic brain injury (TBI) patients is well known, little information is available regarding the role of free radicals in the improvement induced by physical exercise in an experimental model of TBI induced by fluid percussion injury (FPI). Thus, we investigated whether 6 weeks of swimming training protects against oxidative damage (measured by protein carbonylation and thiobarbituric acid-reactive substances-TBARS) and neurochemical alterations represented by immunodetection of alpha subunit and activity of Na(+),K(+)-ATPase after FPI in cerebral cortex of rats. Statistical analysis revealed that physical training protected against FPI-induced TBARS and protein carbonylation increase. In addition, physical training was effective against Na(+),K(+)-ATPase enzyme activity inhibition and alpha(1) subunit level decrease after FPI. Pearson's correlation analysis revealed that the decrease in levels of catalytic alpha(1) subunit of Na(+),K(+)-ATPase induced FPI correlated with TBARS and protein carbonylation content increase. Furthermore, the effective protection exerted by physical training against FPI-induced free radical correlated with the immunocontent of the catalytic alpha(1) subunit maintenance. These data suggest that TBI-induced reactive oxygen species (ROS) generation decreases Na(+),K(+)-ATPase activity by decreasing the total number of enzyme molecules, and that physical exercise protects against this effect. Therefore, the effective protection of selected targets, such as Na(+),K(+)-ATPase induced by physical training, supports the idea that physical training may exert prophylactic effects on neuronal cell dysfunction and damage associated with TBI.

Na+,K+-ATPase activity impairment after experimental traumatic brain injury: relationship to spatial learning deficits and oxidative stress.

Traumatic brain injury (TBI) is a devastating disease that commonly causes persistent mental disturbances and cognitive deficits. Although studies indicate that oxidative stress and functional deficits occurring after TBI are interrelated events, the knowledge of the mechanisms underlying the development of such cognitive deficits has been limited. Thus, in the present study, we investigated the effect of fluid percussion brain injury (FPI) on a spatial learning task and levels of oxidative stress markers, namely, protein carbonylation and thiobarbituric acid-reactive substances (TBARS) and Na+,K+-ATPase activity 1 or 3 months after FPI in rats. Statistical analysis revealed that FPI increased the scape latency and mean number of error in Barnes maze test 1 and 3 months after FPI. We also found that protein carbonylation and TBARS content increased in the parietal cortex 1 and 3 months after FPI. In addition, 3 months after FPI, protein carbonylation levels increased both in ipsilateral and contralateral cortices of FPI animals. Indeed, statistical analysis revealed a decrease in Na+,K+-ATPase activity in the cerebral cortex of 1 month FPI animals. Furthermore, the decrease in enzyme activity found 3 months was larger, when compared with 1 month after FPI. These results suggest that cognitive impairment following TBI may result, at least in part, from increase of two oxidative stress markers, protein carbonylation and TBARS that occurs concomitantly to a decrease in Na+,K+-ATPase activity.