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OBJECTIVE: Schizophrenia (SCZ) is a disabling disorder that continues to defy clinicians and researchers. We investigated the effects of sodium nitroprusside (sNP) in an animal model of SCZ and as an add-on therapy in patients and the relationship between treatment with sNP and activity of the nDel1 enzyme, whose involvement in the pathophysiology of the disorder has been suggested earlier. METHODS: Ndel1 activity was measured following sNP infusions in spontaneously hypertensive rats (SHR; 2.5 or 5.0 mg/kg) and in a double-blind trial with SCZ patients (0.5 µg/kg/min). RESULTS: Ndel1 activity was significantly reduced after sNP infusion in blood of SHR compared to controls, and in patients receiving sNP (t = 7.756, df = 97, p < 0.0001, dcohen = 1.44) compared to placebo. Reduced Ndel1 activity between baseline and the end of the infusion was only seen in patients after treatment with sNP. CONCLUSION: Our findings suggest that SCZ patients may benefit from adjunctive therapy with sNP and that the Ndel1 enzyme is a candidate biomarker of psychopathology in the disorder. Future research should look into the role of Ndel1 in SCZ and the potential effects of sNP and drugs with similar profiles of action in both animals and patients.

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Abstract Introduction The Internet Gaming Disorder Scale - Short Form (IGDS9-SF) assesses the severity, harmful effects and/or consequences of excessive online and offline gaming. Its conciseness and theoretical foundations on current diagnostic criteria of gaming disorders make it a useful resource for clinical and screening settings. Objective To describe the process of cross-cultural adaptation of the IGDS9-SF to the Brazilian context. Methods The cross-cultural adaptation involved the steps of independent translation of the instrument, synthesis version, back-translation, pre-test and elaboration of the final version. Content validity assessment was conducted by a multidisciplinary committee of experts and consisted of both a quantitative analysis (calculation of content validity coefficients - CVC) and a qualitative analysis (assessment of the experts' comments and suggestions). The pre-test sample consisted of 30 gamers with variable sociodemographic characteristics. Results The cross-cultural adaptation of the scale followed the proposed protocol, and the CVC was satisfactory (≥ 0.83) for all the structures and equivalences assessed. Most of the suggestions made by the experts were accepted (mainly adjustments and language standardization). The gamers who participated in the pre-test judged the scale easy to understand and did not suggest changes. Discussion The Brazilian version of the IGDS9-SF showed adequate content validity and is available for researchers and clinicians, as well as for the investigation of additional psychometric characteristics.

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INTRODUCTION: The Internet Gaming Disorder Scale - Short Form (IGDS9-SF) assesses the severity, harmful effects and/or consequences of excessive online and offline gaming. Its conciseness and theoretical foundations on current diagnostic criteria of gaming disorders make it a useful resource for clinical and screening settings. OBJECTIVE: To describe the process of cross-cultural adaptation of the IGDS9-SF to the Brazilian context. METHODS: The cross-cultural adaptation involved the steps of independent translation of the instrument, synthesis version, back-translation, pre-test and elaboration of the final version. Content validity assessment was conducted by a multidisciplinary committee of experts and consisted of both a quantitative analysis (calculation of content validity coefficients - CVC) and a qualitative analysis (assessment of the experts' comments and suggestions). The pre-test sample consisted of 30 gamers with variable sociodemographic characteristics. RESULTS: The cross-cultural adaptation of the scale followed the proposed protocol, and the CVC was satisfactory (≥ 0.83) for all the structures and equivalences assessed. Most of the suggestions made by the experts were accepted (mainly adjustments and language standardization). The gamers who participated in the pre-test judged the scale easy to understand and did not suggest changes. DISCUSSION: The Brazilian version of the IGDS9-SF showed adequate content validity and is available for researchers and clinicians, as well as for the investigation of additional psychometric characteristics.

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Abstract Background Posttraumatic stress disorder consists of a set of symptoms that occurs in response to one or more traumatic events and can occur in postpartum, from traumatic situations related to the birth or to the baby's health in the first days of life. It is important tracking the presence of birth trauma, but there is not available instruments in the Brazilian context for this purpose. Objectives To present the cross-cultural adaptation of City Birth Trauma Scale (BiTS) into Brazilian portuguese. Methods Cross-cultural adaptation involved independent translations, synthesis,back-translation, and submission to the original author's appreciation. After the scale was subjected to face validity, followed by a pilot study with postpartum mothers. Results All steps were performed for the cross-cultural adaptation. Regarding face validity, items evaluated concerning different types of equivalence, presented satisfactory agreement values (≥4.20). Most of the expert's suggestions were followed, being the main ones related to adjustments in prepositions, pronouns and verbal subjects. Pilot study showed that the mothers had been able to understand and respond to the instrument without adjustments. Discussion BiTS's Brazilian version proved to be cross-culturally adapted, ensuring the possibility of intercultural data comparison from the semantic, idiomatic, cultural, and conceptual perspectives. New studies are being conducted to attest its psychometric adequacy.

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Background: Adverse childhood experiences (ACE) affect physical and mental health and may appear as risk factors for the development of different conditions in adult life. Objective: To perform a literature review and meta-analysis on risk indicators for the development of chronic lung diseases in adulthood associated with ACE. Method: We conducted a systematic literature review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the online databases PubMed, PsycINFO, and Web of Science. Quantitative studies involving male and female adults were included. Fixed- and random-effect models were used in the estimation of meta-analytical measures. The heterogeneity between studies was assessed using I2 statistics and Cochran's Q test. Results: A total of 19 studies were selected for the meta-analysis. The analyses showed statistically significant associations between ACE and lung diseases in general (OR = 1.41; CI 95%: 1.28-1.54), besides specific associations with asthma (OR = 1.32; CI 95%: 1.13-1.50) and COPD (OR = 1.44; CI 95%: 1.13-1.76). When the mediating effect of smoking was assessed separately we found a significant - although not quite expressive - association (OR = 1.06; CI 95%: 1.02 to 1.10), which weakens the hypothesis that a direct relationship exists between childhood trauma and the occurrence of lung diseases. Conclusions: ACE are an important risk factor for the development of lung diseases in adulthood, whether through direct or indirect contribution to this outcome, which highlights the relevance of increasing the awareness of health staff for the early detection and intervention in situations of vulnerability or risk in childhood as an important preventative measure.

Antecedentes: Experiencias infantiles adversas (ACE) afectan la salud física y mental y pueden aparecer como factores de riesgo para el desarrollo de diferentes afecciones en la vida adulta.Objetivo: realizar una revisión de la literatura y un metanálisis sobre indicadores de riesgo para el desarrollo de enfermedades pulmonares crónicas en la edad adulta asociadas con ACE.Método: Realizamos una revisión sistemática de la literatura de acuerdo con las pautas PRISMA (Elementos de Referencia para Revisiones Sistemáticas y Metaanálisis) utilizando las bases de datos en línea PubMed, PsycINFO y Web of Science. Se incluyeron estudios cuantitativos con hombres y mujeres adultos. Se utilizaron modelos de efectos fijos y aleatorios en la estimación de medidas meta-analíticas. La heterogeneidad entre los estudios se evaluó mediante estadísticas I 2 y la prueba Q de Cochran.Resultados: Se seleccionaron un total de 19 estudios para el metanálisis. Los análisis mostraron asociaciones estadísticamente significativas entre el ACE y las enfermedades pulmonares en general (OR = 1.41; IC 95%: 1.28­1.54), además de asociaciones específicas con el asma (OR = 1.32; IC 95%: 1.13 ­ 1.50) y EPOC (OR = 1,44; IC 95%: 1,13­1,76). Cuando el efecto mediador del tabaquismo se evaluó por separado, encontramos una asociación significativa (aunque no del todo clara) (OR = 1.06; IC 95%: 1.02 a 1.10), lo que debilita la hipótesis de que existe una relación directa entre el trauma infantil y la ocurrencia de enfermedades pulmonares.Conclusiónes: las experiencias ACE son un factor de riesgo importante para el desarrollo de enfermedades pulmonares en la edad adulta, ya sea a través de una contribución directa o indirecta, lo que resalta la relevancia de aumentar la conciencia del personal de salud para la detección temprana y la intervención en situaciones de vulnerabilidad o riesgo en la infancia como una medida preventiva importante.

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AIM: The Structured Clinical Interview for the DSM is one of the most used diagnostic instruments in clinical research worldwide. The current Clinician Version of the instrument (SCID-5-CV) has not yet been assessed in respect to its psychometric qualities. We aimed to assess the clinical validity and different reliability indicators (interrater test-retest, joint interview, face-to-face vs telephone application) of the SCID-5-CV in a large sample of 180 non-prototypical and psychiatric patients based on interviews conducted by raters with different levels of clinical experience. METHODS: The SCID-5-CV was administered face-to-face and by telephone by 12 psychiatrists/psychologists who took turns as raters and observers. Clinical diagnoses were established according to DSM-5 criteria and the longitudinal, expert, all data (LEAD) procedure. We calculated the percentage of agreement, diagnostic sensitivity and specificity, and the level of agreement (kappa) for diagnostic categories and specific diagnoses. RESULTS: The percentage of positive agreement between the interview and clinical diagnoses ranged between 73% and 97% and the diagnostic sensitivity/specificity were >0.70. In the joint interview, the levels of positive agreement were high (>75%) and kappa levels were >0.70 for most diagnoses. The values were less expressive, but still adequate, for interrater test-retest interviews. CONCLUSION: The SCID-5-CV presented excellent reliability and high specificity as assessed with different methods. The clinical validity of the instrument was also confirmed, which supports its use in daily clinical practice. We highlight the adequacy of the instrument to be used via telephone and the need for careful use by professionals with little experience in psychiatric clinical practice.

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Schizophrenia is a severe mental disorder that affects the anatomy and function of the brain, with an impact on one's thoughts, feelings, and behavior. The purpose of the study was to investigate cerebral blood flow (CBF) and brain connectivity in a group of patients with schizophrenia. Pseudo-continuous arterial spin labeling (pCASL) images were acquired from 28 patients in treatment and 28 age-matched healthy controls. Mean CBF and connectivity patterns were assessed. Schizophrenia patients had decreased CBF in the bilateral frontal pole and superior frontal gyrus, right medial frontal gyrus, triangular and opercular parts of the inferior frontal gyrus, posterior division of the left supramarginal gyrus, superior and inferior divisions of the left lateral occipital cortex, and bilateral occipital pole. Moreover, through different methods to assess connectivity, our results showed abnormal connectivity patterns in regions involved in motor, sensorial, and cognitive functions. Using pCASL, a non-invasive technique, we found CBF deficits and altered functional organization of the brain in schizophrenia patients that are associated with the symptoms and characteristics of the disorder.

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Abstract Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investigated whether SNP would have preventative effects on psychogenic symptoms induced by ketamine in healthy subjects. Methods: Healthy subjects (N = 38) were assigned to distinct groups that received SNP in different doses (0.15, 0.25, and 0.5 mcg/kg/min). First, participants received an infusion of SNP or placebo over 75 minutes. After 10 minutes, they were injected for 1 minute with a bolus of 0.26 mg/kg of ketamine and a maintenance dose was started 5 minutes later, with 0.25 mg/kg/h of ketamine for 50 minutes. Results: Ketamine-induced psychopathological alterations induced were reduced by SNP, as assessed with the Brief Psychological Rating Scale. Scores in the objective subscale of the Clinician-Administered Dissociative States Scale were also lower in SNP sessions compared to placebo. SNP had protective effects against deterioration in facial emotion and identity recognition tasks induced by ketamine. Discussion: Our findings support the view that SNP has preventative properties against psychotic manifestations.

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Abstract Background: Neuroimaging studies are an invaluable source of information about the physiopathology of schizophrenia. Arterial spin labeling (ASL) is a new magnetic resonance technique (MRI) that is able to effectively evaluate brain function without the use of radiation. Objective: To make a systematic review of studies using ASL to compare resting-state regional cerebral blood flow (rCBF) patterns in patients with schizophrenia and healthy controls. Methods: Original articles were searched for on PubMed, Scopus, Web of Science and PsycINFO electronic databases. The search terms used were 'arterial', 'spin', 'labeling', and 'schizophrenia'. Only studies comparing resting-state rCBF were included, a qualitative synthesis was then performed. Results: Ten articles were included in the review among a total of 22. Decreased rCBF in schizophrenia patients was described in the anterior cingulate, cuneus, fusiform gyrus, frontal lobe, left middle frontal gyrus, inferior frontal gyrus, lingual gyrus, middle occipital gyrus, and parietal lobe. The putamen was the only region with increased rCBF in schizophrenia. Discussion: The evidence of the studies reviewed lends support to the concept of hipofrontality in schizophrenia. rCBF alterations were found in regions classically associated with schizophrenia. ASL seems to be valid, and reliable tool to assess schizophrenia.

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The neuronal representation of luminance contrast has not been thoroughly studied in birds. Here we present a detailed quantitative analysis of the contrast response of 120 individual neurons recorded from the visual wulst of awake burrowing owls (Athene cunicularia). Stimuli were sine-wave gratings presented within the cell classical receptive field and optimized in terms of eye preference, direction of drift, and spatiotemporal frequency. As contrast intensity was increased from zero to near 100%, most cells exhibited a monotonic response profile with a compressive, at times saturating, nonlinearity at higher contrasts. However, contrast response functions were found to have a highly variable shape across cells. With the view to capture a systematic trend in the data, we assessed the performance of four plausible models (linear, power, logarithmic, and hyperbolic ratio) using classical goodness-of-fit measures and more rigorous statistical tools for multimodel inferences based on the Akaike information criterion. From this analysis, we conclude that a high degree of model uncertainty is present in our data, meaning that no single descriptor is able on its own to capture the heterogeneous nature of single-unit contrast responses in the wulst. We further show that the generalizability of the hyperbolic ratio model established, for example, in the primary visual cortex of cats and monkeys is not tenable in the owl wulst mainly because most neurons in this area have a much wider dynamic range that starts at low contrast. The challenge for future research will be to understand the functional implications of these findings.

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RATIONALE: The devastating nature of schizophrenia and treatment limitations have triggered a search for early detection methods to enable interventions to be implemented as soon as the first signs and symptoms appear. In this effort, several studies have investigated the cognitive functions in individuals regarded as being in at-risk mental states (ARMS) for psychosis. OBJECTIVE: Our aim was to make a systematic review of the literature regarding basic and social cognition in individuals in ARMS following the guidelines of the PRISMA statement. RESULTS: In general, the results of the 49 articles included in the review show that individuals in ARMS have pervasive cognitive deficits that seem to be greater in individuals who later convert to psychosis. CONCLUSIONS: Cognitive impairment can be detected in individuals considered to be in ARMS according to current classifications and may serve as a risk marker for psychotic conversion; however, the lack of standardized criteria to define ARMS and of homogeneous cognitive assessment methods hamper the generalization of findings from different studies.

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The pharmacokinetic properties of a new molecular entity are important aspects in evaluating the viability of the compound as a pharmacological agent. The sesquiterpene lactone lychnopholide exhibits important biological activities. The objective of this study was to characterize the pharmacokinetics of lychnopholide after intravenous administration of 1.65 mg/kg (n = 5) and oral administration of 3.3 mg/kg (n = 3) lychnopholide in rats (0.2 ± 0.02 kg in weight) through nonlinear mixed effects modeling and non-compartmental pharmacokinetic analysis. A highly sensitive analytical method was used to quantify the plasma lychnopholide concentrations in rats. Plasma protein binding of this compound was over 99 % as determined by a filtration method. A two-compartment body model plus three transit compartments to characterize the absorption process best described the disposition of lychnopholide after both routes of administration. The oral bioavailability was approximately 68 %. The clearance was 0.131 l/min and intercompartmental clearance was 0.171 l/min; steady-state volume of distribution was 4.83 l. The mean transit time for the absorption process was 9.15 minutes. No flip-flop phenomenon was observed after oral administration. The pharmacokinetic properties are favorable for further development of lychnopholide as a potential oral pharmacological agent.

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This is a report on two cases of refractory schizophrenia and two cases of clozapine-resistant schizophrenia successful treated with paliperidone palmitate. To the authors' knowledge, this is the first report of the successful use of paliperidone palmitate in such patients.

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BACKGROUND: Functional neuroimaging studies have consistently shown abnormal limbic activation patterns in socially anxious individuals, but structural data on the amygdala and hippocampus of these patients are scarce. This study explored the existence of structural differences in the whole brain, amygdala, and hippocampus of subjects with clinical and subthreshold social anxiety compared to healthy controls. We hypothesized that there would be volumetric differences across groups, without predicting their direction (i.e. enlargement or reduction). METHODS: Subjects classified as having social anxiety disorder (n = 12), subthreshold social anxiety (n = 12) and healthy controls (n = 14) underwent structural magnetic resonance imaging scans. The amygdala and hippocampus were defined a priori as regions of interest and volumes were calculated by manual tracing. Whole brain volume was calculated using voxel-based morphometry. RESULTS: The bilateral amygdala and left hippocampus were enlarged in socially anxious individuals relative to controls. The volume of the right hippocampus was enlarged in subthreshold social anxiety participants relative to controls. No differences were found across groups in respect to total brain volume. CONCLUSIONS: Our results show amygdalar and hippocampal volume alterations in social anxiety, possibly associated with symptom severity. The time course of such alterations and the cellular and molecular bases of limbic plasticity in social anxiety should be further investigated.

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The potential of the Copaifera langsdorffii leaves extract to prevent stone formation was analyzed by means of an ethylene glycol (EG) animal model of nephrolithiasis and an in vitro crystallization assay. Different doses of the C. langsdorffii leaves extract were administered to rats treated with EG. Urine biochemical parameters were quantified. CaOx deposits count and analysis of osteopontin expression were conducted on kidneys fixed in formalin. The in vitro assay was performed by turbidimetry. Phytochemical analyses of the extract were accomplished by HPLC-UV-DAD, and several compounds were isolated. C. langsdorffii leaf extract was able to avoid stone formation. The number of deposits was 50.30 ± 31.29 at the higher extract dose, compared to the value of 179.5 ± 45.96 achieved with the EG control. Significantly lower oxalate levels and OPN expression and increased citrate levels were observed after extract administration. In the in vitro assay, the extract diluted the formed crystals. Phytochemical analyses showed that the extract is rich in phenolic compounds that are capable of preventing stone formation. Thus, on the basis of our results, we suggest that the C. langsdorffii leaf extract has potential application in the prevention of kidney stone formation.

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BACKGROUND: depression is common in Parkinson's disease (PD), although frequently under-recognised. Among the scales used to investigate depressive features in PD, the Patient Health Questionnaire-9 (PHQ-9) has been largely used, but no specific cut-off scores for depression have been established thus far, which hinders the use of the PHQ-9 in clinical and research settings. OBJECTIVE: we assessed the discriminant validity of the PHQ-9 in order to establish the best cut-off score for the diagnosis of major depression in PD patients. METHOD: one hundred and ten patients with a diagnosis of PD without dementia were evaluated with the Structured Clinical Interview for DSM-IV (SCID), considered as the gold standard for the diagnosis of major depression. Eighty-four PD patients completed the PHQ-9, the 15-item Geriatric Depression Scale (GDS-15) and the Zung Self-rating Depression Scale (SDS). RESULTS: the prevalence of current depression in the sample of PD patients was 25.5%. Maximal discrimination between depressed and non-depressed patients was reached with a cut-off score of 9 in the PHQ-9 (sensitivity of 100% and specificity of 83.1%). The internal consistency of the scale was 0.83 and, when used as a diagnostic instrument, the PHQ-9 had a sensitivity of 52.6% and specificity of 95.4%. The correlation coefficient between the PHQ-9 and the other two scales was 0.63. CONCLUSIONS: the PHQ-9 is an adequate instrument for the screening-but not diagnosis-of depression in PD patients, with optimal sensitivity and specificity attained with a cut-off score of 9.

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