Search

Linkage and association studies in five independently ascertained samples have suggested that polymorphisms of the regulator of G-protein signaling 4 (RGS4) may confer risk for schizophrenia (SCZ). Suggestive evidence for association with bipolar disorder (BD) has also been presented. However, the associated alleles and haplotypes have differed among the samples. Data from other independent samples may clarify the putative associations. Hence, we investigated an independent, ethnically diverse Brazilian population comprising patients with SCZ (n = 271) or BD1 (n = 306), who were contrasted with 576 community-based controls. Parents of 49 SCZ cases and 44 BD cases were available for transmission disequilibrium tests (TDTs). FourRGS4single-nucleotide polymorphisms (SNPs) 1, 4, 7 and 18 putatively associated with SCZ were investigated. In the SCZ samples, significant case–control differences were not observed for individual SNPs or haplotypes, though the TDT suggested transmission distortion similar to that observed in the initial report. For the BD sample, case–control comparisons revealed no significant differences for individual SNPs, but an omnibus test suggested differences in the overall distribution of haplotypes bearing all four SNPs (SNP-EM Omnibus likelihood ratio test;P = 0.003). The TDT revealed over-transmission of allele A at SNP7 (P = 0.016), as well as haplotypes incorporating this allele. However, global tests incorporating all haplotypes yielded only suggestive trends for association (P = 0.19). In conclusion, association with SCZ was not detected in the present analyses. The failure to detect an association may be related to inadequate power or to confounds related to ethnic admixture. Suggestive associations with BD detected here require further investigation in a larger sample. [ABSTRACT FROM AUTHOR]

Introduction: Social anxiety disorder (SAD) is one of the most prevalent anxiety disorders, often not well recognized. In most of the cases, SAD follows an unremitted and chronic course, affecting several areas of the individual functioning (i.e.: relationship, academic, work). Due to its relevance, there is a need for guideline-based treatments for SAD treatment adapted to the Brazilian social and economic reality., Methods: A systematic review was produced by our group assessing several treatment modalities for SAD. The Medical Subject Headings term used was Social Anxiety Disorder or Social Phobia. PubMed, Cochrane, Scielo, ClinicalTrials.gov were searched resulting in 438 articles screened, of which 20 were selected., Results: Selective serotonin reuptake inhibitors are considered first line choices for the treatment of SAD, with great effects and a large database of evidence. Monoamine oxidase inhibitors (MAOIs), benzodiazepines and the anticonvulsants pregabalin and gabapentin are also effective. The serotonin noradrenaline reuptake inhibitor (SNRI) venlafaxine shows divergent results. With regards to psychological interventions, robust data offered evidence for cognitive behavioral therapy (CBT) as a first line option (individual, group and internet delivered). Psychodynamic psychotherapy, exposure and social skills therapy, self-help (with and without support) therapies, cognitive bias modification, virtual reality exposure therapy and mindfulness-based therapy are also effective techniques. Compared to pharmacological agents, psychological interventions are better tolerated and show evidence of long-term benefits., Conclusion: Patient's access to treatments (considering the Brazilian socioeconomic context), adherence, response rates (short and long-term treatment) and side effects must be considered when choosing the best strategy for the treatment of SAD., Competing Interests: The authors report no conflicts of interest.

Introduction: Schizophrenia is a debilitating disorder that affects a significant proportion of the population and leads to impaired functionality and long-term challenges. The first episode of psychosis (FEP) is a critical intervention stage for improving long-term outcomes. The GAPi program was established in São Paulo, Brazil to provide early intervention services and evaluate biomarkers in individuals with FEP. This article delineates the objectives of the GAPi program, detailing its innovative research protocol, examining the clinical outcomes achieved, and discussing the operational challenges encountered during its initial decade of operation., Methods: The study comprised a prospective cohort of antipsychotic-naïve individuals with first-episode psychosis aged between 16 and 35 years. Participants were recruited from a public psychiatric facility in São Paulo. Emphasizing the initiative's commitment to early intervention, clinical assessments were systematically conducted at baseline and at two months, one year, two years, and five years of treatment to capture both short- and medium-term outcomes. Various assessment tools were utilized, including structured interviews, symptom scales, the Addiction Severity Index, and functional assessments., Results: A total of 232 patients were enrolled in the cohort. Among them, 65.95 % completed the 2-month follow-up. Most patients presented with schizophrenia spectrum disorders, followed by bipolar disorder and major depressive disorder with psychotic features. Treatment response rates and remission rates were evaluated at different time points, with promising outcomes observed. The program also assessed socio-demographic factors, substance use, family history, and genetic and biomarker profiles, providing valuable data for research., Discussion: The GAPi program has emerged as the largest ongoing cohort of antipsychotic-naïve first-episode psychosis in Latin America, contributing to the understanding of early psychosis in low- and middle-income countries. Despite operational challenges, the program has demonstrated efficacy in reducing the duration of untreated psychosis and in improving clinical outcomes. A multidisciplinary approach, including pharmacological treatment, psychosocial interventions, and family involvement, has been instrumental in enhancing treatment adherence and long-term prognosis., Conclusion: The GAPi program represents a valuable model for early intervention in first-episode psychosis and provides insights into the pathophysiology, treatment, and long-term outcomes of individuals with schizophrenia and related disorders. Continued research and resource allocation are essential for addressing operational challenges and expanding early intervention services in low- and middle-income countries., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest relevant to the content of this article. This research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Post-traumatic stress disorder (PTSD) is an enduring condition characterized by a chronic course and impairments across several areas. Despite its significance, treatment options remain limited, and remission rates are often low. Ketamine has demonstrated antidepressant properties and appears to be a promising agent in the management of PTSD., Method: A systematic review was conducted in PubMed/MEDLINE, Cochrane Library, Clinicaltrials.gov, Lilacs, Scopus, and Embase, covering studies published between 2012 and December 2022 to assess the effectiveness of ketamine in the treatment of PTSD. Ten studies, consisting of five RCTs, two crossover trials, and three non-randomized trials, were included in the meta-analysis., Results: Ketamine demonstrated significant improvements in PCL-5 scores, both 24 hours after the initial infusion and at the endpoint of the treatment course, which varied between 1 to 4 weeks in each study. Notably, the significance of these differences was assessed using the Two Sample T-test with pooled variance and the Two Sample Welch's T-test, revealing a statistically significant effect for ketamine solely at the endpoint of the treatment course (standardized effect size= 0.25; test power 0.9916; 95% CI = 0.57 to 17.02, p=0.0363). It is important to note that high heterogeneity was observed across all analyses., Conclusions: Our findings suggest that ketamine holds promise as an effective treatment option for PTSD. However, further trials are imperative to establish robust data for this intervention., Competing Interests: Competing interests: None., (© 2024 Giovanni Fioriti Editore s.r.l.)

Purpose: Early treatment of psychotic illness improves outcomes, reduces relapse rates and should not be delayed. Cariprazine is a promising antipsychotic drug and may be a valuable resource when clinicians are in doubt if psychotic symptoms are due to schizophrenia or bipolar disorder., Materials and Methods: We conducted a systematic review and meta-analysis that included seven studies (n = 2896) analyzing the effect of cariprazine in psychotic symptoms assessed by the positive and negative symptoms scale (PANSS)., Results: We found cariprazine to be significantly superior to placebo (Hedges' g = 0.40; 95% CI 0.32-0.49) for acute psychosis independently of primary psychiatric diagnosis and also to be superior to placebo for both schizophrenia (Hedges' g = 0.39; 95% CI 0.29-0.50) and bipolar patients (Hedges' g = 0.43; 95% CI 0.27-0.58)., Conclusions: We propose that cariprazine may be useful in treating psychosis independently of nosological differentiation at the beginning of the treatment Key pointsEarly treatment of psychotic illness with antipsychotic medications improves outcomes and reduces relapse rates.Cariprazine was found to be significantly superior to placebo for acute psychosis independently of primary psychiatric diagnosis.Cariprazine may be useful in treating psychosis independently of nosological differentiation between schizophrenia and bipolar disorder at the beginning of the treatment.

Post-traumatic stress disorder (PTSD) is an anxiety disorder with manifestations somatic resulting from reliving the trauma. The therapy for the treatment of PTSD has limitations, between reduced efficacy and "PTSD pharmacotherapeutic crisis". Scientific evidence has shown that the use of ketamine has benefits for the treatment of depressive disorders and other symptoms present in PTSD compared to other conventional therapies. Therefore, this study aims to analyze the available evidence on the effect of ketamine in the treatment of post-traumatic stress. The systematic review and the meta-analysis were conducted following PRISMA guidelines and RevManager software, using randomized controlled trials and eligible studies of quality criteria for data extraction and analysis. The sample design evaluated included the last ten years, whose search resulted in 594 articles. After applying the exclusion criteria, 35 articles were selected, of which 14 articles were part of the sample, however, only six articles were selected the meta-analysis. The results showed that the ketamine is a promising drug in the management of PTSD with effect more evident performed after 24 h evaluated by MADRS scale. However, the main limitations of the present review demonstrate that more high-quality studies are needed to investigate the influence of therapy, safety, and efficacy.

Background: Dimensional approaches can decompose a construct in a set of continuous variables, improving the characterization of complex phenotypes, such as schizophrenia. However, the five-factor model of the Positive and Negative Syndrome Scale (PANSS), the most used instrument in schizophrenia research, yielded poor fits in most confirmatory factor analysis (CFA) studies, raising concerns about its applications. Thus, we aimed to identify dimensional PANSS CFA models with good psychometric properties by comparing the traditional CFA with three methodological approaches: Bayesian CFA, multilevel modeling, and Multiple Indicators Multiple Causes (MIMIC) modeling., Methods: Clinical data of 700 schizophrenia patients from four centers were analyzed. We first performed a traditional CFA. Next, we tested the three techniques: 1) a Bayesian CFA; 2) a multilevel analysis using the centers as level; and 3) a MIMIC modeling to evaluate the impact of clinical staging on PANSS factors and items., Results: CFA and Bayesian CFA produced poor fit models. However, when adding a multilevel structure to the CFA model, a good fit model emerged. MIMIC modeling yielded significant differences in the factor structure between the clinical stages of schizophrenia. Sex, age, age of onset, and duration of illness did not significantly affect the model fit., Conclusion: Our comparison of different CFA methods highlights the need for multilevel structure to achieve a good fit model and the potential utility of staging models (rather than the duration of illness) to deal with clinical heterogeneity in schizophrenia. Large prospective samples with biological data should help to understand the interplay between psychometrics concerns and neurobiology research., (Copyright © 2018. Published by Elsevier B.V.)

Aim: Construct stability over time is required for reliable inference, but evidence regarding the longitudinal invariance of negative symptoms is still limited. Thus, we examined the longitudinal invariance of the negative dimension using the positive and negative syndrome scale (PANSS) in an antipsychotic-naïve first-episode schizophrenia sample at baseline and after 10 weeks., Methods: Our study was conducted at a specialized early intervention service. PANSS ratings were analysed for 138 patients, and two different models were specified and tested: a unidimensional and a two-correlated factor solution., Results: The unidimensional model fulfilled criteria for longitudinal invariance, whilst the two-correlated did not., Conclusion: Our study provides support for the PANSS negative unidimensional model use to evaluate negative symptoms' longitudinal change following first-episode schizophrenia., (© 2021 John Wiley & Sons Australia, Ltd.)

Schizophrenia has a heritability of 60-80% 1 , much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Schizophrenia is a severe and multifactorial disorder with an unknown causative pathophysiology. Abnormalities in neurodevelopmental and aging processes have been reported. Relative telomere length (RTL) and DNA methylation age (DMA), well-known biomarkers for estimating biological age, are both commonly altered in patients with schizophrenia compared to healthy controls. However, few studies investigated these aging biomarkers in first-episode psychosis (FEP) and in antipsychotic-naïve patients. To cover the existing gap regarding DMA and RTL in FEP and antipsychotic treatment, we aimed to verify whether those aging markers could be associated with psychosis and treatment response. Thus, we evaluated these measures in the blood of FEP antipsychotic-naïve patients and healthy controls (HC), as well as the response to antipsychotics after 10 weeks of treatment with risperidone. RTL was measured in 392 subjects, being 80 FEP and 312 HC using qPCR, while DMA was analyzed in a subset of 60 HC, 60 FEP patients (antipsychotic-naïve) and 59 FEP-10W (after treatment) using the "Multi-tissue Predictor"and the Infinium HumanMethylation450 BeadChip Kit. We observed diminished DMA and longer RTL in FEP patients before treatment compared to healthy controls, indicating a decelerated aging process in those patients. We found no statistical difference between responder and non-responder patients at baseline for both markers. An increased DMA was observed in patients after 10 weeks of treatment, however, after adjusting for blood cell composition, no significant association remained. Our findings indicate a decelerated aging process in the early phases of the disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Brain-derived neurotrophic factor (BDNF) and the immune-inflammatory response system (IRS) have been implicated in the pathophysiology of schizophrenia. However, no research examined the associations between BDNF and immune activation both before and after treatment in antipsychotic-naïve first episode psychosis (AN-FEP). This study aims to examine serum BDNF levels and their association with IRS and the compensatory immune-regulatory reflex system (CIRS) in AN-FEP before and after risperidone treatment. We included 31 AN-FEP and 22 healthy controls. AN-FEP showed reduced levels of BDNF as compared to controls, and BDNF levels normalized after treatment with risperidone. BDNF levels were inversely correlated with a greater IRS response. Higher levels of IRS/CIRS biomarkers were associated with lower levels of BDNF including M1 macrophage, T-helper (Th)-1, Th-2, and Th-17, and T-regulatory (Treg) cell responses. Our findings indicate that AN-FEP is characterized by decreased levels of BDNF, which are normalized after treatment with risperidone. BDNF levels were inversely associated with activated immune-inflammatory pathways. The findings support the hypothesis that, increased IRS is linked to neurotoxicity, and that a decrease in BDNF may be part of the IRS/CIRS responses in FEP and, thus, be involved in the development of psychosis., (Copyright © 2021. Published by Elsevier Ltd.)

Aim: Duration of untreated psychosis (DUP) is one of the few potentially modifiable outcome predictors in psychosis. Previous studies have associated a longer DUP with a poor prognosis, but few of them were performed in countries with low and middle level of income. This study aimed to investigate the DUP in a Brazilian sample of antipsychotic-naïve first-episode psychosis (AN-FEP) patients and its association with clinical characteristics and treatment outcomes in a short-term follow-up., Methods: One hundred forty-five AN-FEP patients between 16 and 40 years were enrolled and were reassessed 10 weeks after risperidone treatment. We investigated the association between DUP and symptom severity, functionality and response to treatment, using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity Scale (CGI) and the Global Assessment of Functionality (GAF) scale. DUP was defined as the period between the onset of the first psychotic symptoms and the first effective antipsychotic treatment. For the analysis, we performed multivariate linear regressions., Results: The DUP's median was 61 days. At baseline, we did not find any significant association between DUP and clinical characteristics. After treatment, the longer DUP predicted worse positive and negative symptom dimensions, worse total PANSS, GAF and CGI scores and poorer response to treatment., Conclusion: Our results showed that DUP is associated with worse outcomes after short treatment, but it does not modify the baseline clinical profile of the AN-FEP patients. Such results reinforce the need to develop early intervention strategies, reducing DUP., (© 2019 John Wiley & Sons Australia, Ltd.)

Purpose: The heterogenic characteristics of affected family members (AFMs) of substance misusing relative (SMR) remain understudied. This study examined the occurrence and correlates of AFMs having more than one relative with substance use problems., Material and Methods: A secondary analysis of a cross-sectional study on the characteristics of affected family members in Brazil was performed (N= 3157). Levels of AFM stress, strain, coping and hopefulness were assessed. Factors associated with AFMs having other substance misusing relatives (other-SMRs) were explored using univariate logistic regressions., Results: The occurrence of having other-SMR was reported by 61.6% of the sample (1945/3157). Of this, 47% (904/1945) reported that the other-SMR was a member of the SMR's immediate family (spouse/partner/children/siblings). The likelihood of having other-SMRs was related to the AFM being female, from a low socioeconomic background, between the age of 35-44 years older, being SMR's mother or wife/girlfriend/fiancée, scoring higher on family member impact, psychological and physical symptoms, withdrawal coping and to have an older SMR., Conclusion: Information about the characteristics of AFMs is key to understanding how the experience of harm associated with the relative's problem might manifest. Our findings offer information that could be used when developing interventions aimed at reducing the harm experienced by AFMs.

Background: Our previous studies showed increased angiotensin I-converting enzyme (ACE) activity in chronic schizophrenia (SCZ) patients compared to healthy control (HC) volunteers, and the relevance of combining ACE genotype and activity for predicting SCZ was suggested., Methods: ACE activity was measured in plasma of ACE insertion/deletion (I/D) genotyped HC volunteers (N = 53) and antipsychotic-naïve first-episode psychosis (FEP) patients (N = 45), assessed at baseline (FEB-B) and also after 2-months (FEP-2M) of treatment with the atypical antipsychotic risperidone., Results: ACE activity measurements showed significant differences among HC, FEP-B and FEP-2M groups (F = 5.356, df = 2, p = 0.005), as well as between HC and FEP-2M (post-hoc Tukey's multiple comparisons test, p = 0.004). No correlation was observed for ACE activity increases and symptom severity reductions in FEP as assessed by total PANSS (r = -0.131, p = 0.434). FEP subgrouped by ACE I/D genotype showed significant ACE activity increases, mainly in the DD genotype subgroup. No correlation between ACE activity and age was observed in FEP or HC groups separately (r = 0.210, p = 0.392), but ACE activity levels differences observed between these groups were influenced by age., Conclusions: The importance of measuring the ACE activity in blood plasma, associated to ACE I/D genotyping to support the follow-up of FEP patients did not show correlation with general symptoms amelioration in the present study. However, new insights into the influence of age and I/D genotype for ACE activity changes in FEP individuals upon treatment was demonstrated., (© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.)

Aim: We investigated the DNA methylation profile over LINE-1 in antipsychotic-naive, first-episode psychosis-patients (n = 69) before and after 2 months of risperidone treatment and in healthy controls (n = 62). Materials & methods: Patients were evaluated using standardized scales and classified as responders and nonresponders. DNA from blood was bisulfite converted and LINE-1 fragments were amplified and pyrosequencing was performed. Results: Lower LINE-1 methylation was observed in antipsychotic-naive first-episode psychosis patients than in healthy controls. Lower DNA methylation levels before treatment were associated with poor risperidone responses. A positive correlation was observed between LINE-1 methylation levels and positive symptoms response. Conclusion: Our study brings new insight regarding how epigenomic studies and clinical correlation studies can supplement psychosis treatment.

Objective: German psychiatrist Kurt Schneider proposed the concept of first-rank symptoms (FRS) of schizophrenia in 1959. However, their relevance for diagnosis and prediction of treatment response are still unclear. Most studies have investigated FRS in chronic or medicated patients. The present study sought to evaluate whether FRS predict remission, response, or improvement in functionality in antipsychotic-naive first-episode psychosis., Methods: Follow-up study of 100 patients at first episode of psychosis (FEP), with no previous treatment, assessed at baseline and after 2 months of treatment. The participants were evaluated with the standardized Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) and for presence of FRS., Results: Logistic regression analysis showed that, in this sample, up to three individual FRS predicted remission: voices arguing, voices commenting on one's actions, and thought broadcasting., Conclusion: Specific FRS may predict remission after treatment in FEP patients. This finding could give new importance to Kurt Schneider's classic work by contributing to future updates of diagnostic protocols and improving estimation of prognosis.

We evaluated disagreement between reported symptoms and a final diagnosis of depression, anxiety, withdrawal, psychosis, or delirium through regression models assessing individual and combined diagnoses. Highest disagreement rates were reported for services classified as others (88.2%), general surgery (78.5%), and bone marrow transplant (77.7%). Disagreement rates varied widely across different diagnoses, with anxiety having the highest disagreement rate (63.3%), whereas psychosis had the lowest disagreement rate (10.6%). When evaluating kappa coefficients, the highest agreement occurred with diagnoses of withdrawal and psychosis (0.66% and 0.51%, respectively), whereas anxiety and depression presented the lowest values (0.31% and 0.11%, respectively). The best-performing predictive model for most outcomes was random forest, with the most important predictors being specialties other than the ones focused on single systems, older age, lack of social support, and the requester being a resident. Monitoring disagreement rates and their predictors provides information that could lead to quality improvement and safety programs.

Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders that pose important challenges for diagnosis by sharing common symptoms, such as delusions and hallucinations. The underlying pathophysiology of both disorders remains largely unknown, and the identification of biomarkers with potential to support diagnosis is highly desirable. In a previous study, we successfully discriminated SCZ and BD patients from healthy control (HC) individuals by employing proton magnetic resonance spectroscopy ( 1 H-NMR). In this study, 1 H-NMR data treated by chemometrics, principal component analysis (PCA) and supervised partial least-squares discriminant analysis (PLS-DA), provided the identification of metabolites present only in BD (as for instance the 2,3-diphospho-D-glyceric acid, N-acetyl aspartyl-glutamic acid, monoethyl malonate) or only in SCZ (as isovaleryl carnitine, pantothenate, mannitol, glycine, GABA). This may represent a set of potential biomarkers to support the diagnosis of these mental disorders, enabling the discrimination between SCZ and BD, and among these psychiatric patients and HC (as 6-hydroxydopamine was present in BD and SCZ but not in HC). The presence or absence of these metabolites in blood allowed the categorization of 182 independent subjects into one of these three groups. In addition, the presented data suggest disturbances in metabolic pathways in SCZ and BD, which may provide new and important information to support the elucidation and/or new insights into the neurobiology underlying these mental disorders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: The World Health Organization (WHO) Department of Mental Health and Substance Abuse appointed a Working Group on Sexual Disorders and Sexual Health in order to revise and propose changes to ICD-10 categories., Aim: Analyze ethical and legal implications in Brazil of the proposed ICD-11 diagnostic criteria for paraphilic disorders., Methods: A forensic working group of Brazilian experts in collaboration with representatives of WHO reviewed the proposed modifications to the classification of Disorders of Sexual Preference in ICD-10 (F65), which is recommended to be replaced by Paraphilic Disorders in ICD-11. Proposals were reviewed through a medicolegal lens, using a legal and policy analysis guide put forth by WHO. The premise of this review was to understand that, although the ICD classification is intended to provide a basis for clinical and statistical health interventions, medical diagnostics may also be entangled in the complex legal, normative, and political environment of various countries., Main Outcome Measure: The most important proposed change to this section is to limit the concept of paraphilic disorders primarily to patterns of sexual arousal involving a focus on others who are unwilling or unable to consent, but this change has not affected the ethical and legal aspects of psychiatric functioning in the Brazil., Results: Because Brazilian criminal law is directed toward criminal behavior and not to specific psychiatric diagnoses, the changes proposed for ICD-11 are not expected to create obstacles to health services or to modify criminal sentencing., Clinical Implications: Although ICD-11 has a number of changes in its content, there are no significant clinical implications in the Brazilian context, but a better clarity of conceptual definitions and diagnostic criteria., Strengths & Limitations: The study is conducted with people from different Brazilian states, which is important for a comprehensive view. On the other hand, considering that it is a very heterogeneous country, there is the limitation that an even wider scope of the study is not possible., Conclusion: In the Brazilian context, the new guidelines for paraphilic disorders contribute to clinical utility and are not expected to create difficulties related to the legal, social, and economic consequences of sexual offenses in the country. Abdalla-Filho E, de Jesus Mari J, Diehl A, et al. Forensic Implications of the New Classification of ICD-11 Paraphilic Disorders in Brazil. J Sex Med 2019; 16:1814-1819., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Brazil is the world's biggest consumer of crack cocaine, and dependence is a major public health issue. This is the first study to investigate the prevalence of potentially harmful adulterants present in hair samples from Brazilian patients with crack cocaine dependence., Method: We evaluated adulterants in hair samples extracted by convenience from 100 patients admitted at the 48 hour-observation unit of Centro de Referência de Álcool, Tabaco e Outras Drogas (CRATOD), Brazil's largest center for addiction treatment. A cross-sectional analysis was performed with the data obtained., Results: Adulterants were found in 97% of the analyzed hair samples. The most prevalent adulterant was lidocaine (92%), followed by phenacetin (69%) and levamisole (31%)., Conclusion: Adulterants were widely prevalent in hair samples from crack users treated at CRATOD: at least one adulterant was present in virtually all the hair samples collected. This points to a need to monitor adverse effects in the clinical setting in order to provide this high-risk group of patients with prompt and effective care related to the acute and chronic complications associated with these adulterants.

Objective: To present the essential guidelines for pharmacological management of patients with psychomotor agitation in Brazil., Methods: This is a systematic review of articles retrieved from the MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and SciELO databases published from 1997 to 2017. Other relevant articles in the literature were also used to develop these guidelines. The search strategy used structured questions formulated using the PICO model, as recommended by the Guidelines Project of the Brazilian Medical Association. Recommendations were summarized according to their level of evidence, which was determined using the Oxford Centre for Evidence-based Medicine system and critical appraisal tools., Results: Of 5,362 articles retrieved, 1,731 abstracts were selected for further reading. The final sample included 74 articles that met all inclusion criteria. The evidence shows that pharmacologic treatment is indicated only after non-pharmacologic approaches have failed. The cause of the agitation, side effects of the medications, and contraindications must guide the medication choice. The oral route should be preferred for drug administration; IV administration must be avoided. All subjects must be monitored before and after medication administration., Conclusion: If non-pharmacological strategies fail, medications are needed to control agitation and violent behavior. Once medicated, the patient should be monitored until a tranquil state is possible without excessive sedation., Systematic Review Registry Number: CRD42017054440.

Background: Major depressive disorder (MDD) is one of the leading causes of disability in the world. However, treatment options are still limited, and marked by high refractoriness rates, new approaches are needed to optimize clinical improvement. Trigeminal nerve stimulation (TNS) is an innovative neuromodulation strategy consisting on the application of an electric current over the trigeminal nerve that propagates stimuli towards brain areas involved in mood control., Objective: We examined the effects of TNS in MDD after a 10-day experimental protocol., Methods: This was a randomized, double blind, and sham-controlled phase II study with 24 patients with severe MDD. Patients underwent a 10-day intervention protocol and were assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17) at following three observation points: baseline (T1), after 10 days (T2), and after one month of the last stimulation session (T3). Main clinical outcome analysis of variance (ANOVA) was performed., Results: Patients in the active group presented a mean reduction of 36.15% in depressive symptoms after the stimulation protocol. There was a significant interaction between group and time regarding HDRS-17 scores (F = 3.18; df = 2; p = 0.0456). Post hoc analyses exhibited a statistically significant difference between active and sham group symptoms at T2 (p = 0.040) and T3 (p = 0.026), which highlights the sustained amelioration of depressive symptoms., Conclusion: The present study found amelioration of depressive symptoms for patients undergoing a 10-day stimulation protocol of TNS, and this was sustained after one month of follow-up., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Our previous studies showed reduced Ndel1 enzyme activity in patients with chronic schizophrenia (SCZ), and only a subtle NDEL1 mRNA increases in antipsychotic-naïve first-episode psychosis (FEP) individuals compared to matched healthy controls (HC). Aiming to refine the evaluation of Ndel1 enzyme activity in early stages of psychosis, we compared 3 groups composed by (1) subjects at ultra-high-risk (UHR) for psychosis, (2) a cohort comprising antipsychotic-naïve FEP individuals (assessed in three moments, at baseline (FEP-0), and after 2 months (FEP-2 M) and one year (FEP-1Y) of treatment with risperidone), and (3) a HC group. There was no significant difference in Ndel1 enzyme activity between UHR and HC, but this activity was significantly lower in FEP compared to HC. Conversely, Ndel1 activity in HC groups was higher than in FEP even before (FEP-0) or after the treatment with risperidone (FEP-2 M and FEP-1Y), and with progressive decrease of Ndel1 activity and significant improvement of symptoms observed after this treatment. In addition, a positive correlation was observed for Ndel1 activity with clinical symptoms as assessed by PANSS, while a negative correlation was seen for GAF scores. Our results suggest that reductions in Ndel1 activity in FEP may be possibly related to responses to the illness, rather than to the pharmacological effects of antipsychotics, which might be acting essentially in the symptoms suppression. This hypothesis might be further evaluated in prospective long-term follow-up studies with a larger sample cohort., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cognitive deficits are core symptoms of schizophrenia that occur from the early stages of the disorder. There is reliable evidence that cognitive deficits are associated with outcomes in schizophrenia; thus, early treatment could be particularly important. Studies with different neuromodulation techniques involving subjects with schizophrenia suggest that application of transcranial direct current stimulation (tDCS) with inhibitory stimulation over the left temporo-parietal cortex and excitatory stimulation over the left dorsolateral prefrontal cortex could ameliorate positive, negative, and cognitive symptoms. The aim of the present study protocol is to evaluate the efficacy of tDCS in the treatment of cognitive symptomatology in the early stages of psychosis., Methods/design: Seventy patients in the early stages of psychosis will be randomly allocated to receive 20 min of active 2-mA tDCS or sham stimulation once a day for 10 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporo-parietal cortex. Neuropsychological and psychiatric assessments will be performed at baseline and at 1 and 3 months following the end of the intervention (sustained effect)., Discussion: The development and utilization of potentially effective neuroenhancement tools such as the non-invasive brain stimulation technique tDCS for the treatment and rehabilitation of cognitive impairment in the early stages of schizophrenia may contribute to improving outcomes of the disorder and eventually provide a further understanding of the nature of the complex and dynamic neural processes underlying those abnormalities., Trial Registration: ClinicalTrials.gov, NCT03071484 . Registered on 7 March 2017.

We investigated the role of DGCR2, a corticogenesis-related gene, on schizophrenia (SZ) and its subphenotypes, including brain morphology. A total of 221 SZ patients, 263 controls and 70 antipsychotic-naïve first episode of psychosis (FEP) were genotyped for 17 DGCR2 polymorphisms. While no association between DGCR2 polymorphisms and SZ was found, the missense variant rs2072123 was associated to left rostral anterior cingulate thickness, showing that DGCR2 seems not to be associated directly with the SZ but might be influencing the brain morphology. We also showed a DGCR2 downregulation in SZ patients when compared to controls and FEP., (Copyright © 2019. Published by Elsevier B.V.)