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Abstract Background Schizophrenia (SCZ) is a severe mental disorder of multifactorial origin in which the role of amino acids is relatively unknown. Based on the hypothesis that there is an imbalance in amino acid levels in individuals with SCZ compared with healthy controls (HCs), the aim of this study was to identify the 20 proteinogenic amino acids involved in protein synthesis. Methods This study included 43 sex‐ and age‐matched individuals: 20 HCs and 23 with SCZ diagnosed using the Diagnostic and Statistical Manual of Mental Disorders criteria. Using proton nuclear magnetic resonance, we identified the serum levels of the 20 amino acids proteinogenic. We perform multivariate statistical exploratory analyzes to identify compounds, quantify, and identify the main biomarkers of SCZ. Results We identified the serum levels of 19 of the 20 amino acids. Cysteine, the main precursor of glutathione, was not detected. Multivariate exploratory analysis identified lysine, Tryptophan (TRP), and glutamate as possible biomarkers of SCZ. Both lysine and TRP levels were lower and glutamate levels were higher in individuals with SCZ than in HCs. The observed reduction in plasma TRP levels in SCZ was attributed to the activation of the kynurenine pathway and has implications for serotonin synthesis. A strong positive correlation was observed between lysine and TRP, and a weak negative correlation between lysine and glutamate. This result is consistent with the lysine catalysis process because lysine degradation generates glutamate and favors an increase in dopamine. Conclusions The results are consistent with the lysine catalysis process because lysine degradation generates glutamate and favors an increase in dopamine. We were unable to identify any studies suggesting a relationship between lysine catabolism and SCZ pathophysiology, but we recognize this association as innovative.

Despite the functional impact of cognitive deficit in people with psychosis, objective cognitive assessment is not typically part of routine clinical care. This is partly due to the length of traditional assessments and the need for a highly trained administrator. Brief, automated computerised assessments could help to address this issue. We present data from an evaluation of PsyCog, a computerised, non-verbal, mini battery of cognitive tests. Healthy Control (HC) (N = 135), Clinical High Risk (CHR) (N = 233), and First Episode Psychosis (FEP) (N = 301) participants from a multi-centre prospective study were assessed at baseline, 6 months, and 12 months. PsyCog was used to assess cognitive performance at baseline and at up to two follow-up timepoints. Mean total testing time was 35.95 min (SD = 2.87). Relative to HCs, effect sizes of performance impairments were medium to large in FEP patients (composite score G = 1.21, subtest range = 0.52–0.88) and small to medium in CHR patients (composite score G = 0.59, subtest range = 0.18–0.49). Site effects were minimal, and test-retest reliability of the PsyCog composite was good (ICC = 0.82–0.89), though some practice effects and differences in data completion between groups were found. The present implementation of PsyCog shows it to be a useful tool for assessing cognitive function in people with psychosis. Computerised cognitive assessments have the potential to facilitate the evaluation of cognition in psychosis in both research and in clinical care, though caution should still be taken in terms of implementation and study design.

Socioeconomic disadvantage (SED) has been consistently associated with early life mental health problems. SED has been shown to impact multiple biological systems, including the regulation of neurotrophic proteins, immune-inflammatory and oxidative stress markers, which, conversely, have been reported to be relevant to physiological and pathological neurodevelopment This study investigated the relationship between SED, different domains of psychopathology, serum levels of interleukin-6 (IL6), thiobarbituric acid-reactive substance (TBARS) and brain-derived neurotrophic factor (BDNF). We hypothesized that a composite of socioeconomic risk would be associated with psychopathology and altered levels of peripheral biomarkers. In addition, we hypothesized that SED would moderate the associations between mental health problems, IL6, TBARS and BDNF.Using a cross-sectional design, we measured the serum levels of IL6, TBARS and BDNF in 495 children aged 6 to 12. We also investigated socio-demographic characteristics and mental health problems using the Child Behaviour Checklist (CBCL) DSM-oriented scales. SED was evaluated using a cumulative risk model. Generalized linear models were used to assess associations between SED, biomarkers levels and psychopathology. SED was significantly associated with serum levels of IL6 (RR = 1.026, 95% CI 1.004; 1.049, p = 0.020) and TBARS (RR = 1.077, 95% CI 1.028; 1.127, p = 0.002). The association between SED and BDNF was not statistically significant (RR = 1.031, 95% CI 0.997; 1.066, p = 0.077). SED was also significantly associated with all CBCL DSM-oriented scales (all p < 0.05), whereas serum biomarkers (i.e. IL6, TBARS, BDNF) were associated with specific subscales. Moreover, the associations between serum biomarkers and domains of psychopathology were moderated by SED, with stronger correlations between mental health problems, IL6, TBARS, and BDNF being observed in children with high SED.In children, SED is highly associated with mental health problems. Our findings suggest that this association may be moderated via effects on multiple interacting neurobiological systems.

The objective of this descriptive study was to map mental health research in Brazil, providing an overview of infrastructure, financing and policies mental health research. As part of the Atlas-Research Project, a WHO initiative to map mental health research in selected low and middle-income countries, this study was carried out between 1998 and 2002. Data collection strategies included evaluation of governmental documents and sites and questionnaires sent to key professionals for providing information about the Brazilian mental health research infrastructure. In the year 2002, the total budget for Health Research was US$101 million, of which US$3.4 million (3.4) was available for Mental Health Research. The main funding sources for mental health research were found to be the São Paulo State Funding Agency (Fapesp, 53.2%) and the Ministry of Education (CAPES, 30.2%). The rate of doctors is 1.7 per 1,000 inhabitants, and the rate of psychiatrists is 2.7 per 100,000 inhabitants estimated 2000 census. In 2002, there were 53 postgraduate courses directed to mental health training in Brazil (43 in psychology, six in psychiatry, three in psychobiology and one in psychiatric nursing), with 1,775 students being trained in Brazil and 67 overseas. There were nine programs including psychiatry, neuropsychiatry, psychobiology and mental health, seven of them implemented in Southern states. During the five-year period, 186 students got a doctoral degree (37 per year) and 637 articles were published in Institute for Scientic Information (ISI)-indexed journals. The investment channeled towards postgraduate and human resource education programs, by means of grants and other forms of research support, has secured the country a modest but continuous insertion in the international knowledge production in the mental health area.

A maconha é a droga ilícita mais utilizada. Apesar disto, apenas um pequeno número de estudos investigaram as conseqüências neurotóxicas de longo prazo do uso de cannabis. As técnicas de neuroimagem se constituem em poderosos instrumentos para investigar alterações neuroanatômicas e neurofuncionais e suas correlações clínicas e neuropsicológicas. Uma revisão computadorizada da literatura foi conduzida nos indexadores MEDLINE e PsycLIT entre 1966 e novembro de 2004 com os termos 'cannabis', 'marijuana', 'neuroimaging', 'magnetic resonance', 'computed tomography', 'positron emission tomography', 'single photon emission computed tomography", 'SPET', 'MRI' e 'CT'. Estudos de neuroimagem estrutural apresentam resultados conflitantes, com a maioria dos estudos não relatando atrofia cerebral ou alterações volumétricas regionais. Contudo, há uma pequena evidência de que usuários de longo prazo que iniciaram um uso regular no início da adolescência apresentam atrofia cerebral assim como redução na substância cinzenta. Estudos de neuroimagem funcional relatam aumento na atividade neural em regiões que podem estar relacionadas com intoxicação por cannabis e alteração do humor (lobos frontais mesial e orbital) e redução na atividade de regiões relacionadas com funções cognitivas prejudicadas durante a intoxicação aguda. A questão crucial se efeitos neurotóxicos residuais ocorrem após o uso prolongado e regular de maconha permanece obscura, não existindo até então estudo endereçando esta questão diretamente. Estudos de neuroimagem com melhores desenhos, combinados com avaliação cognitiva, podem ser elucidativos neste aspecto.Cannabis is the most widely used illicit drug. Despite this, only a small number of studies have investigated the long-term neurotoxic consequences of cannabis use. Structural and functional neuroimaging techniques are powerful research tools to investigate possible cannabis-induced pathophysiological changes. A computer literature review was conducted in the MEDLINE and PsycLIT databases between 1966 and November of 2004 with the search terms 'cannabis', 'marijuana', 'neuroimaging', 'magnetic resonance', 'computed tomography', 'positron emission tomography', 'single photon emission computed tomography", 'SPET', 'MRI' and 'CT'. Structural neuroimaging studies have yielded conflicting results. Most studies report no evidence of cerebral atrophy or regional changes in tissue volumes, and one study suggested that long-term users who started regular use on early adolescence have cerebral atrophy as well as reduction in gray matter. However, several methodological shortcomings limit the interpretation of these results.Functional neuroimaging studies have reported increases in neural activity in regions that may be related with cannabis intoxication or mood-change effects (orbital and mesial frontal lobes, insula, and anterior cingulate) and decreases in activity of regions related with cognitive functions impaired during acute intoxication.The important question whether residual neurotoxic effects occur after prolonged and regular use of cannabis remains unclear, with no study addressing this question directly. Better designed neuroimaging studies, combined with cognitive evaluation, may be elucidative on this issue.

A esquizofrenia é um transtorno psiquiátrico devastador cuja fisiopatologia ainda está para ser esclarecida. Apesar de uma disfunção dopaminérgica estar bem estabelecida na esquizofrenia, há uma série de evidências sugerindo o envolvimento do sistema glutamatérgico na fisiopatologia do transtorno. Este artigo faz uma breve revisão de alguns aspectos básicos do funcionamento dos receptores glutamatérgicos com ênfase nos receptores N-metil-D-aspartato (NMDA). Apresenta evidências científicas sugerindo uma disfunção do sistema glutamatérgico na esquizofrenia (hipofunção de receptores NMDA). E discute as interações entre os sistemas dopaminérgico e glutamatérgico; mais especificamente como os estados hiperdopaminérgicos encontrados na esquizofrenia podem estar associados a uma alteração glutamatérgica.

Schizophrenia is a neurodevelopmental disorder with high heritability. Several lines of evidence indicate that the PRODH gene may be related to the disorder. Therefore, our study investigates the effects of 12 polymorphisms of PRODH on schizophrenia and its phenotypes. To further evaluate the roles of the associated variants in the disorder, we have conducted magnetic resonance imaging (MRI) scans to assess cortical volumes and thicknesses. A total of 192 patients were evaluated using the Structured Clinical Interview for DSM-IV (SCID), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) instruments. The study included 179 controls paired by age and gender. The samples were genotyped using the real-time polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-PCR and Sanger sequencing methods. A sample of 138 patients and 34 healthy controls underwent MRI scans. One polymorphism was associated with schizophrenia (rs2904552), with the G-allele more frequent in patients than in controls. This polymorphism is likely functional, as predicted by PolyPhen and SIFT, but it was not associated with brain morphology in our study. In summary, we report a functional PRODH variant associated with schizophrenia that may have a neurochemical impact, altering brain function, but is not responsible for the cortical reductions found in the disorder.

BACKGROUND: Early life social adversity can influence stress response mechanisms and is associated with anxious behaviour and reductions in callosal area later in life. OBJECTIVE: To evaluate the association between perceptions of parental bonding in childhood/adolescence, hypothalamic-pituitary-adrenal (HPA) axis response, and callosal structural integrity in adult victims of severe urban violence with and without PTSD. METHODS: Seventy-one individuals with PTSD and 62 without the disorder were assessed with the Parental Bonding Instrument (PBI). The prednisolone suppression test was administered to assess cortisol levels, and magnetic resonance imaging was used to assess the total area of the corpus callosum (CC), as well as the areas of callosal subregions. RESULTS: The PBI items related to the perception of 'not having a controlling mother' (OR 4.84; 95%CI [2.26-10.3]; p=0.01), 'having a caring father' (OR 2.46; 95'%CI [1.18-5.12]; p=0.02), and 'not having controlling parents' (OR 2.70; 95%CI [1.10-6.63]; p=0.04) were associated with a lower risk of PTSD. The PTSD group showed a blunted response to the prednisolone suppression test, with lower salivary cortisol levels upon waking up (p=0.03). Individuals with PTSD had smaller total CC area than those without the disorder, but these differences were not statistically significant (e-value =0.34). CONCLUSIONS: Healthy parental bonding, characterized by the perception of low parental control and high affection, were associated with a lower risk of PTSD in adulthood, suggesting that emotional enrichment and the encouragement of autonomy are protective against PTSD in adulthood.

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.

OBJECTIVE: Estimate the prevalence of psychotropic drugs use in the city of Rio de Janeiro, Brazil, and establish its relationship with the presence of mental disorders. METHODS: A probabilistic sample of non-institutionalized individuals, from the general population of Rio de Janeiro (n = 1208;turn out:81%), 15 years or older, who were interviewed using the Composite International Diagnostic Interview 2.1 (depression, anxiety-phobia, OCD\PTSD, alcoholism sections), and asked about their psychotropic use during a 12 and one-month period before the interview. Data were collected between June/2007-February/2008.The prevalence was estimated with a confidence interval of 95%. The associations between psychotropics use and mental disorders were analyzed through a logistic regression model (Odds Ration - OR). RESULTS: The one-month prevalence of psychotropic drug use was 6.55%, 3.19% for men and 9.13% for women. Antidepressants were the most frequently used drug (2.78%), followed by anorectics (1.65%), tranquilizers (1.61%) and mood stabilizers (1.23%). General practitioners issued the highest number of prescriptions (46.3%), followed by psychiatrists (29.3%); 86.6% of the psychotropic drugs used were paid for by the patient himself. Individuals with increased likelihood of using psychotropic drugs were those that had received a psychiatric diagnosis during a one-month period before the study (OR:3.93), females (OR:1.82), separated/divorced (OR:2.23), of increased age (OR:1.03), with higher income (OR:2.96), and family history of mental disorder (OR:2.59); only 16% of the individuals with a current DSM IV diagnosis were using a psychotropic drug; 17% among individuals with a depression-related diagnosis and 8% with Phobic Anxiety Disorders-related diagnosis used psychotropics. CONCLUSION: Approximately 84% of individuals displaying some mental disorder did not use psychotropic drugs, which indicates an important gap between demand and access to treatment. A significant failure is evident in the health system for patients with mental disorders; this could be due to health workers' inability to recognize mental disorders among individuals.

We report analyses of a Brazilian study of early onset schizophrenia (BEOS) families. We genotyped 22 members of 4 families on a linkage SNP array and report here non-parametric linkage analyses using MERLIN® software. We found suggestive evidence for linkage on two chromosomal regions, 13q32 and 11p15.4. A LOD score of 2.71 was observed at 13q32 with a one LOD interval extending from 60.63-92.35 cM. From simulations, this LOD score gave a genome-wide empirical corrected p = 0.33, after accounting for all markers tested. Similarly 11p15.4 showed the same maximum LOD of 2.71 and a narrower one LOD interval of 4-14 cM. Of these, 13q32 has been reported to be linked to schizophrenia by multiple different studies. Thus, our study provides additional supporting evidence for an aetiological role of variants at 13q32 in schizophrenia.

Abstract Recently, several studies have investigated the neurodevelopment of psychiatric disorders using brain data acquired via structural magnetic resonance imaging (sMRI). These analyses have shown the potential of sMRI data to provide a relatively precise characterization of brain structural biomarkers. Despite these advances, a relatively unexplored question is how reliable and consistent a model is when assessing subjects from other independent datasets. In this study, we investigate the performance and generalizability of the same model architecture trained from distinct datasets comprising youths in diverse stages of neurodevelopment and with different mental health conditions. We employed models with the same 3D convolutional neural network (CNN) architecture to assess autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), brain age, and a measure of dimensional psychopathology, the Child Behavior Checklist (CBCL) total score. The investigated datasets include the Autism Brain Imaging Data Exchange II (ABIDE-II, N = 580), Attention Deficit Hyperactivity Disorder (ADHD-200, N = 922), Brazilian High-Risk Cohort Study (BHRCS, N = 737), and Adolescent Brain Cognitive Development (ABCD, N = 11,031). Models’ performance and interpretability were assessed within each dataset (for diagnosis tasks) and inter-datasets (for age estimation). Despite the demographic and phenotypic differences of the subjects, all models presented significant estimations for age (p value

Abstract Crime is a major public problem in low- and middle-income countries (LMICs) and its preventive measures could have great social impact. The extent to which multiple modifiable risk factors among children and families influence juvenile criminal conviction in an LMIC remains unexplored; however, it is necessary to identify prevention targets. This study examined the association between 22 modifiable individual and family exposures assessed in childhood (5–14 years, n = 2511) and criminal conviction at a 7-year follow-up (13–21 years, n = 1905, 76% retention rate) in a cohort of young people in Brazil. Population attributable risk fraction (PARF) was computed for significant risk factors. Criminal convictions were reported for 81 (4.3%) youths. Although most children living in poverty did not present criminal conviction (89%), poverty at baseline was the only modifiable risk factor significantly associated with crime (OR 4.14, 99.8% CI 1.38–12.46) with a PARF of 22.5% (95% CI 5.9–36.1%). It suggests that preventing children’s exposure to poverty would reduce nearly a quarter of subsequent criminal convictions. These findings highlight the importance of poverty in criminal conviction, as it includes several deprivations and suggest that poverty eradication interventions during childhood may be crucial for reducing crime among Brazilian youth.

The neurobiological factors associated with the emergence of major depressive disorder (MDD) in adolescence are still unclear. Previous cross-sectional studies have documented aberrant connectivity in resting-state functional magnetic resonance imaging (rs-fMRI) networks. However, whether these findings precede MDD onset has not been established. This scoping review mapped key methodological aspects and main findings of longitudinal rs-fMRI studies of MDD in adolescence. Three sets of neuroimaging methods to analyze rs-fMRI data were identified: seed-based analysis, independent component analysis, and network-based approaches. Main findings involved aberrant connectivity within and between the default mode network (DMN), the cognitive control network (CCN), and the salience network (SN). Accordingly, we utilized Menon’s (2011) triple-network model for neuropsychiatric disorders to summarize key results. Adolescent MDD was associated with hyperconnectivity within the SN and between DMN and SN, as well as hypoconnectivity within the CCN. These findings suggested that dysfunctional connectivity among the three main large-scale brain networks preceded MDD onset. However, there was high heterogeneity in neuroimaging methods and sampling procedures, which may limit comparisons between studies. Future studies should consider some level of harmonization for clinical instruments and neuroimaging methods.

Objective: Subjective well-being (SWB) is impaired in individuals with depressive disorders. The aim of this study was to assess individuals in the general population identified as having depression and compared to SWB of those with antidepressants use. Methods: A household study with a probability sample (N = 3744) was conducted in São Paulo and Rio de Janeiro, Brazil, from 2007 to 2008. The Composite International Diagnostic Interview (CIDI) was used to diagnose depression and the Subjective Well-Being Inventory was used to attain the individual's perception of SWB. To estimate the association between SWB and diagnosis of depression, Poisson regression analyses were performed controlling the effects of sociodemographic variables, family history of mental health, other psychiatric diagnoses, and antidepressants use. Results: In the general population, poor SWB was associated to psychiatric diagnosis (depression and others); the productive age; living alone (single; separated or widowed); lower schooling; higher income; history of mental illness in the family; the non-practice of religion and the use of antidepressants. In the exclusive population of patients diagnosed with depression, the poor SWB was associated only to marital status. Twenty two percent of the individuals with depression used antidepressants, and this was not associated to their perceived SWB. Limitation: The main limitation of study was the use of psychotropic medication used as a proxy to identify individuals who made use of health services or received treatment. Conclusion: The individuals diagnosed with depression in the general population had a poorer perception of their SWB, and that SWB was not associated to antidepressants use.

AbstractBackground.Sex differences in cognitive functioning have long been recognized in schizophrenia patients and healthy controls (HC). However, few studies have focused on patients with an at-risk mental state (ARMS) for psychosis. Thus, the aim of the present study was to investigate sex differences in neurocognitive performance in ARMS patients compared with HC.Methods.The data analyzed in this study were collected within the multicenter European Gene–Environment Interactions study (11 centers). A total of 343 ARMS patients (158 women) and 67 HC subjects (33 women) were included. All participants completed a comprehensive neurocognitive battery. Linear mixed effects models were used to explore whether sex differences in cognitive functioning were present in the total group (main effect of sex) and whether sex differences were different for HC and ARMS (interaction between sex and group).Results.Women performed better in social cognition, speed of processing, and verbal learning than men regardless of whether they were ARMS or HC. However, only differences in speed of processing and verbal learning remained significant after correction for multiple testing. Additionally, ARMS patients displayed alterations in attention, current IQ, speed of processing, verbal learning, and working memory compared with HC.Conclusions.Findings indicate that sex differences in cognitive functioning in ARMS are similar to those seen between healthy men and women. Thus, it appears that sex differences in cognitive performance may not be specific for ARMS, a finding resembling that in patients with schizophrenic psychoses.

TRODAT-1 is a radiopharmaceutical derived from tropane and linked to tecnecium-99m ([99mTc] TRODAT-1) has been used in studies of dopamine transporter (DAT) in central nervous system. Associated with the SPECT technique of acquisition, is able to detect changes in neurological disorders like Parkinson´s disease, evaluating the binding potential (BP) of DAT. The aim of this study was to evaluate the influence of the image reconstruction methods, Filtered Back Projection (FBP) and iterative reconstruction (OSEM), in BP values at the striatal region in 30 healthy volunteers. Images were analyzed by visual inspection and semi-quantitative analysis. Regions of interest (ROI) were made over striatal areas on both sides. Nonparametric Wilcoxon statistical analysis was performed between the BP values from the FBP and OSEM methods. Our results showed that the reconstruction methods have a statistical significant BP values difference in the total striatum (Z = -2,2787 p = 0.005), right striatum (Z = -2,602 p = 0.009) and left striatum (Z= 2,746 p = 0.006). The effect size was calculated to see if there influence in this test: the "large effect size" for all measurements was observed (total striatum r= -0.51; right striatum r= -0.48; left striatum r= -0.50). FBP is the usual method of reconstruction for brain SPECT images, and our results showed influence of the OSEM method in BP. It is concluded that the method of image reconstruction adopted should be standardized to avoid incorrect evaluations of BP values using [99mTc]TRODAT-1.