Country-level gender inequality is associated with structural differences in the brains of women and men.

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.

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

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

Deviations from a typical development of the cerebellum in youth are associated with psychopathology, executive functions and educational outcomes.

BACKGROUND: Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement. METHODS: Children and adolescents aged 6-17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses. RESULTS: Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control. CONCLUSIONS: Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.

Serum immune markers and transition to psychosis in individuals at clinical high risk.

Individuals at clinical high risk (CHR) for psychosis have been found to have altered cytokine levels, but whether these changes are related to clinical outcomes remains unclear. We addressed this issue by measuring serum levels of 20 immune markers in 325 participants (n = 269 CHR, n = 56 healthy controls) using multiplex immunoassays, and then followed up the CHR sample to determine their clinical outcomes. Among 269 CHR individuals, 50 (18.6 %) developed psychosis by two years. Univariate and machine learning techniques were used to compare levels of inflammatory markers in CHR subjects and healthy controls, and in CHR subjects who had (CHR-t), or had not (CHR-nt) transitioned to psychosis. An ANCOVA identified significant group differences (CHR-t, CHR-nt and controls) and post-hoc tests indicated that VEGF levels and the IL-10/IL-6 ratio were significantly higher in CHR-t than CHR-nt, after adjusting for multiple comparisons. Using a penalised logistic regression classifier, CHR participants were distinguished from controls with an area-under the curve (AUC) of 0.82, with IL-6 and IL-4 levels the most important discriminating features. Transition to psychosis was predicted with an AUC of 0.57, with higher VEGF level and IL-10/IL-6 ratio the most important discriminating features. These data suggest that alterations in the levels of peripheral immune markers are associated with the subsequent onset of psychosis. The association with increased VEGF levels could reflect altered blood-brain-barrier (BBB) permeability, while the link with an elevated IL-10/IL-6 ratio points to an imbalance between anti- and pro-inflammatory cytokines.

Replication of a predictive model for youth ADHD in an independent sample from a developing country.

BACKGROUND: Very few predictive models in Psychiatry had their performance validated in independent external samples. A previously developed multivariable demographic model for attention-deficit/hyperactivity disorder (ADHD) accurately predicted young adulthood ADHD using clinical and demographical information collected in childhood in three samples from developed countries, but failed to replicate its performance in a sample from a developing country. Furthermore, consolidated risk factors for ADHD were not included among its predictors. METHODS: Participants were 1905 children and adolescents from a community-based sample and followed from ages 6 to 14 years at baseline to ages 14 to 23 years (mean age 18) at follow-up. We applied the intercept and weights of the original model to the data, calculating the predicted probability of each participant according to the set of predictors collected in childhood, and compared the estimates with the actual outcome (ADHD) collected during adolescence and young adulthood. We explored the performance of the original model, and of models including novel predictors (prematurity, family history of ADHD, and polygenic risk score for ADHD). RESULTS: The observed area under the curve of the original model was .76 (95% Confidence Interval .70 to .82). The multivariable demographical model outperformed single variable models using only prematurity, family history, or the ADHD PRS. Adding either of these variables, or all at once, did not improve the performance of the original demographical model. CONCLUSIONS: Our findings suggest that the originally developed ADHD predictive model is suitable for use in different settings for clinical and research purposes.

Influence of cannabis use on incidence of psychosis in people at clinical high risk.

AIMS: Evidence for case-control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome. METHODS: Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale. RESULTS: During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome. CONCLUSIONS: These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder.

Longitudinal associations between positive attributes and psychopathology and their interactive effects on educational outcomes.

Psychopathology is associated with impaired learning and early termination of schooling, whereas positive attributes are associated with better educational outcomes. However, it is important to understand if and how psychopathology and positive attributes longitudinally impact each other so we could shed light on where to intervene to promote educational outcomes through these constructs. A large prospective school-based community cohort of youths (5-15 years of age, 45% female) were assessed and followed up for 3 years (n = 2010; 80% retention). We assessed the longitudinal impact of positive attributes (Youth Strength Inventory) and psychopathology (bifactor model of Strengths and Difficulties Questionnaire) using a cross-lagged panel model. We also used generalized mixed effects models to investigate how these both constructs predict school dropout and literacy, adjusting for confounders and testing their interaction. Positive attributes negatively predicted, and were negatively predicted by, the general factor of psychopathology and conduct problems in the cross-lagged panel model. Positive attributes (OR = 0.57, 95% CI [0.44, 0.73], p < 0.001) and specific conduct symptoms (OR = 2.33, 95% CI [1.64, 3.33], p < 0.001) predicted school dropout, whereas the general factor of psychopathology predicted lower literacy ability (ß = - 0.08, 95% CI [- 0.11, - 0.05], p < 0.001). However, the protective association of positive attributes on school dropout decreases as the general factor of psychopathology increases. These findings provide new evidence that positive attributes and psychopathology mutually influence each other over development and have interactive effects on educational outcomes.

Childhood poverty and mental health disorders in early adulthood: evidence from a Brazilian cohort study.

BACKGROUND: We examined the association between childhood poverty and mental health disorders (MHD) in childhood and early adulthood. We also investigated whether the association between poverty in childhood and MHD is mediated by exposure to stressful life events (SLE). METHODS: We used data from a prospective community cohort of young people assessed at baseline (M = 9.7 years, SD = 1.9), first (M = 13.5 years, SD = 1.9), and second (M = 18.2 years, SD = 2.0) follow-ups (N = 1,590) in Brazil. Poverty was assessed using a standardized classification. Exposure to 20 different SLE was measured using the Life History instrument. Psychiatric diagnoses were evaluated using the Development and Well-Being Assessment. Latent growth models investigated the association between poverty at baseline and the growth of any MHD, externalizing, and internalizing disorders. Mediation models evaluated whether the association between childhood poverty and MHD in early adulthood was mediated by exposure to SLE. RESULTS: Poverty affected 11.4% of the sample at baseline and was associated with an increased propensity for presenting externalizing disorders in adolescence or early adulthood (standardized estimate = 0.27, p = 0.016). This association was not significant for any disorder or internalizing disorders. Childhood poverty increased the likelihood of externalizing disorders in early adulthood through higher exposure to SLE (OR = 1.07, 95 CI% 1.01-1.14). Results were only replicated among females in stratified analyses. CONCLUSIONS: Childhood poverty had detrimental consequences on externalizing MHD in adolescence, especially among females. Poverty and SLE are preventable risk factors that need to be tackled to reduce the burden of externalizing disorders in young people.

Neuroimaging of Dopamine Transporter Density in the Striatum of Disordered Gamblers.

The aim of the present research was to add to the growing literature on dopamine and gambling disorder (GD) by assessing whether GD is associated with dopamine transporter (DAT) density in the ventral striatum compared to healthy controls and whether DAT density was associated with key characteristics of GD (e.g., abstinence, craving). In a cross-sectional investigation using single-photon emission computed tomography with a technetium-99m-labeled tropane derivative as a radiotracer with SPECT imaging, fifteen participants with GD and 15 controls (non-gambling individuals, matched for age, gender, handedness, and smoking status) were measured. The GD group completed self-reported questionnaires regarding gambling. Striatal DAT density did not differ between the two groups. Conversely, striatal DAT density correlated significantly with various measures of recent gambling, but not with measures of chronic gambling. Multivariate analysis, adjusted for age and smoking status, showed that DAT density in the left striatum correlated positively with time spent gambling and gambling craving in the last month, whereas DAT density in the right striatum correlated negatively with abstinence self-efficacy. The results suggests that DAT density in the striatum is associated with recent gambling activity and gambling expectation.

Relationship between jumping to conclusions and clinical outcomes in people at clinical high-risk for psychosis.

BACKGROUND: Psychosis is associated with a reasoning bias, which manifests as a tendency to 'jump to conclusions'. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes. METHODS: In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A 'beads' task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point. RESULTS: There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ. CONCLUSIONS: In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.

Effects of socioeconomic status in cognition of people with schizophrenia: results from a Latin American collaboration network with 1175 subjects.

BACKGROUND: Cognition heavily relies on social determinants and genetic background. Latin America comprises approximately 8% of the global population and faces unique challenges, many derived from specific demographic and socioeconomic variables, such as violence and inequality. While such factors have been described to influence mental health outcomes, no large-scale studies with Latin American population have been carried out. Therefore, we aim to describe the cognitive performance of a representative sample of Latin American individuals with schizophrenia and its relationship to clinical factors. Additionally, we aim to investigate how socioeconomic status (SES) relates to cognitive performance in patients and controls. METHODS: We included 1175 participants from five Latin American countries (Argentina, Brazil, Chile, Colombia, and Mexico): 864 individuals with schizophrenia and 311 unaffected subjects. All participants were part of projects that included cognitive evaluation with MATRICS Consensus Cognitive Battery and clinical assessments. RESULTS: Patients showed worse cognitive performance than controls across all domains. Age and diagnosis were independent predictors, indicating similar trajectories of cognitive aging for both patients and controls. The SES factors of education, parental education, and income were more related to cognition in patients than in controls. Cognition was also influenced by symptomatology. CONCLUSIONS: Patients did not show evidence of accelerated cognitive aging; however, they were most impacted by a lower SES suggestive of deprived environment than controls. These findings highlight the vulnerability of cognitive capacity in individuals with psychosis in face of demographic and socioeconomic factors in low- and middle-income countries.

Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis.

Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58-3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current work supports further evaluation of NMDAR autoantibodies as a possible prognostic biomarker and aetiological factor in a subset of people already meeting CHR criteria.

Unraveiling the correlation among neurodevelopmental and inflammatory biomarkers in patients with chronic schizophrenia.

INTRODUCTION: Nuclear distribution element like-1 (Ndel1) is a cytosolic oligopeptidase, which was suggested as a potential biomarker of aberrant neurodevelopment and early stage of schizophrenia (SCZ). The involvement of Ndel1 in neurite outgrowth, neuronal migration and neurodevelopment was demonstrated. Moreover, Ndel1 cleaves neuropeptides, including the endogenous antipsychotic peptide neurotensin, and lower Ndel1 activity was reported in SCZ patients compared with healthy controls (HCs). Changes in brain-derived neurotrophic factor (BDNF) and inflammatory cytokines levels were also implicated in SCZ. OBJECTIVE: This preliminary study aimed to investigate the interactions between these immune and neurodevelopmental/neurotrophic biomarkers, namely BDNF and the recently identified SCZ biomarker Ndel1. RESULTS: We observed lower Ndel1 activity and IL-4 levels, and higher BDNF levels, in plasma of SCZ (N = 23) compared with HCs (N = 29). Interestingly, significant correlation between Ndel1 activity and IL-4 levels was observed in SCZ, while no correlation with any other evaluated interleukins (namely IL-2, IL-8, IL-10 and IL-17A) or BDNF levels was noticed. CONCLUSION: Although this hypothesis needs to be further explored for a better understanding of the mechanisms by which these altered pathways are associated to each other in SCZ, we suggest that Ndel1 and the inflammatory marker IL-4 are directly correlated.

Long-term stability of the cortical volumetric profile and the functional human connectome throughout childhood and adolescence.

There is compelling evidence showing that between-subject variability in several functional and structural brain features is sufficient for unique identification in adults. However, individuation of brain functional connectomes depends on the stabilization of neurodevelopmental processes during childhood and adolescence. Here, we aimed to (1) evaluate the intra-subject functional connectome stability over time for the whole brain and for large scale functional networks and (2) determine the long-term identification accuracy or 'fingerprinting' for the cortical volumetric profile and the functional connectome. For these purposes, we analysed a longitudinal cohort of 239 children and adolescents scanned in two sessions with an interval of approximately 3 years (age range 6-15 years at baseline and 9-18 years at follow-up). Corroborating previous results using short between-scan intervals in children and adolescents, we observed a moderate identification accuracy (38%) for the whole functional profile. In contrast, identification accuracy using cortical volumetric profile was 95%. Among the large-scale networks, the default-mode (26.8%), the frontoparietal (23.4%) and the dorsal-attention (27.6%) networks were the most discriminative. Our results provide further evidence for a protracted development of specific individual structural and functional connectivity profiles.

Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities.

BACKGROUND: Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear. AIMS: We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed. METHOD: This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model. RESULTS: A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (P = 0.006). Controls showed a positive correlation between total grey matter volume and income (R = 0.14, P = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (R = -0.076, P = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure. CONCLUSIONS: Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.

Mononitrate Isosorbide as an Adjunctive Therapy in Schizophrenia: A Randomized Controlled Crossover Trial.

BACKGROUND: Schizophrenia is a complex disabling mental disorder, and many patients present poor response to available treatments. Accumulating evidence about the role of the glutamate/nitric oxide pathway in mediating the positive and negative symptoms of schizophrenia suggests potential benefits of drugs that modulate this system. The aim of this study was to test the efficacy of isosorbide mononitrate (ISMN) as an adjunctive therapy for symptomatic outpatients with schizophrenia. METHODS: This was a 2-month randomized, double-blind, placebo-controlled trial with 24 schizophrenia patients. Participants were treated with ISMN 50 mg for 1 month and placebo for another month in a crossover design. The Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, Global Assessment of Functioning, and MATRICS Cognitive Consensual Battery were used for symptom assessment and arterial spin labeling was used to assess brain activation patterns. RESULTS: We found significant differences in the total, general, and positive subscales of the PANSS, Global Assessment of Functioning scores, and Clinical Global Impression scores during treatment with ISMN relative to placebo. No treatment effects were found comparing scores in the MATRICS Cognitive Consensual Battery and the negative subscale of the PANSS between the active and placebo conditions. A post hoc analysis of neuroimaging data showed reduced activity in the thalamus in subgroup of patients with severe psychopathology. CONCLUSIONS: Schizophrenia patients with persistent symptoms showed significant improvement after 4 weeks of treatment with ISMN 50 mg/d compared with placebo. Isosorbide mononitrate added beneficial effects to antipsychotic treatment in terms of positive symptoms and functioning.

Is treatment-resistant schizophrenia associated with distinct neurobiological callosal connectivity abnormalities?

BACKGROUND: Resistance to antipsychotic treatment affects up to 30% of patients with schizophrenia. Although the time course of development of treatment-resistant schizophrenia (TRS) varies from patient to patient, the reasons for these variations remain unknown. Growing evidence suggests brain dysconnectivity as a significant feature of schizophrenia. In this study, we compared fractional anisotropy (FA) of brain white matter between TRS and non-treatment-resistant schizophrenia (non-TRS) patients. Our central hypothesis was that TRS is associated with reduced FA values. METHODS: TRS was defined as the persistence of moderate to severe symptoms after adequate treatment with at least two antipsychotics from different classes. Diffusion-tensor brain MRI obtained images from 34 TRS participants and 51 non-TRS. Whole-brain analysis of FA and axial, radial, and mean diffusivity were performed using Tract-Based Spatial Statistics (TBSS) and FMRIB's Software Library (FSL), yielding a contrast between TRS and non-TRS patients, corrected for multiple comparisons using family-wise error (FWE) < 0.05. RESULTS: We found a significant reduction in FA in the splenium of corpus callosum (CC) in TRS when compared to non-TRS. The antipsychotic dose did not relate to the splenium CC. CONCLUSION: Our results suggest that the focal abnormality of CC may be a potential biomarker of TRS.

Evaluation of Ongoing Participation of People with Schizophrenia in a Mutual Support Group as a Complementary Intervention to Outpatient Psychiatric Treatment.

This study aims to evaluate a group of people with schizophrenia undergoing outpatient treatment and who participate in a mutual support intervention, compared to another group of people with the same diagnosis, but attending only the usual outpatient treatment. This is a prospective study, with two measurements between six months. The mutual support group was initially composed of 16 people and the treatment as usual group was composed of 15 people. Clinical (medication adherence and functioning) and Recovery (hope, well-being, recovery and internalized stigma) outcomes were assessed. Nonparametric tests were used to verify differences in measurements between groups and between two moments. A higher level of internalized stigma and a decrease in the adherence to drug treatment in the treatment as usual group were verified. When comparing the pre-post difference between groups, there was a greater increase in adherence to drug treatment in the mutual support group. Our data point to more favorable results in the mutual support group, showing that ongoing participation in these groups is an important tool for the recovery process and for the treatment itself.

A study in first-episode psychosis patients: does angiotensin I-converting enzyme (ACE) activity associated with genotype predict symptoms severity reductions after treatment with the atypical antipsychotic risperidone?

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.

Are serum brain-derived neurotrophic factor concentrations related to brain structure and psychopathology in late childhood and early adolescence?

OBJECTIVE: Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence. METHODS: Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder. RESULTS: Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers. CONCLUSIONS: No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.