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Schizophrenia (SZ) is a chronic debilitating disease. Subjects with SZ have significant shorter life expectancy. Growing evidence suggests that a process of pathological accelerated aging occurs in SZ, leading to early development of severe clinical diseases and worse morbimortality. Furthermore, unaffected relatives can share certain endophenotypes with subjects with SZ. We aim to characterize accelerated aging as a possible endophenotype of schizophrenia by using a machine learning (ML) model of peripheral biomarkers to accurately differentiate subjects with SZ (n = 35), their unaffected siblings (SB, n = 36) and healthy controls (HC, n = 47). We used a random forest algorithm that included biomarkers related to aging: eotaxins CCL-11 and CCL-24; the oxidative stress markers thiobarbituric acid-reactive substances (TBARS), protein carbonyl content (PCC), glutathione peroxidase (GPx); and telomere length (TL). The ML algorithm of biomarkers was able to distinguish individuals with SZ from HC with prediction accuracy of 79.7%, SZ from SB with 62.5% accuracy and SB from HC with 75.5% accuracy. These results support the hypothesis that a pathological accelerated aging might occur in SZ, and this pathological aging could be an endophenotype of the disease, once this profile was also observed in SB, suggesting that SB might suffer from an accelerated aging in some level.

SummaryBackgroundSocial 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.AimsWe 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.MethodThis 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.ResultsA 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.ConclusionsOur 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.

Introduction Social isolation has been associated with poor sleep quality and mental health problems during the COVID-19 pandemic. However, most studies have investigated heterogeneous samples subjected to varying social distancing policies and did not focus on a single local profile subject to homogeneous prevention policies. Objective To evaluate the impact of the COVID-19 pandemic on mental health and sleep quality in a specific region in the South of Brazil where the populations have similar culture and local governments have adopted similar social distancing policies. Methods This study was conducted with 327 individuals aged 18-72 years, living in the Vale do Taquari area, Brazil. We assessed sociodemographic variables with a standardized protocol, symptoms of depression, anxiety, and stress with the Depression, Anxiety and Stress Scale-21 (DASS-21), sleep quality with the Pittsburgh Sleep Quality Index (PSQI), and post-traumatic stress symptoms with the Impact of Event Scale (IES-R), using a web-based online survey. Results Our results showed that sleep dysfunction moderated the effects of age on psychological symptoms, indicating that younger participants who had poorer sleep quality had worse mental health. Furthermore, participants with more perceived stress during the pandemic and more sleep dysfunction reported more symptoms of anxiety and post-traumatic stress. Conclusion Psychological symptoms were not related to social isolation duration but were related to the subjective perception that the pandemic interfered with life and generated stressful situations. These results may help governments make important decisions about protection and isolation measures in future waves of COVID-19 infection.

Verbal memory (VM) is impaired in schizophrenia (SZ) and bipolar disorder (BD), and predicts psychosocial functioning. However, there is a lack of research exploring the role of VM component processes, including semantic clustering, in these disorders. Semantic clustering might impact this association, as effective semantic memory strategies may reflect unimpaired executive control, leading to an adequate functioning. We aimed to investigate VM components in SZ and BD, and the role of semantic clustering in the relationship between VM and functioning.We included 495 participants (156 SZ, 172 BD, and 167 healthy controls (HC)) that underwent an assessment using the Hopkins Verbal Learning Test - Revised for VM and the Functioning Assessment Short Test for psychosocial functioning. We compared groups through ANOVAs and investigated the effect of semantic clustering in the relationship between VM total immediate free recall and functioning through linear regression models.SZ had worse overall VM performance compared to BD, which performed worse than HCs. HCs used more semantic clustering than SZ and BD, but there were no differences between the two clinical groups. In HCs, semantic clustering impacted the relationship between VM performance and functioning, while no interaction was observed in SZ or BD.Cross-sectional design; no medication effects or other cognitive functions were assessed.SZ and BD may use an alternative cognitive pathway in which the relationship between VM and functioning is independent of complex cognitive processes such as semantic clustering, supporting the cognitive remediation targeting of VM in these disorders.

For years, the management of schizophrenia has represented a challenge for clinicians, with antipsychotic treatments usually resulting in relapses and new hospitalizations. Clozapine has been shown to be an effective medication for treatment-resistant schizophrenia (TRS), but is currently underused due to its potential side effects. Nevertheless, research has suggested that clozapine reduces future hospitalizations in patients with TRS. This study aims to verify the rates of hospitalizations in patients with TRS under long-term use of clozapine. We retrospectively analyzed clinical data from 52 individuals with TRS before and after the use of clozapine. The mean duration of treatment with and without clozapine was 6.6 (± 3.9) and 8.5 years (± 6.6), respectively. Patients had a median of 0.5 (0.74) hospitalizations per year before the use of clozapine and 0 (0.74) hospitalizations after it (p = 0.001). Therefore, the use of clozapine resulted in an expected reduction in the number of hospitalizations per year in individuals with TRS.

BackgroundCognition 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.MethodsWe 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.ResultsPatients 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.ConclusionsPatients 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.

Evidence has shown heterogeneity of cognitive function among patients with bipolar disorder (BD). Our study aims to replicate recent findings of cognitive subgroups, as well as we assessed subjective cognitive difficulties and functioning in each cluster.Hierarchical cluster analysis was conducted to examine whether there were distinct neurocognitive subgroups based on neurocognitive battery. Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and Functioning Assessment Short Test (FAST) were used to assess subjective cognitive difficulties and functional impairment.We found three distinct subgroups: a first cluster with intact cognition (n = 30, 43.5%), a second cluster with selective cognitive impairment (n = 23, 33.3%), and a third cluster with globally cognitive impairment (n = 16, 23.3%). The intact group had more years of education (p .001) and higher estimated IQ (p .001) than globally and selectively impaired subgroups. Additionally, they were younger (p = .011), had an earlier age at bipolar diagnosis (p .037) and earlier age of first hospitalization (p .035) compared to individuals with globally cognitive impairment.This is a cross-sectional design with a small sample including only patients from a tertiary hospital.Our results give support to the existence of a continuum of severity from patients without impairment to those with poor cognitive functioning. Patients in the intact group seem to have higher cognitive reserve than other two groups. However, they also experienced cognitive complaints and some degree of functional impairment. These findings suggest the importance of using a combo of instruments (e.g., objective and subjective cognitive measures plus functioning instruments) for a complete assessment of patients with BD.

Mesmo entre os especialistas mais dedicados, a prática clínica da Neuroendocrinologia é conhecida por sua larga complexidade. Os temas e subtemas a partir dos quais se pode dividir a especialidade são inúmeros e precisam ser tratados com o devido cuidado, assegurando aos profissionais médicos referências confiáveis para as abordagens e aplicações mais adequadas em sua rotina. O Guia Prático em Neuroendocrinologia é o resultado da reunião dos principais nomes da área e uma iniciativa do Departamento de Neuroendocrinologia da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM). Em 28 capítulos escritos em uma linguagem acessível, o guia oferece uma literatura que, ao assimilar a complexidade da Neuroendocrinologia, enfoca as lacunas de conhecimento de endocrinologistas de todo o país, visando transformá-las em informações consistentes e atualizadas para o melhor atendimento dos pacientes.

BackgroundSubjects with bipolar disorder (BD) show heterogeneous cognitive profile and that not necessarily the disease will lead to unfavorable clinical outcomes. We aimed to identify clinical markers of severity among cognitive clusters in individuals with BD through data-driven methods.MethodsWe recruited 167 outpatients with BD and 100 unaffected volunteers from Brazil and Spain that underwent a neuropsychological assessment. Cognitive functions assessed were inhibitory control, processing speed, cognitive flexibility, verbal fluency, working memory, short- and long-term verbal memory. We performed hierarchical cluster analysis and discriminant function analysis to determine and confirm cognitive clusters, respectively. Then, we used classification and regression tree (CART) algorithm to determine clinical and sociodemographic variables of the previously defined cognitive clusters.ResultsWe identified three neuropsychological subgroups in individuals with BD: intact (35.3%), selectively impaired (34.7%), and severely impaired individuals (29.9%). The most important predictors of cognitive subgroups were years of education, the number of hospitalizations, and age, respectively. The model with CART algorithm showed sensitivity 45.8%, specificity 78.4%, balanced accuracy 62.1%, and the area under the ROC curve was 0.61. Of 10 attributes included in the model, only three variables were able to separate cognitive clusters in BD individuals: years of education, number of hospitalizations, and age.ConclusionThese results corroborate with recent findings of neuropsychological heterogeneity in BD, and suggest an overlapping between premorbid and morbid aspects that influence distinct cognitive courses of the disease.

Cognitive deficits are a core aspect of psychotic disorders; however, it is not clear to which extent different pharmacological treatments could distinctly impact these outcomes. Hence, we conducted a systematic review and ten network meta-analyses of randomized controlled trials to compare the effect of antipsychotics on cognitive performance of individuals with psychotic disorders. Fifty-four trials were included in the analyses, enrolling 5866 patients. Compared to other antipsychotics, amisulpride performed better on verbal learning; quetiapine on composite score, attention and verbal learning; lurasidone on composite score; olanzapine on composite score and most cognitive domains; perphenazine on composite score, executive function, working memory, and verbal learning; risperidone on executive function and verbal learning; sertindole on processing speed; and ziprasidone on composite score, working memory, and verbal learning. Oppositely, haloperidol performed poorer on all cognitive domains, occupying the last positions in all rankings; and clozapine performed poorer on composite score, executive function, verbal learning, and visuoconstruction. We hope that these results should be taken into account when assessing and treating individuals with psychosis.

Objective To investigate associations between body mass index (BMI), white matter fractional anisotropy (FA), and C-reactive protein (CRP) in a group of individuals with bipolar disorder (BD) during euthymia and compare them with a control group of healthy subjects (CTR). Methods The sample consisted of 101 individuals (BD n = 35 and CTR n = 66). Regions of interest (ROI) were defined using a machine learning approach. For each ROI, a regression model tested the association between FA and BMI, controlling for covariates. Peripheral CRP levels were assayed, correlated with BMI, and included in a mediation analysis. Results BMI predicted the FA of the right cingulate gyrus in BD (AdjR2 = 0.312 F(3) = 5.537 p = 0.004; β = -0.340 p = 0.034), while there was no association in CTR. There was an interaction effect between BMI and BD diagnosis (F(5) = 3.5857 p = 0.012; Fchange = 0.227 AdjR2 = 0.093; β = -1.093, p = 0.048). Furthermore, there was a positive correlation between BMI and CRP in both groups (AdjR2 = 0.170 F(3) = 7.337 p < 0.001; β = 0.364 p = 0.001), but it did not act as a mediator of the effect on FA. Conclusion Higher BMI is associated with right cingulate microstructure in BD, but not in CTR, and this effect could not be explained by inflammatory mediation alone.

Previous studies have suggested that subjects participating in schizophrenia research are not representative of the demographics of the global population of people with schizophrenia, particularly in terms of gender and geographical location. We here explored if this has evolved throughout the decades, examining changes in geographical location, gender and age of participants in studies of schizophrenia published in the last 50 years. We examined this using a meta-analytical approach on an existing database including over 3,000 studies collated for another project. We found that the proportion of studies and participants from low-and-middle income countries has significantly increased over time, with considerable input from studies from China. However, it is still low when compared to the global population they represent. Women have been historically under-represented in studies, and still are in high-income countries. However, a significantly higher proportion of female participants have been included in studies over time. The age of participants included has not changed significantly over time. Overall, there have been improvements in the geographical and gender representation of people with schizophrenia. However, there is still a long way to go so research can be representative of the global population of people with schizophrenia, particularly in geographical terms.

Background: Verbal memory impairment may be considered an endophenotype in schizophrenia (SZ), also affecting the siblings of SZ subjects. Furthermore, the immune-inflammatory system response has an important modulatory effect on brain processes, especially on memory circuits. Objective: Investigating the relationship between TNF-α and IL-6 and memory performance in patients with SZ, their unaffected siblings (SB) and healthy controls (HC). Methods: 35 subjects with SZ, 36 SB, and 47 HC underwent a neurocognitive assessment for verbal memory by means of the revised Hopkins Verbal Learning Test (HVLT-R) in addition to serum cytokines analyses. Results: SZ patients performed worse in HVLT-R than SB and HC, but SB and HC were not different. Regarding the biomarker levels, we found significant results of TNF-α for both groups. However, we did not find differences between groups after multiple-comparisons analysis. There were no significant correlations between episodic verbal memory, TNF-α, and IL-6. Conclusion: The results are compatible with the hypothesis that deficits in verbal memory of individuals with SZ could be secondary to inadequate functioning of cognitive processing areas, such as proactive cognitive control.

Background Social and environmental factors such as poverty or violence, modulate the risk and course of schizophrenia, but how they affect the brain in patients with psychosis remains unclear. We here studied how they are related to brain structure in schizophrenia and healthy controls in Latin America, where these factors are large and unequally distributed. Methods This is an MRI multi-center study in patients with schizophrenia and healthy controls from six Latin American cities: Buenos Aires, Medellin, Mexico City, Santiago, Sao Paulo and Porto Alegre. Total and voxel-level gray matter volumes obtained from T1-weighted MRI images and their relationship with income and homicide rates were analyzed using a general linear model. Results 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total gray matter volume in the two groups (P=0.006). Controls showed a positive correlation between total gray matter volume and income (R=0.14, P=0.02). Surprisingly, this relationship was not present in 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, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure. Discussion Our results highlight the interplay between the environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as those from low and middle-income countries: potentially less brain vulnerability (less gray matter loss) is sufficient to become unwell in adverse (poor) environments. The development of algorithms exploring clinically-useful information from structural brain images in psychosis should include representative samples from low and middle-income countries.

Background Sexual function is highly neglected in individuals with schizophrenia (SZ). Clinicians usually underestimate the rates of sexual dysfunctions in these patients, and this group does not spontaneously complain about it. Sexual dysfunction in this population could reach up to 80% and its known to affect all domains of sexual function. Moreover, it may be linked to stigma and discrimination factors. Medication side effects on sexuality concern more than any other side effects, and it is known to be a major cause of poor quality of life and non-adherence to medication. Furthermore, the relationship between sexual dysfunction and other psychiatric symptoms in SZ is still unclear. Our aim was to describe the sexual dysfunction in chronic patients with SZ and its relation to negative, positive and depressive symptoms. Methods A convenience and exploratory sample of 57 patients (age 43.75±10.38, 69% men, 86,2% single) were recruited from an university outpatient schizophrenia clinic, in Porto Alegre – Brazil. Participants were assessed using Arizona Sexual Experience Scale (ASEX), Medication Adherence Rating Scale (MARS), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Inventory and demographic information. Sexual dysfunction was considered following the ASEX scoring criteria. Results Sexual dysfunction was present in 51,8% of the patients, assessed by ASEX. Women showed increased sexual dysfunction than men (χ2=22,727, p < .001). There were no differences between patients that reported sexual dysfunction and the ones who did not regarding age, duration of illness and medication adherence assessed by MARS (p > .05). Additionally, there were no differences between groups on positive and negative symptoms assessed by PANSS. Interestingly, patients with sexual dysfunction had increased depressive symptoms compared to patients with a good perceived sexual function (t(54) = -3.326, p = .002). Calgary total scores were positively correlated with ASEX total scores (r = .369, p = .005). Nevertheless, we did not find significant correlations between ASEX total scores and other scales. Scores found on MARS (8.07±1.5) suggest that this sample is highly adherent to prescribed treatment. Discussion This is an exploratory and preliminary study that shows and reinforces the idea that sexual dysfunction is importantly prevalent and remains as a neglected issue in individuals with schizophrenia, as are the depressive symptoms. We showed that there is an association between these two domains, which might indicate a need for change of perspective for the pharmacological and psychosocial approaches currently used. In addition to the dopaminergic blockage by antipsychotics that lead to reduction in positive symptoms, we believe there is a need to look for depression symptoms to access, prevent and treat sexual dysfunction. Inattention to this event may result in abrupt treatment discontinuation and relapse. Curiously, the fact that we did not find any correlations between sexual evaluations and PANSS scores would suggest that sexual dysfunction in chronic patients could differ from others stages of the disease. The size of our sample and the fact that we did not access hormones and prolactin levels are important limitations of this study. However this is an exploratory study that provided clues on the subject, allowing to address further investigation taking into account the limitations.

BACKGROUND: Schizophrenia (SZ) is associated with increased somatic morbidity typically related to processes of aging, such as cardiovascular disease and metabolic abnormalities. Furthermore, individuals with SZ have increased mortality and reduced life span. These observations of increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, may indicate that subjects with SZ have a pathological accelerated aging However, although there is evidence supporting this hypothesis, the neurobiological underpinnings are still unclear. Therefore, this presentation aims to suggest possible mechanisms to this hypothesis. A suggested biomarker of aging is the length of telomeres (TL), which are DNA-protein structures that protect the ends of chromosomes and progressively shorten with each cell division. Inflammatory processes, such as dysregulation in cytokines, may influence TL. The pro-inflammatory chemokine CCL11, a type of cytokine, was described as an age-related systemic factor associated with decreased neurogenesis in hippocampus and impaired memory in mice, that was increased in chronic but not in recent onset individuals with SZ. Thus, these biomarkers could be associated with brain volume loss and memory impairments, which might be behavioral and structural outcomes of aging. METHODS: We included 48 individuals with SZ and 64 healthy subjects (HC). Participants had the same socioeconomic and educational background. They underwent clinical and memory assessments, structural T1 MRI 1.5T, and had their peripheral blood drawn for biochemical analysis. Comparisons of group means and correlations were performed. We aimed to evaluate the relationships of TL and CCL11 (aging and inflammatory biomarkers, respectively), gray matter (GM) volume, and episodic memory performance in individuals with SZ compared to HC. RESULTS: Our results showed that SZ had shorter TL and increased CCL11 compared to HC. Additionally, individuals with SZ had reduced GM volume and worse episodic memory performance than HC. In SZ, shorter TL was related to increased CCL11, and both biomarkers were related to reduced GM volume, all of which were related to worse memory performance. Older age was only associated with reduced GM, but longer duration of illness was related with all the aforementioned variables. TL mediated the effects of duration of illness to memory performance. In HC, there were no significant correlations except for the expected relationship between memory and GM. CONCLUSIONS: We saw associations between increased CCL11, shorter TL, reduced GM volume, and decreased episodic memory in SZ, which were all related to longer duration of illness. These results suggest that it is not age itself, but the impact of the disease associated with a pathological aging that might lead to a worse outcome. Chronic pro-inflammatory processes could influence the body’s capacity to absorb damage over time. This could have impacts on the brain that might lead to structural and functional consequences, such as loss of GM, which in turn could elicit behavioral impairments, such as memory deficits. Although preliminary, our data point to potentially important mechanisms related to neural and cognitive impairment associated with psychosis consistent with the hypothesis of accelerated aging in SZ.

Social and environmental factors are known risk factors and modulators of mental health disorders. We here conducted a nonsystematic review of the neuroimaging literature studying the effects of poverty, urbanicity, and community violence, highlighting the opportunities of studying non-Western developing societies such as those in Latin America. Social and environmental factors in these communities are widespread and have a large magnitude, as well as an unequal distribution, providing a good opportunity for their characterization. Studying the effect of poverty in these settings could help to explore the brain effect of economic improvements, disentangle the effect of absolute and relative poverty, and characterize the modulating impact of poverty on the underlying biology of mental health disorders. Exploring urbanicity effects in highly unequal cities could help identify the specific factors that modulate this effect as well as examine a possible dose–response effect by studying megacities. Studying brain changes in those living among violence, which is particularly high in places such as Latin America, could help to characterize the interplay between brain predisposition and exposure to violence. Furthermore, exploring the brain in an adverse environment should shed light on the mechanisms underlying resilience. We finally provide examples of two methodological approaches that could contribute to this field, namely a big cohort study in the developing world and a consortium-based meta-analytic approach, and argue about the potential translational value of this research on the development of effective social policies and successful personalized medicine in disadvantaged societies. Fil: Crossley, Nicolas A.. Pontificia Universidad Católica de Chile; Chile Fil: Alliende, Luz Maria. Pontificia Universidad Católica de Chile; Chile Fil: Ossandon, Tomas. Pontificia Universidad Católica de Chile; Chile Fil: Castañeda, Carmen Paz. Instituto Psiquiátrico Dr. José Horwitz Barak; Chile Fil: González Valderrama, Alfonso. Instituto Psiquiátrico Dr. José Horwitz Barak; Chile. Universidad Finis Terrae.; Chile Fil: Undurraga, Juan. Universidad del Desarrollo; Chile. Instituto Psiquiátrico Dr. José Horwitz Barak; Chile Fil: Castro, Mariana Nair. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Guinjoan, Salvador Martín. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Díaz Zuluaga, Ana M.. Universidad de Antioquia; Colombia Fil: Pineda-Zapata, Julián A.. Instituto de Alta Tecnología Médica; Colombia Fil: López-Jaramillo, Carlos. Hospital Universitario San Vicente Fundación; Colombia. Universidad de Antioquia; Colombia Fil: Reyes Madrigal, Francisco. Instituto Nacional de Neurología y Neurocirugía; México Fil: León-Ortíz, Pablo. Instituto Nacional de Neurología y Neurocirugía; México Fil: de la Fuente-Sandoval, Camilo. Instituto Nacional de Neurología y Neurocirugía; México Fil: Czepielewski, Leticia Sanguinetti. Hospital de Clinicas de Porto Alegre; Brasil Fil: Gama, Clarissa S.. Hospital de Clinicas de Porto Alegre; Brasil Fil: Zugman, Andre. Universidade Federal de Sao Paulo; Brasil Fil: Gadelha, Ary. Universidade Federal de Sao Paulo; Brasil Fil: Jackowski, Andrea. Universidade Federal de Sao Paulo; Brasil Fil: Bressan, Rodrigo. Universidade Federal de Sao Paulo; Brasil

Introduction The Internet has seen rapid growth in the number of websites focusing on mental health content. Considering the increased need for access to accurate information about mental health treatment, it is important to understand the promotion of this information online. Objective To analyze BuzzFeed’s Mental Health Week (BFMHW) interactions on its own website and in related social media platforms (Facebook, Twitter and YouTube) using metrics of information delivery in mental health topics. Methods We extracted social media metrics from the 20 posts with the highest number of BuzzFeed interactions on the BFMHW website and from 41 videos available on the BFMHW playlist created by the BuzzFeed Video profile on YouTube. We analyzed the format and content used in BuzzFeed’s publishing methods as well as the following social media metrics: exposure (presence online, views and time online), influence (likes) and engagement (comments, shares, replies and BuzzFeed interactions). Results Analysis of the variables revealed that audience engagement is associated with the number of medias in which the content is published: views on YouTube and shares on Facebook (0.71, p

Schizophrenia (SZ) is associated with broad burden. The clinical manifestations of SZ are related to pathophysiological alterations similar to what is seen in normal aging. Our aim was to evaluate the differences in telomere length (TL), a biomarker of cellular aging, in subjects with SZ (n=36), unaffected siblings (SB, n=36) and healthy controls (HC, n=47). SZ had shorter TL compared to HC, but no difference was found in SB comparing to SZ. These findings indicate that a pathological accelerated aging profile could be present in the course of SZ and further studies are needed to confirm TL as potential endophenotype, especially in at risk populations.

Background Episodic verbal memory primarily indicates acquisition or registration of memory for verbally presented information, being one of the main neuropsychological impaired functions in individuals with schizophrenia. Furthermore, it appears to be more susceptible than other memory systems to early neuronal dysfunction, supporting hypotheses about a neuroprogressive course of schizophrenia (SZ). On the other hand, it is unclear if such memory dysfunction in schizophrenia could not only be associated with illness progression, but also with neurodevelopment markers such as premorbid crystallized intellectual functioning (IQ). Therefore, we aimed to better understand the relationship between years of illness (YOI), IQ and episodic verbal memory in individuals with SZ. Methods We included 218 individuals with confirmed diagnosis of SZ from 3 separate centers (Hospital de Clínicas de Porto Alegre, Brazil; Hospital de Clínicas da Universidade Federal do Paraná, Brazil, and Hospital Clínic de Barcelona, Spain). All participants were informed about study procedures and signed consent before assessment. Participants underwent cognitive assessment with Hopkins Verbal Learning Test (HVLT) for episodic memory and Wechsler Abbreviated Scale of Intelligence for estimated crystallized premorbid IQ. We conducted a mediational analysis to estimate the effect sizes of years of illness in predicting memory deficits considering the indirect effect of IQ as a mediator, as well as age and sex as covariates. Results There was a significant indirect effect of years of illness on HVLT immediate recall through IQ, ab=-.119 CI 95% [-.248, -.013]. The mediator could account for more than a third of the total effect, PM=.39. The direct effect of years of illness on immediate recall was only a trend (c: -.09, p= .068), while the total effect counting IQ was significant (c’=-.15, p=.007). Discussion The effect sizes of IQ were greater than the direct effect of years of illness on memory deficits in our sample. This finding implicates that neurodevelopment markers such as IQ may be as important as disease progression itself in predicting cognitive outcomes in SZ. While patients with lower premorbid IQ appears to be more prone to memory deficits, those with better early intellectual development appears to count on a protective effect. Neuroprogression in schizophrenia would be an addition of neurodevelopment and disease progression. These results help to give new lights on the heterogeneity in the course of schizophrenia, different trajectories and the need of more personalized approach. Further prospective studies are mandatory.

Maltreatments in childhood may have implications for neurodevelopment that could remain throughout life. Childhood trauma seems to be associated with the onset of bipolar disorder (BD), and its occurrence might accentuate the overall disease impairments related to cognitive deficits in BD. We aimed to evaluate the effects of a history of childhood trauma to estimated intellectual functioning (IQ) of individuals with BD. We included 72 subjects with BD during euthymia. Participants underwent a clinical interview and were assessed through the Childhood Trauma Questionnaire (CTQ) and Wechsler Abbreviated Scale of Intelligence (WASI). Most prevalent trauma subtypes were emotional abuse and neglect (54.1%). A linear regression model that included perceived childhood trauma, family history of severe mental disorders, age at diagnosis and psychotic symptoms during the first episode as main factors showed that only childhood trauma had a significant effect in predicting estimated IQ. Therefore, the history of childhood trauma in individuals with BD may play a role in intellectual development, suggesting that adversities during development result in decreased general cognitive abilities. These results reinforce the need to promote early interventions to protect childhood and to promote the well-being of children, contributing to the growth of healthy adults.

BACKGROUND: Cognitive impairments are core symptoms in schizophrenia. Among them, memory deficits seem to be strongly related to several outcomes, such as psychosocial functioning and accelerated aging. However, the neurobiological mechanisms associated with this dysfunction are still unclear. One hypothesis would be related to white matter microstructural abnormalities, considering that neuronal connectivity underlies cognitive processing. Therefore, we aimed to study the relationship between white matter integrity in major tracts using diffusion tensor imaging (DTI) and episodic memory and working memory in individuals with schizophrenia (SZ) compared to healthy controls (HC). METHODS: This was a cross-sectional study. We included 100 participants, 43 individuals with SZ that were medicated according to guidelines and stable for at least 6 months, and 52 unaffected individuals. All participants were informed about study procedures and signed consent before assessment. Research protocol was conducted in accordance with the Helsinki Declaration. The Institutional Review Board approved the study protocol. Participants underwent cognitive assessment with Hopkins Verbal Learning Test for episodic memory and Letter-Number Sequencing subtest from WAIS-III for working memory. Diffusion tensor imaging was performed on a Philips Achieva 1.5T scanner and was processed in FreeSurfer 5.3 TRACULA. We performed exploratory linear regression models separately for patients and controls with the sum of left and right fractional anisotropy (FA) predicting memory performance, controlling for age, sex, and years of education. The pathways analyzed were: corticospinal tract (CST), inferior longitudinal fasciculus (ILF), uncinate fasciculus (UNC), anterior thalamic radiation (ATR), cingulum – cingulate gyrus (supracallosal) bundle (CCG), cingulum – angular (infracallosal) bundle (CAB), superior longitudinal fasciculus – parietal bundle (SLFP), superior longitudinal fasciculus – temporal bundle (SLFT), corpus callosum – forceps minor (FMIN) and forceps major (FMAJ). RESULTS: Individuals with SZ did not show differences among FA of white matter tracts (p > .05), although they had worse episodic and working memory performances compared to HC (p < .001). Episodic memory was not predicted by any of the white matter pathways analyzed (p > .05). Conversely, findings regarding verbal working memory were different between groups, showing that it was predicted only by CAB in SZ (t = 2.303, p = .027, Beta = .307; model: F = 5.209, p = 0.002, R2Adj = .286), whereas in HC it was predicted only by CST (t = -2.203, p = .032, Beta = -.266; model: F = 9.262, p < 0.001, R2Adj = .389). DISCUSSION: Decreased white matter integrity in cingulum-angular bundle, which are posterior fibers of the cingulum with parahippocampal connections, was related to worse working memory performance in schizophrenia. This finding implicates cingulate bundle neuronal connectivity abnormalities to higher-order cognitive processes, what may underlie the mechanisms of memory impairment in schizophrenia.

Clozapine is more efficacious than first-generation antipsychotics for positive and negative symptoms, although it is related with serious adverse effects. Because of this profile, it could also have an impact on cognition. Therefore, we evaluated learning ability of 31 treatment-resistant individuals with SZ using clozapine uninterruptedly for 18.23 ± 4.71 years and 26 non-treatment-resistant using other antipsychotics that never used clozapine. Long-term treatment with clozapine did not improve verbal learning ability better than other antipsychotics. Although clozapine has a unique profile for reducing clinical symptoms, it may not have an additional benefit for cognition when started later on the course of schizophrenia.

There is growing evidence showing that bipolar disorder is associated with persistent cognitive deficits. However, the exact meaning and impact of cognitive deficits in bipolar disorder is still not entirely known, even though they have been associated with poor psychosocial functioning. This study aims to summarize cognitive and psychosocial functioning findings of remitted bipolar patients. We conducted an extensive Medline search of the published English literature for the period January 2000– March 2014 using a variety of search terms to find relevant articles. Bibliographies of retrieved papers were further analysed for publications of interest. Our results showed that: (1) all mood states of bipolar disorder are associated with cognitive impairment. However, the euthymic state is associated with less impairment than the other states; (2) there is a strong association between clinical factors (i.e, duration of illness, number of episodes, residual mood symptoms, comorbidities) and cognitive impairment in euthymic bipolar patients, although these factors do not account fully for these deficits; (3) cognitive deficits, in particular, verbal learning and executive dysfunctions may contribute to poor functioning. In conclusion, our review suggests that cognitive deficits are strongly associated with mood episodes; such deficits persist, in lower degree, during remission. Impairment on cognitive performance may explain, in part, poor long–term functioning in remitted bipolar patients. It highlights that psychosocial interventions in combination with pharmacotherapy should be considered to improve cognition and enhance the level of functioning. Therefore, studies assessing the efficacy of novel strategies focused on cognitive and functional status are an important area of future investigation in bipolar disorder.

Impairment on episodic memory (EM) has been strongly correlated with psychiatric disorders, including schizophrenia (SZ) and bipolar disorder (BD). Morevover, the effects of course and progression of the illness on cognitive functioning have not been well established. The aim of the present study is to assess performance of episodic memory in BD and SZ according to their clinical stages. Subjects who met DSM-IV criteria for bipolar disorder (n=43) and schizophrenia (31), on euthymia or clinical remission, were recruited from the outpatients facilities at Hospital de Clinicas de Porto Alegre (Brazil). They were classified into two clinical stages (early or late for BD, and recent onset or chronic for SZ) and compared to 54 healthy controls. Episodic memory performance was assessed by means the Hopkins Verbal Learning Test-Revised (HVLT-R) that measures verbal learning and episodic memory in both disorders. Our results showed that patients in early stage of BD (EBD) performed better performance on the total immediate free recall (p

INTRODUCTION: Schizophrenia is frequently associated with a debilitating course and prominent impairment in social and occupational functioning. Although the criteria for classification into stages have not been defined in the literature, illness duration and functioning seem to be good candidates.OBJECTIVE:To compare functioning of patients with schizophrenia at different stages of the disease (early vs. late) and healthy sex- and age-matched controls.METHODS: This double-blinded, case-controlled study included 79 individuals: 23 patients with schizophrenia diagnosed up to 5 years earlier; 19 patients with schizophrenia diagnosed at least 20 years earlier; and healthy matched controls. Diagnoses were established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis I Disorder. Functioning was assessed using the Functioning Assessment Short Test (FAST).RESULTS: Patients in the early stage had significantly higher scores than healthy controls in total FAST and in autonomy, occupational functioning, cognitive functioning and interpersonal relationships. Individuals in the late stage had significantly poorer functioning than controls in all domains. The comparison of functioning between the two groups of patients revealed no significant differences, except in occupational functioning, in which late stage patients had a poorer performance.CONCLUSION: Functioning impairment in schizophrenia tends to remain stable despite illness duration. Therefore, functioning should be effectively assessed at an early stage, as illness duration alone may not be the most reliable criterion to stage patients with schizophrenia. INTRODUÇÃO:A esquizofrenia está frequentemente associada a um curso debilitante e a um importante comprometimento no funcionamento social e ocupacional. Embora os critérios para classificação em diferentes estágios ainda não tenham sido definidos, a duração da doença e a funcionalidade têm sido apontadas como bons candidatos.OBJETIVO:Comparar a funcionalidade de indivíduos com esquizofrenia no estágio inicial e final com controles saudáveis correspondentes em idade e sexo.MÉTODOS: Neste estudo caso-controle, duplo-cego, foram incluídos 79 pacientes: 23 com diagnóstico de esquizofrenia feito até 5 anos atrás (estágio inicial); 19 diagnosticados há pelo menos 20 anos (estágio final); e controles saudáveis pareados. O diagnóstico foi estabelecido pela Entrevista Clínica Estruturada para Transtornos do Eixo I do Manual Diagnóstico e Estatístico de Transtornos Mentais, 4ª edição (DSM-IV). A funcionalidade foi avaliada através da escala Teste Breve de Avaliação Funcional (FAST).RESULTADOS: Os pacientes em estágio inicial tiveram escores significativamente maiores do que controles saudáveis na escala FAST (escore total e domínios autonomia, funcionamento ocupacional, funcionamento cognitivo e relações interpessoais). Os indivíduos em estágio final apresentaram funcionalidade pior que os controles em todos os domínios. A comparação entre os dois grupos não mostrou diferenças, exceto no funcionamento ocupacional, em que os pacientes em estágio final apresentaram um desempenho pior.CONCLUSÃO: O prejuízo da funcionalidade na esquizofrenia tende a permanecer estável ao longo da doença. Portanto, a funcionalidade deve ser avaliada nos estágios iniciais da doença, já que a duração da doença por si só pode não ser o critério mais confiável para definir o estágio de pacientes com esquizofrenia.

Schizophrenia (SZ) is associated with increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, which may suggest that pathological accelerated aging occurs in SZ. Therefore, we aim to evaluate the relationships of age, telomere length (TL), and CCL11 (aging and inflammatory biomarkers, respectively), gray matter (GM) volume and episodic memory performance in individuals with SZ compared to healthy controls (HC). One hundred twelve participants (48 SZ and 64 HC) underwent clinical and memory assessments, structural MRI, and had their peripheral blood drawn for biomarkers analysis. Comparisons of group means and correlations were performed. Participants with SZ had decreased TL and GM volume, increased CCL11, and worse memory performance compared to HC. In SZ, shorter TL was related to increased CCL11, and both biomarkers were related to reduced GM volume, all of which were related to worse memory performance. Older age was only associated with reduced GM, but longer duration of illness was related with all the aforementioned variables. Younger age of disease onset was associated with increased CCL11 levels and worse memory performance. In HC, there were no significant correlations except between memory and GM. Our results are consistent with the hypothesis of accelerated aging in SZ. These results may indicate that it is not age itself, but the impact of the disease associated with a pathological accelerated aging that leads to impaired outcomes in SZ.

Objective:: To assess cognitive performance and psychosocial functioning in patients with bipolar disorder (BD), in unaffected siblings, and in healthy controls. Methods:: Subjects were patients with BD (n=36), unaffected siblings (n=35), and healthy controls (n=44). Psychosocial functioning was accessed using the Functioning Assessment Short Test (FAST). A sub-group of patients with BD (n=21), unaffected siblings (n=14), and healthy controls (n=22) also underwent a battery of neuropsychological tests: California Verbal Learning Test (CVLT), Stroop Color and Word Test, and Wisconsin Card Sorting Test (WCST). Clinical and sociodemographic characteristics were analyzed using one-way analysis of variance or the chi-square test; multivariate analysis of covariance was used to examine differences in neuropsychological variables. Results:: Patients with BD showed higher FAST total scores (23.90±11.35) than healthy controls (5.86±5.47; p < 0.001) and siblings (12.60±11.83; p 0.001). Siblings and healthy controls also showed statistically significant differences in FAST total scores (p = 0.008). Patients performed worse than healthy controls on all CVLT sub-tests (p < 0.030) and in the number of correctly completed categories on WCST (p = 0.030). Siblings did not differ from healthy controls in cognitive tests. Conclusion:: Unaffected siblings of patients with BD may show poorer functional performance compared to healthy controls. FAST scores may contribute to the development of markers of vulnerability and endophenotypic traits in at-risk populations.

Background Obesity is associated with both structural and functional changes of the central nervous system, and is frequent in psychiatry settings. The increased prevalence of obesity in schizophrenia (SCZ) and bipolar disorder (BD) is associated with illness severity, functioning impairment and cognitive deficits. It cannot be attributed to biases inherent in treatment-seeking samples, given that this association is detectable even in drug-naïve patients. Diffusion tensor imaging (DTI) analyses of major brain fibers in both disorders show shared abnormalities of white matter. DTI has been employed as a highly sensitive tool to investigate microstructural changes in white matter structure. While gray matter alterations in obesity point to a consistent reduction with increasing body mass index (BMI), volumetric changes in white matter are more complex and less conclusive. Fractional anisotropy (FA) is the most commonly used parameter as it is the best estimate of fiber integrity as well as axonal and myelin degeneration, and has been reported an association with BMI in depressed BD patients, but not explored in SCZ nor in comparison with a control group (CTR). The aim of this study was to analyze the relationship between obesity and brain alterations assessed by DTI in SCZ, BD and CTR. Methods In one-hundred fifty (N=150) individuals (SCZ:49; BD:35; CTR:66) were administered clinical rating scales, collected sociodemographic data and submitted to magnetic resonance imaging (MRI) acquisition in a 1.5 T machine. Linear regression models were performed independently for each group in order to test the relationship of BMI on each brain fiber FA, using gender, age and years of disease for the patients as covariates. Results The mean BMI was different among groups (F(143)6.533; P= .002), higher in BD group (BD 29.69 ± 6.55; CTR: 25.54 ± 4.25; SCZ: 26.42 ± 6.02). In BD, the model that predicted FA in the left cingulate gyrus endings was significant controlling for covariates (F(4,21)= 3.273; p = .031; Adj. R2= .384), with a main effect of BMI (t=-2.870; p= .009; β=- .531). For SCZ and CTR groups, we did not find significant models to predict brain fiber FAs from BMI controlling for covariates. Discussion BMI was associated with reduced FA in cingulate gyrus in BD, implying that obesity may play a role in microstructure damage in the limbic system. These findings are in consonance with the literature and may be related with processing of emotional and cognitive responses disrupted in BD. Conversely, it did not predicted FA in SCZ or CTR connection bundles, possibly because of the lower BMI levels in these groups. Also, we were not able to control for treatment adherence, a variable correlated with both white matter integrity and weight gain. At last, obesity appears to be correlated with white matter microstructure in a heterogeneous and disease specific course depending on the underlying psychopathology, showing association with impairment in BD but not SCZ and CTR. Further studies are needed to explore the role of treatment in the interpretation of these findings.

BACKGROUND: Individuals with schizophrenia show different cognitive deficits across domains. One of the main neuropsychological impaired functions is episodic verbal memory, which is an important predictor of daily-life functioning in SZ and is more susceptible than other memory systems to neuronal dysfunction, having a higher risk of early deterioration. Furthermore, its dysfunction has been widely connected with cortical and subcortical brain abnormalities. Growing evidence indicates that inflammatory mechanisms may be important features underlying cognitive impairment. Specifically, different cytokines might influence synaptic plasticity, neurogenesis, and memory processes. Our hypothesis would be that memory dysfunction in schizophrenia could be related to biological abnormalities such as in cytokine imbalances. Therefore, this presentation will show results from studies that aimed to investigate the relationship of TNF-α and IL-6, and CCL11 to verbal episodic memory performance in individuals with SZ compared to unaffected subjects (HC). METHODS: We included individuals with SZ and healthy controls (HC) that underwent clinical and memory assessment (HVLT-R), assessment of blood levels of cytokines, and T1 structural MRI 1.5T. RESULTS: Individuals with SZ performed worse than HC in immediate and delayed memory recall. Regarding biomarker levels, we did not find significant differences between groups for TNF-α and IL-6 but found statistically increased CCL11 levels in SZ compared to HC. We did not observe significant correlations between memory and TNF-α and IL-6 but found a significant relationship between CCL11 and memory performance in SZ. Moreover, increased CCL11 was related to reduced total gray matter volume in SZ. CONCLUSIONS: Episodic memory deficits are more associated to a pro-inflammatory cytokine related to accelerated aging than to cytokines related to the neurobiology of memory, and this immune imbalance is linked to structural brain changes. These findings strengthen the hypothesis that chronic pro-inflammatory processes could influence the brain through mechanisms such as neuroinflammation, which in turn could lead to structural and functional consequences, such as loss of gray matter and memory deficits.

Objectives: Depressive symptoms are associated with worse outcomes in patients with bipolar disorder (BD). However, scarce data are available regarding neurocognitive profiles across different areas of functioning among BD patients with moderate and severe depression. Our objective was to assess cognition and global functioning in a group of patients with bipolar depression. Methods: Data were available for 100 patients with bipolar depression (78% female) and 70 controls (64% female) paired by age and education level. Cognitive function was assessed with a neuropsychological test battery. Functioning was assessed with the Functioning Assessment Short Test. Results: In patients, severe depression was associated with poorer cognitive performance on measures of executive function. Patients with severe depression showed worse global functioning than those with moderate depression (z = 2.54, p = 0.011). In patients with severe depression, lower global functioning was associated with lower scores in working memory (r = -0.200, p = 0.010), and executive function (r = -0.210, p = 0.007; and r = 0.293, p < 0.001). Conclusion: Our findings suggest cognitive impairment and global functioning impairment are associated with the severity of depressive symptoms in bipolar depression. Intensive treatment of depressive symptoms in patients with BD is crucial to improve cognitive functioning and, consequently, functional outcomes.

Background Individuals with schizophrenia (SZ) have marked functional impairments in wide range of domains, such as employment, independent living and interpersonal relationships. Several clinical, cognitive and psychological factors have been shown to predict functional outcomes. However, current pharmacological and psychosocial treatments have failed to rehabilitate patients, which indicates that the mechanisms of functional outcomes are not completely clear. Therefore, we aimed to better understand the relationship between intellectual and cognitive performance to functional outcome of subjects with SZ compared to unaffected individuals. Considering the neurodevelopmental course of SZ, our hypothesis was that premorbid crystallized IQ would interact with cognition to influence functionality. Methods We included 188 individuals with confirmed diagnosis of SZ and 268 unaffected subjects (HC) from two separate multisite studies conducted by the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) consortium. We used the following variables for the analysis: a) Estimated crystallized premorbid intellectual functioning (IQ): Wechsler Test of Adult Reading (WTAR); b) Cognitive performance: Dot Probe Expectancy task (DPX) and Relational and Item-Specific Encoding task (RISE) from CNTRACS; c) Functional capacity: UCSD Performance-based Skills Assessment – Brief (UPSA-B). We conducted linear regressions to predict functional outcome considering demographic, intellectual, and cognitive variables, as well as the interaction between cognition and IQ in participants with SZ and HC separately. Results Participants with SZ had worse cognitive performance and premorbid IQ, and poorer functional outcome compared to HC. For the prediction of UPSA-B, the regression model that included cognition and IQ as predictors and age and parental SES as covariates was significant in SZ (F(4, 124) = 8.473, p < .001, Adj. R2 = .189), with the both variables showing significant main effects: IQ (β = .311, t = 3.324, p = .001) and cognition (β = .216, t = 2.630, p = .0010). When we included the IQ x cognition interaction (F(5, 123) = 7.035, p < .001, Adjusted R2 = .191), it did not significantly improve the model (F = 1.224, p = 0.27), and the interaction was not significant (β = -.11, t = -1.106, p = .27). In HC, the regression model with only main effects was similar to what was seen in SZ (F(4,313) = 27.62, p < .001, Adj. R2 = .25), with main effects of IQ (β = .239, t = 4.418, p < .001) and cognition (β = .349, t = 6.891, p < .001) (Figure 1). However, when we included the IQ x cognition interaction (F(5,312) = 24.15, p < .001, Adjusted R2 = .27), the interaction was significant (β = -.139, t = -2.801, p = .005) and accounted for a significant increase in variance over and above the other main effects (F = 7.8452, p = .005). Discussion In SZ, both higher IQ and better cognitive performance were independent predictors of better functioning. However, in HC, functionality was predicted by the interaction between IQ and cognition, with the form of the interaction suggesting that for HC participants with higher IQ, there was less effect of cognition on predicting better functioning. Conversely, in HC with lower premorbid IQ, better cognitive performance has a stronger effect in predicting better functioning. The fact that both IQ and cognition had independent relationships to functional outcome in SZ could help explain the limited clinically significant results found in previous studies of cognitive remediation and psychosocial interventions that did not also consider the impact of premorbid IQ. Future studies could focus on early interventions to prevent functional impairments through the stimulation of early intellectual development.

BACKGROUND: Bipolar disorder (BD) is a significant cause of functional, cognitive, and social impairment. However, classic studies of functioning and social skills have not investigated how BD may impact behavior on the Internet. Given that the digital age has been changing the way people communicate, this study aims to investigate the pattern of Internet use in patients with BD. METHODS: This cross-sectional study assessed 30 patients with BD I or II and 30 matched controls. Patients were not in an acute mood episode, according to DSM-IV. A standard protocol examined sociodemographic variables and social behavior on the Internet, assessed by Facebook number of friends (FBN) and lifetime estimated number of offline contacts (social network number, SNN). RESULTS: SNN (p

OBJECTIVE Clinical staging has increasingly been considered suitable for psychiatric disorders such as bipolar disorder. A staging model of bipolar disorder could help clinicians understand the mechanisms underlying the course of the illness and guide prognosis and therapy. This study aimed to investigate differences in functional status and cognitive functioning in patients in different clinical stages of bipolar disorder. METHOD Subjects who met DSM-IV criteria for bipolar disorder (n = 54) were recruited from the Bipolar Disorders Program at Hospital de Clinicas de Porto Alegre (Brazil) from October 2012 to October 2013. All patients had been in remission (score < 7 on the 17-item HDRS and the YMRS) for at least 1 month before assessment. They were classified into 4 clinical stages according to the model described by Kapczinski et al and compared to 43 healthy controls. Functional status was assessed by using the Functioning Assessment Short Test (FAST). Neuropsychological measures were performed to investigate cognitive functioning. RESULTS Significant differences in functional status were found between patients in all stages compared to controls (F = 33.014, P < .001), except for stage I (P = .104). Additionally, a very strong linear association was found between FAST scores and clinical stages, with FAST scores increasing from stage I to IV (F = 149.55, P < .001). In the bipolar group, stage I was associated with better occupational functioning than stage II (F = 48.344, P = .003). Stage IV patients experienced greater impairment in autonomy than stage III patients (F = 26.646, P = .004), and stage III patients experienced poorer autonomy than those in stage II (P = .004). With regard to cognitive measures, patients in late stages (stages III and IV) were more impaired than healthy controls (P < .001). A similar performance was found between patients in early stages (stages I and II) and healthy controls. DISCUSSION This study showed progressive functional changes from stage I to stage IV of bipolar disorder, with a greater impairment in patients in later stages of the illness. FAST scores seem to have a good discriminant ability to distinguish between patients in early versus late stages of bipolar disorder and could therefore contribute to the development of a bipolar disorder staging system.

Cognitive deficits have been recognized as a core feature of schizophrenia (SZ) and are present in most patients. Verbal memory (VM), working memory (WM), and executive function (EF) are domains commonly impaired in patients with SZ. These latter domains have been related to the genetic risk of the disorder characterizing as possible endophenotypes. In order to study neurocognitive endophenotypes in a Brazilian population with elevated genetic risks to develop SZ, we measured VM (Hopkins Verbal Learning Test Revised), WM (Letter–Number Sequencing and Digit Span) and EF (Stroop Test) in 90 subjects (45 unaffected siblings of patients with SZ and 45 matched healthy controls). No differences were found in EF and WM (Letter–Number Sequencing and Digit Span). However, in VM, siblings of patients performed worse than controls on the immediate recall and delayed recall. Our results suggest that VM impairment could be considered an endophenotype of SZ.

OBJECTIVE: Summarize data on metabolic syndrome (MS) in bipolar disorder (BD). METHODS: A systematic review of the literature was conducted using the Medline, Embase and PsycInfo databases, using the keywords metabolic syndrome, insulin resistance and metabolic X syndrome and cross-referencing them with bipolar disorder or mania. The following types of publications were candidates for review: (i) clinical trials, (ii) studies involving patients diagnosed with bipolar disorder or (iii) data about metabolic syndrome. A 5-point quality scale was used to assess the methodological weight of the studies. RESULTS: Thirty-nine articles were selected. None of studies reached the maximum quality score of 5 points. The prevalence of MS was significantly higher in BD individuals when compared to a control group. The analysis of MS subcomponents showed that abdominal obesity was heterogeneous. Individuals with BD had significantly higher rates of hypertriglyceridemia than healthy controls. When compared to the general population, there were no significant differences in the prevalence of low HDL-c in individuals with BD. Data on hypertension were also inconclusive. Rates of hyperglycemia were significantly greater in patients with BD compared to the general population. CONCLUSIONS: The overall results point to the presence of an association between BD and MS, as well as between their subcomponents. Pontifícia Universidade Católica do Rio Grande do Sul Developmental Cognitive Neuroscience Research Group Universidade Federal de São Paulo (UNIFESP) Program for Recognition and Intervention for Individuals in At-Risk Mental States Universidade Federal de São Paulo (UNIFESP) Interdisciplinary Laboratory of Clinical Neurosciences UNIFESP, Program for Recognition and Intervention for Individuals in At-Risk Mental States UNIFESP, Interdisciplinary Laboratory of Clinical Neurosciences SciELO