Objective: Obstacles for computational tools in psychiatry include gathering robust evidence and keeping implementation costs reasonable. We report a systematic review of automated speech evaluation for the psychosis spectrum and analyze the value of information for a screening program in a healthcare system with a limited number of psychiatrists (Maputo, Mozambique). Methods: Original studies on speech analysis for forecasting of conversion in individuals at clinical high risk (CHR) for psychosis, diagnosis of manifested psychotic disorder, and first-episode psychosis (FEP) were included in this review. Studies addressing non-verbal components of speech (e.g., pitch, tone) were excluded. Results: Of 168 works identified, 28 original studies were included. Valuable speech features included direct measures (e.g., relative word counting) and mathematical embeddings (e.g.: word-to-vector, graphs). Accuracy estimates reported for schizophrenia diagnosis and CHR conversion ranged from 71 to 100% across studies. Studies used structured interviews, directed tasks, or prompted free speech. Directed-task protocols were faster while seemingly maintaining performance. The expected value of perfect information is USD 9.34 million. Imperfect tests would nevertheless yield high value. Conclusion: Accuracy for screening and diagnosis was high. Larger studies are needed to enhance precision of classificatory estimates. Automated analysis presents itself as a feasible, low-cost method which should be especially useful for regions in which the physician pool is insufficient to meet demand.
Objective: Population neuroscience is an emerging field that combines epidemiology and neuroscience to study how genes and the environment shape typical and atypical brain functioning. The objective of this study was to review key studies on population neuroscience from low- and middle-income countries (LMICs) and to identify potential gaps vis-à-vis studies conducted in high-income countries. Methods: We conducted a systematic review to search for longitudinal cohort studies investigating the development of psychiatric disorders in children and adolescents in LMICs. We performed an electronic search in the EMBASE and MEDLINE databases from inception to July 5th, 2019. Results: We found six cohorts from four countries that met our search criteria: three cohorts from Brazil, one from China, one from South Africa, and one from Mauritius. Relevant examples of findings from these studies are reported. Conclusion: Our results demonstrate the impact of the valuable science output these cohort designs promote, allowing LMICs to have a share in frontline global psychiatry research. National and international funding agencies should invest in LMIC population neuroscience in order to promote replication and generalization of research from high-income countries.
Resumo Objetivos: compreender os aspectos positivos e negativos das experiências relacionadas ao trabalho relatadas por indivíduos com esquizofrenia, usuários de um ambulatório de especialidades envolvido em um programa de inclusão laboral. Métodos: estudo com abordagem qualitativa e observacional. Onze participantes responderam a uma pergunta norteadora aberta: “o que você percebe como aspectos positivos e negativos na sua experiência de trabalho?”. Os dados foram categorizados por meio de análise temática. Resultados: foram identificadas 4 categorias: sobrecarga e falta de informação/orientação no trabalho; a importância da remuneração; assumindo responsabilidades, esperança e superação; a vivência da doença, o cuidado com a saúde e o trabalho. O estudo mostrou a importância de buscar estratégias eficazes de inclusão laboral para indivíduos com esquizofrenia, que considerem as especificidades da doença e os fatores estressantes relacionados ao trabalho como potenciais desencadeadores de sofrimento físico e emocional. Conclusão: é fundamental investir em ações que possibilitem efetiva inclusão laboral de pessoas com esquizofrenia. Tais medidas devem contemplar os portadores de esquizofrenia, suas famílias, as empresas e os profissionais dos serviços de saúde mental. As especificidades da doença, as necessidades, os interesses e o potencial da pessoa devem ser considerados.
Abstract Objectives: to understand the positive and negative aspects of work-related experiences reported by individuals with schizophrenia who use a specialty outpatient clinic involved in a work inclusion program. Methods: observational qualitative approach study. Eleven participants answered an open guiding question: “what do you see as positive and negative in your work experience?”. Data were categorized by thematic analysis. Results: four categories were identified: overload and lack of information/guidance at work; the importance of remuneration; assuming responsibility, hope and overcoming; disease experience, health and work care. The study showed the importance of seeking effective labor inclusion strategies for individuals with schizophrenia. These strategies have to consider the disease specificities and work-related stressors as potential triggers of physical and emotional distress. Conclusion: it is essential to invest in actions that enable effective labor inclusion of people with schizophrenia. Such measures should include individuals with schizophrenia, their families, the companies and mental health professionals, taking into accountthe disease specificities, the person’s needs, interests and potential.
Objective: German psychiatrist Kurt Schneider proposed the concept of first-rank symptoms (FRS) of schizophrenia in 1959. However, their relevance for diagnosis and prediction of treatment response are still unclear. Most studies have investigated FRS in chronic or medicated patients. The present study sought to evaluate whether FRS predict remission, response, or improvement in functionality in antipsychotic-naive first-episode psychosis. Methods: Follow-up study of 100 patients at first episode of psychosis (FEP), with no previous treatment, assessed at baseline and after 2 months of treatment. The participants were evaluated with the standardized Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) and for presence of FRS. Results: Logistic regression analysis showed that, in this sample, up to three individual FRS predicted remission: voices arguing, voices commenting on one’s actions, and thought broadcasting. Conclusion: Specific FRS may predict remission after treatment in FEP patients. This finding could give new importance to Kurt Schneider’s classic work by contributing to future updates of diagnostic protocols and improving estimation of prognosis.
Objective: In schizophrenia, scores reflecting deficits in different cognitive processes are strongly correlated, making it difficult to establish a solid relationship between different cognitive mechanisms and other features of this disorder. The objective of this study was to explore whether three frequently postulated executive functions (updating, shifting, and inhibition) could be compared between groups and considered independently in terms of their respective roles in functional outcome. Methods: This study relied on confirmatory factor analysis of schizophrenia patients (n=141) and healthy controls (n=119). The main analyses examined the degree to which three executive functions (updating, set-shifting, and inhibition) could be separated in schizophrenia and compared this model among groups. Structural equation modeling analysis was also performed to examine the extent to which executive function components contribute to functional outcome in schizophrenia. Results: Multiple-group confirmatory factor analysis with unconstrained model parameters indicated that the full three-factor model may fit the data in both groups (χ2 = 61.48, degrees of freedom = 34, p < 0.001, comparative fit index = 0.95; standardized root mean square residual = 0.037; root mean square error of approximation = 0.04; Akaike’s information criteria = 169.49; normed fit index = 0.90), although there was also a good data fit for the patient group with a two-factor model. In the patient group, structural equation modeling suggested that shifting and (principally) updating were associated with the general measure of functional outcome (regression path coefficients: 0.34, p < 0.005; 0.39, p < 0.005, respectively), although when combined the mechanisms fail to contribute. Conclusion: This data suggests that the factor structure may be similar but not identical between groups, and both updating and shifting may play an important role in functional outcome in schizophrenia.
Abstract Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investigated whether SNP would have preventative effects on psychogenic symptoms induced by ketamine in healthy subjects. Methods: Healthy subjects (N = 38) were assigned to distinct groups that received SNP in different doses (0.15, 0.25, and 0.5 mcg/kg/min). First, participants received an infusion of SNP or placebo over 75 minutes. After 10 minutes, they were injected for 1 minute with a bolus of 0.26 mg/kg of ketamine and a maintenance dose was started 5 minutes later, with 0.25 mg/kg/h of ketamine for 50 minutes. Results: Ketamine-induced psychopathological alterations induced were reduced by SNP, as assessed with the Brief Psychological Rating Scale. Scores in the objective subscale of the Clinician-Administered Dissociative States Scale were also lower in SNP sessions compared to placebo. SNP had protective effects against deterioration in facial emotion and identity recognition tasks induced by ketamine. Discussion: Our findings support the view that SNP has preventative properties against psychotic manifestations.
Objective: Work is considered one of the main forms of social organization; however, few individuals with schizophrenia find work opportunities. The purpose of this study was to evaluate the relationship between schizophrenia symptoms and job acquisition. Method: Fifty-three individuals diagnosed with schizophrenia from an outpatient treatment facility were included in an 18-month follow-up study. After enrollment, they participated in a prevocational training group. At the end of training (baseline) and 18 months later, sociodemographic, clinical data and occupational history were collected. Positive and negative symptoms (Positive and Negative Syndrome Scale – PANSS), depression (Calgary Depression Scale), disease severity (Clinical Global Impression – CGI), functionality (Global Assessment of Functioning – GAF), personal and social performance (Personal and Social Performance – PSP) and cognitive functions (Measurement and Treatment Research to Improve Cognition in Schizophrenia – MATRICS battery) were applied at baseline and at the end of the study. Results: Those with some previous work experience (n=19) presented lower scores on the PANSS, Calgary, GAF, CGI and PSP scales (p < 0.05) than those who did not work. Among those who worked, there was a slight worsening in positive symptoms (positive PANSS). Conclusions: Individuals with less severe symptoms were more able to find employment. Positive symptom changes do not seem to affect participation at work; however, this calls for discussion about the importance of employment support.
Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. Results: We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. Conclusion: These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.
ABSTRACT Objective To adapt and investigate the validity reliability study of the Brazilian version of the Recovery Assessment Scale-RAS in people with schizophrenia. Methods Stage 1 – professional translation to Portuguese, adaptation, and back-translation of the RAS; Stage 2 – RAS was presented to 12 outpatients with schizophrenia to evaluate if they would be able to understand and respond to the instrument; Stage 3 – patients with schizophrenia (n = 104) were assessed with the Brazilian version of the RAS, functional outcomes measures, quality of life and symptoms scales. Results Results showed good internal consistency and retest reliability, and convergent validity between the RAS and quality of life measures (r = 0.58; p < 0.001), occupational functioning (r = 0.40; p < 0.001), independent living skills (r = 0.24; p < 0,02), functionality (CGI, r = -0.31; p < 0.003) and symptoms of schizophrenia, including PANSS total score total (r = -0.21; p < 0.05), PANSS negative (r = -0.28; p < 0.007), PANSS positive (r = -0.08; p = 0.48), and Calgary Depression Scale (r = -0.27; p < 0.01)]. Exploratory factor analysis yielded six factors, four of these very similar to previous studies. Conclusion This study suggests that the word “superação” (“overcome”) better reflects the concept of “recovery” in Brazilian Portuguese. The Brazilian version of RAS is a valid and reliable instrument to evaluate the process of recovery in people with schizophrenia.
RESUMO Objetivo Adaptar para o Brasil e investigar a confiabilidade e validade da Recovery Assessment Scale (RAS) em pessoas com esquizofrenia. Métodos Etapa 1 – foi realizada tradução profissional para o português, adaptação e retrotradução da RAS. Etapa 2 – estudo-piloto em um grupo de 12 pessoas com esquizofrenia para garantir compreensão dos itens da escala. Etapa 3 – As pessoas com esquizofrenia (N = 104) foram submetidas à versão brasileira da RAS e a instrumentos de funcionalidade, qualidade de vida e sintomas para busca de evidências de validade. Resultados Os resultados revelaram bons índices de consistência interna e de precisão teste e reteste dos instrumentos. Foram estabelecidas evidências de validade convergente entre a RAS e medidas de qualidade de vida (r = 0,58; p < 0,001), funcionamento ocupacional (r = 0,40; p < 0,001), habilidades de vida independente (r = 0,24; p < 0,02), gravidade (CGI, r = -0,31; p < 0,003) sintomas da esquizofrenia: PANSS total (r = -0,21; p < 0,05), PANSS negativa (r = -0,28; p < 0.007), PANSS positiva (r = -0.08; p = 0,437)] e depressão [Calgary (r = -0,27; p < 0,01)]. A análise fatorial exploratória revelou seis fatores, sendo quatro destes similares a estudos prévios. Conclusão A partir deste estudo, considerou-se que a palavra “superação” reflete melhor o conceito de “recovery”. A versão brasileira da escala RAS é um instrumento válido e reprodutível para aferir a capacidade de “superação” das pessoas com esquizofrenia.
Objective: Schizophrenia is a multifactorial disorder. It is known that a combination of extensive multiple common alleles may be involved in its etiology, each contributing with a small to moderate effect, and, possibly, some rare alleles with a much larger effect size. We aimed to perform a systematic review of association studies between schizophrenia (and its subphenotypes) and polymorphisms in the CNR1 gene, which encodes cannabinoid receptors classically implicated in schizophrenia pathophysiology, as well as to present unpublished results of an association study in a Brazilian population. Methods: Two reviewers independently searched for eligible studies and extracted outcome data using a structured form. Papers were retrieved from PubMed and ISI Web of Knowledge using the search term schizophrenia in combination with CNR1 or CB1 or cannabinoid receptor. Twenty-four articles met our inclusion criteria. We additionally present data from a study of our own comparing 182 patients with schizophrenia and 244 healthy controls. Results: No consistent evidence is demonstrated. Conclusion: Some seemingly positive association studies stress the need for further investigations of the possible role of endocannabinoid genetics in schizophrenia.
Abstract Background: Studies found inconsistent frequencies of social anxiety disorder (SAD) in Parkinson's disease (PD) (9.7%-50%). Previous reports did not test the impact of applying DSM-IV restrictive criteria that recommends the exclusion of secondary cases when diagnosing SAD in PD. Objective: Our aim is to estimate the frequency of social anxiety according to DSM-IV criteria and according to an inclusive broader approach. Methods: One hundred and ten PD patients were assessed for the presence of SAD using SCID-I, diagnosis of social anxiety were determined according to two different criteria: following and not following DSM-IV recommendation for exclusion of cases though to be secondary to a general medical condition. Results: SAD was present in 34 (31%) of patients, but 17 (15.5%) were secondary to a general medical condition. Patients with SAD were significantly younger, had earlier disease onset, had more severe PD symptoms, and were more frequently depressed. There was no difference in demographic and clinical features between primary and secondary SAD. Discussion: We conclude that the use of different diagnostic criteria may have a massive impact in the estimation of frequency of SAD in PD.
Objective: To investigate if verbal fluency impairment in schizophrenia reflects executive function deficits or results from degraded semantic store or inefficient search and retrieval strategies. Method: Two groups were compared: 141 individuals with schizophrenia and 119 healthy age and education-matched controls. Both groups performed semantic and phonetic verbal fluency tasks. Performance was evaluated using three scores, based on 1) number of words generated; 2) number of clustered/related words; and 3) switching score. A fourth performance score based on the number of clusters was also measured. Results: SZ individuals produced fewer words than controls. After controlling for the total number of words produced, a difference was observed between the groups in the number of cluster-related words generated in the semantic task. In both groups, the number of words generated in the semantic task was higher than that generated in the phonemic task, although a significant group vs. fluency type interaction showed that subjects with schizophrenia had disproportionate semantic fluency impairment. Working memory was positively associated with increased production of words within clusters and inversely correlated with switching. Conclusion: Semantic fluency impairment may be attributed to an inability (resulting from reduced cognitive control) to distinguish target signal from competing noise and to maintain cues for production of memory probes.
Objectives: To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patients and healthy controls and to investigate the correlations between HCC and psychopathology. Methods: Twenty-four drug-naïve FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1) was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS) was used to assess symptom severity. Hair samples (2-3 cm long) obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol. Results: Two-way analysis of covariance (ANCOVA) with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029) on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score. Conclusions: Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis, as assessed by long-term (3-month) cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission.
PURPOSE: To describe a new technique for isolation of a mesenchymal stem cells (MSCs) population from the olfactory mucosa in rabbits. METHODS: Olfactory stem cells (OSCs) were retrieved from under the cribriform plate of the Ethmoid bone. Several assays were accomplished to characterize the cell population and attest its viability in vitro. The cells were submitted to flow cytometry with the antibodies CD34, CD45, CD73, CD79, CD90 and CD105 and also they were induced to differentiate in three lineages. Functional evaluation involved analysis of in vitro growth behavior, colony forming unit like fibroblasts (CFU-f) and cryopreservation response. Further transduction with Green Fluorescent Protein (GFP) was also performed. RESULTS: The OSCs showed mesenchymal features, as positive response to CD34, CD73 and CD90 antibodies and plasticity. Additionally, these cells have high proliferated rate, and they could be cultured through many passages and kept the ability to proliferate and differentiate after cryopreservation. The positive response to the transduction signalizes the possibility of cellular tracking in vivo. This is a desirable feature in case those cells are used for pre-clinical trials. CONCLUSION: The cells harvested were mesenchymal stem cells and the technique described is therefore efficient for rabbit olfactory stem cells isolation.