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Increasing the proportion of locally produced plant protein in currently meat-rich diets could substantially reduce greenhouse gas emissions and loss of biodiversity1. However, plant protein production is hampered by the lack of a cool-season legume equivalent to soybean in agronomic value2. Faba bean (Vicia faba L.) has a high yield potential and is well suited for cultivation in temperate regions, but genomic resources are scarce. Here, we report a high-quality chromosome-scale assembly of the faba bean genome and show that it has expanded to a massive 13 Gb in size through an imbalance between the rates of amplification and elimination of retrotransposons and satellite repeats. Genes and recombination events are evenly dispersed across chromosomes and the gene space is remarkably compact considering the genome size, although with substantial copy number variation driven by tandem duplication. Demonstrating practical application of the genome sequence, we develop a targeted genotyping assay and use high-resolution genome-wide association analysis to dissect the genetic basis of seed size and hilum colour. The resources presented constitute a genomics-based breeding platform for faba bean, enabling breeders and geneticists to accelerate the improvement of sustainable protein production across the Mediterranean, subtropical and northern temperate agroecological zones.
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Produtos Agrícolas , Diploide , Variação Genética , Genoma de Planta , Genômica , Melhoramento Vegetal , Proteínas de Plantas , Vicia faba , Cromossomos de Plantas/genética , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Variações do Número de Cópias de DNA/genética , DNA Satélite/genética , Amplificação de Genes/genética , Genes de Plantas/genética , Variação Genética/genética , Genoma de Planta/genética , Estudo de Associação Genômica Ampla , Geografia , Melhoramento Vegetal/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Recombinação Genética , Retroelementos/genética , Sementes/anatomia & histologia , Sementes/genética , Vicia faba/anatomia & histologia , Vicia faba/genética , Vicia faba/metabolismoRESUMO
BACKGROUND: Although diagnostic instability in first-episode psychosis (FEP) is of major concern, little is known about its determinants. This very long-term follow-up study aimed to examine the diagnostic stability of FEP diagnoses, the baseline predictors of diagnostic change and the timing of diagnostic change. METHODS: This was a longitudinal and naturalistic study of 243 subjects with FEP who were assessed at baseline and reassessed after a mean follow-up of 21 years. The diagnostic stability of DSM-5 psychotic disorders was examined using prospective and retrospective consistencies, logistic regression was used to establish the predictors of diagnostic change, and survival analysis was used to compare time to diagnostic change across diagnostic categories. RESULTS: The overall diagnostic stability was 47.7%. Schizophrenia and bipolar disorder were the most stable diagnoses, with other categories having low stability. Predictors of diagnostic change to schizophrenia included a family history of schizophrenia, obstetric complications, developmental delay, poor premorbid functioning in several domains, long duration of untreated continuous psychosis, spontaneous dyskinesia, lack of psychosocial stressors, longer duration of index admission, and poor early treatment response. Most of these variables also predicted diagnostic change to bipolar disorder but in the opposite direction and with lesser effect sizes. There were no significant differences between specific diagnoses regarding time to diagnostic change. At 10-year follow-up, around 80% of the diagnoses had changed. CONCLUSIONS: FEP diagnoses other than schizophrenia or bipolar disorder should be considered as provisional. Considering baseline predictors of diagnostic change may help to enhance diagnostic accuracy and guide therapeutic interventions.
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Transtornos Psicóticos , Esquizofrenia , Humanos , Seguimentos , Estudos Retrospectivos , Estudos Prospectivos , Transtornos Psicóticos/psicologia , Esquizofrenia/diagnósticoRESUMO
BACKGROUND: Evidence suggests a possible relationship between exposure to childhood adversity (CA) and functional impairment in psychosis. However, the impact of CA on long-term outcomes of psychotic disorders remains poorly understood. METHODS: Two hundred and forty-three patients were assessed at their first episode of psychosis for CA and re-assessed after a mean of 21 years of follow-up for several outcome domains, including symptoms, functioning, quality of life, cognitive performance, neurological dysfunction, and comorbidity. The unique predictive ability of CA exposure for outcomes was examined using linear regression analysis controlling for relevant confounders, including socioeconomic status, family risk of schizophrenia, and obstetric complications. RESULTS: There were 54% of the patients with a documented history of CA at mild or higher levels. CA experiences were more prevalent and severe in schizophrenia than in other psychotic disorders (p < 0.001). Large to very large effect sizes were observed for CA predicting most role functioning variables and negative symptoms (ΔR2 between 0.105 and 0.181). Moderate effect sizes were observed for positive symptoms, personal functioning, impaired social cognition, impaired immediate verbal learning, poor global cognition, internalized stigma, poor personal recovery, and drug abuse severity (ΔR2 between 0.040 and 0.066). A dose-response relationship was observed between levels of CA and severity of outcome domains. CONCLUSION: Our results suggest a strong and widespread link between early adversity exposure and outcomes of psychotic disorders. Awareness of the serious long-term consequences of CA should encourage better identification of those at risk and the development of effective interventions.
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BACKGROUND: First-episode psychotic disorders comprise a heterogeneous phenotype with a complex etiology involving numerous common small-effect genetic variations and a wide range of environmental exposures. We examined whether a family of schizophrenia spectrum disorder (FH-Sz) interacts with an environmental risk score (ERS-Sz) regarding the outcome of patients with non-affective first episode psychosis (NAFEP). METHODS: We included 288 patients with NAFEP who were evaluated after discharge from an intensive 2-year program. We evaluated three outcome measures: symptomatic remission, psychosocial functioning, and personal recovery. We analyzed the main and joint associations of a FH-Sz and the ERS-Sz on the outcomes by using the relative excess risk due to interaction (RERI) approach. RESULTS: A FH-Sz showed a significant association with poor symptomatic remission and psychosocial functioning outcomes, although there was no significant interaction between a FH-Sz and the ERS-Sz on these outcomes. The ERS-Sz did not show a significant association with poor symptomatic remission and psychosocial functioning outcomes, even though the magnitude of the interaction between ERS-Sz and FH-Sz with the later outcome was moderate (RERI = 6.89, 95% confidence interval -16.03 to 29.81). There was no association between a FH-Sz and the ERS-Sz and personal recovery. CONCLUSIONS: Our results provide further empirical support regarding the contribution of FH-Sz to poor symptomatic remission and poor psychosocial functioning outcomes in patients with NAFEP.
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BACKGROUND: Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances. METHODS: We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis-Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups. RESULTS: FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio. CONCLUSIONS: Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.
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Disfunção Cognitiva , Transtornos Psicóticos , Esquizofrenia , Gravidez , Feminino , Humanos , Transtornos Psicóticos/diagnóstico , Esquizofrenia/complicações , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: Little is known about the relationship between social exclusion and cognitive impairment in psychosis. We conducted a long-term cohort study of first-episode psychosis to examine the association between comprehensive measures of cognitive impairment and social exclusion assessed at follow-up. METHODS: A total of 173 subjects with first-episode psychosis were assessed after a 20-year follow-up for 7 cognitive domains and 12 social exclusion indicators. Associations between sets of variables were modeled using multivariate regression, where social exclusion indicators were the dependent variables, cognitive domains were the independent variables, and age, gender, and duration of follow-up were covariates. RESULTS: The total scores on the measures of cognition and social exclusion were strongly associated (ß = - .469, ∆R2 = 0.215). Participants with high social exclusion were 4.24 times more likely to have cognitive impairment than those with low social exclusion. Verbal learning was the cognitive function most related to social exclusion domains, and legal capacity was the exclusion domain that showed the strongest relationships with individual cognitive tests. Neurocognition uniquely contributed to housing, work activity, income, and educational attainment, whereas social cognition uniquely contributed to neighborhood deprivation, family and social contacts, and discrimination/stigma. Neurocognition explained more unique variance (11.5%) in social exclusion than social cognition (5.5%). CONCLUSION: The domains of cognitive impairment were strongly and differentially related to those of social exclusion. Given that such an association pattern is likely bidirectional, a combined approach, both social and cognitive, is of paramount relevance in addressing the social exclusion experienced by individuals with psychotic disorders.
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PURPOSE: People with psychotic disorders have high levels of social exclusion; however, little is known about its early predictors. We present a long-term observational cohort study aimed at examining early risk factors for later social exclusion. METHODS: A total of 243 subjects were assessed at their first psychotic episode for early risk factors including sociodemographic variables, familial risk of major mental disorders, perinatal complications, childhood factors, and adolescent factors and re-assessed after a mean follow-up of 21 years for 12 social exclusion domains: leisure activities, housing, work, income, neighborhood deprivation, educational attainment, physical and mental health, family and social support, legal competence, and discrimination. The ability of risk factors to predict social exclusion was examined using hierarchical linear regression. RESULTS: Overall social exclusion was independently predicted by low parental socio-economic status, length of follow-up, familial risk of schizophrenia, obstetric complications, neurodevelopmental delay, poor childhood adjustment, childhood adversity, poor adolescent social networks, poor adolescent adjustment, and low premorbid IQ. The model explained 58.2% of the variance in total social exclusion score. Each social exclusion domain was predicted by a different set of variables, which explained between 17.8 and 57.0% of their variance, although low socio-economic status, familial risk of schizophrenia, obstetric complications, childhood adversity, and poor social networks predicted most of the social exclusion domains. CONCLUSION: Early risk factors strongly predicted later social exclusion. A multifaceted approach to preventing later social exclusion is crucial in people with a first episode of psychosis and early risk factors of social exclusion.
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Hepatocellular carcinoma (HCC) is the most common primary liver tumor and is associated with high mortality rates. Approximately 80% of cases occur in cirrhotic livers, posing a significant challenge for appropriate therapeutic management. Adequate screening programs in high-risk groups are essential for early-stage detection. The extent of extrahepatic tumor spread and hepatic functional reserve are recognized as two of the most influential prognostic factors. In this retrospective multicenter study, we utilized machine learning (ML) methods to analyze predictors of mortality at the time of diagnosis in a total of 208 patients. The eXtreme gradient boosting (XGB) method achieved the highest values in identifying key prognostic factors for HCC at diagnosis. The etiology of HCC was found to be the variable most strongly associated with a poorer prognosis. The widely used Barcelona Clinic Liver Cancer (BCLC) classification in our setting demonstrated superiority over the TNM classification. Although alpha-fetoprotein (AFP) remains the most commonly used biological marker, elevated levels did not correlate with reduced survival. Our findings suggest the need to explore new prognostic biomarkers for individualized management of these patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Aprendizado de Máquina , alfa-Fetoproteínas , Humanos , alfa-Fetoproteínas/química , Biomarcadores Tumorais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
The vascular endothelial growth factor-A (VEGFA) system is a complex set of proteins, with multiple isoforms and receptors, including both angiogenic (VEGFxxx, VEGFR2) and antiangiogenic members (VEGFxxxb, VEGFR1 and soluble forms of VEGFR). The members of the VEGF system affect the proliferation, survival, and migration of endothelial and nonendothelial cells and are involved in the regulation of follicular angiogenesis and development. The production of VEGF by secondary follicles stimulates preantral follicular development by directly affecting follicular cells and promoting the acquisition of the follicular vasculature and downstream antrum formation. Additionally, the pattern of expression of the components of the VEGF system may provide a proangiogenic milieu capable of triggering angiogenesis and stimulating follicular cells to promote antral follicle growth, whereas, during atresia, this milieu becomes antiangiogenic and blocks follicular development.
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Folículo Ovariano , Fator A de Crescimento do Endotélio Vascular , Feminino , Humanos , Folículo Ovariano/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo , Isoformas de Proteínas/metabolismoRESUMO
BACKGROUND: There is strong evidence supporting the association between environmental factors and increased risk of non-affective psychotic disorders. However, the use of sound statistical methods to account for spatial variations associated with environmental risk factors, such as urbanicity, migration, or deprivation, is scarce in the literature. METHODS: We studied the geographical distribution of non-affective first-episode psychosis (NA-FEP) in a northern region of Spain (Navarra) during a 54-month period considering area-level socioeconomic indicators as putative explanatory variables. We used several Bayesian hierarchical Poisson models to smooth the standardized incidence ratios (SIR). We included neighborhood-level variables in the spatial models as covariates. RESULTS: We identified 430 NA-FEP cases over a 54-month period for a population at risk of 365,213 inhabitants per year. NA-FEP incidence risks showed spatial patterning and a significant ecological association with the migrant population, unemployment, and consumption of anxiolytics and antidepressants. The high-risk areas corresponded mostly to peripheral urban regions; very few basic health sectors of rural areas emerged as high-risk areas in the spatial models with covariates. DISCUSSION: Increased rates of unemployment, the migrant population, and consumption of anxiolytics and antidepressants showed significant associations linked to the spatial-geographic incidence of NA-FEP. These results may allow targeting geographical areas to provide preventive interventions that potentially address modifiable environmental risk factors for NA-FEP. Further investigation is needed to understand the mechanisms underlying the associations between environmental risk factors and the incidence of NA-FEP.
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Autofertility describes the ability of faba bean flowers to self-fertilize thereby ensuring the productivity of this crop in the absence of pollinators or mechanical disturbance. In the legume crop faba bean (Vicia faba L.), lack of autofertility in a context of insufficient pollination can lead to a severe decrease in grain yield. Here we performed the first QTL analysis aimed at identifying the genomic regions controlling autofertility in this crop. We combined pod and seed setting scores from a recombinant inbred population (RIL) segregating for autofertility in different environments and years with measurements of morphological floral traits and pollen production and viability. This approach revealed 19 QTLs co-localizing in six genomic regions. Extensive co-localization was evident for various floral features whose QTLs clustered in chrs. I, II and V, while other QTLs in chrs. III, IV and VI revealed co-localization of flower characteristics and pod and seed set data. The percentage of phenotypic variation explained by the QTLs ranged from 8.9 for style length to 25.7 for stigma angle. In the three QTLs explaining the highest phenotypic variation (R 2 > 20), the marker alleles derived from the autofertile line Vf27. We further inspected positional candidates identified by these QTLs which represent a valuable resource for further validation. Our results advance the understanding of autofertility in faba bean and will aid the identification of responsible genes for genomic-assisted breeding in this crop.
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Vicia faba , Mapeamento Cromossômico , Fenótipo , Melhoramento Vegetal , Locos de Características Quantitativas/genética , Vicia faba/genéticaRESUMO
Phenotype validation of endogenous psychosis is a problem that remains to be solved. This study investigated the neuropsychological performance of endogenous psychosis subtypes according to Wernicke-Kleist-Leonhard's classification system (WKL). The participants included consecutive admissions of patients with schizophrenia spectrum disorder or mood disorder with psychotic symptoms (N = 98) and healthy comparison subjects (N = 50). The patients were assessed by means of semi-structured interviews and diagnosed through the WKL system into three groups: a manic-depressive illness and cycloid psychosis group (MDC), unsystematic schizophrenia (USch) and systematic schizophrenia (SSch). All the participants completed a comprehensive neuropsychological battery. The three Leonhard's psychosis subtypes showed a common neuropsychological profile with differences in the severity of impairment relative to healthy controls. MDC patients showed better performance on premorbid intelligence, verbal memory and global cognitive index than USch and SSch patients, and they showed better performance on processing speed, and working memory than SSch patients. USch patients outperformed SSch patients in verbal memory, working memory and global cognitive index. Neuropsychological performance showed a modest accuracy for classification into the WKL nosology. Our results suggest the existence of a common profile of cognitive impairment cutting across WKL subtypes of endogenous psychosis but with significant differences on a severity continuum. In addition, classification accuracy in the three WKL subtypes by means of neuropsychological performance was modest, ranging between 40 and 64% of correctly classified patients.
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Transtorno Bipolar , Transtornos Psicóticos , Esquizofrenia , Transtorno Bipolar/psicologia , Humanos , Transtornos do Humor , Testes Neuropsicológicos , Fenótipo , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Esquizofrenia/diagnósticoRESUMO
Self-reported and interview-based measures can be considered coprimary measures of cognitive performance. We aimed to ascertain to what extent cognitive impairment in psychotic disorders, as assessed with a neuropsychological battery, is associated with subjective cognitive complaints compared to difficulties in daily activities caused by cognitive impairment. We assessed 114 patients who had a psychotic disorder with a set of neuropsychological tests and two additional measures: the Cognitive Assessment Interview-Spanish version (CAI-Sp) and the Frankfurt Complaint Questionnaire (FCQ). Patients also underwent a clinical assessment. The CAI-Sp correlated significantly with all the clinical dimensions, while the FCQ correlated only with positive and depressive symptoms. The CAI-Sp correlated significantly with all cognitive domains, except for verbal memory and social cognition. The FCQ was associated with attention, processing speed and working memory. The combination of manic and depressive symptoms and attention, processing speed, working memory and explained 38-46% of the variance in the patients' CAI-Sp. Education and negative symptoms, in combination with attention, processing speed, and executive functions, explained 54-59% of the CAI-Sp rater's variance. Only negative symptoms explained the variance in the CAI-Sp informant scores (37-42%). Depressive symptoms with attention and working memory explained 15% of the FCQ variance. The ability to detect cognitive impairment with the CAI-Sp and the FCQ opens the possibility to consider these instruments to approximate cognitive impairment in clinical settings due to their ease of application and because they are less time-consuming for clinicians.
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Disfunção Cognitiva , Transtornos Psicóticos , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Humanos , Testes Neuropsicológicos , Transtornos Psicóticos/complicações , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , AutorrelatoRESUMO
Living donor liver transplantation (LDLT) enjoys widespread use in Asia, but remains limited to a handful of centers in North America and comprises only 5% of liver transplants performed in the United States. In contrast, living donor kidney transplantation is used frequently in the United States, and has evolved to commonly include paired exchanges, particularly for ABO-incompatible pairs. Liver paired exchange (LPE) has been utilized in Asia, and was recently reported in Canada; here we report the first LPE performed in the United States, and the first LPE to be performed on consecutive days. The LPE performed at our institution was initiated by a nondirected donor who enabled the exchange for an ABO-incompatible pair, and the final recipient was selected from our deceased donor waitlist. The exchange was performed over the course of 2 consecutive days, and relied on the use and compliance of a bridge donor. Here, we show that LPE is feasible at centers with significant LDLT experience and affords an opportunity to expand LDLT in cases of ABO incompatibility or when nondirected donors arise. To our knowledge, this represents the first exchange of its kind in the United States.
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Transplante de Fígado , Doadores Vivos , Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Canadá , Humanos , América do NorteRESUMO
BACKGROUND: Ascochyta blight caused by Ascochyta fabae Speg. and broomrape (Orobanche crenata) are among the economically most significant pathogens of faba bean. Several QTLs conferring resistance against the two pathogens have been identified and validated in different genetic backgrounds. The aim of this study was to saturate the most stable QTLs for ascochyta and broomrape resistance in two Recombinant Inbred Line (RIL) populations, 29H x Vf136 and Vf6 x Vf136, to identify candidate genes conferring resistance against these two pathogens. RESULTS: We exploited the synteny between faba bean and the model species Medicago truncatula by selecting a set of 219 genes encoding putative WRKY transcription factors and defense related proteins falling within the target QTL intervals, for genotyping and marker saturation in the two RIL populations. Seventy and 50 of the candidate genes could be mapped in 29H x Vf136 and Vf6 x Vf136, respectively. Besides the strong reduction of the QTL intervals, the mapping process allowed replacing previous dominant and pedigree-specific RAPD flanking markers with robust and transferrable SNP markers, revealing promising candidates for resistance against the two pathogens. CONCLUSIONS: Although further efforts in association mapping and expression studies will be required to corroborate the candidate genes for resistance, the fine-mapping approach proposed here increases the genetic resolution of relevant QTL regions and paves the way for an efficient deployment of useful alleles for faba bean ascochyta and broomrape resistance through marker-assisted breeding.
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Ascomicetos/patogenicidade , Resistência à Doença/genética , Medicago truncatula/genética , Orobanche/parasitologia , Locos de Características Quantitativas , Vicia faba/genética , Vicia faba/microbiologia , Vicia faba/parasitologia , Produtos Agrícolas/genética , Produtos Agrícolas/microbiologia , Produtos Agrícolas/parasitologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Marcadores Genéticos , Variação Genética , SinteniaRESUMO
BACKGROUND: Previous literature supports antipsychotics' (AP) efficacy in acute first-episode psychosis (FEP) in terms of symptomatology and functioning but also a cognitive detrimental effect. However, regarding functional recovery in stabilised patients, these effects are not clear. Therefore, the main aim of this study is to investigate dopaminergic/anticholinergic burden of (AP) on psychosocial functioning in FEP. We also examined whether cognitive impairment may mediate these effects on functioning. METHODS: A total of 157 FEP participants were assessed at study entry, and at 2 months and 2 years after remission of the acute episode. The primary outcomes were social functioning as measured by the functioning assessment short test (FAST). Cognitive domains were assessed as potential mediators. Dopaminergic and anticholinergic AP burden on 2-year psychosocial functioning [measured with chlorpromazine (CPZ) and drug burden index] were independent variables. Secondary outcomes were clinical and socio-demographic variables. RESULTS: Mediation analysis found a statistical but not meaningful contribution of dopaminergic receptor blockade burden to worse functioning mediated by cognition (for every 600 CPZ equivalent points, 2-year FAST score increased 1.38 points). Regarding verbal memory and attention, there was an indirect effect of CPZ burden on FAST (b = 0.0045, 95% CI 0.0011-0.0091) and (b = 0.0026, 95% CI 0.0001-0.0006) respectively. However, only verbal memory post hoc analyses showed a significant indirect effect (b = 0.009, 95% CI 0.033-0.0151) adding premorbid IQ as covariate. We did not find significant results for anticholinergic burden. CONCLUSION: CPZ dose effect over functioning is mediated by verbal memory but this association appears barely relevant.
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Antipsicóticos , Transtornos Psicóticos , Humanos , Antipsicóticos/efeitos adversos , Funcionamento Psicossocial , Memória , Clorpromazina , Antagonistas Colinérgicos/efeitos adversos , Testes NeuropsicológicosRESUMO
BACKGROUND: Motor abnormalities (MAs) are the primary manifestations of schizophrenia. However, the extent to which MAs are related to alterations of subcortical structures remains understudied. METHODS: We aimed to investigate the associations of MAs and basal ganglia abnormalities in first-episode psychosis (FEP) and healthy controls. Magnetic resonance imaging was performed on 48 right-handed FEP and 23 age-, gender-, handedness-, and educational attainment-matched controls, to obtain basal ganglia shape analysis, diffusion tensor imaging techniques (fractional anisotropy and mean diffusivity), and relaxometry (R2*) to estimate iron load. A comprehensive motor battery was applied including the assessment of parkinsonism, catatonic signs, and neurological soft signs (NSS). A fully automated model-based segmentation algorithm on 1.5T MRI anatomical images and accurate corregistration of diffusion and T2* volumes and R2* was used. RESULTS: FEP patients showed significant local atrophic changes in left globus pallidus nucleus regarding controls. Hypertrophic changes in left-side caudate were associated with higher scores in sensory integration, and in right accumbens with tremor subscale. FEP patients showed lower fractional anisotropy measures than controls but no significant differences regarding mean diffusivity and iron load of basal ganglia. However, iron load in left basal ganglia and right accumbens correlated significantly with higher extrapyramidal and motor coordination signs in FEP patients. CONCLUSIONS: Taken together, iron load in left basal ganglia may have a role in the emergence of extrapyramidal signs and NSS of FEP patients and in consequence in the pathophysiology of psychosis.
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Gânglios da Base/fisiopatologia , Processamento de Imagem Assistida por Computador , Agitação Psicomotora/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Adulto , Atrofia , Encéfalo , Imagem de Tensor de Difusão , Feminino , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Negative symptoms are a core dimension of schizophrenia and other psychoses that account for a large degree of the poor functional outcomes related to these disorders. Newer assessment scales for negative symptoms, such as the Clinical Assessment Interview for Negative Symptoms (CAINS), provide evidence for separate dimensions of motivational and pleasure (MAP) and expression (EXP) dimensions. This study was aimed at extending the analysis of the clinical, functional and cognitive correlates of CAINS dimensions in a sample of patients with psychotic disorders (n = 98) and 50 healthy controls.A psychopathological evaluation was conducted by using the Comprehensive Assessment of Symptoms and History (CASH). To assess the extrapyramidal signs, the UKU scale was used. Community functioning was evaluated by means of real-world and functional attainment measures. Additionally, a full neuropsychological test battery was administered. Pearson correlation and hierarchical multiple linear regression analyses were performed to identify the influencing and predictive factors associated with the CAINS dimensions.The MAP and EXP dimensions showed strong associations with the Scale for the Assessment of Negative Symptoms (SANS) items and were not significantly associated with extra-pyramidal or cognitive deficits. The MAP and EXP CAINS dimensions revealed good predictive validity for real-world functioning and functional attainment measures.These findings suggest that the CAINS scale endorses good convergent validity for the assessment of negative symptoms and is very useful in the prediction of psychosocial functioning. In addition, the CAINS dimensions might provide advantages over old assessment scales on disentangling the complex associations between negative symptoms and cognitive impairment.
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Transtornos Psicóticos , Estudos de Casos e Controles , Cognição/fisiologia , Estado Funcional , Humanos , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Fatores de RiscoRESUMO
Trypanosoma cruzi infection in women of reproductive age is associated with congenital transmission and adverse pregnancy outcomes. The placenta is a key barrier to infection. Gene expression profiles of term placental environment from T. cruzi-seropositive (SP) and -seronegative (SN) mothers were characterized by RNA-Seq. Nine pools of placental RNA paired samples were used: three from SN and six from SP tissues. Each pool consisted of female/male newborns and vaginal/cesarean delivery binomials. No newborn was congenitally infected. T. cruzi satellite DNA quantitative PCR in placental tissues and maternal and neonatal blood, and parasite 18S quantitative RT-PCR from placental RNA were negative, except in three SP women's bloodstream. To identify pathways associated with maternal T. cruzi infection, a gene-set association analysis was implemented: SP placental samples showed overexpression of inflammatory response and lymphocytic activation, whereas numerous biosynthetic processes were down-regulated. About 42 genes showed a significant fold-change between SP and SN groups. KISS1 and CGB5 were down-regulated, whereas KIF12, HLA-G, PRG2, TAC3, FN1, and ATXN3L were up-regulated. Several expressed genes in SP placentas encode proteins associated with preeclampsia and miscarriage. This first transcriptomics study in human term placental environment shows a placental response that may affect the fetus while protecting it from parasite infection; this host response could be responsible for the low rate of congenital transmission in chronic Chagas disease.
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Doença de Chagas/genética , Feto/metabolismo , Regulação da Expressão Gênica , Placenta/metabolismo , Complicações Infecciosas na Gravidez/genética , Trypanosoma cruzi/genética , Adolescente , Adulto , Doença de Chagas/complicações , Doença de Chagas/parasitologia , Feminino , Feto/parasitologia , Perfilação da Expressão Gênica , Humanos , Recém-Nascido , Masculino , Placenta/parasitologia , Gravidez , Complicações Infecciosas na Gravidez/parasitologia , Adulto JovemRESUMO
BACKGROUND: Cognitive deficits are a core feature of early stages in schizophrenia. However, the extent to which antipsychotic (AP) have a deleterious effect on cognitive performance remains under debate. We aim to investigate whether anticholinergic loadings and dose of AP drugs in first episode of psychosis (FEP) in advanced phase of remission are associated with cognitive impairment and the differences between premorbid intellectual quotient (IQ) subgroups. METHODS: Two hundred and sixty-six patients participated. The primary outcomes were cognitive dimensions, dopaminergic/anticholinergic load of AP [in chlorpromazine equivalents (Eq-CPZ) and the Anticholinergic Risk Scale (ARS), respectively]. RESULTS: Impairments in processing speed, verbal memory and global cognition were significantly associated with high Eq-CPZ and verbal impairment with high ARS score. Moreover, this effect was higher in the low IQ subgroup. CONCLUSIONS: Clinicians should be aware of the potential cognitive impairment associated with AP in advanced remission FEP, particularly in lower premorbid IQ patients.