RESUMO
BACKGROUND: Psychosis is related to neurochemical changes in deep-brain nuclei, particularly suggesting dopamine dysfunctions. We used an magnetic resonance imaging-based technique called quantitative susceptibility mapping (QSM) to study these regions in psychosis. QSM quantifies magnetic susceptibility in the brain, which is associated with iron concentrations. Since iron is a cofactor in dopamine pathways and co-localizes with inhibitory neurons, differences in QSM could reflect changes in these processes. METHODS: We scanned 83 patients with first-episode psychosis and 64 healthy subjects. We reassessed 22 patients and 21 control subjects after 3 months. Mean susceptibility was measured in 6 deep-brain nuclei. Using linear mixed models, we analyzed the effect of case-control differences, region, age, gender, volume, framewise displacement (FD), treatment duration, dose, laterality, session, and psychotic symptoms on QSM. RESULTS: Patients showed a significant susceptibility reduction in the putamen and globus pallidus externa (GPe). Patients also showed a significant R2* reduction in GPe. Age, gender, FD, session, group, and region are significant predictor variables for QSM. Dose, treatment duration, and volume were not predictor variables of QSM. CONCLUSIONS: Reduction in QSM and R2* suggests a decreased iron concentration in the GPe of patients. Susceptibility reduction in putamen cannot be associated with iron changes. Since changes observed in putamen and GPe were not associated with symptoms, dose, and treatment duration, we hypothesize that susceptibility may be a trait marker rather than a state marker, but this must be verified with long-term studies.
Assuntos
Dopamina , Transtornos Psicóticos , Humanos , Encéfalo/metabolismo , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Ferro/metabolismo , Transtornos Psicóticos/diagnóstico por imagemRESUMO
BACKGROUND AND HYPOTHESIS: Abnormal functional connectivity between brain regions is a consistent finding in schizophrenia, including functional magnetic resonance imaging (fMRI) studies. Recent studies have highlighted that connectivity changes in time in healthy subjects. We here examined the temporal changes in functional connectivity in patients with a first episode of psychosis (FEP). Specifically, we analyzed the temporal order in which whole-brain organization states were visited. STUDY DESIGN: Two case-control studies, including in each sample a subgroup scanned a second time after treatment. Chilean sample included 79 patients with a FEP and 83 healthy controls. Mexican sample included 21 antipsychotic-naïve FEP patients and 15 healthy controls. Characteristics of the temporal trajectories between whole-brain functional connectivity meta-states were examined via resting-state functional MRI using elements of network science. We compared the cohorts of cases and controls and explored their differences as well as potential associations with symptoms, cognition, and antipsychotic medication doses. STUDY RESULTS: We found that the temporal sequence in which patients' brain dynamics visited the different states was more redundant and segregated. Patients were less flexible than controls in changing their network in time from different configurations, and explored the whole landscape of possible states in a less efficient way. These changes were related to the dose of antipsychotics the patients were receiving. We replicated the relationship with antipsychotic medication in the antipsychotic-naïve FEP sample scanned before and after treatment. CONCLUSIONS: We conclude that psychosis is related to a temporal disorganization of the brain's dynamic functional connectivity, and this is associated with antipsychotic medication use.
Assuntos
Antipsicóticos , Transtornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Imageamento por Ressonância MagnéticaRESUMO
22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental disorder that represents one of the greatest known risk factors for psychosis. Previous studies in psychotic subjects without the deletion have identified a dopaminergic dysfunction in striatal regions, and dysconnectivity of striatocortical systems, as an important mechanism in the emergence of psychosis. Here, we used resting-state functional MRI to examine striatocortical functional connectivity in 22q11.2DS patients. We used a 2 × 2 factorial design including 125 subjects (55 healthy controls, 28 22q11.2DS patients without a history of psychosis, 10 22q11.2DS patients with a history of psychosis, and 32 subjects with a history of psychosis without the deletion), allowing us to identify network effects related to the deletion and to the presence of psychosis. In line with previous results from psychotic patients without 22q11.2DS, we found that there was a dorsal to ventral gradient of hypo- to hyperstriatocortical connectivity related to psychosis across both patient groups. The 22q11.2DS was additionally associated with abnormal functional connectivity in ventral striatocortical networks, with no significant differences identified in the dorsal system. Abnormalities in the ventral striatocortical system observed in these individuals with high genetic risk to psychosis may thus reflect a marker of illness risk.
Assuntos
Síndrome de DiGeorge/complicações , Estriado Ventral/fisiopatologia , Adolescente , Síndrome de DiGeorge/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Testes de Estado Mental e Demência/estatística & dados numéricos , Estriado Ventral/anatomia & histologia , Adulto JovemRESUMO
BACKGROUND: Evidence suggests the incidence of non-affective psychotic disorders (NAPDs) varies across persons and places, but data from the Global South is scarce. We aimed to estimate the treated incidence of NAPD in Chile, and variance by person, place and time. METHODS: We used national register data from Chile including all people, 10-65 years, with the first episode of NAPD (International Classification of Diseases, Tenth Revision: F20-F29) between 1 January 2005 and 29 August 2018. Denominators were estimated from Chilean National Census data. Our main outcome was treated incidence of NAPD and age group, sex, calendar year and regional-level population density, multidimensional poverty and latitude were exposures of interest. RESULTS: We identified 32 358 NAPD cases [12 136 (39.5%) women; median age-at-first-contact: 24 years (interquartile range 18-39 years)] during 171.1 million person-years [crude incidence: 18.9 per 100 000 person-years; 95% confidence interval (CI) 18.7-19.1]. Multilevel Poisson regression identified a strong age-sex interaction in incidence, with rates peaking in men (57.6 per 100 000 person-years; 95% CI 56.0-59.2) and women (29.5 per 100 000 person-years; 95% CI 28.4-30.7) between 15 and 19 years old. Rates also decreased (non-linearly) over time for women, but not men. We observed a non-linear association with multidimensional poverty and latitude, with the highest rates in the poorest regions and those immediately south of Santiago; no association with regional population density was observed. CONCLUSION: Our findings inform the aetiology of NAPDs, replicating typical associations with age, sex and multidimensional poverty in a Global South context. The absence of association with population density suggests this risk may be context-dependent.
Assuntos
Transtornos Psicóticos , Adolescente , Adulto , Transtornos Psicóticos Afetivos , Chile/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pobreza , Transtornos Psicóticos/psicologia , Adulto JovemRESUMO
The 22q11 deletion syndrome is a genetic disorder associated with a high risk of developing psychosis, and is therefore considered a neurodevelopmental model for studying the pathogenesis of schizophrenia. Studies have shown that localized abnormal functional brain connectivity is present in 22q11 deletion syndrome like in schizophrenia. However, it is less clear whether these abnormal cortical interactions lead to global or regional network disorganization as seen in schizophrenia. We analyzed from a graph-theory perspective fMRI data from 40 22q11 deletion syndrome patients and 67 healthy controls, and reconstructed functional networks from 105 brain regions. Between-group differences were examined by evaluating edge-wise strength and graph theoretical metrics of local (weighted degree, nodal efficiency, nodal local efficiency) and global topological properties (modularity, local and global efficiency). Connectivity strength was globally reduced in patients, driven by a large network comprising 147 reduced connections. The 22q11 deletion syndrome network presented with abnormal local topological properties, with decreased local efficiency and reductions in weighted degree particularly in hub nodes. We found evidence for abnormal integration but intact segregation of the 22q11 deletion syndrome network. Results suggest that 22q11 deletion syndrome patients present with similar aberrant local network organization as seen in schizophrenia, and this network configuration might represent a vulnerability factor to psychosis.
Assuntos
Síndrome da Deleção 22q11/patologia , Conectoma/estatística & dados numéricos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia , Descanso/fisiologia , Síndrome da Deleção 22q11/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Adulto JovemRESUMO
INTRODUCTION: Little is known about predictors of clinical response to clozapine treatment in treatment-resistant psychosis. Most published cohorts are small, providing inconsistent results. We aimed to identify baseline clinical predictors of future clinical response in patients who initiate clozapine treatment, mainly focusing on the effect of age, duration of illness, baseline clinical symptoms and homelessness. METHODOLOGY: Retrospective cohort of patients with treatment-resistant schizophrenia, aged between 15 and 60â¯years, that initiated clozapine between 2014 and 2017. Sociodemographic characteristics, years from illness diagnosis, and clinical presentation before the initiation of clozapine were collected and analyzed. All-cause discontinuation at two years follow-up was used as the primary measure of clozapine response. RESULTS: 261 patients were included with a median age at illness diagnosis of 23â¯years old (IQR 19-29) and a median age at clozapine initiation of 25 (IQR: 21-33). 72.33% (183/253) continued clozapine after two years follow-up. Being homeless was associated to higher clozapine non-adherence, with an OR of 2.78 (95%CI 1.051-7.38) (pâ¯=â¯0.039, controlled by gender). Older age at clozapine initiation and longer delay from first schizophrenia diagnosis to clozapine initiation were also associated with higher clozapine non-adherence, with each year increasing the odds of discontinuation by 1.043 (95%CI 1.02-1.07; pâ¯=â¯0.001) and OR 1.092 (95%CI 1.01-1.18;pâ¯=â¯0.032) respectively. CONCLUSION: Starting clozapine in younger patients or shortly after schizophrenia diagnosis were associated with better adherence.
Assuntos
Antipsicóticos , Clozapina , Transtornos Psicóticos , Esquizofrenia , Adolescente , Adulto , Idoso , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Estudos Retrospectivos , Esquizofrenia/tratamento farmacológico , Adulto JovemRESUMO
Background: Cannabis use among young people in Chile has increased significantly in the last years. There is a consistent link between cannabis and psychosis. Aim: To compare cannabis use in patients with a first episode of psychosis and healthy controls. Material and Methods: We included 74 patients aged 20 ± 3 years (78% males) admitted to hospital with a first episode of psychosis and a group of 60 healthy controls aged 23 ± 4 years (63% males). Cannabis consumption was assessed, including age of first time use and length of regular use. Results: Patients with psychosis reported a non-significantly higher frequency of life-time cannabis use. Patients had longer periods of regular cannabis use compared with healthy subjects (Odds ratio [OR] 2.4; 95% confi-dence intervals [CI] 1.14-5.05). Patients also used cannabis for the first time at an earlier age (16 compared with 17 years, p < 0.0). The population attributable fraction for regular cannabis use associated with hospital admissions due to psychosis was 17.7% (95% CI 1.2-45.5%). Conclusions: Cannabis use is related to psychosis in this Chilean group of patients. This relationship is stronger in patients with early exposure to the drug and longer the regular use. One of every five admissions due to psychosis is associated with cannabis consumption. These data should influence cannabis legisla-tion and the public policies currently being discussed in Chile.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Transtornos Psicóticos , Cannabis , Transtornos Psicóticos/epidemiologia , Estudos de Casos e Controles , Chile/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Cannabis use among young people in Chile has increased significantly in the last years. There is a consistent link between cannabis and psychosis. AIM: To compare cannabis use in patients with a first episode of psychosis and healthy controls. MATERIAL AND METHODS: We included 74 patients aged 20 ± 3 years (78% males) admitted to hospital with a first episode of psychosis and a group of 60 healthy controls aged 23 ± 4 years (63% males). Cannabis consumption was assessed, including age of first time use and length of regular use. RESULTS: Patients with psychosis reported a non-significantly higher frequency of life-time cannabis use. Patients had longer periods of regular cannabis use compared with healthy subjects (Odds ratio [OR] 2.4; 95% confi-dence intervals [CI] 1.14-5.05). Patients also used cannabis for the first time at an earlier age (16 compared with 17 years, p < 0.0). The population attributable fraction for regular cannabis use associated with hospital admissions due to psychosis was 17.7% (95% CI 1.2-45.5%). CONCLUSIONS: Cannabis use is related to psychosis in this Chilean group of patients. This relationship is stronger in patients with early exposure to the drug and longer the regular use. One of every five admissions due to psychosis is associated with cannabis consumption. These data should influence cannabis legisla-tion and the public policies currently being discussed in Chile.
Assuntos
Cannabis , Transtornos Psicóticos , Adolescente , Adulto , Estudos de Casos e Controles , Chile/epidemiologia , Feminino , Humanos , Masculino , Transtornos Psicóticos/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
AIM: Studies conducted in the United States have highlighted a higher prevalence of metabolic alterations (MA) in Latino population and Latino psychotic patients. Metabolic risk in psychosis is known to be present from initial stages of the disease. To better characterize this population, we explored the prevalence of MA and metabolic syndrome (MS) in early psychosis patients in a Latin American country. METHODS: Transversal, observational study comparing the prevalence of MA and MS in patients with early psychosis from an outpatient program in Chile (n = 148) with a community representative sample from the 2009-2010 National Health Survey (n = 568). ANOVA and regression analysis were performed obtaining odds ratio for MA and MS. RESULTS: The prevalence of MS was 44.7% in patients compared to 11.4% in the community sample (odds ratio [OR] 5.28, confidence interval [CI] 95% 3.07-9.08; P-value <0.001). There was no effect of gender. Subgroup analyses showed no significant association of MS with clozapine/olanzapine use, treatment duration or tobacco use. There was an association between treatment duration and hypertriglyceridemia (P = 0.024; OR 1.02, CI 95% 1.00-1.04) and obesity (P = 0.007; OR 5.93, CI 95% 1.82-20.22). Clozapine/olanzapine use was associated with hyperglycaemia (P = 0.007; OR 6.04, CI 95% 1.63-22.38) and high low density lipoprotein (P = 0.033 ANOVA; OR 5.28, CI 95% 1.14-24.37). CONCLUSION: Latino psychotic patients have a high risk of MA and MS at initial stages of the disease which is not entirely explained by the higher risk in the whole Latino population, is irrespective of gender, and does not seem to be entirely a response to atypical antipsychotic use.
Assuntos
Antipsicóticos/efeitos adversos , Síndrome Metabólica/epidemiologia , Transtornos Psicóticos/epidemiologia , Adolescente , Chile/epidemiologia , Comorbidade , Feminino , Humanos , América Latina , Masculino , Síndrome Metabólica/induzido quimicamente , Prevalência , Transtornos Psicóticos/diagnóstico , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Failure to respond to antipsychotic medication in schizophrenia is a common clinical scenario with significant morbidity. Recent studies have highlighted that many patients present treatment-resistance from disease onset. We here present an analysis of clozapine prescription patterns, used as a real-world proxy marker for treatment-resistance, in a cohort of 1195 patients with schizophrenia from a Latin-American cohort, to explore the timing of emergence of treatment resistance and possible subgroup differences. METHODS: Survival analysis from national databases of clozapine monitoring system, national disease notification registers, and discharges from an early intervention ward. RESULTS: Echoing previous studies, we found that around 1 in 5 patients diagnosed with schizophrenia were eventually prescribed clozapine, with an over-representation of males and those with a younger onset of psychosis. The annual probability of being prescribed clozapine was highest within the first year (probability of 0.11, 95% confidence interval of 0.093-0.13), compared to 0.018 (0.012-0.024) between years 1 and 5, and 0.006 (0-0.019) after 5years. Age at psychosis onset, gender, dose of clozapine used, and compliance with hematological monitoring at 12months, was not related to the onset of treatment resistance. A similar pattern was observed in a subgroup of 230 patients discharged from an early intervention ward with a diagnosis of non-affective first episode of psychosis. CONCLUSIONS: Our results highlight that treatment resistance is frequently present from the onset of psychosis. Future studies will shed light on the possible different clinical and neurobiological characteristics of this subtype of psychosis.