Browsing by Author "González, Alfonso"
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Publication Differences of affective and non-affective psychoses in early intervention services from Latin America(2022) Cerqueira, Raphael; Ziebold, Carolina; Cavalcante, Daniel; Oliveira, Giovany; Vásquez, Javiera; Undurraga, Juan; González, Alfonso; Nachar, Ruben; López, Carlos; Noto, Cristiano; Crossley, Nicolas; Gadelha, AryBackground: Psychosis presentation can be affected by genetic and environmental factors. Differentiating between affective and non-affective psychosis (A-FEP and NA-FEP, respectively) may influence treatment decisions and clinical outcomes. The objective of this paper is to examine differences between patients with A-FEP or NA-FEP in a Latin American sample. Methods: Patients from two cohorts of patients with a FEP recruited from Brazil and Chile. Subjects included were aged between 15 and 30 years, with an A-FEP or NA-FEP (schizophrenia-spectrum disorders) according to DSM-IV-TR. Sociodemographic data, duration of untreated psychosis and psychotic/mood symptoms were assessed. Generalized estimating equation models were used to assess clinical changes between baseline-follow-up according to diagnosis status. Results: A total of 265 subjects were included. Most of the subjects were male (70.9 %), mean age was 21.36 years. A-FEP and NA-FEP groups were similar in almost all sociodemographic variables, but A-FEP patients had a higher probability of being female. At baseline, the A-FEP group had more manic symptoms and a steeper reduction in manic symptoms scores during the follow- up. The NA-FEP group had more negative symptoms at baseline and a higher improvement during follow-up. All domains of The Positive and Negative Syndrome Scale improved for both groups. No difference for DUP and depression z-scores at baseline and follow-up. Limitations: The sample was recruited at tertiary hospitals, which may bias the sample towards more severe cases. Conclusions: This is the largest cohort comparing A-FEP and NA-FEP in Latin America. We found that features in FEP patients could be used to improve diagnosis and support treatment decisions.Publication Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis(2022) Ramírez, Juan; Tepper, Ángeles; Alliende, Luz; Mena, Carlos; Castañeda, Carmen; Iruretagoyena, Bárbara; Nachar, Ruben; Reyes, Francisco; León, Pablo; Mora, Ricardo; Ossandon, Tomas; González, Alfonso; Undurraga, Juan; De la Fuente, Camilo; Crossley, NicolasBackground 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.Item Effects of socioeconomic status in cognition of people with schizophrenia: results from a Latin American collaboration network with 1175 subjects(2021) Sanguinetti, Letícia; Alliende, Luz Maria; Castañeda, Carmen Paz; Castro, Mariana; Guinjoan, Salvador; Massuda, Raffael; Berberian, Arthur; Fonseca, Ana; Gadelha, Ary; Bressan, Rodrigo; Crivelaro, Marisa; Louzã, Mario; Undurraga, Juan; González, Alfonso; Nacha, Rubén; Nieto, Rodrigo; Montes, Cristian; Silva, Hernán; Langer, Álvaro; Schmidt, Carlos; Mayol, Rocío; Díaz, Ana; Valencia, Johanna; López, Carlos; Solís, Rodolfo; Reyes, Francisco; De la Fuente, Camilo; Crossley, Nicolás; Gama, ClarissaBackground. Cognition heavily relies on social determinants and genetic background. Latin America comprises approximately 8% of the global population and faces unique challenges, many derived from specific demographic and socioeconomic variables, such as violence and inequality. While such factors have been described to influence mental health outcomes, no large-scale studies with Latin American population have been carried out. Therefore, we aim to describe the cognitive performance of a representative sample of Latin American individuals with schizophrenia and its relationship to clinical factors. Additionally, we aim to investigate how socioeconomic status (SES) relates to cognitive performance in patients and controls. Methods. We included 1175 participants from five Latin American countries (Argentina, Brazil, Chile, Colombia, and Mexico): 864 individuals with schizophrenia and 311 unaffected subjects. All participants were part of projects that included cognitive evaluation with MATRICS Consensus Cognitive Battery and clinical assessments. Results. Patients showed worse cognitive performance than controls across all domains. Age and diagnosis were independent predictors, indicating similar trajectories of cognitive aging for both patients and controls. The SES factors of education, parental education, and income were more related to cognition in patients than in controls. Cognition was also influenced by symptomatology. Conclusions. Patients did not show evidence of accelerated cognitive aging; however, they were most impacted by a lower SES suggestive of deprived environment than controls. These findings highlight the vulnerability of cognitive capacity in individuals with psychosis in face of demographic and socioeconomic factors in low- and middle-income countries.Item Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome(2022) Tepper, Ángeles; Cuiza, Analía; Alliende, Luz; Mena, Carlos; Ramirez, Juan; Iruretagoyena, Bárbara; Ornstein, Claudia; Fritsch, Rosemarie; Nachar, Ruben; González, Alfonso; Undurraga, Juan; Cruz, Juan; Nachar, Ruben; González, Alfonso; Undurraga, Juan; Cruz, Juan; Tejos, Cristian; Fornito, Alex; Repetto, Gabriela; Crossley, Nicolás22q11.2 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.Item Gender, age and geographical representation over the past 50 years of schizophrenia research(2022) Alliende, Luz María; Czepielewski, Leticia; Aceituno, David; Castañeda, Carmen Paz; Diaz, Camila; Iruretagoyena, Bárbara; Mena, Carlos; Mena, Cristian; Ramírez, Juan Pablo; Tepper, Ángeles; Vásquez, Javiera; Fonseca, Lais; Machado, Viviane; Hernández, Camilo; Vargas, Cristian; Gómez, Gladys; Kobayashi, Luis; Moncada, Tomás; Evans, Sara; Bressan, Rodrigo; Gama, Clarissa; López, Carlos; De la Fuente, Camilo; González, Alfonso; Undurraga, Juan; Gadelha, Ary; Crossley, Nicolás; ANDES NetworkPrevious 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.Item Predictors of clozapine discontinuation at 2 years in treatment-resistant schizophrenia(2021) Iruretagoyena, Bárbara; Castañeda, Carmen Paz; Mena, Cristian; Diaz, Camila; Nachar, Ruben; Ramirez, Juan Pablo; González, Alfonso; Undurraga, JuanIntroduction: 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 60 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 23 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) (p = 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; p = 0.001) and OR 1.092 (95%CI 1.01-1.18;p = 0.032) respectively. Conclusion: Starting clozapine in younger patients or shortly after schizophrenia diagnosis were associated with better adherence.Publication Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis(2023) García Saborit, Marisleydis; Jara, Alejandro; Muñoz, Néstor; Milovic, Carlos; Tepper, Angeles; Alliende, Luz María; Mena, Carlos; Iruretagoyena, Bárbara; Ramírez-Mahaluf, Juan Pablo; Díaz, Camila; Nachar, Ruben; Castañeda, Carmen Paz; González, Alfonso; Undurraga, Juan; Crossley, Nicolás; Tejos, CristianBackground: 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.Item Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities(2021) Crossley, Nicolas; Zugman, Andre; Reyes, Francisco; Czepielewski, Leticia; Castro, Mariana; Diaz, Ana; Pineda, Julian; Reckziegel, Ramiro; Gadelha, Ary; Jackowski, Andrea; Noto, Cristiano; Alliende, Luz; Iruretagoyena, Bárbara; Ossandon, Tomas; Ramírez, Juan; Castañeda, Carmen; González, Alfonso; Nachar, Ruben; León, Pablo; Undurraga, Juan; De la Fuente, Camilo; Bressan, Rodrigo; ANDES NetworkBackground: Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear. Aims: We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed. Method: This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model. Results: A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (P = 0.006). Controls showed a positive correlation between total grey matter volume and income (R = 0.14, P = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (R = -0.076, P = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure. Conclusions: Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.Publication The enduring gap in educational attainment in schizophrenia according to the past 50 years of published research: a systematic review and meta-analysis(2022) Crossley, Nicolás; Alliende, Luz; Czepielewski, Leticia; Aceituno, David; Castañeda, Carmen; Diaz, Camila; Iruretagoyena, Bárbara; Mena, Carlos; Mena, Cristian; Ramírez, Juan; Tepper, Angeles; Vásquez, Javiera; Fonseca, Lais; Machado, Viviane; Hernández, Camilo; Vargas, Cristian; Gómez, Gladys; Kobayashi, Luis; Moncada, Tomás; Arango, Celso; Barch, Deanna; Carter, Cameron; Correll, Christoph; Freimer, Nelson; McGuire, Philip; Evans, Sara; Undurraga, Eduardo; Bressan, Rodrigo; Gama, Clarissa; López, Carlos; De la Fuente, Camilo; González, Alfonso; Undurraga, Juan; Gadelha, AryBackground: Educational attainment is associated with wellbeing and health, but patients with schizophrenia achieve lower levels of education than people without. Several effective interventions can ameliorate this situation. However, the magnitude of the education gap in schizophrenia and its change over time are unclear. We aimed to reconstruct the trajectories of educational attainment in patients with schizophrenia and, if reported, their healthy comparator controls. Methods: We did a systematic review and meta-analysis including all studies reporting on patients with schizophrenia (of mean age ≥18 years) and describing the number of years of education of the participants, with or without healthy controls. There were no other design constraints on studies. We excluded studies that included only patients with other schizophrenia spectrum disorders and studies that did not specify the number of years of education of the participants. 22 reviewers participated in retrieving data from a search in PubMed and PsycINFO (Jan 1, 1970, to Nov 24, 2020). We estimated the birth date of participants from their mean age and publication date, and meta-analysed these data using random-effects models, focusing on educational attainment, the education gap, and changes over time. The primary outcome was years of education. The protocol was registered on PROSPERO (CRD42020220546). Findings: From 32 593 initial references, we included 3321 studies reporting on 318 632 patients alongside 138 675 healthy controls (170 941 women and 275 821 men from studies describing sex or gender; data on ethnicity were not collected). Patients' educational attainment increased over time, mirroring that of controls. However, patients with schizophrenia in high-income countries had 19 months less education than controls (-1·59 years, 95% CI -1·66 to -1·53; p<0·0001), which is equivalent to a Cohen's d of -0·56 (95% CI -0·58 to -0·54) and implies an odds ratio of 2·58 for not completing 12 years of education (ie, not completing secondary education) for patients compared with controls. This gap remained stable throughout the decades; the rate of change in number of total years of education in time was not significant (annual change: 0·0047 years, 95% CI -0·0005 to 0·0099; p=0·078). For patients in low-income and middle-income countries, the education gap was significantly smaller than in high-income countries (smaller by 0·72 years, 0·85 to 0·59; p<0·0001), yet there was evidence that this gap was widening over the years, approaching that of high-income countries (annual change: -0·024 years, -0·037 to -0·011; p=0·0002). Interpretation: Patients with schizophrenia have faced persistent inequality in educational attainment in the last century, despite advances in psychosocial and pharmacological treatment. Reducing this gap should become a priority to improve their functional outcomes. Funding: Ciencia y Tecnología para el Desarrollo (CYTED) to the Latin American Network for the Study of Early Psychosis (ANDES).