Browsing by Author "Alliende, Luz"
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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 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 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).