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Project Title
Dinamica de redes y circuitos neuronales del cerebro durante estados de reposo en salud y enfermedad
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Internal ID
ACT1414
Principal Investigator
Tomas Ossandon
Status
TERMINADO
Start Date
15 November 2014
End Date
18 November 2014
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Now showing 1 - 10 of 14
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Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis

2022 , Juan P Ramirez-Mahaluf , Ángeles Tepper , Luz Maria Alliende , Carlos Mena , Carmen Paz Castañeda , Barbara Iruretagoyena , Ruben Nachar , Francisco Reyes-Madrigal , Pablo León-Ortiz , Ricardo Mora-Durán , Tomas Ossandon , Alfonso Gonzalez-Valderrama , UNDURRAGA FOURCADE, JUAN PABLO , Camilo de la Fuente-Sandoval , Nicolas A Crossley

Abstract 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.

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Lithium treatment for unipolar major depressive disorder: Systematic review

2019 , Juan Undurraga , Kang Sim , Leonardo Tondo , Ariel Gorodischer , Emilio Azua , Kai Hong Tay , David Tan , Ross J Baldessarini

Background: The potential value of lithium treatment in particular aspects of unipolar major depressive disorder remains uncertain. Methods: With reports of controlled trials identified by systematic searching of Medline, Cochrane Library, and PsycINFO literature databases, we summarized responses with lithium and controls followed by selective random-effects meta-analyses. Results: We identified 36 reports with 39 randomized controlled trials: six for monotherapy and 12 for adding lithium to antidepressants for acute major depression, and 21 for long-term treatment. Data for monotherapy of acute depression were few and inconclusive. As an adjunct to antidepressants, lithium was much more effective than placebo ( p<0.0001). For long-term maintenance treatment, lithium was more effective than placebo in monotherapy ( p=0.011) and to supplement antidepressants ( p=0.038), and indistinguishable from antidepressant monotherapy. Conclusions: The findings indicate efficacy of lithium as a treatment for some aspects of major depressive disorder, especially as an add-on to antidepressants and for long-term prophylaxis. It remains uncertain whether some benefits of lithium treatment occur with many major depressive disorder patients, or if efficacy is particular to a subgroup with bipolar disorder-like characteristics or mixed-features.

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Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis

2023 , Marisleydis García Saborit , Alejandro Jara , Néstor Muñoz , Carlos Milovic , Angeles Tepper , Luz María Alliende , Carlos Mena , Bárbara Iruretagoyena , Juan Pablo Ramirez-Mahaluf , Camila Diaz , Ruben Nachar , Carmen Paz Castañeda , Alfonso González , UNDURRAGA FOURCADE, JUAN PABLO , Nicolas Crossley , Cristian Tejos

Abstract 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.

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Brain state-dependent recruitment of high-frequency oscillations in the human hippocampus

2017 , BILLEKE BOBADILLA, PABLO ERNESTO , Tomas Ossandon , Marcelo Stockle , Marcela Perrone-Bertolotti , Philippe Kahane , Jean-Philippe Lachaux , Pablo Fuentealba

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Clinical characterization of rapid cycling bipolar disorder: Association with attention deficit hyperactivity disorder

2018 , Alberto Aedo , Andrea Murru , Raúl Sanchez , Iria Grande , Eduard Vieta , Juan Undurraga

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Morbidity in Depressive Disorders

2017 , Ross J. Baldessarini , Alberto Forte , Valerio Selle , Kang Sim , Leonardo Tondo , Juan Undurraga , Gustavo H. Vázquez

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Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals

2022 , Sean R. McWhinney , Katharina Brosch , Vince D. Calhoun , Benedicto Crespo-Facorro , Nicolas A. Crossley , Udo Dannlowski , Erin Dickie , Lorielle M. F. Dietze , Gary Donohoe , Stefan Du Plessis , Stefan Ehrlich , Robin Emsley , Petra Furstova , David C. Glahn , Alfonso Gonzalez- Valderrama , Dominik Grotegerd , Laurena Holleran , Tilo T. J. Kircher , Pavel Knytl , Marian Kolenic , Rebekka Lencer , Igor Nenadić , Nils Opel , Julia-Katharina Pfarr , Amanda L. Rodrigue , Kelly Rootes-Murdy , Alex J. Ross , Kang Sim , Antonín Škoch , Filip Spaniel , Frederike Stein , Patrik Švancer , Diana Tordesillas-Gutiérrez , UNDURRAGA FOURCADE, JUAN PABLO , Javier Váquez-Bourgon , Aristotle Voineskos , Esther Walton , Thomas W. Weickert , Cynthia Shannon Weickert , Paul M. Thompson , Theo G. M. van Erp , Jessica A. Turner , Tomas Hajek

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Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome

2021 , Ángeles Tepper , Analía Cuiza , Luz María Alliende , Carlos Mena , Juan Pablo Ramirez-Mahaluf , Barbara Iruretagoyena , Claudia Ornstein , Rosemarie Fritsch , Ruben Nachar , Alfonso González-Valderrama , UNDURRAGA FOURCADE, JUAN PABLO , Juan Pablo Cruz , Cristian Tejos , Alex Fornito , REPETTO LISBOA, MARIA GABRIELA , Nicolas Crossley

Abstract 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.

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High prevalence of metabolic alterations in Latin American patients at initial stages of psychosis

2019 , Barbara Iruretagoyena , Carmen P. Castañeda , UNDURRAGA FOURCADE, JUAN PABLO , Rubén Nachar , Cristian Mena , Carlos Gallardo , Nicolas A. Crossley , Alfonso Gonzalez‐Valderrama

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Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities

2020 , Nicolas A. Crossley , Andre Zugman , Francisco Reyes-Madrigal , Leticia S. Czepielewski , Mariana N. Castro , Ana M. Diaz-Zuluaga , Julian A. Pineda-Zapata , Ramiro Reckziegel , Ary Gadelha , Andrea Jackowski , Cristiano Noto , Luz M. Alliende , Barbara Iruretagoyena , Tomas Ossandon , Juan P. Ramirez-Mahaluf , Carmen P. Castañeda , Alfonso Gonzalez-Valderrama , Ruben Nachar , Pablo León-Ortiz , UNDURRAGA FOURCADE, JUAN PABLO , Carlos López-Jaramillo , Salvador M. Guinjoan , Clarissa S. Gama , Camilo de la Fuente-Sandoval , Rodrigo A. Bressan

SummaryBackgroundSocial 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.AimsWe 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.MethodThis 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.ResultsA 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.ConclusionsOur 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.

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