Dinamica de redes y circuitos neuronales del cerebro durante estados de reposo en salud y enfermedad

Project Title

Partner Organisations

Facultad de Medicina Clínica Alemana Universidad del Desarrollo

Internal ID

ACT1414

Principal Investigator

Tomas Ossandon

Type

basic research

Status

TERMINADO

Start Date

November 15, 2014

End Date

November 18, 2014

Investigators

UNDURRAGA FOURCADE, JUAN PABLO

Publications

Now showing 1 - 10 of 16

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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
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background and Hypothesis</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Design</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>
Scopus© Citations 17 1
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Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome
(2021)
Ángeles Tepper
;
Analía Cuiza
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Luz María Alliende
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Carlos Mena
;
Juan Pablo Ramirez-Mahaluf
<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
1Scopus© Citations 6
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Morbidity in Depressive Disorders
(2017)
Ross J. Baldessarini
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Alberto Forte
;
Valerio Selle
;
Kang Sim
;
Leonardo Tondo
5Scopus© Citations 60
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Uso de cannabis en jóvenes hospitalizados por un primer episodio de psicosis: un estudio caso-control
(2020)
Carmen Paz Castañeda
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Luz María Alliende
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Bárbara Iruretagoyena
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Rubén Nachar
;
Felipe Mancilla
Scopus© Citations 2 13
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Effects of socioeconomic status in cognition of people with schizophrenia: results from a Latin American collaboration network with 1175 subjects
(2021)
Letícia Sanguinetti Czepielewski
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Luz Maria Alliende
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Carmen Paz Castañeda
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Mariana Castro
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Salvador M. Guinjoan
<jats:title>Abstract</jats:title><jats:sec id="S0033291721002403_sec_a1"><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="S0033291721002403_sec_a2" sec-type="methods"><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="S0033291721002403_sec_a3" sec-type="results"><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="S0033291721002403_sec_a4" sec-type="conclusions"><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>
4Scopus© Citations 28
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Direct comparison of tricyclic and serotonin-reuptake inhibitor antidepressants in randomized head-to-head trials in acute major depression: Systematic review and meta-analysis
(2017)
Juan Undurraga
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Ross J Baldessarini
Scopus© Citations 39 3
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Imaging Social and Environmental Factors as Modulators of Brain Dysfunction: Time to Focus on Developing Non-Western Societies
(2019)
Nicolas A. Crossley
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Luz Maria Alliende
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Tomas Ossandon
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Carmen Paz Castañeda
;
Alfonso González-Valderrama
Scopus© Citations 15 2
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Lithium treatment for unipolar major depressive disorder: Systematic review
(2019)
Juan Undurraga
;
Kang Sim
;
Leonardo Tondo
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Ariel Gorodischer
;
Emilio Azua
<jats:sec><jats:title>Background:</jats:title><jats:p> The potential value of lithium treatment in particular aspects of unipolar major depressive disorder remains uncertain. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> 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. </jats:p></jats:sec>
Scopus© Citations 64 8
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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
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Francisco Reyes-Madrigal
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Leticia S. Czepielewski
;
Mariana N. Castro
<jats:title>Summary</jats:title><jats:sec id="S0007125020001439_sec_a1"><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a2"><jats:title>Aims</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a3" sec-type="methods"><jats:title>Method</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a4" sec-type="results"><jats:title>Results</jats:title><jats:p>A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (<jats:italic>P</jats:italic> = 0.006). Controls showed a positive correlation between total grey matter volume and income (<jats:italic>R</jats:italic> = 0.14, <jats:italic>P</jats:italic> = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (<jats:italic>R</jats:italic> = −0.076, <jats:italic>P</jats:italic> = 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.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a5" sec-type="conclusions"><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>
Scopus© Citations 10 1
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Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis
(2023)
Marisleydis García Saborit
;
Alejandro Jara
;
Néstor Muñoz
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Carlos Milovic
;
Angeles Tepper
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>
Scopus© Citations 1 1

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