Browsing by Author "Nachar, Ruben"

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    Differences of affective and non-affective psychoses in early intervention services from Latin America
    (2022) Cerqueira, Raphael O.; Ziebold, Carolina; Cavalcante, Daniel; Oliveira, Giovany; Vasquez Nuñez, Javiera Eugenia; Undurraga, Juan; Gonzalez-Valderrama, Alfonso; Nachar, Ruben; Lopez-Jaramillo, Carlos; Noto, Cristiano; Crossley Karmelic, Nicolas Andres; Gadelha, Ary
    Background: Psychosis presentation can be affected by genetic and environmental factors. Differentiating be-tween 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 ac-cording 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.
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    Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis
    (2023) Ramirez-Mahaluf, Juan P.; Tepper, Angeles; Maria Alliende, Luz; Mena, Carlos; Castaneda, Carmen Paz; Iruretagoyena, Barbara; Nachar, Ruben; Reyes-Madrigal, Francisco; Leon-Ortiz, Pablo; Mora-Duran, Ricardo; Ossandon, Tomas; Gonzalez-Valderrama, Alfonso; Undurraga, Juan; De la Fuente-Sandoval, Camilo; Crossley, Nicolas A.
    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-naive 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-naive 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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    Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome
    (OXFORD UNIV PRESS, 2021) Tepper, Angeles; Cuiza Vasquez Analia; Alliende, Luz María; Mena, Carlos; Ramirez Mahaluf, Juan Pablo; Iruretagoyena, Barbara; Ornstein, Claudia; Fritsch, Rosemarie; Nachar, Ruben; Gonzalez Valderrama, Alfonso; Undurraga, Juan; Pablo Cruz, Juan; Tejos, Cristian; Fornito, Alex; Repetto, Gabriela; Crossley, Nicolas
    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 x 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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    Intra and inter-individual variability in functional connectomes of patients with First Episode of Psychosis
    (Elsevier Inc., 2023) Tepper, Ángeles; Vásquez Núñez, Javiera; Ramirez-Mahaluf, Juan Pablo; Aguirre, Juan Manuel; Barbagelata, Daniella; Maldonado, Elisa; Díaz Dellarossa, Camila; Nachar, Ruben; González-Valderrama, Alfonso; Undurraga, Juan; Goñi, Joaquín; Crossley, Nicolás
    © 2023 The Author(s)Patients with Schizophrenia may show different clinical presentations, not only regarding inter-individual comparisons but also in one specific subject over time. In fMRI studies, functional connectomes have been shown to carry valuable individual level information, which can be associated with cognitive and behavioral variables. Moreover, functional connectomes have been used to identify subjects within a group, as if they were fingerprints. For the particular case of Schizophrenia, it has been shown that there is reduced connectome stability as well as higher inter-individual variability. Here, we studied inter and intra-individual heterogeneity by exploring functional connectomes’ variability and related it with clinical variables (PANSS Total scores and antipsychotic's doses). Our sample consisted of 30 patients with First Episode of Psychosis and 32 Healthy Controls, with a test–retest approach of two resting-state fMRI scanning sessions. In our patients’ group, we found increased deviation from healthy functional connectomes and increased intragroup inter-subject variability, which was positively correlated to symptoms’ levels in six subnetworks (visual, somatomotor, dorsal attention, ventral attention, frontoparietal and DMN). Moreover, changes in symptom severity were positively related to changes in deviation from healthy functional connectomes. Regarding intra-subject variability, we were unable to replicate previous findings of reduced connectome stability (i.e., increased intra-subject variability), but we found a trend suggesting that result. Our findings highlight the relevance of variability characterization in Schizophrenia, and they can be related to evidence of Schizophrenia patients having a noisy functional connectome.
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    Predictors of clozapine discontinuation at 2 years in treatment-resistant schizophrenia
    (ELSEVIER, 2021) Iruretagoyena Bruce Barbara Arantzazu; Castañeda, Carmen Paz; Mena, Cristian; Diaz, Camila; Nachar, Ruben; Ramirez Mahaluf Juan Pablo; González Valderrama, Alfonso; Undurraga, Juan; Maccabe, James H; Crossley, Nicolas A
    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