Browsing by Author "Crossley, Nicolás"

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    Abnormal brain network community structure related to psychological stress in schizophrenia
    (2023) Castro, Mariana N.; Bocaccio, Hernan; De Pino, Gabriela; Sanchez, Stella M.; Wainsztein, Agustina E.; Drucaroff, Lucas; Costanzo, Elsa Y.; Crossley, Nicolás; Villarreal, Mirta F.; Guinjoan, Salvador M.
    Recent functional imaging studies in schizophrenia consistently report a disruption of brain connectivity. However, most of these studies analyze the brain connectivity during resting state. Since psychological stress is a major factor for the emergence of psychotic symptoms, we sought to characterize the brain connectivity reconfiguration induced by stress in schizophrenia. We tested the hypothesis that an alteration of the brain's integration-segregation dynamic could be the result of patients with schizophrenia facing psychological stress. To this end, we studied the modular organization and the reconfiguration of networks induced by a stress paradigm in forty subjects (twenty patients and twenty controls), thus analyzing the dynamics of the brain in terms of integration and segregation processes by using 3T-fMRI. Patients with schizophrenia did not show statistically significant differences during the control task compared with controls, but they showed an abnormal community structure during stress condition and an under-connected reconfiguration network with a reduction of hub nodes, suggesting a deficit of integration dynamic with a greater compromise of the right hemisphere. These results provide evidence that schizophrenia has a normal response to undemanding stimuli but shows a disruption of brain functional connectivity between key regions involved in stress response, potentially leading to altered functional brain dynamics by reducing integration capacity and showing deficits recruiting right hemisphere regions. This could in turn underlie the hyper-sensitivity to stress characteristic of schizophrenia.
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    Altered Temporal Dynamics of Resting-State Functional Magnetic Resonance Imaging in Adolescent-Onset First-Episode Psychosis
    (Oxford Univ. Press, 2023) Masias Bruns, Mireia; Ramírez Mahaluf, Juan Pablo; Valli, Isabel; Ortuno, Maria; Ilzarbe, Daniel; de la Serna, Elena; Navarro, Olga Puig; Crossley, Nicolás; Ballester, Miguel Angel Gonzalez; Baeza, Inmaculada; Piella, Gemma; Castro-Fornieles, Josefina; Sugranyes, Gisela
    Dynamic functional connectivity (dFC) alterations have been reported in patients with adult-onset and chronic psychosis. We sought to examine whether such abnormalities were also observed in patients with first episode, adolescent-onset psychosis (AOP), in order to rule out potential effects of chronicity and protracted antipsychotic treatment exposure. AOP has been suggested to have less diagnostic specificity compared to psychosis with onset in adulthood and occurs during a period of neurodevelopmental changes in brain functional connections. Study Design Seventy-nine patients with first episode, AOP (36 patients with schizophrenia-spectrum disorder, SSD; and 43 with affective psychotic disorder, AF) and 54 healthy controls (HC), aged 10 to 17 years were included. Participants underwent clinical and cognitive assessments and resting-state functional magnetic resonance imaging. Graph-based measures were used to analyze temporal trajectories of dFC, which were compared between patients with SSD, AF, and HC. Within patients, we also tested associations between dFC parameters and clinical variables. Study Results Patients with SSD temporally visited the different connectivity states in a less efficient way (reduced global efficiency), visiting fewer nodes (larger temporal modularity, and increased immobility), with a reduction in the metabolic expenditure (cost and leap size), relative to AF and HC (effect sizes: Cohen's D, ranging 0.54 to.91). In youth with AF, these parameters did not differ compared to HC. Connectivity measures were not associated with clinical severity, intelligence, cannabis use, or dose of antipsychotic medication. Conclusions dFC measures hold potential towards the development of brain-based biomarkers characterizing adolescent-onset SSD.
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    Andes network-studying early psychosis in Latin America
    (2019) Crossley, Nicolás; Guinjoan, S.; Rivera, G.; Jackowski, A.; Gadelha, A.; Elkis, H.; Louza, M.; Gama, C.; Evans-Lacko, S.; Castaneda, C.P.; Undurraga Fourcade, Eduardo Andrés; Cordoba, R.; Bressan, R.
    Background Our knowledge about schizophrenia is largely based on studies in developed countries such as the United States, Western Europe or Japan. Their findings have pointed to several risk factors or modulators of response which unfortunately are more prevalent and stronger in low and middle-income countries. These include exposure to violence and trauma, poor perinatal care, or limited (and potentially late) access to healthcare. In this context, there is a pressing need to raise information from these countries about psychosis. We here present to the SIRS community the Latin American Consortium ANDES whose main aim is to study early psychosis within the Latin American context. Methods This is a descriptive study characterizing the groups and the cohorts of patients included that are part of the ANDES network. Results 15 different groups from 6 different countries from Latin America are part of the network, including Argentina, Bolivia, Brazil, Chile, Colombia and Mexico. The network includes several early intervention clinical services, such as those in São Paulo and Santiago, who receive jointly around 5 new cases of first episode a week. ANDES also integrates three groups studying ultra-high-risk subjects (2 in São Paulo, 1 in Mexico). All groups have already acquired data from studies on first episode patients whose characteristics will be presented. Available data includes clinical and sociodemographic information from more than 1,000 patients, cognitive assessments using MATRICS from more than 500 patients, and 600 MRI T1 scans, DTI and resting-state fMRI (350 patients and 250 controls). Discussion ANDES is a unique opportunity to study psychosis in deprived settings which are frequently less represented in research publications. The inequality present in Latin America provides opportunities to study the effect of exposures to an adverse environment within this population.
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    Clozapine-associated neutropenia in Latin America : incidence report of 5380 Chilean users
    (2019) Mena, Cristián I.; Nachar, Rubén A.; Crossley, Nicolás; González Valderrama, Alfonso A.
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    Connectome hubs at resting state in children and adolescents: Reproducibility and psychopathological correlation
    (2016) Sato, Joao Ricardo; Biazoli, Claudinei Eduardo Jr.; Salum, Giovanni Abrahão; Gadelga, Ary; Crossley, Nicolás
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    Connectomic correlates of response to treatment in first-episode psychosis
    (2017) Crossley, Nicolás; Marques, T.; Taylor, H.; Chaddock, C.; Dell'Acqua, F.; Reinders, A.; Mondelli, V.; DiForti, M.; Simmons, A.; David, A.; Kapur, S.; Pariante, C.; Murray, R.; Dazzan, P.
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    Default mode network maturation and psychopathology in children and adolescents
    (2016) Sato, J.; Salum, G.; Gadelha, A.; Crossley, Nicolás; Vieira, G.; Manfro, G.; Zugman, A.; Picon, F.; Pan, P.; Hoexter, M.; Anes, M.; Moura, L.; Del'Aquilla, M.; Amaro, E.; Mcguire, P.; Lacerda, A.
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    Diversity matters: opportunities in the study of the genetics of psychotic disorders in low- and middle-income countries in Latin America
    (2021) Fonseca, Lais; Sena, Brena F.; Crossley, Nicolás; Lopez Jaramillo, Carlos; Koenen, Karestan; Freimer, Nelson B.; Bressan, Rodrigo A.; Belangero, Sintia I.; Santoro, Marcos L.; Gadelha, Ary
    Lack of diversity regarding genetic and environmental backgrounds weakens the generalization and clinical applicability of research findings on psychotic disorders. Notably, Latin Americans have been generally neglected in genetic studies, comprising less than 2% of genome-wide association study samples. But Latin American populations represent a unique opportunity for research, given the exceptionally high ethnic admixture of this group. Increasing genetic diversity is essential to improve the fine mapping of known regions associated with psychotic disorders, discover novel genetic associations, and replicate studies. Additionally, Latin America is characterized by massive social, political, and economic inequalities, all known risk factors for mental health issues, including psychotic disorders. This article aims to 1) discuss the challenges and advantages of studying Latin America's particular genetic makeup and environmental context; 2) review previous studies conducted in the region; and 3) describe three Latin American research initiatives in progress: the Neuropsychiatric Genetics of Psychosis in Mexican Populations (NeuroMEX), the Paisa, and the Latin American Network for the Study of Early Psychosis (ANDES) studies.
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    Early treatment resistance in a Latin-American cohort of patients with schizophrenia
    (2018) Mena, Cristián; González Valderrama, Alfonso; Iruretagoyena, Bárbara; Undurraga, Juan; Crossley, Nicolás
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    Finding the psychosis’ fingerprint: dealing with different clinical presentations and intra-individual variance of patients with schizophrenia in resting-state fMRI data
    (2022) Tepper, Ángeles; Crossley, Nicolás; Pontificia Universidad Católica de Chile. Escuela de Medicina
    La esquizofrenia es un desorden psicótico muy heterogéneo, con gran variabilidad en los perfiles clínicos que presentan los pacientes. Estudios de resonancia magnética funcional en reposo han mostrado que los circuitos estriatocorticales ventral y dorsal son relevantes en un amplio espectro de la enfermedad. Estos estudios tradicionales de neuroimágenes, sin embargo, se basan en la estimación de características a nivel de grupo, y no permiten evaluar características a nivel individual, que pueden ser relevantes en un trastorno tan heterogéneo como la esquizofrenia. Esta tesis consta de cuatro capítulos. En el primer capítulo, implementamos un pipeline de preprocesamiento adecuado para nuestros datos de resonancia magnética funcional. En el segundo capítulo, examinamos la conectividad funcional estriatocortical de una población con riesgo genético de desarrollar esquizofrenia (pacientes con el síndrome de la deleción del 22q11.2). En el tercer capítulo, nos enfocamos hacia la heterogeneidad de la esquizofrenia y exploramos variabilidades inter e intra-individuales usando tres medidas similares a los fingerprints. Por último, en el cuarto capítulo, exploramos enfoques de descomposición de conectomas basados en análisis de componentes principales (PCA) y análisis de componentes independientes (ICA), con el fin de identificar sustratos neurales relacionados con cambios en las expresiones sintomáticas de los pacientes.
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    Genetic and Structural Brain Correlates of Cognitive Subtypes Across Youth at Family Risk for Schizophrenia and Bipolar Disorder
    (2022) Valli, I.; De la Serna, E.; Pariente, J. C.; Calvet Mirabent, A.; Borras, R.; Ilzarbe, D.; Baeza, I.; Rosa Justicia, M.; Garcia Rizo, C.; Vieta, E.; Mas, S.; Castro Fornieles, J.; Sugranyes, G.; Crossley, Nicolás; Young, A. H.; Moreno, D.; Segura, A. G.; Martín Martinez, N.; Díaz Caneja, C. M.
    Objective: Cognitive impairment is an important feature of Schizophrenia (SZ) and Bipolar Disorder (BP) with severity across the two disorders characterized by significant heterogeneity. Youth at family risk for SZ and BP were clustered based on cognitive function and examined in terms of the clinical, genetic, and brain imaging correlates of cluster membership. Method: One hundred sixty participants, 32 offspring of patients with SZ, 59 offspring of patients with BP and 69 offspring of healthy control parents underwent clinical and cognitive assessments, genotyping and structural MRI. K-means clustering was used to group family risk participants based on cognitive measures. Clusters were compared in terms of cortical and subcortical brain measures as well as polygenic risk scores. Results: Participants were grouped in 3 clusters with intact, intermediate, and impaired cognitive performance. The intermediate and impaired clusters had lower total brain surface area compared with the intact cluster, with prominent localization in frontal and temporal cortices. No between-cluster differences were identified in cortical thickness and subcortical brain volumes. The impaired cluster also had poorer psychosocial functioning and worse PRS-COG compared with the other 2 clusters and with offspring of healthy control parents, while there was no significant between-cluster difference in terms of PRS-SZ and PRS-BP. PRS-COG predicted psychosocial functioning, yet this effect did not appear to be mediated by an effect of PRS-COG on brain area. Conclusion: Stratification based on cognition may help to elucidate the biological underpinnings of cognitive heterogeneity across SZ and BP risk.
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    High prevalence of metabolic alterations in Latin American patients at initial stages of psychosis
    (2019) Iruretagoyena, B.; Castañeda, C.P.; Undurraga, J.; Nachar, R.; Mena, C.; Gallardo, C.; Crossley, Nicolás; Gonzalez-Valderrama, A.
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    How mental health care should change as a consequence of the COVID-19 pandemic
    (2020) Moreno, C.; Arango, C.; Wykes, T.; Wykes, T.; Galderisi, S.; Nordentoft, M.; Crossley, Nicolás; Jones, N.; Cannon, M.; Correll, C. U.; Byrne L.; Krystal J.H.; Carr, S.; Chen, E. Y. H.; Gorwood, P.; Johnson, S.; Kärkkäinen, H.; Krystal, J. H.; Lee, J.; Lieberman, J.
    The unpredictability and uncertainty of the COVID-19 pandemic; the associated lockdowns, physical distancing, and other containment strategies; and the resulting economic breakdown could increase the risk of mental health problems and exacerbate health inequalities. Preliminary findings suggest adverse mental health effects in previously healthy people and especially in people with pre-existing mental health disorders. Despite the heterogeneity of worldwide health systems, efforts have been made to adapt the delivery of mental health care to the demands of COVID-19. Mental health concerns have been addressed via the public mental health response and by adapting mental health services, mostly focusing on infection control, modifying access to diagnosis and treatment, ensuring continuity of care for mental health service users, and paying attention to new cases of mental ill health and populations at high risk of mental health problems. Sustainable adaptations of delivery systems for mental health care should be developed by experts, clinicians, and service users, and should be specifically designed to mitigate disparities in health-care provision. Thorough and continuous assessment of health and service-use outcomes in mental health clinical practice will be crucial for defining which practices should be further developed and which discontinued. For this Position Paper, an international group of clinicians, mental health experts, and users of mental health services has come together to reflect on the challenges for mental health that COVID-19 poses. The interconnectedness of the world made society vulnerable to this infection, but it also provides the infrastructure to address previous system failings by disseminating good practices that can result in sustained, efficient, and equitable delivery of mental health-care delivery. Thus, the COVID-19 pandemic could be an opportunity to improve mental health services.
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    HPA-axis function and grey matter volume reductions : imaging the diathesis-stress model in individuals at ultra-high risk of psychosis
    (2016) Valli, I.; Crossley, Nicolás; Day, F.; Stone, J.; Tognin, S.; Mondelli, V.; Howes, O.; Valmaggia, L.; Pariante, C.; Mcguire, P.
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    Implementation of early psychosis services in Latin America: A scoping review
    (John Wiley and Sons Inc, 2021) Aceituno Farías, David; Mena, C.; Vera, N.; González Valderrama, A.; Gadelha, A.; Diniz, E.; Crossley, Nicolás; Pennington, Mark; Prina, M.
    The evidence of the effectiveness and cost-effectiveness of early intervention for psychosis (EIP) services has motivated their implementation worldwide. However, complex interventions of such EIP services require local adaptations to successfully match population needs and cultural differences. Latin America is a heterogenous region where EIP services are progressively being adopted. Our aim is to map such initiatives in the region with a focus on implementation outcomes. Methods: A scoping review following the Preferred Reporting Items for Systematic review and Meta-Analysis extension for Scoping Reviews guidelines was conducted. International and regional databases were searched for publications describing EIP programmes in the region. Besides mapping the services, we described implementation outcomes based on the Standards for Reporting Implementation Studies Checklist. Results: Ten articles describing seven EIP initiatives from the region were found. Four countries were represented: Argentina, Brazil, Chile and Mexico. The implementation outcomes reporting was heterogenous, although it was possible to ascertain EIP services are feasible and adequate for the region's context. Also, there is some evidence of effectiveness in terms of reducing hospitalizations and improving symptoms. Information about fidelity measures was scarce and there was no information about costs or cost-effectiveness. Conclusions: Only a small proportion of Latin American countries have adopted EIP services. Although these programmes seem to be feasible and effective, data on other implementation outcomes, such as fidelity, cultural appropriateness, cost-effectiveness and affordability are not available. This might in part explain why this effective approach has not been yet scaled-up at nationwide levels.
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    Integrated metastate functional connectivity networks predict change in symptom severity in clinical high risk for psychosis
    (2021) Gifford, G.; Crossley, Nicolás; Morgan, S.; Kempton, M. J.; Dazzan, P.; Modinos, G.; Azis, M.; Samson, C.; Bonoldi, I.; Quinn, B.; Smart, S. E.; Antoniades, M.; Bossong, M. G.; Broome, M. R.; Pérez C., José Ricardo; Howes, O. D.; Stone, J. M.; Allen, P.; Grace, A. A.; McGuire, P.
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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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    Meta-connectomics : human brain network and connectivity meta-analyses
    (2016) Crossley, Nicolás; Fox, P.; Bullmore, E.
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    Network-Level Dysconnectivity in Drug-Naive First-Episode Psychosis: Dissociating Transdiagnostic and Diagnosis-Specific Alterations
    (2017) Crossley, Nicolás; Gong, Q.; Hu, X.; Pettersson, W.; Xu, X.; Lui, S.; Wu, M.; Zhu, H.; Mechelli, A.