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Project Title
Development of novel imaging techniques to study the brain in severe mental health disorders
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Internal ID
ACT192064
Principal Investigator
Cristian Tejos (PUC)
Start Date
2019

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Abnormal nodal and global network organization in resting state functional MRI from subjects with the 22q11 deletion syndrome

2021 , Teuntje A. D. Pelgrim , Matthijs G. Bossong , Analía Cuiza , Luz María Alliende , Carlos Mena , Angeles Tepper , Juan Pablo Ramirez-Mahaluf , Barbara Iruretagoyena , Claudia Ornstein , Rosemarie Fritsch , Juan Pablo Cruz , Cristian Tejos , REPETTO LISBOA, MARIA GABRIELA , Nicolas Crossley

AbstractThe 22q11 deletion syndrome is a genetic disorder associated with a high risk of developing psychosis, and is therefore considered a neurodevelopmental model for studying the pathogenesis of schizophrenia. Studies have shown that localized abnormal functional brain connectivity is present in 22q11 deletion syndrome like in schizophrenia. However, it is less clear whether these abnormal cortical interactions lead to global or regional network disorganization as seen in schizophrenia. We analyzed from a graph-theory perspective fMRI data from 40 22q11 deletion syndrome patients and 67 healthy controls, and reconstructed functional networks from 105 brain regions. Between-group differences were examined by evaluating edge-wise strength and graph theoretical metrics of local (weighted degree, nodal efficiency, nodal local efficiency) and global topological properties (modularity, local and global efficiency). Connectivity strength was globally reduced in patients, driven by a large network comprising 147 reduced connections. The 22q11 deletion syndrome network presented with abnormal local topological properties, with decreased local efficiency and reductions in weighted degree particularly in hub nodes. We found evidence for abnormal integration but intact segregation of the 22q11 deletion syndrome network. Results suggest that 22q11 deletion syndrome patients present with similar aberrant local network organization as seen in schizophrenia, and this network configuration might represent a vulnerability factor to psychosis.

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The incidence of non-affective psychotic disorders in Chile between 2005 and 2018: results from a national register of over 30 000 cases

2020 , Alfonso González-Valderrama , Hannah E. Jongsma , Cristián Mena , Carmen Paz Castañeda , Rubén Nachar , UNDURRAGA FOURCADE, JUAN PABLO , Nicolás Crossley , David Aceituno , Barbara Iruretagoyena , Carlos Gallardo , Pilar Mondaca , Matías Monje , Matías Irarrazaval , Cynthia Zavala , Lucia Valmaggia , James B. Kirkbride

AbstractBackgroundEvidence suggests the incidence of non-affective psychotic disorders (NAPDs) varies across persons and places, but data from the Global South is scarce. We aimed to estimate the treated incidence of NAPD in Chile, and variance by person, place and time.MethodsWe used national register data from Chile including all people, 10–65 years, with the first episode of NAPD (International Classification of Diseases, Tenth Revision: F20–F29) between 1 January 2005 and 29 August 2018. Denominators were estimated from Chilean National Census data. Our main outcome was treated incidence of NAPD and age group, sex, calendar year and regional-level population density, multidimensional poverty and latitude were exposures of interest.ResultsWe identified 32 358 NAPD cases [12 136 (39.5%) women; median age-at-first-contact: 24 years (interquartile range 18–39 years)] during 171.1 million person-years [crude incidence: 18.9 per 100 000 person-years; 95% confidence interval (CI) 18.7–19.1]. Multilevel Poisson regression identified a strong age–sex interaction in incidence, with rates peaking in men (57.6 per 100 000 person-years; 95% CI 56.0–59.2) and women (29.5 per 100 000 person-years; 95% CI 28.4–30.7) between 15 and 19 years old. Rates also decreased (non-linearly) over time for women, but not men. We observed a non-linear association with multidimensional poverty and latitude, with the highest rates in the poorest regions and those immediately south of Santiago; no association with regional population density was observed.ConclusionOur findings inform the aetiology of NAPDs, replicating typical associations with age, sex and multidimensional poverty in a Global South context. The absence of association with population density suggests this risk may be context-dependent.

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Differences of affective and non-affective psychoses in early intervention services from Latin America

2022 , Raphael O. Cerqueira , Carolina Ziebold , Daniel Cavalcante , Giovany Oliveira , Javiera Vásquez , UNDURRAGA FOURCADE, JUAN PABLO , Alfonso González-Valderrama , Ruben Nachar , Carlos Lopez-Jaramillo , Cristiano Noto , Nicolas Crossley , Ary Gadelha

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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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Prodromal phase: Differences in prodromal symptoms, risk factors and markers of vulnerability in first episode mania versus first episode psychosis with onset in late adolescence or adulthood

2022 , Norma Verdolini , Roger Borràs , Giulio Sparacino , Marina Garriga , Maria Sagué‐Vilavella , Santiago Madero , Roberto Palacios‐Garrán , Maria Serra , Maria Florencia Forte , Estela Salagre , Alberto Aedo , Pilar Salgado‐Pineda , Irene Montoro Salvatierra , Vanessa Sánchez Gistau , Edith Pomarol‐Clotet , Josep Antoni Ramos‐Quiroga , Andre F. Carvalho , Clemente Garcia‐Rizo , UNDURRAGA FOURCADE, JUAN PABLO , María Reinares , Anabel Martinez Aran , Miguel Bernardo , Eduard Vieta , Isabella Pacchiarotti , Silvia Amoretti

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Mapping Subcortical Brain Alterations in 22q11.2 Deletion Syndrome: Effects of Deletion Size and Convergence With Idiopathic Neuropsychiatric Illness

2020 , Christopher R.K. Ching , Boris A. Gutman , Daqiang Sun , Julio Villalon Reina , Anjanibhargavi Ragothaman , Dmitry Isaev , Artemis Zavaliangos-Petropulu , Amy Lin , Rachel K. Jonas , Leila Kushan , Laura Pacheco-Hansen , Ariana Vajdi , Jennifer K. Forsyth , Maria Jalbrzikowski , Geor Bakker , Therese van Amelsvoort , Kevin M. Antshel , Wanda Fremont , Wendy R. Kates , Linda E. Campbell , Kathryn L. McCabe , Michael C. Craig , Eileen Daly , Maria Gudbrandsen , Clodagh M. Murphy , Declan G. Murphy , Kieran C. Murphy , Ania Fiksinski , Sanne Koops , Jacob Vorstman , T. Blaine Crowley , Beverly S. Emanuel , Raquel E. Gur , Donna M. McDonald-McGinn , David R. Roalf , Kosha Ruparel , J. Eric Schmitt , Elaine H. Zackai , Courtney A. Durdle , Naomi J. Goodrich-Hunsaker , Tony J. Simon , Anne S. Bassett , Nancy J. Butcher , Eva W.C. Chow , Fidel Vila-Rodriguez , Adam Cunningham , Joanne Doherty , David E. Linden , Hayley Moss , Michael J. Owen , Marianne van den Bree , Nicolas A. Crossley , REPETTO LISBOA, MARIA GABRIELA , Paul M. Thompson , Carrie E. Bearden

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Gender, age and geographical representation over the past 50 years of schizophrenia research

2022 , Luz María Alliende , Leticia S. Czepielewski , David Aceituno , Carmen Paz Castañeda , Camila Diaz , Barbara Iruretagoyena , Carlos Mena , Cristian Mena , Juan Pablo Ramirez-Mahaluf , Ángeles Tepper , Javiera Vasquez , Lais Fonseca , Viviane Machado , Camilo E. Hernández , Cristian Vargas-Upegui , Gladys Gomez-Cruz , Luis F. Kobayashi-Romero , Tomas Moncada-Habib , Sara Evans-Lacko , Rodrigo Bressan , Clarissa S. Gama , Carlos Lopez-Jaramillo , Camilo de la Fuente-Sandoval , Alfonso Gonzalez-Valderrama , UNDURRAGA FOURCADE, JUAN PABLO , Ary Gadelha , Nicolas A. Crossley

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Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium

2021 , Gustavo H. Vázquez , Anees Bahji , UNDURRAGA FOURCADE, JUAN PABLO , Leonardo Tondo , Ross J. Baldessarini

Background: Successful treatment of major depressive disorder (MDD) can be challenging, and failures ("treatment-resistant depression" [TRD]) are frequent. Steps to address TRD include increasing antidepressant dose, combining antidepressants, adding adjunctive agents, or using nonpharmacological treatments. Their relative efficacy and tolerability remain inadequately tested. In particular, the value and safety of increasingly employed second-generation antipsychotics (SGAs) and new esketamine, compared to lithium as antidepressant adjuncts remain unclear. Methods: We reviewed randomized, placebo-controlled trials and used random-effects meta-analysis to compare odds ratio (OR) versus placebo, as well as numbers-needed-to-treat (NNT) and to-harm (NNH), for adding SGAs, esketamine, or lithium to antidepressants for major depressive episodes. Results: Analyses involved 49 drug-placebo pairs. By NNT, SGAs were more effective than placebo (NNT = 11 [CI: 9–15]); esketamine (7 [5–10]) and lithium (5 [4–10]) were even more effective. Individually, aripiprazole, olanzapine+fluoxetine, risperidone, and ziprasidone all were more effective (all NNT < 10) than quetiapine (NNT = 13), brexpiprazole (16), or cariprazine (16), with overlapping NNT CIs. Risk of adverse effects, as NNH for most-frequently reported effects, among SGAs versus placebo was 5 [4–6] overall, and highest with quetiapine (NNH = 3), lowest with brexpiprazole (19), 5 (4–6) for esketamine, and 9 (5–106) with lithium. The risk/benefit ratio (NNH/NNT) was 1.80 (1.25–10.60) for lithium and much less favorable for esketamine (0.71 [0.60–0.80]) or SGAs (0.45 [0.17–0.77]). Conclusions: Several modern antipsychotics and esketamine appeared to be useful adjuncts to antidepressants for acute major depressive episodes, but lithium was somewhat more effective and better tolerated. Limitations: Most trials of adding lithium involved older, mainly tricyclic, antidepressants, and the dosing of adjunctive treatments were not optimized.

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Emotional intelligence: a comparison between patients after first episode mania and those suffering from chronic bipolar disorder type I

2022 , Cristina Varo , Silvia Amoretti , Giulio Sparacino , Esther Jiménez , Brisa Solé , Caterina del Mar Bonnin , Laura Montejo , Maria Serra , Carla Torrent , Estela Salagre , Antoni Benabarre , Pilar Salgado-Pineda , Irene Montoro Salvatierra , Pilar A. Sáiz , María Paz García-Portilla , Vanessa Sánchez-Gistau , Edith Pomarol-Clotet , Josep Antoni Ramos-Quiroga , Isabella Pacchiarotti , Clemente Garcia-Rizo , UNDURRAGA FOURCADE, JUAN PABLO , María Reinares , Anabel Martinez-Aran , Eduard Vieta , Norma Verdolini

Abstract Background Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients. Methods The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model. Results In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (s.e.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, s.e. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (β = −0.293, p = 0.034) and verbal memory performance (β = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains. Conclusions Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.

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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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