Browsing by Author "Arango, Celso"
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Item A normative chart for cognitive development in a genetically selected population(2021) Fiksinski, Ania; Bearden, Carrie; Bassett, Anne; Kahn, René; Zinkstok, Janneke; Hooper, Stephen R; Tempelaar, Wanda; McDonald, Donna; Swillen, Ann; Emanuel, Beverly; Morrow, Bernice; Gur, Raquel; Chow, Eva; Van den Bree, Marianne; Vermeesch, Joris; Warren, Stephen; Owen, Michael; Van Amelsvoort, Therese; Eliez, Stephan; Gothelf, Doron; Arango, Celso; Kates, Wendy; Simon, Tony; Murphy, Kieran; Repetto, Gabriela; Heine, Damian; Vicari, Stefano; Cubells, Joseph; Armando, Marco; Philip, Nicole; Campbell, Linda; García, Sixto; Schneider, Maude; Shashi, Vandana; 22q11DS International Consortium on Brain and Behavior; Vorstman, Jacob; Breetvelt, ElemiCertain pathogenic genetic variants impact neurodevelopment and cause deviations from typical cognitive trajectories. Understanding variant-specific cognitive trajectories is clinically important for informed monitoring and identifying patients at risk for comorbid conditions. Here, we demonstrate a variant-specific normative chart for cognitive development for individuals with 22q11.2 deletion syndrome (22q11DS). We used IQ data from 1365 individuals with 22q11DS to construct variant-specific normative charts for cognitive development (Full Scale, Verbal, and Performance IQ). This allowed us to calculate Z-scores for each IQ datapoint. Then, we calculated the change between first and last available IQ assessments (delta Z-IQ-scores) for each individual with longitudinal IQ data (n = 708). We subsequently investigated whether using the variant-specific IQ-Z-scores would decrease required sample size to detect an effect with schizophrenia risk, as compared to standard IQ-scores. The mean Z-IQ-scores for FSIQ, VIQ, and PIQ were close to 0, indicating that participants had IQ-scores as predicted by the normative chart. The mean delta-Z-IQ-scores were equally close to 0, demonstrating a good fit of the normative chart and indicating that, as a group, individuals with 22q11DS show a decline in IQ-scores as they grow into adulthood. Using variant-specific IQ-Z-scores resulted in 30% decrease of required sample size, as compared to the standard IQ-based approach, to detect the association between IQ-decline and schizophrenia (p < 0.01). Our findings suggest that using variant-specific normative IQ data significantly reduces required sample size in a research context, and may facilitate a more clinically informative interpretation of IQ data. This approach allows identification of individuals that deviate from their expected, variant-specific, trajectory. This group may be at increased risk for comorbid conditions, such as schizophrenia in the case of 22q11DS.Publication Country-level gender inequality is associated with structural differences in the brains of women and men(2023) Zugman, André; Alliende, Luz María; Medel, Vicente; Bethlehem, Richard A.I.; Seidlitz, Jakob; Ringlein, Grace; Arango, Celso; Arnatkevičiūtė, Aurina; Asmal, Laila; Bellgrove, Mark; Benegal, Vivek; Bernardo, Miquel; Billeke, Pablo; Bosch-Bayard, Jorge; Bressan, Rodrigo; Busatto, Geraldo F.; Castro, Mariana N.; Chaim-Avancini, Tiffany; Compte, Albert; Costanzi, Monise; Czepielewsk, Leticia; Dazzan, Paola; Fuente-Sandoval, Camilo de la; Forti, Marta Di; Díaz-Caneja, Covadonga M.; Díaz-Zuluaga, Ana María; Ples, Stefan Du; Duran, Fabio L. S.; Fittipaldi, Sol; Fornito, Alex; Freimer, Nelson B.; Gadelha, Ary; Gama, Clarissa S.; Garani, Ranjini; Garcia-Rizo, Clemente; Gonzalez Campo, Cecilia; Gonzalez-Valderrama, Alfonso; Guinjoan, Salvador; Holla, Bharath; Undurraga, JuanGender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.Item Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs(2022) Sønderby, Ida; Ching, Christopher; Thomopoulos, Sophia; Van der Meer, Dennis; Sun, Daqiang; Villalon, Julio; Agartz, Ingrid; Amunts, Katrin; Arango, Celso; Armstrong, Nicola; Ayesa, Rosa; Bakker, Geor; Bassett, Anne; Boomsma, Dorret; Bülow, Robin; Butcher, Nancy; Calhoun, Vince; Caspers, Svenja; Chow, Eva; Cichon, Sven; Ciufolini, Simone; Craig, Michael; Crespo, Benedicto; Cunningham, Adam; Dale, Ander; Dazzan, Paola; De Zubicaray, Greig; Djurovic, Srdjan; Doherty, Joanne; Donohoe, Gary; Draganski, Bogdan; Durdle, Courtney; Ehrlich, Stefan; Emanuel, Beverly; Espeseth, Thomas; Fisher, Simon; Ge, Tian; Glahn, David; Grabe, Hans; Gur, RaquelThe Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.Publication The enduring gap in educational attainment in schizophrenia according to the past 50 years of published research: a systematic review and meta-analysis(2022) Crossley, Nicolás; Alliende, Luz; Czepielewski, Leticia; Aceituno, David; Castañeda, Carmen; Diaz, Camila; Iruretagoyena, Bárbara; Mena, Carlos; Mena, Cristian; Ramírez, Juan; Tepper, Angeles; Vásquez, Javiera; Fonseca, Lais; Machado, Viviane; Hernández, Camilo; Vargas, Cristian; Gómez, Gladys; Kobayashi, Luis; Moncada, Tomás; Arango, Celso; Barch, Deanna; Carter, Cameron; Correll, Christoph; Freimer, Nelson; McGuire, Philip; Evans, Sara; Undurraga, Eduardo; Bressan, Rodrigo; Gama, Clarissa; López, Carlos; De la Fuente, Camilo; González, Alfonso; Undurraga, Juan; Gadelha, AryBackground: Educational attainment is associated with wellbeing and health, but patients with schizophrenia achieve lower levels of education than people without. Several effective interventions can ameliorate this situation. However, the magnitude of the education gap in schizophrenia and its change over time are unclear. We aimed to reconstruct the trajectories of educational attainment in patients with schizophrenia and, if reported, their healthy comparator controls. Methods: We did a systematic review and meta-analysis including all studies reporting on patients with schizophrenia (of mean age ≥18 years) and describing the number of years of education of the participants, with or without healthy controls. There were no other design constraints on studies. We excluded studies that included only patients with other schizophrenia spectrum disorders and studies that did not specify the number of years of education of the participants. 22 reviewers participated in retrieving data from a search in PubMed and PsycINFO (Jan 1, 1970, to Nov 24, 2020). We estimated the birth date of participants from their mean age and publication date, and meta-analysed these data using random-effects models, focusing on educational attainment, the education gap, and changes over time. The primary outcome was years of education. The protocol was registered on PROSPERO (CRD42020220546). Findings: From 32 593 initial references, we included 3321 studies reporting on 318 632 patients alongside 138 675 healthy controls (170 941 women and 275 821 men from studies describing sex or gender; data on ethnicity were not collected). Patients' educational attainment increased over time, mirroring that of controls. However, patients with schizophrenia in high-income countries had 19 months less education than controls (-1·59 years, 95% CI -1·66 to -1·53; p<0·0001), which is equivalent to a Cohen's d of -0·56 (95% CI -0·58 to -0·54) and implies an odds ratio of 2·58 for not completing 12 years of education (ie, not completing secondary education) for patients compared with controls. This gap remained stable throughout the decades; the rate of change in number of total years of education in time was not significant (annual change: 0·0047 years, 95% CI -0·0005 to 0·0099; p=0·078). For patients in low-income and middle-income countries, the education gap was significantly smaller than in high-income countries (smaller by 0·72 years, 0·85 to 0·59; p<0·0001), yet there was evidence that this gap was widening over the years, approaching that of high-income countries (annual change: -0·024 years, -0·037 to -0·011; p=0·0002). Interpretation: Patients with schizophrenia have faced persistent inequality in educational attainment in the last century, despite advances in psychosocial and pharmacological treatment. Reducing this gap should become a priority to improve their functional outcomes. Funding: Ciencia y Tecnología para el Desarrollo (CYTED) to the Latin American Network for the Study of Early Psychosis (ANDES).Item Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome(2020) Davies, Robert W.; Fiksinski, Ania M.; Breetvelt, Elemi J.; Williams, Nigel M.; Hooper, Stephen R.; Monfeuga, Thomas; Bassett, Anne S.; Owen, Michael J.; Gur, Raquel E.; Morrow, Bernice E.; McDonald-McGinn, Donna M.; Swillen, Ann; Chow, Eva W. C.; Bree, Marianne van den; Emanuel, Beverly S.; Vermeesch, Joris R.; Amelsvoort, Therese van; Arango, Celso; Armando, Marco; Campbell, Linda E.; Cubells, Joseph F.; Eliez, Stephan; Garcia-Minaur, Sixto; Gothelf, Doron; Kates, Wendy R.; Murphy, Kieran C.; Murphy, Clodagh M.; Murphy, Declan G.; Philip, Nicole; Repetto, Gabriela; Shashi, Vandana; Simon, Tony J.; Suñer, Damiàn Heine; Vicari, Stefano; Scherer, Stephen W.; Bearden, Carrie E.; Vorstman, Jacob A. S.; International 22q11.2 Brain and Behavior ConsortiumThe 22q11.2 deletion syndrome (22q11DS) is associated with a 20-25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two polygenic scores, derived for schizophrenia and intelligence, and evaluated their use for individual risk prediction in 22q11DS. Polygenic scores were not only associated with schizophrenia and baseline intelligence quotient (IQ), respectively, but schizophrenia polygenic score was also significantly associated with cognitive (verbal IQ) decline and nominally associated with sub-threshold psychosis. Furthermore, in comparing the tail-end deciles of the schizophrenia and IQ polygenic score distributions, 33% versus 9% of individuals with 22q11DS had schizophrenia, and 63% versus 24% of individuals had intellectual disability. Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants.