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 Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis(2024) Wannan, Cassandra M. J.; Nelson, Barnaby; Addington, Jean; Allott, Kelly; Anticevic, Alan; Arango, Celso; Baker, Justin T.; Bearden, Carrie E.; Billah, Tashrif; Bouix, Sylvain; Broome, Matthew R.; Buccilli, Kate; Cadenhead, Kristin S.; Calkins, Monica E.; Cannon, Tyrone D.; Cecci, Guillermo; Chen, Eric Yu Hai; Cho, Kang Ik K; Choi, Jimmy; Clark, Scott R.; Coleman, Michael J.; Conus, Philippe; Cheryl M Corcoran, Cheryl M.; Cornblatt, Barbara; Diaz-Caneja, Covadonga M.; Dwyer, Dominic; Ebdrup, Bjorn H.; Ellman, Lauren M.; Fusar-Poli, Paolo; Galindo, Liliana; Gaspar, Pablo A.; Gerber, Carla; Birkedal Glenthøj, Louise; Glynn, Robert; Harms , Michael; Horton, Leslie E.; Kahn, René S.; Kambeitz-Ilankovic, Joseph; Kane, John M.; Castillo-Passi, RolandoThis article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHRPublication Baseline clinical characterization of participants in the Accelerating Medicines Partnership Schizophrenia Program(2025) Addington, Jean; Liu, Lu; Chu, Monica; Jungert, Karl; Penzel, Nora; Pasternak, Ofer; Farina, Emily; Carrion, Ricardo E.; Corcoran, Cheryl M.; Mittal, Vijay A.; Strauss, Gregory P.; Yung, Alison R.; Alameda, Luis; Arango, Celso; Borders, Owen; Bouix, Sylvain; Breitborde, Nicholas J. K.; Broome, Matthew R.; Cadenhead, Kristin S.; Castillo-Passi, Rolando I.; Chen, Eric Yu Hai; Choi, Jimmy; Coleman, Michael J.; Conus, Philippe; Diaz-Caneja, Covadonga M.; Ellman, Lauren M.; Fusar Poli, Paolo; Gaspar, Pablo A.; Gerber, Carla; Glenthøj, Louise Birkedal; Horton, Leslie E.; Hui, Christy Lai Ming; Kambeitz, Joseph; Kambeitz-Ilankovic, Lana; Kapur, Tina; Kelly, Sinead; Kerr, Melissa J.; Keshavan, Matcheri S.; Kim, Minah; Kim, Sung-WanBackground. This paper focuses on the baseline clinical characterization of the participants in the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program. The AMP SCZ program is designed to investigate a wide array of clinical variables and biomarkers in a total of 2040 clinical high-risk (CHR) participants and 652 community control (CC) participants. Methods. The dataset analyzed includes 1642 individuals at clinical high risk for psychosis and 519 CCs. Key measures include the Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the Structured Interview for Psychosis-Risk Syndromes, which determined CHR criteria and the severity of attenuated psychotic symptoms (APS). Other measures included the Structured Clinical Interview for DSM-5, scales to assess negative symptoms, depression, suicidal ideation, substance use, social and role functioning, and a selection of patient-reported outcomes. Results. CHR participants presented with more severe ratings on all clinical measures and poorer functioning relative to the CC. There were a few significant small associations between measures of APS and other clinical measures. Conclusion. The results from this study support previous research indicating that CHR individuals face serious clinical challenges beyond the risk of developing psychosis. Findings indicate significant associations among various clinical measures, underscoring the complex nature of the CHR population. Limitations are acknowledged, including the preliminary nature of the data and the need for more in-depth analyses from AMP SCZ papers already in progress. Future work will focus on longitudinal data and further exploration of clinical variables and their relationship with biomarkers.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 Human development, inequality, and their associations with brain structure across 29 countries(2025) Medel, Vicente; Alliende, Luz M.; Bethlehem, Richard; 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; Castro, Mariana; Chaim-Avancini, Tiffany; Costanzi, Monise; Czepielewski,Leticia; Dazzan, Paola; Fuente-Sandoval, Camilo de la; Diaz-Caneja, Covadonga M.; Forti, Marta Di; Diaz-Zuluaga, Ana Maria; Plessis, Stefan Du; Duran, Fabio; Fittipaldi, Sol; Fornito, Alex; Freimer, Nelson; Gadelha, Ary; Gama, Clarissa; Garani, Ranjini; Garcia-Rizo, Clemente; Gonzalez Campo, Cecilia; Gonzalez-Valderrama, Alfonso; Guinjoan, Salvador; Ivanovic, Daniza; Undurraga, Juan; Zamorano, FranciscoBackground The macro-social and environmental conditions in which people live, such as the level of a country’s development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults. Methods We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country’s level of development and inequality. Results Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain. Conclusions Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants’ brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.Publication Sample Ascertainment and recruitment sources in the Accelerating Medicines Partnership Schizophrenia Program(2025) Addington, Jean; Shalev, Amy; Liu, Lu; Jahraus, Cari; Chu, Monica; Farina, Emily; Fusar Poli, Paolo; Marcy, Patricia J.; Nunez, Angela R.; Calkins, Monica E.; Alameda, Luis; Arango, Celso; Borders, Owen; Bouix, Sylvain; Breitborde, Nicholas J. K.; Broome, Matthew R.; Cadenhead, Kristin S.; Carrion, Ricardo E.; Castillo-Passi, Rolando I.; Chen, Eric Yu Hai; Choi, Jimmy; Coleman, Michael J.; Conus, Philippe; Corcoran, Cheryl M.; Diaz-Caneja, Covadonga M.; Ellman, Lauren M.; Gaspar, Pablo A.; Gerber, Carla; Glenthøj, Louise Birkedal; Horton, Leslie E.; Hui, Christy Lai Ming; Kambeitz, Joseph; Kambeitz-Ilankovic, Lana; Kapur, Tina; Kelly, Sinead; Kerr, Melissa J.; Keshavan, Matcheri S.; Kim, Minah; Kim, Sung-Wan; Koutsouleris, NikolaosBackground. This paper presents the recruitment sources of clinical high-risk (CHR) and community controls (CC) from the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program, which aims to study various clinical variables and biomarkers in 2040 CHR and 652 CC participants. Methods. A total of 1640 CHR and 514 CC had recruitment source data. The Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the SIPS was utilized to assess CHR criteria and severity of attenuated psychotic symptoms (APSs), and the Global Functioning: Social Scale was used for social functioning. Participants were recruited through various methods, including referrals from healthcare providers, schools, and community agencies, and self-referrals via outreach efforts and advertising. Results. Participants were recruited from 13 different sources, with self-referral being the most common for both CHR and CC. Other notable sources included child and youth services and psychiatric hospitals and departments. Regional differences in recruitment patterns were observed across continents. Differences in age, APS, and social functioning for CHR participants were examined in the top 5 recruitment sources. Overall, self-referred individuals were typically older, with less severe APS and higher levels of functioning, whereas those from adult community mental health services had poorer functioning and more severe APS. The remaining recruitment groups fell between these 2 extremes. Conclusion. This paper highlights the diverse recruitment sources for the AMP SCZ program. Self-referral was a significant source, particularly in North America, reflecting changing help-seeking behaviors influenced by the internet and social media. The findings underscore the importance of understanding recruitment sources to optimize future CHR research.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.