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5. The genetic architecture of youth anxiety: a study protocol

Author

McAusland, Laina, Burton, Christie L., Bagnell, Alexa, Boylan, Khrista, Hatchard, Taylor, Lingley-Pottie, Patricia, Al Maruf, Abdullah, McGrath, Patrick, Newton, Amanda S., Rowa, Karen, Schachar, Russell J., Shaheen, S-M, Stewart, Sam, Arnold, Paul D., Crosbie, Jennifer, Mattheisen, Manuel, Soreni, Noam, Stewart, S. Evelyn, and Meier, Sandra

Published
2024
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8. Novel Psychiatric Disorder 6 Months After Traumatic Brain Injury in Children and Adolescents.

Author

Hesselink, John, Ewing-Cobbs, Linda, Schachar, Russell, Chapman, Sandra, Bigler, Erin, Wilde, Elisabeth, Saunders, Ann, Yang, Tony, Tymofiyeva, Olga, Levin, Harvey, Max, Jeffrey, Drake, Imogen, and Vaida, Florin

Subjects
Childhood Neuropsychiatric Disorders, Traumatic Brain Injury, Child, Humans, Adolescent, Child, Preschool, Brain Injuries, Mental Disorders, Brain Injuries, Traumatic, Magnetic Resonance Imaging, Prefrontal Cortex
Abstract

OBJECTIVE: To investigate the factors predictive of novel psychiatric disorders in the interval 0-6 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years consecutively hospitalized for mild to severe TBI at five hospitals were recruited. Participants were evaluated at baseline (soon after injury) for pre-injury characteristics including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, family function, family psychiatric history, and adaptive function. In addition to the psychosocial variables, injury severity and lesion location detected with acquisition of a research MRI were measured to develop a biopsychosocial predictive model for development of novel psychiatric disorders. Psychiatric outcome, including occurrence of a novel psychiatric disorder, was assessed 6 months after the injury. RESULTS: The recruited sample numbered 177 children, and 141 children (80%) returned for the six-month assessment. Of the 141 children, 58 (41%) developed a novel psychiatric disorder. In univariable analyses, novel psychiatric disorder was significantly associated with lower SES, higher psychosocial adversity, and lesions in frontal lobe locations, such as frontal white matter, superior frontal gyrus, inferior frontal gyrus, and orbital gyrus. Multivariable analyses found that novel psychiatric disorder was independently and significantly associated with frontal-lobe white matter, superior frontal gyrus, and orbital gyrus lesions. CONCLUSION: The results demonstrate that occurrence of novel psychiatric disorders following pediatric TBI requiring hospitalization is common and has identifiable psychosocial and specific biological predictors. However, only the lesion predictors were independently related to this adverse psychiatric outcome.

Published
2023

11. Trans-ancestry meta-analysis of genome wide association studies of inhibitory control

Author

Arnatkeviciute, Aurina, Lemire, Mathieu, Morrison, Claire, Mooney, Michael, Ryabinin, Peter, Roslin, Nicole M., Nikolas, Molly, Coxon, James, Tiego, Jeggan, Hawi, Ziarih, Fornito, Alex, Henrik, Walter, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Artiges, Eric, Garavan, Hugh, Nigg, Joel, Friedman, Naomi P., Burton, Christie, Schachar, Russell, Crosbie, Jennifer, and Bellgrove, Mark A.

Published
2023
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12. Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments

Author

Vainieri, Isabella, Martin, Joanna, Rommel, Anna-Sophie, Asherson, Philip, Banaschewski, Tobias, Buitelaar, Jan, Cormand, Bru, Crosbie, Jennifer, Faraone, Stephen V, Franke, Barbara, Loo, Sandra K, Miranda, Ana, Manor, Iris, Oades, Robert D, Purves, Kirstin L, Ramos-Quiroga, J Antoni, Ribasés, Marta, Roeyers, Herbert, Rothenberger, Aribert, Schachar, Russell, Sergeant, Joseph, Steinhausen, Hans-Christoph, Vuijk, Pieter J, Doyle, Alysa E, and Kuntsi, Jonna

Subjects
Attention Deficit Hyperactivity Disorder (ADHD), Genetics, Prevention, Human Genome, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Child, Humans, Young Adult, Attention Deficit Disorder with Hyperactivity, Cognitive Dysfunction, Genome-Wide Association Study, Phenotype, Reaction Time, Case-Control Studies, ADHD, attention, cognition, inhibition, polygenic risk scores, reaction time variability, Neurosciences, Public Health and Health Services, Psychology, Psychiatry
Abstract

BackgroundA recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).MethodsThe discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8-40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.ResultsWhen combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).ConclusionsWe detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.

Published
2022

14. Atypical Brain Aging and Its Association With Working Memory Performance in Major Depressive Disorder

Author

Adamson, Chris, Adler, Sophie, Alexander-Bloch, Aaron F., Anagnostou, Evdokia, Anderson, Kevin M., Areces-Gonzalez, Ariosky, Astle, Duncan E., Auyeung, Bonnie, Ayub, Muhammad, Bae, Jong Bin, Ball, Gareth, Baron-Cohen, Simon, Beare, Richard, Bedford, Saashi A., Benegal, Vivek, Bethlehem, Richard A.I., Beyer, Frauke, Blangero, John, Cábez, Manuel Blesa, Boardman, James P., Borzage, Matthew, Bosch-Bayard, Jorge F., Bourke, Niall, Bullmore, Edward T., Calhoun, Vince D., Chakravarty, Mallar M., Chen, Christina, Chertavian, Casey, Chetelat, Gaël, Chong, Yap S., Corvin, Aiden, Costantino, Manuela, Courchesne, Eric, Crivello, Fabrice, Cropley, Vanessa L., Crosbie, Jennifer, Crossley, Nicolas, Delarue, Marion, Delorme, Richard, Desrivieres, Sylvane, Devenyi, Gabriel, Di Biase, Maria A., Dolan, Ray, Donald, Kirsten A., Donohoe, Gary, Dorfschmidt, Lena, Dunlop, Katharine, Edwards, Anthony D., Elison, Jed T., Ellis, Cameron T., Elman, Jeremy A., Eyler, Lisa, Fair, Damien A., Fletcher, Paul C., Fonagy, Peter, Franz, Carol E., Galan-Garcia, Lidice, Gholipour, Ali, Giedd, Jay, Gilmore, John H., Glahn, David C., Goodyer, Ian M., Grant, P.E., Groenewold, Nynke A., Gudapati, Shreya, Gunning, Faith M., Gur, Raquel E., Gur, Ruben C., Hammill, Christopher F., Hansson, Oskar, Hedden, Trey, Heinz, Andreas, Henson, Richard N., Heuer, Katja, Hoare, Jacqueline, Holla, Bharath, Holmes, Avram J., Huang, Hao, Ipser, Jonathan, Jack, Clifford R., Jr., Jackowski, Andrea P., Jia, Tianye, Jones, David T., Jones, Peter B., Kahn, Rene S., Karlsson, Hasse, Karlsson, Linnea, Kawashima, Ryuta, Kelley, Elizabeth A., Kern, Silke, Kim, Ki-Woong, Kitzbichler, Manfred G., Kremen, William S., Lalonde, François, Landeau, Brigitte, Lerch, Jason, Lewis, John D., Li, Jiao, Liao, Wei, Liston, Conor, Lombardo, Michael V., Lv, Jinglei, Mallard, Travis T., Marcelis, Machteld, Mathias, Samuel R., Mazoyer, Bernard, McGuire, Philip, Meaney, Michael J., Mechelli, Andrea, Misic, Bratislav, Morgan, Sarah E., Mothersill, David, Ortinau, Cynthia, Ossenkoppele, Rik, Ouyang, Minhui, Palaniyappan, Lena, Paly, Leo, Pan, Pedro M., Pantelis, Christos, Park, Min Tae M., Paus, Tomas, Pausova, Zdenka, Paz-Linares, Deirel, Binette, Alexa Pichet, Pierce, Karen, Qian, Xing, Qiu, Anqi, Raznahan, Armin, Rittman, Timothy, Rodrigue, Amanda, Rollins, Caitlin K., Romero-Garcia, Rafael, Ronan, Lisa, Rosenberg, Monica D., Rowitch, David H., Salum, Giovanni A., Satterthwaite, Theodore D., Schaare, H. Lina, Schabdach, Jenna, Schachar, Russell J., Schöll, Michael, Schultz, Aaron P., Seidlitz, Jakob, Sharp, David, Shinohara, Russell T., Skoog, Ingmar, Smyser, Christopher D., Sperling, Reisa A., Stein, Dan J., Stolicyn, Aleks, Suckling, John, Sullivan, Gemma, Thyreau, Benjamin, Toro, Roberto, Traut, Nicolas, Tsvetanov, Kamen A., Turk-Browne, Nicholas B., Tuulari, Jetro J., Tzourio, Christophe, Vachon-Presseau, Étienne, Valdes-Sosa, Mitchell J., Valdes-Sosa, Pedro A., Valk, Sofie L., van Amelsvoort, Therese, Vandekar, Simon N., Vasung, Lana, Vértes, Petra E., Victoria, Lindsay W., Villeneuve, Sylvia, Villringer, Arno, Vogel, Jacob W., Wagstyl, Konrad, Wang, Yin-Shan S., Warfield, Simon K., Warrier, Varun, Westman, Eric, Westwater, Margaret L., Whalley, Heather C., White, Simon R., Witte, A. Veronica, Yang, Ning, Yeo, B.T. Thomas, Yun, Hyuk Jin, Zalesky, Andrew, Zar, Heather J., Zettergren, Anna, Zhou, Juan H., Ziauddeen, Hisham, Zimmerman, Dabriel, Zugman, Andre, Zuo, Xi-Nian N., Ho, Natalie C.W., Nogovitsyn, Nikita, Metzak, Paul, Ballester, Pedro L., Hassel, Stefanie, Rotzinger, Susan, Poppenk, Jordan, Lam, Raymond W., Taylor, Valerie H., Milev, Roumen, Frey, Benicio N., Harkness, Kate L., Addington, Jean, and Kennedy, Sidney H.

Published
2024
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16. Novel Oppositional Defiant Disorder 6 Months After Traumatic Brain Injury in Children and Adolescents.

Author

Hesselink, John, Levin, Harvey, Ewing-Cobbs, Linda, Schachar, Russell, Chapman, Sandra, Bigler, Erin, Wilde, Elisabeth, Saunders, Ann, Yang, Tony, Tymofiyeva, Olga, Arif, Hattan, Max, Jeffrey, Lowet, Daniel, Kolan, Anish, and Vaida, Florin

Subjects
Oppositional Defiant Disorder, Pediatric Traumatic Brain Injury, Adolescent, Attention Deficit and Disruptive Behavior Disorders, Brain Injuries, Brain Injuries, Traumatic, Child, Child, Preschool, Humans, Magnetic Resonance Imaging, Social Class
Abstract

OBJECTIVE: The investigators aimed to assess predictive factors of novel oppositional defiant disorder (ODD) among children and adolescents in the first 6 months following traumatic brain injury (TBI). METHODS: Children ages 5-14 years who experienced a TBI were recruited from consecutive admissions to five hospitals. Testing of a biopsychosocial model that may elucidate the development of novel ODD included assessment soon after injury (baseline) of preinjury characteristics, including psychiatric disorders, adaptive function, family function, psychosocial adversity, family psychiatric history, socioeconomic status, injury severity, and postinjury processing speed (which may be a proxy for brain injury). MRI analyses were also conducted to examine potential brain lesions. Psychiatric outcome, including that of novel ODD, was assessed 6 months after the injury. RESULTS: A total of 177 children and adolescents were recruited for the study, and 134 who were without preinjury ODD, conduct disorder, or disruptive behavior disorder not otherwise specified (DBD NOS) returned for the 6-month assessment. Of those who returned 6 months postinjury, 11 (8.2%) developed novel ODD, and none developed novel conduct disorder or DBD NOS. Novel ODD was significantly associated with socioeconomic status, preinjury family functioning, psychosocial adversity, and processing speed. CONCLUSIONS: These findings show that an important minority of children with TBI developed ODD. Psychosocial and injury-related variables, including socioeconomic status, lower family function, psychosocial adversity, and processing speed, significantly increase risk for this outcome.

Published
2022

17. The AL-Gaussian Distribution as the Descriptive Model for the Internal Proactive Inhibition in the Standard Stop Signal Task

Author

Soltanifar, Mohsen, Escobar, Michael, Dupuis, Annie, Chevrier, Andre, and Schachar, Russell

Subjects
Statistics - Methodology
Abstract

Measurements of response inhibition components of reactive inhibition and proactive inhibition within the stop signal paradigm have been of special interest for researchers since the 1980s. While frequentist nonparametric and Bayesian parametric methods have been proposed to precisely estimate the entire distribution of reactive inhibition, quantified by stop signal reaction times(SSRT), there is no method yet in the stop-signal task literature to precisely estimate the entire distribution of proactive inhibition. We introduce an Asymmetric Laplace Gaussian (ALG) model to describe the distribution of proactive inhibition. The proposed method is based on two assumptions of independent trial type(go/stop) reaction times, and Ex-Gaussian (ExG) models for them. Results indicated that the four parametric, ALG model uniquely describes the proactive inhibition distribution and its key shape features; and, its hazard function is monotonically increasing as are its three parametric ExG components. In conclusion, both response inhibition components can be uniquely modeled via variations of the four parametric ALG model described with their associated similar distributional features., Comment: KEYWORDS Proactive Inhibition, Reaction Times, Ex-Gaussian, Asymmetric Laplace Gaussian, Bayesian Parametric Approach, Hazard function

Published
2021
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18. A Bayesian Mixture Modelling of Stop Signal Reaction Time Distributions

Author

Soltanifar, Mohsen, Escobar, Michael, Dupuis, Annie, and Schachar, Russell

Subjects
Statistics - Methodology
Abstract

The distribution of single Stop Signal Reaction Times (SSRT) in the stop signal task (SST) as a measurement of the latency of the unobservable stopping process has been modeled with a nonparametric method by Hans Colonius (1990) and with a Bayesian parametric method by Eric-Jan Wagenmakers and colleagues (2012). These methods assume equal impact of the preceding trial type (go/stop) in the SST trials on the SSRT distributional estimation without addressing the case of the violated assumption. This study presents the required model by considering two-state mixture model for the SSRT distribution. It then compares the Bayesian parametric single SSRT and mixture SSRT distributions in the usual stochastic order at the individual and the population level under the ex-Gaussian distributional format. It shows that compared to a single SSRT distribution, the mixture SSRT distribution is more diverse, more positively skewed, more leptokurtic, and larger in stochastic order. The size of the disparities in the results also depends on the choice of weights in the mixture SSRT distribution. This study confirms that mixture SSRT indices as a constant or distribution are significantly larger than their single SSRT counterparts in the related order. This offers a vital improvement in the SSRT estimations., Comment: 26 pages, 7 figures

Published
2020
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21. Differential stress response to psychological and physical stressors in children using spatial versus response-dependent navigation strategies

Author

West, Greg L, Kurdi, Vanessa, Fouquet, Celine, Schachar, Russell, Boivin, Michel, Hastings, Paul, Robaey, Philippe, and Bohbot, Veronique D

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Behavioral and Social Science, Pediatric, Mental Health, Clinical Research, Basic Behavioral and Social Science, Mental health, Caudate nucleus, Cortisol, Development, Hippocampus, Navigational strategies, Stress response, Clinical sciences
Abstract

Previous work from our lab has shown that basal cortisol levels are different between healthy young adults who spontaneously use caudate nucleus-dependent response strategies compared to young adults who use hippocampus-dependent spatial navigation strategies. Young adults who use caudate nucleus dependent strategies display lower basal cortisol levels compared to those who use hippocampus-dependent strategies. In the current study, we assessed navigation strategies in children using a virtual navigation task and measured cortisol at baseline as well as cortisol reactivity to both a psychological and to a physical stressor. Replicating what is observed in adults, we found that children who used caudate nucleus-dependent navigation strategies displayed lower cortisol levels at baseline compared to those who used hippocampus-dependent strategies. The psychological stressor, knowledge that a blood draw would be performed by a nurse, caused a significant increase in cortisol uniquely in response learners. The physical stressor, the actual blood draw, produced a significant increase in cortisol amongst spatial learners that was then comparable to levels observed in response learners. Lower baseline cortisol and higher cortisol psychological stress response observed amongst children who used response strategies may therefore reflect early biological changes during development which may have an impact later in life when considering risk for neuropsychiatric disorders.

Published
2021

23. Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder.

Author

Burton, Christie L, Lemire, Mathieu, Xiao, Bowei, Corfield, Elizabeth C, Erdman, Lauren, Bralten, Janita, Poelmans, Geert, Yu, Dongmei, Shaheen, S-M, Goodale, Tara, Sinopoli, Vanessa M, OCD Working Group of the Psychiatric Genomics Consortium, Soreni, Noam, Hanna, Gregory L, Fitzgerald, Kate D, Rosenberg, David, Nestadt, Gerald, Paterson, Andrew D, Strug, Lisa J, Schachar, Russell J, Crosbie, Jennifer, and Arnold, Paul D

Subjects
OCD Working Group of the Psychiatric Genomics Consortium, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of all currently available OCD cases. Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. A locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase δ) was significantly associated with OC traits at the genome-wide significance level (p = 2.48 × 10-8). rs7856850 was also associated with OCD in a meta-analysis of OCD case/control genome-wide datasets (p = 0.0069). The direction of effect was the same as in the community sample. Polygenic risk scores from OC traits were significantly associated with OCD in case/control datasets and vice versa (p's

Published
2021

24. Systematic comparisons of different quality control approaches applied to three large pediatric neuroimaging datasets

Author

Nakua, Hajer, Hawco, Colin, Forde, Natalie J., Joseph, Michael, Grillet, Maud, Johnson, Delaney, Jacobs, Grace R., Hill, Sean, Voineskos, Aristotle N., Wheeler, Anne L., Lai, Meng-Chuan, Szatmari, Peter, Georgiades, Stelios, Nicolson, Rob, Schachar, Russell, Crosbie, Jennifer, Anagnostou, Evdokia, Lerch, Jason P., Arnold, Paul D., and Ameis, Stephanie H.

Published
2023
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25. Factor Structure of Repetitive Behaviors across Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder

Author

Brierley, Noah J., McDonnell, Christina G., Parks, Kaitlyn M. A., Schulz, Samantha E., Dalal, Tyler C., Kelley, Elizabeth, Anagnostou, Evdokia, Nicolson, Robert, Georgiades, Stelios, Crosbie, Jennifer, Schachar, Russell, Liu, Xudong, and Stevenson, Ryan A.

Abstract

Restricted interests and repetitive behaviors (RRBs) are core symptoms of autism spectrum disorder (ASD), and commonly occur in attention-deficit/hyperactivity disorder (ADHD). Little is known about how RRBs manifest in ADHD. We quantified and compared factor structures of RRBs in children with ASD (n = 634) or ADHD (n = 448), and related factors to sex and IQ. A four-factor solution emerged, including Stereotypy, Self-Injury, Compulsions, and Ritualistic/Sameness. Factor structures were equivalent across diagnoses, though symptoms were more severe in ASD. IQ negatively correlated with Stereotypy, Self-Injury, and Compulsions in ASD, and negatively correlated with Compulsions and Ritualistic/Sameness behaviors in ADHD. In ASD only, females exhibited higher Self-Injury. Thus, patterns of RRBs are preserved across ASD and ADHD, but severity and relationship with IQ differed.

Published
2021
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26. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author

Consortium, Cross-Disorder Group of the Psychiatric Genomics, Lee, Phil H, Anttila, Verneri, Won, Hyejung, Feng, Yen-Chen A, Rosenthal, Jacob, Zhu, Zhaozhong, Tucker-Drob, Elliot M, Nivard, Michel G, Grotzinger, Andrew D, Posthuma, Danielle, Wang, Meg M-J, Yu, Dongmei, Stahl, Eli A, Walters, Raymond K, Anney, Richard JL, Duncan, Laramie E, Ge, Tian, Adolfsson, Rolf, Banaschewski, Tobias, Belangero, Sintia, Cook, Edwin H, Coppola, Giovanni, Derks, Eske M, Hoekstra, Pieter J, Kaprio, Jaakko, Keski-Rahkonen, Anna, Kirov, George, Kranzler, Henry R, Luykx, Jurjen J, Rohde, Luis A, Zai, Clement C, Agerbo, Esben, Arranz, MJ, Asherson, Philip, Bækvad-Hansen, Marie, Baldursson, Gísli, Bellgrove, Mark, Belliveau, Richard A, Buitelaar, Jan, Burton, Christie L, Bybjerg-Grauholm, Jonas, Casas, Miquel, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Cormand, Bru, Crosbie, Jennifer, Dalsgaard, Søren, Demontis, Ditte, Doyle, Alysa E, Dumont, Ashley, Elia, Josephine, Grove, Jakob, Gudmundsson, Olafur O, Haavik, Jan, Hakonarson, Hakon, Hansen, Christine S, Hartman, Catharina A, Hawi, Ziarih, Hervás, Amaia, Hougaard, David M, Howrigan, Daniel P, Huang, Hailiang, Kuntsi, Jonna, Langley, Kate, Lesch, Klaus-Peter, Leung, Patrick WL, Loo, Sandra K, Martin, Joanna, Martin, Alicia R, McGough, James J, Medland, Sarah E, Moran, Jennifer L, Mors, Ole, Mortensen, Preben B, Oades, Robert D, Palmer, Duncan S, Pedersen, Carsten B, Pedersen, Marianne G, Peters, Triinu, Poterba, Timothy, Poulsen, Jesper B, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Ribasés, Marta, Rothenberger, Aribert, Rovira, Paula, Sánchez-Mora, Cristina, Satterstrom, F Kyle, Schachar, Russell, Artigas, Maria Soler, Steinberg, Stacy, Stefansson, Hreinn, Turley, Patrick, Walters, G Bragi, Team, 23andMe Research, Werge, Thomas, Zayats, Tetyana, and Arking, Dan E

Subjects
Neurosciences, Serious Mental Illness, Human Genome, Schizophrenia, Intellectual and Developmental Disabilities (IDD), Brain Disorders, Genetics, Pediatric, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Mental health, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mental Disorders, Neurogenesis, Quantitative Trait Loci, Cross-Disorder Group of the Psychiatric Genomics Consortium. Electronic address: plee0@mgh.harvard.edu, Cross-Disorder Group of the Psychiatric Genomics Consortium, GWAS, Psychiatric genetics, cross-disorder genetics, functional genomics, gene expression, genetic architecture, genetic correlation, neurodevelopment, pleiotropy, psychiatric disorders, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

Published
2019

28. Cortico-amygdalar connectivity and externalizing/internalizing behavior in children with neurodevelopmental disorders

Author

Nakua, Hajer, Hawco, Colin, Forde, Natalie J., Jacobs, Grace R., Joseph, Michael, Voineskos, Aristotle N., Wheeler, Anne L., Lai, Meng-Chuan, Szatmari, Peter, Kelley, Elizabeth, Liu, Xudong, Georgiades, Stelios, Nicolson, Rob, Schachar, Russell, Crosbie, Jennifer, Anagnostou, Evdokia, Lerch, Jason P., Arnold, Paul D., and Ameis, Stephanie H.

Published
2022
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29. Concurrent Validity of the ABAS-II Questionnaire with the Vineland II Interview for Adaptive Behavior in a Pediatric ASD Sample: High Correspondence Despite Systematically Lower Scores

Author

Dupuis, Annie, Moon, Michael J., Brian, Jessica, Georgiades, Stelios, Levy, Tomer, Anagnostou, Evdokia, Nicolson, Rob, Schachar, Russell, and Crosbie, Jennifer

Abstract

We examined the correlation between interviewer-administered Vineland Adaptive Behavior Scale II (VABS-II) and the parent-rated Adaptive Behavior Assessment System II (ABAS-II) questionnaire in 352 participants (ages 1.5-20.8 years) with autism spectrum disorder (ASD) to determine if ABAS could be used as a screen to reduce the number of VABS interviews. Corresponding domain scores between the two measures were highly correlated but scores were significantly lower on the ABAS-II. Screening with ABAS-II significantly reduced the number of VABS-II interviews required with little cost to overall accuracy. The ABAS-II provides a cost- and time-saving alternative to the VABS-II to rule out functional impairment; however, scores are not strictly comparable between the two measures.

Published
2021
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30. Dataset factors influencing age-related changes in brain structure and function in neurodevelopmental conditions

Author

Vandewouw, Marlee M, primary, Ye, Yifan J, additional, Crosbie, Jennifer, additional, Schachar, Russell J, additional, Iaboni, Alana, additional, Georgiades, Stelios, additional, Nicolson, Robert, additional, Kelley, Elizabeth, additional, Ayub, Muhammad, additional, Jones, Jessica, additional, Arnold, Paul D, additional, Taylor, Margot J, additional, Lerch, Jason P, additional, Anagnostou, Evdokia, additional, and Kushki, Azadeh, additional

Published
2024
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31. Atypical brain aging and its association with working memory performance in major depressive disorder

Author

Ho, Natalie C.W., primary, Bethlehem, Richard AI., additional, Seidlitz, Jakob, additional, Nogovitsyn, Nikita, additional, Metzak, Paul, additional, Ballester, Pedro L., additional, Hassel, Stefanie, additional, Rotzinger, Susan, additional, Poppenk, Jordan, additional, Lam, Raymond W., additional, Taylor, Valerie H., additional, Milev, Roumen, additional, Adamson, Chris, additional, Adler, Sophie, additional, Alexander-Bloch, Aaron F., additional, Anagnostou, Evdokia, additional, Anderson, Kevin M., additional, Areces-Gonzalez, Ariosky, additional, Astle, Duncan E., additional, Auyeung, Bonnie, additional, Ayub, Muhammad, additional, Bae, Jong Bin, additional, Ball, Gareth, additional, Baron-Cohen, Simon, additional, Beare, Richard, additional, Bedford, Saashi A., additional, Benegal, Vivek, additional, Bethlehem, Richard A.I., additional, Beyer, Frauke, additional, Blangero, John, additional, Blesa Cábez, Manuel, additional, Boardman, James P., additional, Borzage, Matthew, additional, Bosch-Bayard, Jorge F., additional, Bourke, Niall, additional, Bullmore, Edward T., additional, Calhoun, Vince D., additional, Chakravarty, Mallar M., additional, Chen, Christina, additional, Chertavian, Casey, additional, Chetelat, Gaël, additional, Chong, Yap S., additional, Corvin, Aiden, additional, Costantino, Manuela, additional, Courchesne, Eric, additional, Crivello, Fabrice, additional, Cropley, Vanessa L., additional, Crosbie, Jennifer, additional, Crossley, Nicolas, additional, Delarue, Marion, additional, Delorme, Richard, additional, Desrivieres, Sylvane, additional, Devenyi, Gabriel, additional, Di Biase, Maria A., additional, Dolan, Ray, additional, Donald, Kirsten A., additional, Donohoe, Gary, additional, Dorfschmidt, Lena, additional, Dunlop, Katharine, additional, Edwards, Anthony D., additional, Elison, Jed T., additional, Ellis, Cameron T., additional, Elman, Jeremy A., additional, Eyler, Lisa, additional, Fair, Damien A., additional, Fletcher, Paul C., additional, Fonagy, Peter, additional, Franz, Carol E., additional, Galan-Garcia, Lidice, additional, Gholipour, Ali, additional, Giedd, Jay, additional, Gilmore, John H., additional, Glahn, David C., additional, Goodyer, Ian M., additional, Grant, P.E., additional, Groenewold, Nynke A., additional, Gudapati, Shreya, additional, Gunning, Faith M., additional, Gur, Raquel E., additional, Gur, Ruben C., additional, Hammill, Christopher F., additional, Hansson, Oskar, additional, Hedden, Trey, additional, Heinz, Andreas, additional, Henson, Richard N., additional, Heuer, Katja, additional, Hoare, Jacqueline, additional, Holla, Bharath, additional, Holmes, Avram J., additional, Huang, Hao, additional, Ipser, Jonathan, additional, Jack, Clifford R., additional, Jackowski, Andrea P., additional, Jia, Tianye, additional, Jones, David T., additional, Jones, Peter B., additional, Kahn, Rene S., additional, Karlsson, Hasse, additional, Karlsson, Linnea, additional, Kawashima, Ryuta, additional, Kelley, Elizabeth A., additional, Kern, Silke, additional, Kim, Ki-Woong, additional, Kitzbichler, Manfred G., additional, Kremen, William S., additional, Lalonde, François, additional, Landeau, Brigitte, additional, Lerch, Jason, additional, Lewis, John D., additional, Li, Jiao, additional, Liao, Wei, additional, Liston, Conor, additional, Lombardo, Michael V., additional, Lv, Jinglei, additional, Mallard, Travis T., additional, Marcelis, Machteld, additional, Mathias, Samuel R., additional, Mazoyer, Bernard, additional, McGuire, Philip, additional, Meaney, Michael J., additional, Mechelli, Andrea, additional, Misic, Bratislav, additional, Morgan, Sarah E., additional, Mothersill, David, additional, Ortinau, Cynthia, additional, Ossenkoppele, Rik, additional, Ouyang, Minhui, additional, Palaniyappan, Lena, additional, Paly, Leo, additional, Pan, Pedro M., additional, Pantelis, Christos, additional, Park, Min Tae M., additional, Paus, Tomas, additional, Pausova, Zdenka, additional, Paz-Linares, Deirel, additional, Pichet Binette, Alexa, additional, Pierce, Karen, additional, Qian, Xing, additional, Qiu, Anqi, additional, Raznahan, Armin, additional, Rittman, Timothy, additional, Rodrigue, Amanda, additional, Rollins, Caitlin K., additional, Romero-Garcia, Rafael, additional, Ronan, Lisa, additional, Rosenberg, Monica D., additional, Rowitch, David H., additional, Salum, Giovanni A., additional, Satterthwaite, Theodore D., additional, Schaare, H. Lina, additional, Schabdach, Jenna, additional, Schachar, Russell J., additional, Schöll, Michael, additional, Schultz, Aaron P., additional, Sharp, David, additional, Shinohara, Russell T., additional, Skoog, Ingmar, additional, Smyser, Christopher D., additional, Sperling, Reisa A., additional, Stein, Dan J., additional, Stolicyn, Aleks, additional, Suckling, John, additional, Sullivan, Gemma, additional, Thyreau, Benjamin, additional, Toro, Roberto, additional, Traut, Nicolas, additional, Tsvetanov, Kamen A., additional, Turk-Browne, Nicholas B., additional, Tuulari, Jetro J., additional, Tzourio, Christophe, additional, Vachon-Presseau, Étienne, additional, Valdes-Sosa, Mitchell J., additional, Valdes-Sosa, Pedro A., additional, Valk, Sofie L., additional, van Amelsvoort, Therese, additional, Vandekar, Simon N., additional, Vasung, Lana, additional, Vértes, Petra E., additional, Victoria, Lindsay W., additional, Villeneuve, Sylvia, additional, Villringer, Arno, additional, Vogel, Jacob W., additional, Wagstyl, Konrad, additional, Wang, Yin-Shan S., additional, Warfield, Simon K., additional, Warrier, Varun, additional, Westman, Eric, additional, Westwater, Margaret L., additional, Whalley, Heather C., additional, White, Simon R., additional, Witte, A. Veronica, additional, Yang, Ning, additional, Yeo, B.T. Thomas, additional, Yun, Hyuk Jin, additional, Zalesky, Andrew, additional, Zar, Heather J., additional, Zettergren, Anna, additional, Zhou, Juan H., additional, Ziauddeen, Hisham, additional, Zimmerman, Dabriel, additional, Zugman, Andre, additional, Zuo, Xi-Nian N., additional, Frey, Benicio N., additional, Harkness, Kate L., additional, Addington, Jean, additional, and Kennedy, Sidney H., additional

Published
2024
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33. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.

Author

Demontis, Ditte, Walters, Raymond K, Martin, Joanna, Mattheisen, Manuel, Als, Thomas D, Agerbo, Esben, Baldursson, Gísli, Belliveau, Rich, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Dumont, Ashley, Eriksson, Nicholas, Gandal, Michael, Goldstein, Jacqueline I, Grasby, Katrina L, Grove, Jakob, Gudmundsson, Olafur O, Hansen, Christine S, Hauberg, Mads Engel, Hollegaard, Mads V, Howrigan, Daniel P, Huang, Hailiang, Maller, Julian B, Martin, Alicia R, Martin, Nicholas G, Moran, Jennifer, Pallesen, Jonatan, Palmer, Duncan S, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Poterba, Timothy, Poulsen, Jesper Buchhave, Ripke, Stephan, Robinson, Elise B, Satterstrom, F Kyle, Stefansson, Hreinn, Stevens, Christine, Turley, Patrick, Walters, G Bragi, Won, Hyejung, Wright, Margaret J, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Andreassen, Ole A, Asherson, Philip, Burton, Christie L, Boomsma, Dorret I, Cormand, Bru, Dalsgaard, Søren, Franke, Barbara, Gelernter, Joel, Geschwind, Daniel, Hakonarson, Hakon, Haavik, Jan, Kranzler, Henry R, Kuntsi, Jonna, Langley, Kate, Lesch, Klaus-Peter, Middeldorp, Christel, Reif, Andreas, Rohde, Luis Augusto, Roussos, Panos, Schachar, Russell, Sklar, Pamela, Sonuga-Barke, Edmund JS, Sullivan, Patrick F, Thapar, Anita, Tung, Joyce Y, Waldman, Irwin D, Medland, Sarah E, Stefansson, Kari, Nordentoft, Merete, Hougaard, David M, Werge, Thomas, Mors, Ole, Mortensen, Preben Bo, Daly, Mark J, Faraone, Stephen V, Børglum, Anders D, and Neale, Benjamin M

Subjects
ADHD Working Group of the Psychiatric Genomics Consortium, Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Brain, Humans, Genetic Predisposition to Disease, Risk, Cohort Studies, Attention Deficit Disorder with Hyperactivity, Gene Expression Regulation, Polymorphism, Single Nucleotide, Adolescent, Child, Child, Preschool, Female, Male, Genome-Wide Association Study, Genetic Loci, Clinical Research, Mental Health, Human Genome, Pediatric, Prevention, Genetics, Brain Disorders, Attention Deficit Hyperactivity Disorder (ADHD), Behavioral and Social Science, Aetiology, 2.1 Biological and endogenous factors, Mental health, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.

Published
2019

34. Correction: Meta-analysis of genome-wide association studies of hoarding symptoms in 27,537 individuals

Author

Strom, Nora I., Smit, Dirk J. A., Silzer, Talisa, Iyegbe, Conrad, Burton, Christie L., Pool, René, Lemire, Mathieu, Crowley, James J., Hottenga, Jouke-Jan, Ivanov, Volen Z., Larsson, Henrik, Lichtenstein, Paul, Magnusson, Patrik, Rück, Christian, Schachar, Russell J., Wu, Hei Man, Meier, Sandra M., Crosbie, Jennifer, Arnold, Paul D., Mattheisen, Manuel, Boomsma, Dorret I., Mataix-Cols, David, and Cath, Danielle

Published
2022
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35. Meta-analysis of genome-wide association studies of hoarding symptoms in 27,651 individuals

Author

Strom, Nora I., Smit, Dirk J. A., Silzer, Talisa, Iyegbe, Conrad, Burton, Christie L., Pool, René, Lemire, Mathieu, Crowley, James J., Hottenga, Jouke-Jan, Ivanov, Volen Z., Larsson, Henrik, Lichtenstein, Paul, Magnusson, Patrik, Rück, Christian, Schachar, Russell J., Wu, Hei Man, Meier, Sandra M., Crosbie, Jennifer, Arnold, Paul D., Mattheisen, Manuel, Boomsma, Dorret I., Mataix-Cols, David, and Cath, Danielle

Published
2022
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37. Genome-Wide Association Study of Obsessive-Compulsive Symptoms including 33,943 individuals from the general population

Author

Strom, Nora I., primary, Burton, Christie L., additional, Iyegbe, Conrad, additional, Silzer, Talisa, additional, Antonyan, Lilit, additional, Pool, René, additional, Lemire, Mathieu, additional, Crowley, James J., additional, Hottenga, Jouke-Jan, additional, Ivanov, Volen Z., additional, Larsson, Henrik, additional, Lichtenstein, Paul, additional, Magnusson, Patrik, additional, Rück, Christian, additional, Schachar, Russell, additional, Wu, Hei Man, additional, Cath, Danielle, additional, Crosbie, Jennifer, additional, Mataix-Cols, David, additional, Boomsma, Dorret I., additional, Mattheisen, Manuel, additional, Meier, Sandra M., additional, Smit, Dirk J. A., additional, and Arnold, Paul D., additional

Published
2024
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38. Racial/Ethnic Disparities in Psychiatric Traits and Diagnoses within a Community-based Sample of Children and Youth: Disparités raciales/ethniques dans les traits et diagnostics psychiatriques au sein d’un échantillon communautaire d’enfants et de jeunes

Author

Dissanayake, Andrew, primary, Dupuis, Annie, additional, Burton, Christie L., additional, Soreni, Noam, additional, Peters, Paul, additional, Gajaria, Amy, additional, Arnold, Paul D., additional, Schachar, Russell, additional, and Crosbie, Jennifer, additional

Published
2024
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46. Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology

Author

Bedford, Saashi A., primary, Lai, Meng-Chuan, additional, Lombardo, Michael V, additional, Chakrabarti, Bhismadev, additional, Ruigrok, Amber, additional, Suckling, John, additional, Anagnostou, Evdokia, additional, Lerch, Jason P, additional, Taylor, Margot, additional, Nicolson, Rob, additional, Stelios, Georgiades, additional, Crosbie, Jennifer, additional, Schachar, Russell, additional, Kelley, Elizabeth, additional, Jones, Jessica, additional, Arnold, Paul D, additional, Courchesne, Eric, additional, Pierce, Karen, additional, Eyler, Lisa T, additional, Campbell, Kathleen, additional, Carter Barnes, Cynthia, additional, Seidlitz, Jakob, additional, Alexander-Bloch, Aaron F, additional, Bullmore, Edward T, additional, Baron-Cohen, Simon, additional, and Bethlehem, Richard AI, additional

Published
2023
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47. Dorsal striatal functional connectivity and repetitive behaviour dimensions in children and youth with neurodevelopmental disorders

Author

Choi, Eun Jung, primary, Vandewouw, Marlee M., additional, Taylor, Margot J., additional, Stevenson, Ryan A., additional, Arnold, Paul D., additional, Brian, Jessica, additional, Crosbie, Jennifer, additional, Kelley, Elizabeth, additional, Liu, Xudong, additional, Jones, Jessica, additional, Lai, Meng-Chuan, additional, Schachar, Russell J., additional, Lerch, Jason P., additional, and Anagnostou, Evdokia, additional

Published
2023
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