Browsing by Author "Campbell, Linda E."

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    Mapping Subcortical Brain Alterations in 22q11.2 Deletion Syndrome: Effects of Deletion Size and Convergence With Idiopathic Neuropsychiatric Illness
    (2020) Ching, Christopher R.K.; Gutman, Boris A.; Sun, Daqiang; Villalon Reina, Julio; Ragothaman, Anjanibhargavi; Isaev, Dmitry; Zavaliangos-Petropulu, Artemis; Lin, Amy; Jonas, Rachel K.; Kushan, Leila; Pacheco-Hansen, Laura; Vajdi, Ariana; Forsyth, Jennifer K.; Jalbrzikowski, Maria; Bakker, Geor; Amelsvoort, Therese van; Antshel, Kevin M.; Fremont, Wanda; Kates, Wendy R.; Campbell, Linda E.; McCabe, Kathryn L.; Craig, Michael C.; Daly, Eileen; Gudbrandsen, Maria; Murphy, Clodagh M.; Murphy, Declan G.; Murphy, Kieran C.; Fiksinski, Ania; Koops, Sanne; Vorstman, Jacob; Crowley, Blaine; Emanuel, Beverly S.; Gur, Raquel E.; McDonald-McGinn, Donna M.; Roalf, David R.; Ruparel, Kosha; Schmitt, J. Eric; Zackaile, Elaine H.; Durdle, Courtney A.; Goodrich-Hunsaker, Naomi J.; Simon, Tony J.; Bassett, Anne S.; Butcher, Nancy J.; Chow, Eva W.C.; Vila-Rodriguez, Fidel; Cunningham, Adam; Doherty, Joanne; Linden, David E.; Moss, Hayley; Owen, Michael J.; Bree, Marianne van den; Crossley, Nicolas A.; Repetto, Gabriela; Thompson, Paul M.; Bearden, Carrie E.
    Objective: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group. Methods: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6–56 years; 49% female). Results: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen’s d values, 20.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen’s d values, 20.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. Conclusions: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.
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    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 Consortium
    The 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.

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