TY - JOUR
T1 - Accelerated Cortical Thinning in Schizophrenia Is Associated With Rare and Common Predisposing Variation to Schizophrenia and Neurodevelopmental Disorders
AU - González-Peñas, Javier
AU - Alloza, Clara
AU - Brouwer, Rachel
AU - Díaz-Caneja, Covadonga M.
AU - Costas, Javier
AU - González-Lois, Noemí
AU - Gallego, Ana Guil
AU - de Hoyos, Lucía
AU - Gurriarán, Xaquín
AU - Andreu-Bernabeu, Álvaro
AU - Romero-García, Rafael
AU - Fañanas, Lourdes
AU - Bobes, Julio
AU - González-Pinto, Ana
AU - Crespo-Facorro, B.
AU - Martorell, L.
AU - Arrojo, Manuel
AU - Vilella, Elisabet
AU - Gutiérrez-Zotes, Alfonso
AU - Perez-Rando, Marta
AU - Moltó, María Dolores
AU - Fañanas, Lourdes
AU - Rosa de la Cruz, Araceli
AU - Arias, Bárbara
AU - Pinto, Ana González
AU - Crespo-Facorro, B.
AU - Martorell, L.
AU - Muntané, Gerard
AU - Escartí, María José
AU - Rivero, Olga
AU - Parellada, Mara
AU - Moreno, Carmen
AU - Arango, Celso
AU - Buimer, Elizabeth
AU - van Haren, Neeltje
AU - Cahn, Wiepke
AU - O'Donovan, Michael
AU - Kahn, René S.
AU - Pol, Hilleke Hulshoff
AU - Janssen, Joost
AU - Schnack, Hugo
AU - CIBERSAM group
N1 - Publisher Copyright:
© 2024 Society of Biological Psychiatry
PY - 2024/9/1
Y1 - 2024/9/1
N2 - Background: Schizophrenia is a highly heritable disorder characterized by increased cortical thinning throughout the life span. Studies have reported a shared genetic basis between schizophrenia and cortical thickness. However, no genes whose expression is related to abnormal cortical thinning in schizophrenia have been identified. Methods: We conducted linear mixed models to estimate the rates of accelerated cortical thinning across 68 regions from the Desikan-Killiany atlas in individuals with schizophrenia compared with healthy control participants from a large longitudinal sample (ncases = 169 and ncontrols = 298, ages 16–70 years). We studied the correlation between gene expression data from the Allen Human Brain Atlas and accelerated thinning estimates across cortical regions. Finally, we explored the functional and genetic underpinnings of the genes that contribute most to accelerated thinning. Results: We found a global pattern of accelerated cortical thinning in individuals with schizophrenia compared with healthy control participants. Genes underexpressed in cortical regions that exhibit this accelerated thinning were downregulated in several psychiatric disorders and were enriched for both common and rare disrupting variation for schizophrenia and neurodevelopmental disorders. In contrast, none of these enrichments were observed for baseline cross-sectional cortical thickness differences. Conclusions: Our findings suggest that accelerated cortical thinning, rather than cortical thickness alone, serves as an informative phenotype for neurodevelopmental disruptions in schizophrenia. We highlight the genetic and transcriptomic correlates of this accelerated cortical thinning, emphasizing the need for future longitudinal studies to elucidate the role of genetic variation and the temporal-spatial dynamics of gene expression in brain development and aging in schizophrenia.
AB - Background: Schizophrenia is a highly heritable disorder characterized by increased cortical thinning throughout the life span. Studies have reported a shared genetic basis between schizophrenia and cortical thickness. However, no genes whose expression is related to abnormal cortical thinning in schizophrenia have been identified. Methods: We conducted linear mixed models to estimate the rates of accelerated cortical thinning across 68 regions from the Desikan-Killiany atlas in individuals with schizophrenia compared with healthy control participants from a large longitudinal sample (ncases = 169 and ncontrols = 298, ages 16–70 years). We studied the correlation between gene expression data from the Allen Human Brain Atlas and accelerated thinning estimates across cortical regions. Finally, we explored the functional and genetic underpinnings of the genes that contribute most to accelerated thinning. Results: We found a global pattern of accelerated cortical thinning in individuals with schizophrenia compared with healthy control participants. Genes underexpressed in cortical regions that exhibit this accelerated thinning were downregulated in several psychiatric disorders and were enriched for both common and rare disrupting variation for schizophrenia and neurodevelopmental disorders. In contrast, none of these enrichments were observed for baseline cross-sectional cortical thickness differences. Conclusions: Our findings suggest that accelerated cortical thinning, rather than cortical thickness alone, serves as an informative phenotype for neurodevelopmental disruptions in schizophrenia. We highlight the genetic and transcriptomic correlates of this accelerated cortical thinning, emphasizing the need for future longitudinal studies to elucidate the role of genetic variation and the temporal-spatial dynamics of gene expression in brain development and aging in schizophrenia.
KW - Brain imaging
KW - Cortical thinning
KW - Genetics
KW - Schizophrenia
KW - Transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85192488593&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85192488593&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2024.03.011
DO - 10.1016/j.biopsych.2024.03.011
M3 - Article
C2 - 38521159
AN - SCOPUS:85192488593
SN - 0006-3223
VL - 96
SP - 376
EP - 389
JO - Biological psychiatry
JF - Biological psychiatry
IS - 5
ER -