Genetic and Structural Brain Correlates of Cognitive Subtypes Across Youth at Family Risk for Schizophrenia and Bipolar Disorder

Isabel Valli; Elena De la Serna; Alex G Segura; Jose C Pariente; Angels Calvet-Mirabent; Roger Borras; Daniel Ilzarbe; Dolores Moreno; Nuria Martín-Martínez; Inmaculada Baeza; Mireia Rosa-Justicia; Clemente Garcia-Rizo; Covadonga M Díaz-Caneja; Nicolas A Crossley; Allan H Young; Eduard Vieta; Sergi Mas; Josefina Castro-Fornieles; Gisela Sugranyes

doi:10.1016/j.jaac.2022.05.011

Isabel Valli, Elena De la Serna, Alex G Segura, Jose C Pariente, Angels Calvet-Mirabent, Roger Borras, Daniel Ilzarbe, Dolores Moreno, Nuria Martín-Martínez, Inmaculada Baeza, Mireia Rosa-Justicia, Clemente Garcia-Rizo, Covadonga M Díaz-Caneja, Nicolas A Crossley, Allan H Young, Eduard Vieta, Sergi Mas, Josefina Castro-Fornieles, Gisela Sugranyes

Original language	English
Pages (from-to)	74-83
Number of pages	10
Journal	Journal of the American Academy of Child and Adolescent Psychiatry
Volume	62
Issue number	1
Early online date	13 Jun 2022
DOIs	https://doi.org/10.1016/j.jaac.2022.05.011
E-pub ahead of print	13 Jun 2022
Published	Jan 2023
Additional links	Link to publication in Scopus

Funding Information: This work was supported by the BITRECS project (to I.V.), which received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 754550 and from “La Caixa” Foundation, under agreement LCF/PR/GN18/50310006. The study was also supported by the Spanish Ministry of Health , Instituto de Salud Carlos III co-financed by the European Regional Development Fund ( ERDF ) from the European Commission (PI070066, PI1100683, PI1500467, PI1700741, PI1800696, PI1800976), Fundació La Marató TV3 (091630), the Catalonia Government (2017SGR881), Strategic Plan for Research and Innovation in Health (PERIS) (SLT006/17/00346), the Madrid Regional Government (B2017/BMD-3740AGES-CM-2), Fundació Clínic Recerca Biomèdica (Ajut a la Recerca Pons Bartran), and CIBERSAM. Funding Information: This work was supported by the BITRECS project (to I.V.), which received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 754550 and from “La Caixa” Foundation, under agreement LCF/PR/GN18/50310006. The study was also supported by the Spanish Ministry of Health, Instituto de Salud Carlos III co-financed by the European Regional Development Fund (ERDF) from the European Commission (PI070066, PI1100683, PI1500467, PI1700741, PI1800696, PI1800976), Fundació La Marató TV3 (091630), the Catalonia Government (2017SGR881), Strategic Plan for Research and Innovation in Health (PERIS) (SLT006/17/00346), the Madrid Regional Government (B2017/BMD-3740AGES-CM-2), Fundació Clínic Recerca Biomèdica (Ajut a la Recerca Pons Bartran), and CIBERSAM. Publisher Copyright: © 2022 American Academy of Child and Adolescent Psychiatry

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OBJECTIVE: Cognitive impairment is an important feature of Schizophrenia (SZ) and Bipolar Disorder (BP) with severity across the two disorders characterized by significant heterogeneity. Youth at family risk for SZ and BP were clustered based on cognitive function and examined in terms of the clinical, genetic, and brain imaging correlates of cluster membership.

METHOD: One hundred sixty participants, 32 offspring of patients with SZ, 59 offspring of patients with BP and 69 offspring of healthy control parents underwent clinical and cognitive assessments, genotyping and structural MRI. K-means clustering was used to group family risk participants based on cognitive measures. Clusters were compared in terms of cortical and subcortical brain measures as well as polygenic risk scores.

RESULTS: Participants were grouped in 3 clusters with intact, intermediate, and impaired cognitive performance. The intermediate and impaired clusters had lower total brain surface area compared with the intact cluster, with prominent localization in frontal and temporal cortices. No between-cluster differences were identified in cortical thickness and subcortical brain volumes. The impaired cluster also had poorer psychosocial functioning and worse PRS-COG compared with the other 2 clusters and with offspring of healthy control parents, while there was no significant between-cluster difference in terms of PRS-SZ and PRS-BP. PRS-COG predicted psychosocial functioning, yet this effect did not appear to be mediated by an effect of PRS-COG on brain area.

CONCLUSION: Stratification based on cognition may help to elucidate the biological underpinnings of cognitive heterogeneity across SZ and BP risk.

King's College London

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