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Neurodevelopmental signature of a transcriptome-based polygenic risk score for depression.
Miles, Amy E; Rashid, Sarah S; Dos Santos, Fernanda C; Clifford, Kevan P; Sibille, Etienne; Nikolova, Yuliya S.
Afiliación
  • Miles AE; Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
  • Rashid SS; Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
  • Dos Santos FC; Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
  • Clifford KP; Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
  • Sibille E; Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
  • Nikolova YS; Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address: yuliya.nikolova@camh.ca.
Psychiatry Res ; 339: 116030, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38909414
ABSTRACT
Disentangling the molecular underpinnings of major depressive disorder (MDD) is necessary for identifying new treatment and prevention targets. The functional impact of depression-related transcriptomic changes on the brain remains relatively unexplored. We recently developed a novel transcriptome-based polygenic risk score (tPRS) composed of genes transcriptionally altered in MDD. Here, we sought to investigate effects of tPRS on brain structure in a developmental cohort (Adolescent Brain Cognitive Development study; n = 5124; 2387 female) at baseline (9-10 years) and 2-year follow-up (11-12 years). We tested associations between tPRS and Freesurfer-derived measures of cortical thickness, cortical surface area, and subcortical volume. Across the whole sample, higher tPRS was significantly associated with thicker left posterior cingulate cortex at both baseline and 2-year follow-up. In females only, tPRS was associated with lower right hippocampal volume at baseline and 2-year follow-up, and lower right pallidal volume at baseline. Furthermore, regional subcortical volume significantly mediated an indirect effect of tPRS on depressive symptoms in females at both timepoints. Conversely, tPRS did not have significant effects on cortical surface area. These findings suggest the existence of a sex-specific neurodevelopmental signature associated with shifts towards a more depression-like brain transcriptome, and highlight novel pathways of developmentally mediated MDD risk.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Herencia Multifactorial / Trastorno Depresivo Mayor / Transcriptoma Límite: Adolescent / Child / Female / Humans / Male Idioma: En Revista: Psychiatry Res Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Irlanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Herencia Multifactorial / Trastorno Depresivo Mayor / Transcriptoma Límite: Adolescent / Child / Female / Humans / Male Idioma: En Revista: Psychiatry Res Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Irlanda