Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity.

Autor: Barth B; Integrated Program in Neurosciences, McGill University, Montreal, QC, Canada.; Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.; Ludmer Centre for Neuroinformatics and Mental Health, Douglas Research Centre, McGill University, Montreal, QC, Canada., Arcego DM; Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.; Ludmer Centre for Neuroinformatics and Mental Health, Douglas Research Centre, McGill University, Montreal, QC, Canada., de Mendonça Filho EJ; Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.; Ludmer Centre for Neuroinformatics and Mental Health, Douglas Research Centre, McGill University, Montreal, QC, Canada.; Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada., de Lima RMS; Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.; Ludmer Centre for Neuroinformatics and Mental Health, Douglas Research Centre, McGill University, Montreal, QC, Canada.; Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada., Parent C; Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada., Dalmaz C; Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Portella AK; Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada., Pokhvisneva I; Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada., Meaney MJ; Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.; Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.; Translational Neuroscience Programme, Singapore Institute for Clinical Sciences, Agency for Science, Technology & Research, Singapore, Singapore., Silveira PP; Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada. patricia.silveira@mcgill.ca.; Ludmer Centre for Neuroinformatics and Mental Health, Douglas Research Centre, McGill University, Montreal, QC, Canada. patricia.silveira@mcgill.ca.; Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada. patricia.silveira@mcgill.ca.; Department of Paediatrics, Yong Lin Loon School of Medicine, National University of Singapore, Singapore, Singapore. patricia.silveira@mcgill.ca.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Nov 09; Vol. 14 (1), pp. 27349. Date of Electronic Publication: 2024 Nov 09.
DOI: 10.1038/s41598-024-78465-5
Abstrakt: Cardiometabolic and psychiatric disorders often co-exist and share common early life risk factors, such as low birth weight. However, the biological pathways linking early adversity to adult cardiometabolic/psychiatric comorbidity remain unknown. Dopamine (DA) neurotransmission in the striatum is sensitive to early adversity and influences the development of both cardiometabolic and psychiatric diseases. Here we show that a co-expression based polygenic score (ePGS) reflecting individual variations in the expression of the striatal dopamine transporter gene (SLC6A3) network significantly interacts with birth weight to predict psychiatric and cardiometabolic comorbidities in both adults (UK Biobank, N = 225,972) and adolescents (ALSPAC, N = 1188). Decreased birth weight is associated with an increased risk for psychiatric and cardiometabolic comorbidities, but the effect is dependent on a striatal SLC6A3 ePGS, that reflects individual variation in gene expression of genes coexpressed with the SLC6A3 gene in the striatum. Neuroanatomical analyses revealed that SNPs from the striatum SLC6A3 ePGS were significantly associated with prefrontal cortex gray matter density, suggesting a neuroanatomical basis for the link between early adversity and psychiatric and cardiometabolic comorbidity. Our study reveals that psychiatric and cardiometabolic diseases share common developmental pathways and underlying neurobiological mechanisms that includes dopamine signaling in the striatum.
(© 2024. The Author(s).)
Databáze: MEDLINE
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