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

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Dopamine Plasma Membrane Transport Proteins*/genetics ; Dopamine Plasma Membrane Transport Proteins*/metabolism ; Mental Disorders*/genetics ; Mental Disorders*/epidemiology ; Gene Regulatory Networks* ; Dopamine*/metabolism ; Polymorphism, Single Nucleotide* ; Cardiovascular Diseases*/genetics ; Cardiovascular Diseases*/epidemiology ; Corpus Striatum*/metabolism; Humans ; Male ; Female ; Adult ; Adolescent ; Comorbidity ; Middle Aged ; Adverse Childhood Experiences ; Birth Weight ; Risk Factors ; Multifactorial Inheritance

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).)

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0 (Dopamine Plasma Membrane Transport Proteins)
0 (SLC6A3 protein, human)
VTD58H1Z2X (Dopamine)

Date Created: 20241109 Date Completed: 20241109 Latest Revision: 20241116

20241116

PMC11550826

10.1038/s41598-024-78465-5

39521843