Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity
Abstract 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 stria...
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-78465-5 |
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| author | Barbara Barth Danusa Mar Arcego Euclides José de Mendonça Filho Randriely Merscher Sobreira de Lima Carine Parent Carla Dalmaz André Krumel Portella Irina Pokhvisneva Michael J. Meaney Patricia Pelufo Silveira |
| author_facet | Barbara Barth Danusa Mar Arcego Euclides José de Mendonça Filho Randriely Merscher Sobreira de Lima Carine Parent Carla Dalmaz André Krumel Portella Irina Pokhvisneva Michael J. Meaney Patricia Pelufo Silveira |
| author_sort | Barbara Barth |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-794671e69b204d05ada8dcfbee68e6ba |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-794671e69b204d05ada8dcfbee68e6ba2024-11-10T12:18:20ZengNature PortfolioScientific Reports2045-23222024-11-0114111410.1038/s41598-024-78465-5Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidityBarbara Barth0Danusa Mar Arcego1Euclides José de Mendonça Filho2Randriely Merscher Sobreira de Lima3Carine Parent4Carla Dalmaz5André Krumel Portella6Irina Pokhvisneva7Michael J. Meaney8Patricia Pelufo Silveira9Integrated Program in Neurosciences, McGill UniversityDouglas Mental Health University Institute, McGill UniversityDouglas Mental Health University Institute, McGill UniversityDouglas Mental Health University Institute, McGill UniversityDouglas Mental Health University Institute, McGill UniversityPrograma de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do SulDouglas Mental Health University Institute, McGill UniversityDouglas Mental Health University Institute, McGill UniversityDouglas Mental Health University Institute, McGill UniversityDouglas Mental Health University Institute, McGill UniversityAbstract 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.https://doi.org/10.1038/s41598-024-78465-5 |
| spellingShingle | Barbara Barth Danusa Mar Arcego Euclides José de Mendonça Filho Randriely Merscher Sobreira de Lima Carine Parent Carla Dalmaz André Krumel Portella Irina Pokhvisneva Michael J. Meaney Patricia Pelufo Silveira Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity Scientific Reports |
| title | Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity |
| title_full | Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity |
| title_fullStr | Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity |
| title_full_unstemmed | Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity |
| title_short | Striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity |
| title_sort | striatal dopamine gene network moderates the effect of early adversity on the risk for adult psychiatric and cardiometabolic comorbidity |
| url | https://doi.org/10.1038/s41598-024-78465-5 |
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