Reward Sensitivity of ACC as an Intermediate Phenotype between DRD4-521T and Substance Misuse
The development and expression of the midbrain dopamine system is determined in part by genetic factors that vary across individuals such that dopamine-related genes are partly responsible for addiction vulnerability. However, a complete account of how dopamine-related genes predispose individuals t...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Published: |
2016
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| Online Access: | http://hdl.handle.net/20.500.11937/30511 |
| _version_ | 1848753109740814336 |
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| author | Baker, T. Stockwell, Tim Barnes, G. Haesevoets, R. Holroyd, C. |
| author_facet | Baker, T. Stockwell, Tim Barnes, G. Haesevoets, R. Holroyd, C. |
| author_sort | Baker, T. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | The development and expression of the midbrain dopamine system is determined in part by genetic factors that vary across individuals such that dopamine-related genes are partly responsible for addiction vulnerability. However, a complete account of how dopamine-related genes predispose individuals to drug addiction remains to be developed. Adopting an intermediate phenotype approach, we investigated whether reward-related electrophysiological activity of ACC—a cortical region said to utilize dopamine reward signals to learn the value of extended, context-specific sequences of goal-directed behaviors—mediates the influence of multiple dopamine-related functional polymorphisms over substance use. We used structural equation modeling to examine whether two related electrophysiological phenomena associated with the control and reinforcement learning functions of ACC—theta power and the reward positivity— mediated the relationship between the degree of substance misuse and genetic polymorphisms that regulate dopamine processing in frontal cortex. Substance use data were collected from 812 undergraduate students. One hundred ninety-six returned on a subsequent day to participate in an electrophysiological experiment and to provide saliva samples for DNA analysis. We found that these electrophysiological signals mediated a relationship between the DRD4-521T dopamine receptor genotype and substance misuse. Our results provide a theoretical framework that bridges the gap between genes and behavior in drug addiction and illustrate how future interventions might be individually tailored for specific genetic and neurocognitive profiles. |
| first_indexed | 2025-11-14T08:19:18Z |
| format | Journal Article |
| id | curtin-20.500.11937-30511 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:19:18Z |
| publishDate | 2016 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-305112017-09-13T15:32:48Z Reward Sensitivity of ACC as an Intermediate Phenotype between DRD4-521T and Substance Misuse Baker, T. Stockwell, Tim Barnes, G. Haesevoets, R. Holroyd, C. The development and expression of the midbrain dopamine system is determined in part by genetic factors that vary across individuals such that dopamine-related genes are partly responsible for addiction vulnerability. However, a complete account of how dopamine-related genes predispose individuals to drug addiction remains to be developed. Adopting an intermediate phenotype approach, we investigated whether reward-related electrophysiological activity of ACC—a cortical region said to utilize dopamine reward signals to learn the value of extended, context-specific sequences of goal-directed behaviors—mediates the influence of multiple dopamine-related functional polymorphisms over substance use. We used structural equation modeling to examine whether two related electrophysiological phenomena associated with the control and reinforcement learning functions of ACC—theta power and the reward positivity— mediated the relationship between the degree of substance misuse and genetic polymorphisms that regulate dopamine processing in frontal cortex. Substance use data were collected from 812 undergraduate students. One hundred ninety-six returned on a subsequent day to participate in an electrophysiological experiment and to provide saliva samples for DNA analysis. We found that these electrophysiological signals mediated a relationship between the DRD4-521T dopamine receptor genotype and substance misuse. Our results provide a theoretical framework that bridges the gap between genes and behavior in drug addiction and illustrate how future interventions might be individually tailored for specific genetic and neurocognitive profiles. 2016 Journal Article http://hdl.handle.net/20.500.11937/30511 10.1162/jocn_a_00905 restricted |
| spellingShingle | Baker, T. Stockwell, Tim Barnes, G. Haesevoets, R. Holroyd, C. Reward Sensitivity of ACC as an Intermediate Phenotype between DRD4-521T and Substance Misuse |
| title | Reward Sensitivity of ACC as an Intermediate Phenotype between DRD4-521T and Substance Misuse |
| title_full | Reward Sensitivity of ACC as an Intermediate Phenotype between DRD4-521T and Substance Misuse |
| title_fullStr | Reward Sensitivity of ACC as an Intermediate Phenotype between DRD4-521T and Substance Misuse |
| title_full_unstemmed | Reward Sensitivity of ACC as an Intermediate Phenotype between DRD4-521T and Substance Misuse |
| title_short | Reward Sensitivity of ACC as an Intermediate Phenotype between DRD4-521T and Substance Misuse |
| title_sort | reward sensitivity of acc as an intermediate phenotype between drd4-521t and substance misuse |
| url | http://hdl.handle.net/20.500.11937/30511 |