Is genetic risk of ADHD mediated via dopaminergic mechanism? A study of functional connectivity in ADHD and pharmacologically challenged healthy volunteers with a genetic risk profile
Abstract Recent GWAS allow us to calculate polygenic risk scores for ADHD. At the imaging level, resting-state fMRI analyses have given us valuable insights into changes in connectivity patterns in ADHD patients. However, no study has yet attempted to combine these two different levels of investigat...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-06-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-02003-y |
| _version_ | 1811328379671019520 |
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| author | Oliver Grimm Lara Thomä Thorsten M. Kranz Andreas Reif |
| author_facet | Oliver Grimm Lara Thomä Thorsten M. Kranz Andreas Reif |
| author_sort | Oliver Grimm |
| collection | DOAJ |
| description | Abstract Recent GWAS allow us to calculate polygenic risk scores for ADHD. At the imaging level, resting-state fMRI analyses have given us valuable insights into changes in connectivity patterns in ADHD patients. However, no study has yet attempted to combine these two different levels of investigation. For this endeavor, we used a dopaminergic challenge fMRI study (L-DOPA) in healthy participants who were genotyped for their ADHD, MDD, schizophrenia, and body height polygenic risk score (PRS) and compared results with a study comparing ADHD patients and healthy controls. Our objective was to evaluate how L-DOPA-induced changes of reward-system-related FC are dependent on the individual polygenic risk score. FMRI imaging was used to evaluate resting-state functional connectivity (FC) of targeted subcortical structures in 27 ADHD patients and matched controls. In a second study, we evaluated the effect of ADHD and non-ADHD PRS in a L-DOPA-based pharmaco-fMRI-challenge in 34 healthy volunteers. The functional connectivity between the putamen and parietal lobe was decreased in ADHD patients. In healthy volunteers, the FC between putamen and parietal lobe was lower in ADHD high genetic risk participants. This direction of connectivity was reversed during L-DOPA challenge. Further findings are described for other dopaminergic subcortical structures. The FC between the putamen and the attention network showed the most consistent change in patients as well as in high-risk participants. Our results suggest that FC of the dorsal attention network is altered in adult ADHD as well as in healthy controls with higher genetic risk. |
| first_indexed | 2024-04-13T15:25:06Z |
| format | Article |
| id | doaj.art-fce098b6eae548f087cd9568cc4ee18f |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-13T15:25:06Z |
| publishDate | 2022-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-fce098b6eae548f087cd9568cc4ee18f2022-12-22T02:41:33ZengNature Publishing GroupTranslational Psychiatry2158-31882022-06-011211910.1038/s41398-022-02003-yIs genetic risk of ADHD mediated via dopaminergic mechanism? A study of functional connectivity in ADHD and pharmacologically challenged healthy volunteers with a genetic risk profileOliver Grimm0Lara Thomä1Thorsten M. Kranz2Andreas Reif3Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe UniversityDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe UniversityDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe UniversityDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe UniversityAbstract Recent GWAS allow us to calculate polygenic risk scores for ADHD. At the imaging level, resting-state fMRI analyses have given us valuable insights into changes in connectivity patterns in ADHD patients. However, no study has yet attempted to combine these two different levels of investigation. For this endeavor, we used a dopaminergic challenge fMRI study (L-DOPA) in healthy participants who were genotyped for their ADHD, MDD, schizophrenia, and body height polygenic risk score (PRS) and compared results with a study comparing ADHD patients and healthy controls. Our objective was to evaluate how L-DOPA-induced changes of reward-system-related FC are dependent on the individual polygenic risk score. FMRI imaging was used to evaluate resting-state functional connectivity (FC) of targeted subcortical structures in 27 ADHD patients and matched controls. In a second study, we evaluated the effect of ADHD and non-ADHD PRS in a L-DOPA-based pharmaco-fMRI-challenge in 34 healthy volunteers. The functional connectivity between the putamen and parietal lobe was decreased in ADHD patients. In healthy volunteers, the FC between putamen and parietal lobe was lower in ADHD high genetic risk participants. This direction of connectivity was reversed during L-DOPA challenge. Further findings are described for other dopaminergic subcortical structures. The FC between the putamen and the attention network showed the most consistent change in patients as well as in high-risk participants. Our results suggest that FC of the dorsal attention network is altered in adult ADHD as well as in healthy controls with higher genetic risk.https://doi.org/10.1038/s41398-022-02003-y |
| spellingShingle | Oliver Grimm Lara Thomä Thorsten M. Kranz Andreas Reif Is genetic risk of ADHD mediated via dopaminergic mechanism? A study of functional connectivity in ADHD and pharmacologically challenged healthy volunteers with a genetic risk profile Translational Psychiatry |
| title | Is genetic risk of ADHD mediated via dopaminergic mechanism? A study of functional connectivity in ADHD and pharmacologically challenged healthy volunteers with a genetic risk profile |
| title_full | Is genetic risk of ADHD mediated via dopaminergic mechanism? A study of functional connectivity in ADHD and pharmacologically challenged healthy volunteers with a genetic risk profile |
| title_fullStr | Is genetic risk of ADHD mediated via dopaminergic mechanism? A study of functional connectivity in ADHD and pharmacologically challenged healthy volunteers with a genetic risk profile |
| title_full_unstemmed | Is genetic risk of ADHD mediated via dopaminergic mechanism? A study of functional connectivity in ADHD and pharmacologically challenged healthy volunteers with a genetic risk profile |
| title_short | Is genetic risk of ADHD mediated via dopaminergic mechanism? A study of functional connectivity in ADHD and pharmacologically challenged healthy volunteers with a genetic risk profile |
| title_sort | is genetic risk of adhd mediated via dopaminergic mechanism a study of functional connectivity in adhd and pharmacologically challenged healthy volunteers with a genetic risk profile |
| url | https://doi.org/10.1038/s41398-022-02003-y |
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