Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosis
Abstract Cholinergic dysfunction has been implicated in the pathophysiology of psychosis and psychiatric disorders such as schizophrenia, depression, and bipolar disorder. The basal forebrain (BF) cholinergic nuclei, defined as cholinergic cell groups Ch1-3 and Ch4 (Nucleus Basalis of Meynert; NBM),...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-09-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-02136-0 |
| _version_ | 1817994079349243904 |
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| author | Min Tae M. Park Peter Jeon Leon French Kara Dempster M. Mallar Chakravarty Michael MacKinley Julie Richard Ali R. Khan Jean Théberge Lena Palaniyappan |
| author_facet | Min Tae M. Park Peter Jeon Leon French Kara Dempster M. Mallar Chakravarty Michael MacKinley Julie Richard Ali R. Khan Jean Théberge Lena Palaniyappan |
| author_sort | Min Tae M. Park |
| collection | DOAJ |
| description | Abstract Cholinergic dysfunction has been implicated in the pathophysiology of psychosis and psychiatric disorders such as schizophrenia, depression, and bipolar disorder. The basal forebrain (BF) cholinergic nuclei, defined as cholinergic cell groups Ch1-3 and Ch4 (Nucleus Basalis of Meynert; NBM), provide extensive cholinergic projections to the rest of the brain. Here, we examined microstructural neuroimaging measures of the cholinergic nuclei in patients with untreated psychosis (~31 weeks of psychosis, <2 defined daily dose of antipsychotics) and used magnetic resonance spectroscopy (MRS) and transcriptomic data to support our findings. We used a cytoarchitectonic atlas of the BF to map the nuclei and obtained measures of myelin (quantitative T1, or qT1 as myelin surrogate) and microstructure (axial diffusion; AxD). In a clinical sample (n = 85; 29 healthy controls, 56 first-episode psychosis), we found significant correlations between qT1 of Ch1-3, left NBM and MRS-based dorsal anterior cingulate choline in healthy controls while this relationship was disrupted in FEP (p > 0.05). Case-control differences in qT1 and AxD were observed in the Ch1-3, with increased qT1 (reflecting reduced myelin content) and AxD (reflecting reduced axonal integrity). We found clinical correlates between left NBM qT1 with manic symptom severity, and AxD with negative symptom burden in FEP. Intracortical and subcortical myelin maps were derived and correlated with BF myelin. BF-cortical and BF-subcortical myelin correlations demonstrate known projection patterns from the BF. Using data from the Allen Human Brain Atlas, cholinergic nuclei showed significant enrichment for schizophrenia and depression-related genes. Cell-type specific enrichment indicated enrichment for cholinergic neuron markers as expected. Further relating the neuroimaging correlations to transcriptomics demonstrated links with cholinergic receptor genes and cell type markers of oligodendrocytes and cholinergic neurons, providing biological validity to the measures. These results provide genetic, neuroimaging, and clinical evidence for cholinergic dysfunction in schizophrenia. |
| first_indexed | 2024-04-14T01:48:07Z |
| format | Article |
| id | doaj.art-d14bf40211984453ab21fc97b6dac7b4 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-14T01:48:07Z |
| publishDate | 2022-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-d14bf40211984453ab21fc97b6dac7b42022-12-22T02:19:28ZengNature Publishing GroupTranslational Psychiatry2158-31882022-09-0112111110.1038/s41398-022-02136-0Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosisMin Tae M. Park0Peter Jeon1Leon French2Kara Dempster3M. Mallar Chakravarty4Michael MacKinley5Julie Richard6Ali R. Khan7Jean Théberge8Lena Palaniyappan9Department of Psychiatry, Schulich School of Medicine and Dentistry, Western UniversityDepartment of Medical Biophysics, Western UniversityDepartment of Psychiatry, University of TorontoDepartment of Psychiatry, Dalhousie UniversityDepartments of Psychiatry and Biological and Biomedical Engineering, McGill UniversityRobarts Research Institute, Western UniversityDepartment of Psychiatry, Schulich School of Medicine and Dentistry, Western UniversityDepartment of Medical Biophysics, Western UniversityDepartment of Psychiatry, Schulich School of Medicine and Dentistry, Western UniversityDepartment of Psychiatry, Schulich School of Medicine and Dentistry, Western UniversityAbstract Cholinergic dysfunction has been implicated in the pathophysiology of psychosis and psychiatric disorders such as schizophrenia, depression, and bipolar disorder. The basal forebrain (BF) cholinergic nuclei, defined as cholinergic cell groups Ch1-3 and Ch4 (Nucleus Basalis of Meynert; NBM), provide extensive cholinergic projections to the rest of the brain. Here, we examined microstructural neuroimaging measures of the cholinergic nuclei in patients with untreated psychosis (~31 weeks of psychosis, <2 defined daily dose of antipsychotics) and used magnetic resonance spectroscopy (MRS) and transcriptomic data to support our findings. We used a cytoarchitectonic atlas of the BF to map the nuclei and obtained measures of myelin (quantitative T1, or qT1 as myelin surrogate) and microstructure (axial diffusion; AxD). In a clinical sample (n = 85; 29 healthy controls, 56 first-episode psychosis), we found significant correlations between qT1 of Ch1-3, left NBM and MRS-based dorsal anterior cingulate choline in healthy controls while this relationship was disrupted in FEP (p > 0.05). Case-control differences in qT1 and AxD were observed in the Ch1-3, with increased qT1 (reflecting reduced myelin content) and AxD (reflecting reduced axonal integrity). We found clinical correlates between left NBM qT1 with manic symptom severity, and AxD with negative symptom burden in FEP. Intracortical and subcortical myelin maps were derived and correlated with BF myelin. BF-cortical and BF-subcortical myelin correlations demonstrate known projection patterns from the BF. Using data from the Allen Human Brain Atlas, cholinergic nuclei showed significant enrichment for schizophrenia and depression-related genes. Cell-type specific enrichment indicated enrichment for cholinergic neuron markers as expected. Further relating the neuroimaging correlations to transcriptomics demonstrated links with cholinergic receptor genes and cell type markers of oligodendrocytes and cholinergic neurons, providing biological validity to the measures. These results provide genetic, neuroimaging, and clinical evidence for cholinergic dysfunction in schizophrenia.https://doi.org/10.1038/s41398-022-02136-0 |
| spellingShingle | Min Tae M. Park Peter Jeon Leon French Kara Dempster M. Mallar Chakravarty Michael MacKinley Julie Richard Ali R. Khan Jean Théberge Lena Palaniyappan Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosis Translational Psychiatry |
| title | Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosis |
| title_full | Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosis |
| title_fullStr | Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosis |
| title_full_unstemmed | Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosis |
| title_short | Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosis |
| title_sort | microstructural imaging and transcriptomics of the basal forebrain in first episode psychosis |
| url | https://doi.org/10.1038/s41398-022-02136-0 |
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