Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosis.

Autor: Park MTM; Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London, Canada., Jeon P; Department of Medical Biophysics, Western University, London, Canada.; Robarts Research Institute, Western University, London, Canada.; Lawson Health Research Institute, London, Canada., French L; Department of Psychiatry, University of Toronto, Toronto, Canada., Dempster K; Department of Psychiatry, Dalhousie University, Halifax, Canada., Chakravarty MM; Departments of Psychiatry and Biological and Biomedical Engineering, McGill University, Montreal, Canada.; Cerebral Imaging Centre, Douglas Research Centre, Montreal, Canada., MacKinley M; Robarts Research Institute, Western University, London, Canada., Richard J; Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London, Canada., Khan AR; Department of Medical Biophysics, Western University, London, Canada.; Robarts Research Institute, Western University, London, Canada., Théberge J; Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London, Canada.; Department of Medical Biophysics, Western University, London, Canada.; Lawson Health Research Institute, London, Canada., Palaniyappan L; Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London, Canada. Lena.Palaniyappan@mcgill.ca.; Department of Medical Biophysics, Western University, London, Canada. Lena.Palaniyappan@mcgill.ca.; Robarts Research Institute, Western University, London, Canada. Lena.Palaniyappan@mcgill.ca.; Lawson Health Research Institute, London, Canada. Lena.Palaniyappan@mcgill.ca.; Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Canada. Lena.Palaniyappan@mcgill.ca.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2022 Sep 01; Vol. 12 (1), pp. 358. Date of Electronic Publication: 2022 Sep 01.
DOI: 10.1038/s41398-022-02136-0
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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