Abstract
The exploration of the relationship between gene expression profiles and neural response patterns known to be altered in major depressive disorder provides a unique opportunity to identify novel targets for diagnosis and therapy. Here, we estimated the spatial association between genome-wide transcriptome maps and brain activation patterns from functional magnetic resonance imaging (fMRI) with two established paradigms of great relevance for mood disorders. While task-specific neural responses during emotion processing were primarily associated with expression patterns of genes involved in cellular transport, reward processing was related to neuronal development, synapse regulation, as well as gene transcription. Multimodal integration of single-site and meta-analytic imaging data with risk genes associated with depression revealed a regional susceptibility of functional activity, modulated by master regulators TCF4 and MEF2C. The identification of multiple subordinate genes correlated with fMRI maps and their corresponding regulators presumably will reshape the prospects for neuroimaging genetics.
One Sentence Summary Analysis of the spatial association between whole-brain human gene expression and in-vivo brain activation patterns during emotion and reward processing identified TCF4 and MEF2C as master regulatory genes associated with depressive disorders.
Competing Interest Statement
SK received grants/research support, consulting fees and/or honoraria within the last three years from Angelini, AOP Orphan Pharmaceuticals AG, Celegne GmbH, Eli Lilly, Janssen-Cilag Pharma GmbH, KRKA-Pharma, Lundbeck A/S, Mundipharma, Neuraxpharm, Pfizer, Sanofi, Schwabe, Servier, Shire, Sumitomo Dainippon Pharma Co. Ltd. and Takeda. RL received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR, Heel, and support from Siemens Healthcare regarding clinical research using PET/MR; he is shareholder of BM Health GmbH since 2019. The remaining authors declare no competing interests.