Regional gene expression patterns are associated with task-specific brain activation during reward and emotion processing measured with functional MRI

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 SummaryAnalysis 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.

Correlation of receptor density and mRNA expression patterns in the human cerebral cortex

“…serotonin 1A and 2A (Beliveau et al, 2017;Komorowski et al, 2017;Unterholzner et al, 2020), dopamine D3 (Komorowski et al, 2020b), or enzymes (Lohith et al, 2017) measured using PET. Moreover, associations between mRNA expression patterns and task-specific activations measured by fMRI were revealed for reward and emotion processing (Komorowski et al, 2020a). Contrary to these findings, no relations were discovered between protein distribution and gene expression of monoamine oxidase A (Godbersen et al, 2021) and serotonin transporter (Komorowski et al, 2017).…”