Molecular characterization of the stress network in individuals at risk for schizophrenia

Journal article (2021)

Authors

Mandy Meijer Radboud University Medical Center, Leiden University Medical Center
D.L. Keo Pattern Recognition and Bioinformatics - EEMCS
Judith M.C. van Leeuwen Radboud University Medical Center, University Medical Center Utrecht
Oleh Dzyubachyk Leiden University Medical Center
Onno C. Meijer Leiden University Medical Center
Christiaan H. Vinkers Amsterdam UMC
A.M.E.T.A. Mahfouz Leiden University Medical Center, Pattern Recognition and Bioinformatics - EEMCS
Ahmed Mahfouz Leiden University Medical Center, Pattern Recognition and Bioinformatics - EEMCS
Research Group
Pattern Recognition and Bioinformatics (EEMCS) (TU Delft)
Copyright: © 2021 Mandy Meijer, D.L. Keo, Judith M.C. van Leeuwen, Oleh Dzyubachyk, Onno C. Meijer, Christiaan H. Vinkers, A.M.E.T.A. Mahfouz
DOI: https://doi.org/10.1016/j.ynstr.2021.100307
More Info
expand_more

Published Date

2021

Language

English

Faculty

Electrical Engineering, Mathematics and Computer Science

Department

Intelligent Systems

Research Group

Pattern Recognition and Bioinformatics

Abstract

The biological mechanisms underlying inter-individual differences in human stress reactivity remain poorly understood. We aimed to identify the molecular underpinning of aberrant neural stress sensitivity in individuals at risk for schizophrenia. Linking mRNA expression data from the Allen Human Brain Atlas to task-based fMRI revealed 201 differentially expressed genes in cortex-specific brain regions differentially activated by stress in individuals with low (healthy siblings of schizophrenia patients) or high (healthy controls) stress sensitivity. These genes are associated with stress-related psychiatric disorders (e.g. schizophrenia and anxiety) and include markers for specific neuronal populations (e.g. ADCYAP1, GABRB1, SSTR1, and TNFRSF12A), neurotransmitter receptors (e.g. GRIN3A, SSTR1, GABRB1, and HTR1E), and signaling factors that interact with the corticosteroid receptor and hypothalamic-pituitary-adrenal axis (e.g. ADCYAP1, IGSF11, and PKIA). Overall, the identified genes potentially underlie altered stress reactivity in individuals at risk for schizophrenia and other psychiatric disorders and play a role in mounting an adaptive stress response in at-risk individuals, making them potentially druggable targets for stress-related diseases.