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

Journal Article (2021)
Author(s)

Mandy Meijer (Radboud University Medical Center, Leiden University Medical Center)

D.L. Keo (TU Delft - Pattern Recognition and Bioinformatics)

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)

Ahmed Mahfouz (TU Delft - Pattern Recognition and Bioinformatics, Leiden University Medical Center)

Research Group
Pattern Recognition and Bioinformatics
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 related publication
https://doi.org/10.1016/j.ynstr.2021.100307
More Info
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Publication Year
2021
Language
English
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
Research Group
Pattern Recognition and Bioinformatics
Volume number
14
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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.