Genetic, individual, and familial risk correlates of brain network controllability in major depressive disorder

Hahn, Tim, Winter, Nils R, Ernsting, Jan, Gruber, Marius, Mauritz, Marco J, Fisch, Lukas, Leenings, Ramona, Sarink, Kelvin, Blanke, Julian, Holstein, Vincent
et al (show 20 more authors) (2023) Genetic, individual, and familial risk correlates of brain network controllability in major depressive disorder. MOLECULAR PSYCHIATRY, 28 (3). pp. 1057-1063.

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Many therapeutic interventions in psychiatry can be viewed as attempts to influence the brain's large-scale, dynamic network state transitions. Building on connectome-based graph analysis and control theory, Network Control Theory is emerging as a powerful tool to quantify network controllability-i.e., the influence of one brain region over others regarding dynamic network state transitions. If and how network controllability is related to mental health remains elusive. Here, from Diffusion Tensor Imaging data, we inferred structural connectivity and inferred calculated network controllability parameters to investigate their association with genetic and familial risk in patients diagnosed with major depressive disorder (MDD, n = 692) and healthy controls (n = 820). First, we establish that controllability measures differ between healthy controls and MDD patients while not varying with current symptom severity or remission status. Second, we show that controllability in MDD patients is associated with polygenic scores for MDD and psychiatric cross-disorder risk. Finally, we provide evidence that controllability varies with familial risk of MDD and bipolar disorder as well as with body mass index. In summary, we show that network controllability is related to genetic, individual, and familial risk in MDD patients. We discuss how these insights into individual variation of network controllability may inform mechanistic models of treatment response prediction and personalized intervention-design in mental health.

Item Type: Article
Uncontrolled Keywords: Brain, Humans, Genetic Predisposition to Disease, Magnetic Resonance Imaging, Depressive Disorder, Major, Diffusion Tensor Imaging, Connectome
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Population Health
Depositing User: Symplectic Admin
Date Deposited: 19 Jan 2023 16:09
Last Modified: 19 Oct 2023 09:01
DOI: 10.1038/s41380-022-01936-6
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