| Title: | Energy inefficiency underpinning brain state dysregulation in individuals with major depressive disorder |
| Journal: | Nature Mental Health |
| Published: | 12 Feb 2026 |
| DOI: | https://doi.org/10.1038/s44220-025-00583-4 |
Publication 18290
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Disruptions in brain state dynamics are a hallmark of major depressive disorder (MDD), yet their underlying mechanisms remain unclear. Here, building on network control theory, this case-control study reveals that energy inefficiency, characterized by elevated energy costs and reduced control stability, drives decreased state stability and increased state-switching frequency in MDD. Key brain regions, including the left dorsolateral prefrontal cortex and insula, exhibited impaired energy regulation capacity (a metric validated against cerebral metabolism). Moreover, these region-specific energy patterns were correlated with depressive symptom severity. Neurotransmitter and gene expression association analyses linked these energy deficits to intrinsic biological factors, notably the serotonin 5-HT2A receptor and astrocytes. These findings shed light on the energetic mechanism underlying brain state dysregulation in MDD and its associated biological underpinnings, highlighting brain energy dynamics as a potential biomarker by which to explore therapeutic targets and advance precise interventions for restoring healthy brain dynamics in depression.</p>
9 Authors
- Qianhui Liu
- Hui Xiong
- Weiyang Shi
- Shiqi Di
- Xinle Cheng
- Nianyi Liu
- Na Luo
- Yu Zhang
- Tianzi Jiang
1 Application
| Application ID | Title |
|---|---|
| 88660 | Mapping the brain and genetic basis of high-order human cognition in healthy and diseased population |
Enabling scientific discoveries that improve human health