Intrinsic excitation-inhibition imbalance in major depressive disorder.
Journal of affective disorders June 29, 2026 Yao Ge, Lijuan Chen, Yu Shen et al.
In people with major depressive disorder, the balance between excitation and inhibition across the brain's cortex is disrupted, particularly in the parietal and prefrontal-cingulate regions. Using resting-state functional magnetic resonance imaging data from 254 patients and 451 healthy controls, the Hurst exponent—a proxy for excitation-inhibition balance—was found to be significantly reduced in patients. This imbalance was linked to specific gene expression related to neuronal structure, metabolism, and mitochondrial function, as well as to neurotransmitter systems including GABA, opioid, serotonin, and synaptic density. In a separate trial of 32 patients with treatment-resistant depression, ketamine increased the Hurst exponent in the anterior cingulate and medial prefrontal cortices, suggesting that restoring excitation-inhibition balance may underlie ketamine's antidepressant effects.