Age-related changes in excitation–inhibition balance in major depressive disorder

Summary

Major depressive disorder (MDD) has been associated with abnormalities in the balance between excitatory and inhibitory neurotransmission, yet age-related changes in excitation–inhibition balance remain poorly understood. Yujiro Yoshihara, Taro Suwa, Toshiya Murai, and colleagues at Kyoto University investigated age-related changes in excitation–inhibition balance using 7-Tesla magnetic resonance spectroscopy (7T MRS). The study simultaneously quantified glutamate (Glu) and γ-aminobutyric acid (GABA) in the dorsal anterior cingulate cortex (dACC) of 41 patients with remitted MDD and 35 healthy controls. Healthy controls showed a significant age-related increase in the Glu/GABA ratio, whereas this age-related change was absent in patients with remitted MDD, resulting in a significant group-by-age interaction. In addition, although the Glu/GABA ratio was not associated with depressive symptoms or cognitive performance, the correlation between Glu and GABA was preserved in both groups. This study demonstrates that the normal age-related changes in excitation–inhibition balance observed in healthy individuals are absent in patients with remitted MDD. These findings provide new insights into the pathophysiology of depression and may contribute to the future development of imaging biomarkers. These findings suggest that altered neurochemical aging may represent a characteristic feature of remitted MDD. They also highlight the potential of ultra-high-field MRS for investigating disease-related neurochemical changes and developing imaging biomarkers.

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