Abnormal left prefrontal N100 and its relationship with fronto-limbic metabolism in major depressive disorder

04/06/2026

AI Summary

Left prefrontal N100 amplitudes were significantly greater in low severity MDD than in healthy controls.
In healthy controls N100 amplitude correlated positively with daily life stress; this association was absent in the MDD group.
In MDD higher N100 associated with increased prefrontal SUVs, inverse temporal/parietal/cingulate SUVs, and with more treatment failures in non-treatment-resistant subgroup.

TL;DR (AI Generated)

We sought to elucidate the fundamental processes of frontal inhibitory function by examining the left prefrontal N100 in patients with MDD and healthy controls (HCs).

In the MDD group, higher N100 amplitudes were associated with increased SUVs in the prefrontal cortex (p = 0.037) and inversely correlated with SUVs in the right middle temporal cortex, right inferior parietal cortex, and middle cingulum (SVC-corrected p < 0.05).

These data indicate that the N100 is significantly associated with depression severity and may represent a dynamic, compensatory neurophysiological mechanism aiming to restore the excitatory/inhibitory balance in response to aberrant fronto-limbic metabolism.

Basic summary

Transl Psychiatry. 2026 Jun 3. doi: 10.1038/s41398-026-04107-1. Online ahead of print.

ABSTRACT

Dysfunction within inhibitory GABAergic systems is implicated in the pathophysiology of major depressive disorder (MDD). The N100, a transcranial magnetic stimulation-evoked potential (TEP), reflects inhibitory neural processes mediated by GABA-B receptors. Yet, the relationship between the N100, stress levels, and cerebral glucose metabolism in MDD remains under-investigated. We sought to elucidate the fundamental processes of frontal inhibitory function by examining the left prefrontal N100 in patients with MDD and healthy controls (HCs). Sixty-six patients with MDD and 20 HCs were recruited; the N100 component was derived from single-pulse TEPs targeting the left dorsolateral prefrontal cortex. Patients were stratified into low-severity (score ≤ 16) and high-severity (score ≥17) groups based on the 17-item Hamilton Depression Rating Scale (HDRS-17). Cerebral metabolic activity was estimated using 18F-FDG PET standardized uptake values (SUVs). N100 amplitudes were significantly greater in the low-severity depression group compared to HCs (p = 0.002) and exhibited a positive correlation with daily life stress exclusively in HCs (r = 0.653, p = 0.002). In the MDD group, higher N100 amplitudes were associated with increased SUVs in the prefrontal cortex (p = 0.037) and inversely correlated with SUVs in the right middle temporal cortex, right inferior parietal cortex, and middle cingulum (SVC-corrected p < 0.05). Furthermore, N100 amplitudes correlated positively with the number of treatment failures specifically in the non-treatment-resistant depression (nTRD) subgroup. These data indicate that the N100 is significantly associated with depression severity and may represent a dynamic, compensatory neurophysiological mechanism aiming to restore the excitatory/inhibitory balance in response to aberrant fronto-limbic metabolism.

PMID:42236682 | DOI:10.1038/s41398-026-04107-1

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