TMS-EEG correlate of suicidal ideation in individuals with depression: A multi-site synthesis

BACKGROUND: Suicidal ideation (SI) is a leading risk factor for suicide death, with a lifetime prevalence of 35-40% in psychiatric populations. However, the neurobiology of SI remains poorly understood. Preliminary work suggests an association between SI and neurophysiological measures derived from transcranial magnetic stimulation combined with electroencephalography (TMS-EEG). METHODS: This study aims to test the association between SI and two TMS-EEG measures: the negative peak at 100 ms (N100) and the area under the curve (AUC) of the global mean field amplitude (GMFA). In this multi-site data synthesis, cross-sectional TMS-EEG data from 299 adult participants with major depressive disorder and at least 1 ineffective antidepressant trial were aggregated across five academic medical centers. Single-pulse TMS was delivered to the left dorsolateral prefrontal cortex (DLPFC) with simultaneous EEG recording. RESULTS: The N100 peak amplitude between 80 and 130 ms, as well as the AUC-GMFA between 55 and 275 ms, were extracted for each participant. Ordinal regression analysis revealed a significant positive association between more negative N100 peak amplitude in the left DLPFC and greater severity of SI (OR = 1.52, p = 0.002, 95%CI [1.17; 1.98]), independent of age, sex, depression severity, and study site. There was no significant association between GMFA and SI. CONCLUSION: N100 peak amplitude in the left DLPFC is a neurophysiological correlate of SI which may reflect a neurophysiological link between GABAergic inhibitory dysregulation and the pathophysiology of SI. Further research is needed to validate these findings using sham TMS-EEG and subsequently test the utility of N100 in the left DLPFC as a biomarker of SI and a possible treatment target.