J Affect Disord. 2026 Mar 21:121641. doi: 10.1016/j.jad.2026.121641. Online ahead of print.
ABSTRACT
BACKGROUND: Mismatch negativity (MMN), an electrophysiological index of pre-attentive prediction-error processing, is impaired in major depressive disorder (MDD). However, its utility in distinguishing adolescents with MDD who engage in non-suicidal self-injury (NSSI) from those with suicidal behavior (SB) remains unclear.
METHODS: We recruited 228 adolescents (10-24 years) into four groups: healthy controls (HC), MDD-Only, MDD + NSSI, and MDD + SB (n = 57 each). MMN was recorded using a passive auditory frequency MMN paradigm. Early (100-200 ms) and late (> 200 ms) component latency and amplitude were analyzed via ANOVA, targeted analyses, and spatiotemporal cluster-based permutation tests.
RESULTS: Compared to HC, all MDD groups showed prolonged MMN latency. The MDD + NSSI group exhibited reduced early MMN amplitude at left prefrontal site (F3) relative to non-NSSI groups (p = 0.022). In contrast, the MDD + SB group showed a trend toward prolonged late MMN latency at right prefrontal site (F4) compared to non-SB groups (uncorrected p = 0.063). Spatiotemporal analysis confirmed early (100-200 ms) deficits associated with NSSI and late (200-300 ms) deficits with SB. MMN amplitude (absolute value) at F3 correlated negatively with illness duration (rs = 0.22, p = 0.004).
LIMITATIONS: The cross-sectional design, limited electrode coverage, and absence of a visual distractor task preclude causal inference and source localization.
CONCLUSIONS: Adolescents with MDD + NSSI and MDD + SB show distinct pre-attentive processing deficits, indexed by early and late MMN components respectively. MMN shows promise as a potential neurophysiological biomarker for stratifying MDD subtypes and guiding targeted interventions.
PMID:41871636 | DOI:10.1016/j.jad.2026.121641
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