Auditory P300 Potentials as State Biomarkers for Mild-to-Moderate Depression in Spinocerebellar Ataxia Type 2

Depression is a common comorbidity in spinocerebellar ataxia type 2 (SCA2). Despite P300 endogenous evoked potentials reliably indexing early cognitive deficits, their utility as depression biomarkers remains untested. This study aimed to characterize auditory P300 potentials as biomarkers of comorbid depression in SCA2 patients. Twenty SCA2 patients and age/sex-matched controls were stratified by Beck Depression Inventory-II (BDI-II) into depressed (≥ 14) and non-depressed (< 14) subgroups. Auditory P300 oddball paradigms were recorded, and P300 latency and amplitude analyzed in all participants. Two-way ANOVAs examined main effects and disease×depression interactions on P300 variables. SARA quantified ataxia severity. Two-way ANOVAs revealed significant main effects of disease group and depression status on P300 latency (rank-transformed data) and amplitude (parametric data), without significant interactions. Post-hoc Sidák tests confirmed prolonged latency and reduced amplitude in SCA2 patients vs. controls within both depression strata, and in depressed vs. non-depressed subgroups within each cohort. Spearman correlations demonstrated consistent P300-BDI-II relationships, but not associations between P300 parameters and SARA scores. ANCOVA confirmed independent depression effects on P300 parameters after covariate adjustment in SCA2. Auditory P300 latency and amplitude serve as state-dependent biomarkers for depression in SCA2, independent of motor progression. This supports P300 use as a secondary endpoint in clinical trials, enabling earlier diagnosis and precision medicine for affective symptoms.