Advancing the neuroelectrophysiological understanding of attentional switching dysfunction in major depressive disorder

Table 4 Potential clinical translation pathways for event-related potential biomarkers in major depressive disorder

Clinical application	Description	Example ERP biomarker	Current evidence stage	Challenges
Diagnostic Aid/subtyping	Objective measure to support clinical diagnosis or define cognitively distinct subgroups	Reduced P300 amplitude; blunted LPP to rewards	Promising research evidence; requires large normative databases and defined cut-offs	High inter-individual variability; overlap with other disorders
Predictor of treatment response	Baseline ERP profile predicting likelihood of response to a specific therapy (e.g., CBT, antidepressants)	Pre-treatment RewP or frontal theta activity	Early experimental stage; several promising candidate markers	Need for large, prospective, treatment-specific studies
Monitor of treatment process	ERP changes during treatment signaling engagement of target neural mechanisms	Increase in P300/LPP to positive stimuli during ABM or antidepressant treatment	Conceptually strong; used in mechanistic research studies	Establishing causal links between neural change and clinical outcome
Target for neuromodulation	Using aberrant ERP activity (source-localized) to guide brain stimulation targets	Reduced frontal P300 mapped to DLPFC for rTMS targeting	Experimental; used in some research protocols	Requires combined EEG-source imaging and neuromodulation
Index of functional recovery	ERP normalization associated with recovery of real-world cognitive/occupational function	Correlation between P300 amplitude recovery and return-to-work measures	Longitudinal studies are beginning to explore this	Long timeframes and multifactorial nature of functional outcomes

ERP: Event-related potential; LPP: Late positive potential; RewP: Reward positivity; CBT: Cognitive behavioral therapy; Aid: Assistance in depression; DLPFC: Dorsolateral prefrontal cortex; ABM: Attention bias modification; rTMS: Repetitive transcranial magnetic stimulation; EEG: Electroencephalography.