Neurophysiological handover from MMN to P3a in first-episode and recurrent major depression

Abstract Background Mismatch negativity (MMN) and P3a components are sequential and co-occur. MMN represents the pre-attentive index of deviance detection and P3a represents the attention orienting response. Major depressive disorder (MDD) is characterized by impaired pre-attentive information processing. To assess whether impaired pre-attentive information processing can lead to an impairment of subsequent orienting process as the neurophysiological transmission spreads from MMN to P3a in MDD. Methods MMN/P3a was obtained during a two-tone auditory paradigm with 8% duration deviants in 45 first-episode major depression subjects (F-MD), 40 recurrent major depression subjects (R-MD), and 46 healthy controls (HC). Results Compared with HC, F-MD and R-MD had lower MMN amplitudes and no differences were found between F-MD and R-MD. Notably, R-MD had lower P3a amplitudes and longer P3a latencies compared to HC, while F-MD had no differences. Interestingly, no correlations were found between the severity of depression and the deficits of MMN amplitude. The deficits of P3a amplitude, however, were negatively correlated with the severity of depression in F-MD and R-MD. Furthermore, the P3a amplitude deficits were positively correlated with the number of episodes in R-MD. Limitations Patients were on antidepressant medication. Conclusions The recurrence of depressive episodes can lead to impaired pre-attentive information processing, causing an impairment of subsequent orienting process as the neurophysiological transmission from MMN to P3a. It further suggests that the impaired processing indexed by MMN amplitude may be a stable trait biomarker for the appearance of depression, while P3a amplitude can be used a potential biomarker for recurrence.