Neuroelectrophysiological Mechanisms Of Reward And Punishment Processing In Patients With First Episode Major Depressive Disorder

Objective: Abnormalities of reward and punishment processing impact the emergence and development of maladaptive behavior in patients with major depressive disorder(MDD),which exist important research significance while brain mechanisms are still not clear.This research adopted event-related potentials(ERP)to explore the electrophysiological mechanisms of reward and punishment processing in MDD and the alteration of disease status from two separate stages:(1)Study 1 was a cross-sectional study,combining the monetary incentive delay task and ERP to explore processing abnormalities and neuroelectrophysiological characteristics of reward valence in different stages with first episode MDD patients.(2)Study 2 performed longitudinal design,comparing the differences of reward and punishment processing related neuroelectrophysiological characteristics between remission and baseline,clarifying the development patterns of related neuroelectrophysiological characteristics during reward and punishment processing in MDD.Methods:(1)Study 1 included 67 first-episode and unmedicated MDD patients,and 36 healthy controls(HC).All of the participants completed depression,anxiety symptoms and anhedonia assessment,then performed monetary incentive delay task(MID)while collecting ERP data.For the anticipation stage in the task,this study conducted repeated ANOVAs analyses on cue P2 and cue P3 amplitude.And for the consumption stage,this study conducted repeated ANOVAs analyses on feedback-related negativity(FRN),and late positive potential(LPP).Significantly different ERP components between MDD and HC were conducted correlation analyses with clinical questionnaires.(2)25 firstepisode and unmedicated MDD patients were recruited in study 2,and were followed up regularly while they were treated with antidepressants.Clinical symptoms and ERP data of MID task were collected separately in the first episode and remission stage,comparing the alteration regular of the ERP components under the different disease statuses.between baseline and remission.Correlation analyses were carried out between alteration values of ERP components and clinical questionnaires.Results:(1)The results of study 1 showed that cue P2 and cue P3 amplitudes under the reward and punishment conditions were significantly larger than the neutral condition(all p<0.05)in both MDD and HC groups,but cue P2 and cue P3 amplitudes MDD were significantly smaller than HC during the anticipation stage(F=4.83,p=0.030;F=16.60,p<0.001).During the consumption stage,FRN under the positive feedback and negative feedback in MDD were both larger than those in HC(F=11.67,p=0.001;F=4.43,p=0.038).Conversely,LPP under the positive and negative feedback in MDD were both smaller than HC(F=10.72,p=0.001;F=5.73,p=0.019).LPP induced by positive feedback in the reward context was larger than that in the punishment and neutral context(both p<0.001).Correlation analyses showed that cue P2 and cue P3 under the reward condition were negatively correlated with BDI scores(r=-0.290,p=0.017;r=-0.270,p=0.027).LPP under the positive feedback in the reward and neutral conditions were correlated with consummatory anhedonia scores(r=0.30,p=0.014;r=0.36,p=0.003).(2)The results of study 2 showed that cue P2 and cue P3 failed to yield significant differences between baseline and remission.Cue P2 induced by reward and punishment were significantly larger than the neutral condition(p<0.001;p=0.004),and cue P3 induced by the reward condition was larger than the punishment and neutral condition(p=0.016;p=0.006).During the consumption stage,FRN was not different before and after remission.Under the positive feedback condition,LPP was not different before and after remission,while under the negative feedback condition,larger LPP was observed in remitted MDD than baseline(F=7.95,p=0.009).When receiving the positive feedback,LPP amplitude in the reward context was larger than the neutral condition(p=0.003).And when receiving the negative feedback,LPP in the reward context was larger than the neutral condition(p=0.003).Correlation analyses found that alteration of LPP induced by negative feedback in the punishment was related negatively with the alteration of HAMD(r=-0.418,p=0.042).Conclusion:(1)Neuroelectrophysiological injury in the first episode and unmedicated MDD indicated decreased motivation of pursuing reward and avoiding punishment in MDD,increased sensitivity to punishment as well as appraising deficits related to prediction error during the early feedback stage,and decreased sensitivity to punishment as well as cognition evaluation related to consummatory anhedonia.(2)The neuroelectrophysiological characteristics of abnormal motivation deficits and emotional motivation appraising during the early feedback stage in first episode MDD were likely to be state-independent deficits.While in the late feedback stage,decreased sensitivity to negative feedback indicated a state-dependent neuroelectrophysiological deficit.