Abnormal Reward Processing In Adolescent Depression Is Modulated By Anxiety: An EEG-based Study

Research background and purpose:Depression is one of the most common psychological disorders,which seriously affects the quality of learning,work and life of patients and causes serious socioeconomic burden,and its prevalence is increasing year by year in a global trend of low age.Reward processing dysfunction is thought to play a crucial role in the pathogenesis of depression,and adolescence is an important period for the continuous development and improvement of neural reward circuits,as well as a period of vulnerability to depression.Depression with co-occurring anxiety(or anxious depression)is recognized as a common clinical subtype of depression and has its own unique features compared to anxiety-free depression.The aim of this study was to investigate the effects of co-occurring anxiety in abnormal reward processing and its neural mechanisms in depressed adolescents,with the aim of providing some valuable insights into the clinical diagnosis,treatment,and prognosis of depression.Materials and Methods:This study consisted of two experiments,Experiment 1 combined behavioral experiments with resting-state EEG to analyze the effects of anxiety on reward processing in healthy people,while Experiment 2 examined the effects of anxiety on reward processing in adolescents with depression using both monetary and social types of feedback,using questionnaire and behavioral data and the time-,frequency-,and spatial-domain characteristics of EEG.Experiment 1: A total of 44 healthy subjects(18-24 years old)participated in the experiment,24 males(20.833 ± 1.971 years old)and 20 females(21.100 ± 2.125 years old),who were divided into a high anxiety group(HTA)and a low anxiety group(LTA)according to the level of trait anxiety,with anxiety grouping and gender as two independent variables.The experimental task was a simple behavioral experiment in which subjects were asked to rate face attractiveness as a behavioral measure of subject reward sensitivity after viewing 80 female faces that appeared sequentially,and resting-state EEG data of 200 s duration were first collected from each subject prior to the experiment for microstate analysis,and the behavioral data and microstate analysis results were used for a two-way ANOVA,and subsequently mediated effects analysis was conducted.Experiment 2: Data from a total of 96 subjects were included,including 32controls(HC,15.83±2.079 years,21 males and 14 females),32 depressed patients with co-occurring anxiety(AD,15.35±1.836 years,13 males and 18 females),and 32 depressed patients without co-occurring anxiety(NAD,15.67±1.668 years 18 males and12 females).The experimental task used a simple gambling task and required subjects to rate their current mood after receiving feedback on each trial.Prior to the experiment,each subject completed five scales and collected resting-state EEG data of 200 s duration for microstate analysis,while the EEG data collected in the simple gambling task were used for event-related potential(ERP)and event-related oscillation(ERO)analysis.Among the ERP examined components included reflective pre-stimulus negative(SPN),feedback-related negative(FRN),and P300,and the waveforms of FRN and P300 were separated using t-PCA.ERO focused on the time-frequency window in theta band corresponding to FRN and P300.Result:Experiment 1: Behavioral results showed that males(3.858 ± 0.794)rated attraction to female faces significantly higher than females(3.164 ± 6.646)and that the LTA group(3.207 ± 0.903)rated significantly higher than the HTA group(3.877 ±0.518).The microstates results indicated that the LTA group showed longer and more frequent microstates A and shorter and less frequent microstates D than the HTA group.mediating effect analysis revealed that the duration of microstates A(Duration)had a masking effect in the effect of trait anxiety on face ratings,while the coverage of microstates A(Coverage)partially mediated this process.Experiment 2: Questionnaire and behavioral results showed that compared to the NAD group,the AD group had higher punishment sensitivity,GAD-7,PHQ-9,HAMA questionnaire scores,and self-emotion scores,and all were significantly higher than the HC group,while the opposite was true for the reward sensitivity subscale scores;EEG results: for SPN,at the right frontal electrode(AF4-F4),the SPN wave amplitude was significantly smaller in the HC group than in the NAD group and at the left parieto-occipital electrode(PO3-O1),the SPN wave amplitude in the HC group was significantly larger than that in the AD and NAD groups;for FRN,the FRN wave amplitude was larger in the AD group than in the NAD group,while there was no group difference in ΔFRN;for P300,the P300 wave amplitude 300 was larger in the HC group than in the AD group,and the P300 wave amplitude was larger in the NAD group than in the AD group;after principal component analysis,the PCA-The results of the statistical analysis of FRN and PCA-P300 wave amplitudes were roughly consistent with those before PCA;for ERO corresponding to FRN,only the main effect of feedback type was found,while for ERO corresponding to P300,the HC group was significantly larger than both the AD and NAD groups.The results of the microstate analysis were consistent with Experiment 1,with significantly lower duration,frequency of occurrence,mean GFP,and global interpretation of microstate A in the AD group than in the HC group.Conclusion:Experiments I and II demonstrated the same effects of anxiety in healthy and depressed populations: reduced reward sensitivity and blunted reward processing functions.These results,in terms of questionnaire and behavior,and the time,frequency,and spatial domains of EEG,fully illustrate that adolescent depressed patients with co-occurring anxiety have lower reward sensitivity and more impaired reward processing function relative to depressed patients without co-occurring anxiety.The present study provides new evidence for understanding the relationship between abnormal reward processing and co-occurring anxiety in adolescent depression and contributes to the development of future intervention and treatment strategies for these disorders.