Electroencephaphyisological Mechanisms Of Negativity Bias In Major Depression

Objective:Based on dorsal-ventral model of cognitive emotional interaction in major depression, we aimed to test (1) whether a negativity bias resultes from deficient top-down attentional control causing gain control of negative emotional information, and (2) the correlation between low serotonin (5-HT) function and negativity bias, and to explore the directionality and temporal specificity of such bias in major depression by behavioral performance and event-related potentials (ERPs) in a longitudinal study.Methods:The model and hypothesis were tested step by step from three domains of behavior, neurophysiology and pharmatherapeutics. Study 1 investigated the characteristics of impaired cognitive control and emotional bias, and their relationships, as well as both impaired cognitive control and emotional bias related with depression symptoms in major depressive disorder (MDD).17 first-episode MDD patients and 22 healthy controls performed cognitive tests of Trial Making, Verbal Fluency, Continuous Performance Test, the Wisconsin Card Sorting Test (WCST), and Stroop Color Word Test, as well as the visual choice tasks of Chinese emotional words. After 9-week antidepressants treatment,17 MDD patients were re-administered these tasks. Study 2 explored whether neurophysiological mechanisms of a negativity bias occur as a result of deficient top-down attentional control causing gain control of negative emotional information in MDD.20 nonmedicated patients with a first episode of unipolar MDD and 20 matched controls complete a visual three-stimulus semantic oddball task while electroencephalogram (EEG) activity was recorded. In the tasks, each of the positive and negative categories served in separate runs as task-relevant target or task-irrelevant nontarget, and neutral category as standard. Study 3 investigated the relationship of electroencephaphysiological mechanisms of the negativity bias and selective serotonin re-uptake inhibitors(SSRIstreatment effects. 16 nonmedicated patients with a first episode of unipolar MDD at initial time and after 9-week treatment with SSRIs, and 20 matched controls complete a visual three-stimulus semantic oddball task while electroencephalogram (EEG) activity was recorded.Results:(1) Study 1 showed that first episode MDD patients had impaired performance associated with cognitive control, and the emotional bias was characteristics of impaired processing of positive emotion, and there was a correlation of the choice index of emotion words and the performance associated with cognitive controls. The change of the choice index of positive and negative emotion words predicted the change of depressive symptoms differently. (2) Study 2 showed in the target condition, MDD patients had impaired attentional modulation of positive stimuli at early stage and impaired strategic controls of positive stimuli during later cognitive processing, reflected by enhanced anterior P2 and reduced N2 amplitude elicited by target positive stimuli. In nontarget condition, MDD patients showed impaired inhibition of negative stimuli at early stage, reflected by enhanced P2 amplitude to nontarget negative stimuli. (3) Study 3 showed that in target condition, there was enhanced attention modulation to positive stimuli at early stage and enhanced cognitive controls of positive stimuli at later cognitive stages after 9-week treatment with SSRIs, reflected by decreased anterior P2 amplitude and enhanced anterior N2 amplitude to target positive stimuli across time. In nontarget condition, the ablility of inhibition of negative stimuli was enhanced after treatment with SSRIs, reflected by reduced anterior P2 to nontarget negative stimuli across time. Anterior N2 amplitude to target positive stimuli at initial time was negatively associated with depressive symptoms and negative thoughts after treatment.Conclusions:(1) There is a correlation of emotional bias and impaired cognitive controls in MDD; and (2) the potential mechanism of negativity bias in major depression may be deficits of attentional control on positive stimuli causing relative gain control of negative stimuli at perceptual and post-perceptual stages, and the negativity bias may stem from impaired processing of positive emotional information rather than an enhanced processing of negative emotional information; and (3) the negativity bias onsets at perceptual stage and lasts until post-perceptual stages; and (4)negativity bias might be associated with low 5-HT, and SSRIs treatment effects have the role of improvement of positive emotional processing and the ablility of inhibition of negative stimuli, causing the shift of negativity bias; (5) The choice index of emotion word and the ERPs index of anterior P2 and the N2 elicited by target positive stimuli might provide an objective index for MDD in the diagnosis, the treatment response of antidepressant and prognosis in the future. Objective:We aimed to test (1) the characteristics of impaired cognitive control and emotional bias; and (2) the relationships of impaired cognitive control and emotional bias, and their correlation with depressive symptoms using the peformance of cognitive tests and the choice tases of emotional words in first-episode major depressive disorder (MDD) at initial time and after treatment.Methods:17 first-episode MDD patients and 22 healthy controls performed cognitive tests of Trial Making, Verbal Fluency, Continuous Performance Test (CPT), the Wisconsin Card Sorting Test (WCST), and Stroop Colour Word Test as well as the visual choice tasks of Chinese emotional words. After 9-week antidepressants treatment,17 patients were re-administered the tasks.Results:(1) Cognitive tests:At initial assessment, MDD patients required more time on Trial Making A and Stroop Test-congruent than controls, and performed fewer correct numbers on Stroop Test-incongruent than controls. At follow-up, MDD patients did not differ from controls on cognitive tests. In MDD patients, cognitive tests of Trial Making A and Stroop Test had statistical significance in the comparson across initial time and follow-up. (2) Chinese emotional words choice tasks:MDD patients made more errors of omission during positive than negative block before and after treatment. At follow-up, fewer errors of omission were found during positive block relative to the initial time in MDD patients, and no difference was found on errors of omission during positive block compared to controls. No difference was found on errors of omission during negative block across time in depressed patients and across groups. Nor was on distracter errors. Depressed patients required less time to respond to positive words at follow-up than at initial time, no significant difference was observed for negative across time. (3) The choice index of emotion words were associated with the performance of Trial Making B, WCST, CPT, and Stroop Color Word Test related with cognitive controls. (4) Errors of omission during positive block were positively associated with the scores of depression and negative thoughts at initial time. The performance of cognitive tests associated with cognitive controls was not correlated with the scores of depression and negative thoughts. The change of errors of omission during positive and negative block predicted the change of the Hamilton Depression Rating Scale (HAMD) scores.Conculusions:(1) There were impaired cognitive controls and emotional bias which is characteristic of impaired processing of positive emotion in MDD; and (2) there is a correlation of emotional bias and impaired cognitive controls; and (3) the change of the processing of positive and negative emotional information might correlate with the change of symptoms differently. Objective:we aimed to test whether a negativity bias occurs as a result of deficient top-down attentional control causing gain control of negative emotional information, and to explore the directionality and temporal specificity of such bias in major depression by event-related potentials (ERPs) in first-episode major depressive disorder (MDD). Methods:20 nonmedicated patients with a first episode of unipolar MDD and 20 matched controls complete a visual three-stimulus semantic oddball task while electroencephalogram (EEG) activity was recorded. In the tasks, each of the positive and negative categories served in separate runs as task-relevant target or task-irrelevant nontarget, and neutral category as standard.Results:(1) Behavior data showed that MDD patients had decreased hit rates for positive words, but no difference for negative words compared with controls; and there were significantly lower hit rates for positive words than for negative words in MDD patients; and there was no group difference in reaction time. (2) ERPs data showed that in target condition, MDD patients showed enlarged anterior P2 (～160-260ms) and marginally reduced anterior N2(～260-430ms) elicited by positive target stimuli compared with controls, while no difference was found for anterior P2 and N2 elicited by negative target stimuli between groups. Within group, controls showed significantly decreased anterior P2 (-210-260ms) elicited by target positive stimuli relative to target negative; MDD patients showed significantly reduced N2 elicited by target positive stimuli relative to target negative, and significantly reduced P3 (-400-600ms) elicited by target negative stimuli relative to target positive. In nontarget condition, MDD patients exhibited a marginal enhancement P2 for nontarget negative words compared with controls, while no difference was found to the P2 elicited by nontarget positive words and nor to the N2 elicited by nontarget stimuli including positive and negative words, compared with controls. Within group, controls showed marginally increased P2 (～160-210ms) to nontarget positive words relative to nontarget negative words. Additively, MDD patients showed delayed latency of anterior N2 compared with controls, and MDD patients presented delayed P1 latency (～70-130 ms) for positive words relative to negative over right posterior regions. (3) The relationship of ERP data with the scores of HAMD and automatic thoughts questionnaire (ATQ) showed that the amplitude of the P2 and the N2 elicited by target positive words over frontal-central regions was positively associated with the scores of HAMD and ATQ, so was the amplitude of the P2 (～160-210ms) to nontarget negative words.Conclusions:The electrophysiological data demonstrated that (1) the potential mechanism of negativity bias in major depression may be deficits of attentional control on positive stimuli causing relative gain control of negative stimuli at perceptual and post-perceptual stages; and (2) the negativity bias may stem from impared processing of positive emotional information, rather than an enhanced processing of negative emotional information. (3) The onset of the negativity bias is at perceptual stage and such negativity bias lasts until post-perceptual stages. (4) The ERPs components of anterior P2, N2 and the P3 elicited by target positive stimuli might provide objective index for early detection of MDD in the future. Objective:We aimed to explore the relationship of electroencephaphysiological mechanisms of the negativity bias and selective serotonin re-uptake inhibitors (SSRIs) treatment effects to further test the model of cognitive emotional interaction and to provide objective index for the response of antidepressant treatment and prognosis by SSRIs treatment for 9 weeks in first episode major depression.Methods:16 nonmedicated patients with a first episode of unipolar major depressive disorder (MDD) at initial time and after 9-week SSRIs treatment complete a visual three-stimulus semantic oddball task while electroencephalogram (EEG) activity was recorded.Results:(1) The response rate was 87.5% with 75% total reduction rate of the Hamilton Depression Rating Scale (HAMD-17 item) scores after 9-week treatment in MDD patients.(2) Behavior data showed that after 9-week SSRIs treatment, the hit rates was significantly increased for positive words and marginally for negative words across time; but the hit rateswas still marginally decreased for positive words relative to negative words in MDD patients at follow-up. The reaction time was significantly shortened after 9-week treatment compared with initial time.(3) The ERPs data across time showed that in target condition, there were significantly reduced anterior P2, enhanced anterior N2 and marginally reduced P3 amplitude elicited by target positive words across time, while no difference was found to amplitude of the P2, the N2 and the P3 eilicted by target negative words across time. In nontarget condition, there was significantly reduced anterior P2 elicited by nontarget negative words, and marginally reduced anterior P2 elicited by nontarget positive words across time, while no difference was found to both the N2 and the P3 elicited by nontarget stimuli. There was a significantly fastened N2 latency across time. A shortened P1 latency to positive stimuli over right posterior regions was found across time, while no difference was found to P1 latency to negative stimuli over right posterior regions across time.(4) The amplitude of anterior N2 over frontal-central regions elicited by target positive stimuli at initial time was negatively associated with the HAMD and ATQ scores after 9-week treatment.Conclusions:The electrophysiological data demonstrated that (1) negativity bias might be associated with low 5-HT; and (2) SSRIs treatment effects have the role of enhancement of cortical electrophysiological responses to positive emotional stimuli and suppression brain responses to negative stimuli, resulting in the shift of negativity bias; (3) The ERPs components of anterior N2 elicited by target positive stimuli provide objective index for the response of antidepressant treatment and prognosis of MDD.