Emotional Processing Biases Research Articles

Ketamine Alters Electrophysiological Responses to Emotional Faces in Major Depressive Disorder

BackgroundThe glutamatergic modulator ketamine rapidly reduces depressive symptoms in individuals with treatment-resistant major depressive disorder (MDD). However, ketamine's effects on emotional processing biases remain largely unknown, and understanding these processes may help elucidate ketamine's mechanism of action. MethodsMagnetoencephalography (MEG) was used to investigate ketamine's effects on early visual responses to affective stimuli in individuals with MDD (n=31) and healthy volunteers (HVs; n=24). Participants were enrolled in a double-blind, placebo-controlled, crossover clinical trial and were assessed at baseline and after subanesthetic-dose ketamine and placebo-saline infusions. During MEG recording, participants completed an emotional evaluation task in which they indicated the sex or emotional valence (happy-neutral or sad-angry) of facial stimuli. Source-localized event-related field (ERF) M100 and M170 amplitudes and latencies were extracted from regions of interest. Linear fixed effects models examined interactions between diagnosis, stimulus valence, and drug session for behavioral and MEG data. ResultsIn baseline behavioral analyses, MDD participants exhibited higher accuracy for sad-angry than happy-neutral faces, and HVs responded faster to happy-neutral than sad-angry faces. In the MEG post-infusion analyses, calcarine M100 amplitudes were larger in MDD than HV participants post-placebo but became more similar post-ketamine. Finally, fusiform M170 amplitudes were associated with antidepressant response in MDD participants. LimitationsThe modest sample size and the need to collapse across responses to happy and neutral faces to increase statistical power limit the generalizability of the findings. ConclusionsKetamine rapidly altered emotional stimulus processing in MDD, laying the groundwork for future investigations of biomarkers of antidepressant treatment response. Clinical TrialClinicaltrials.gov, NCT#00088699

Depression severity is associated with impaired facial emotion processing in a large international sample

BackgroundDepression is associated with biases in facial emotion processing, which have an impact on the course and treatment of depression. While decades of research have established a negativity bias in processing in depression, there is still a gap in our understanding of how depression severity impacts sensitivity to detecting differences in emotional faces. MethodsWe examined emotion sensitivity (ES), or the ability to to detect subtle differences in emotional faces, in a large, geographically and culturally diverse, web-based sample (N = 6598, age range = 18–96, 56.50% female, 66% Caucasian). Participants completed ES tasks (fear, anger, or happiness) and a Beck Depression Inventory-II, to determine depression severity. ResultsDepression severity was correlated with overall ES performance as well as ES performance for individual emotions. Higher depression scores were associated with poorer performance in detecting happiness, fear, and anger (ps < .001). Examining performance by region, Eastern countries showed significantly poorer ES performance compared to Western countries, and were significantly more depressed. LimitationsOur sample is non-clinical and self-selected. ConclusionsThis study is an extension of existing research on emotional facial processing, with an approach that takes into consideration the heterogeneity of depression symptoms and corrects psychometric confounds of traditional emotion face processing paradigms. Overall, factors related to severity, task reliability, and facial stimuli should be considered in determining the potential mechanism of facial emotion processing in the onset and course of depression.

M67. UNDERSTANDING SOCIAL COGNITION IN SCHIZOPHRENIA THROUGH THE LENS OF SCHIZOTYPY

BackgroundSocial cognitive deficits are common, detectable across a wide range of tasks and appear to play a key role in influencing poor functioning in schizophrenia. Despite its importance as a treatment target, the factors that underlie social cognitive deficits in schizophrenia remains elusive. Schizotypy appears to be one such factor that can explain the variability in social cognitive deficits seen in schizophrenia. The study’s primary aim was to provide a more comprehensive understanding of social cognitive functioning and its relationship to schizotypy.Methods108 patients and 70 healthy controls completed nine tasks across 4 social cognitive domains based on the SCOPE study. In addition, all participants completed the Schizotypal Personality Questionnaire. Clinical symptoms were also rated using the Brief Psychiatric Rating Scale.ResultsTheory of Mind, social perception, emotion processing and attribution bias were measured in patients with schizophrenia (n = 108) and healthy controls (n = 70). A social cognition composite score was calculated using principal components analysis. Cluster analysis on the derived factor scores revealed 3 clusters. Multiple univariate ANOVAS with Bonferroni correction were used to examine differences between the 3 clusters on each of the 4 social cognition domain scores, which indicated that higher social cognitive performance was related to lower schizotypy. In addition, results indicated that despite differences in the social cognitive performance among patients in the 3 clusters, they did not differ in clinical outcome measures.DiscussionThe primary aim of the study was to address gaps in the current literature by examining the relationship between social cognition and schizotypy. This study built upon past studies which had the tendency to focus on single, discrete domains by comparing the social cognitive performance of patients and controls using an extensive battery of tests, indexing four social cognitive domains. The significant differences on total SPQ score and the SPQ domain scores between the various clusters, coupled with the significant correlations between schizotypy and social cognition, reinforces the utility of schizotypy in refining our understanding of the variation in the degree of social cognitive deficits in schizophrenia. In conclusion, this study substantiates the importance of understanding the relationship between social cognition and schizotypy. This could support and pave the way for the development and implementation of targeted social cognitive interventions catered to the patients’ level of deficit.

Emotional recognition training modifies neural response to emotional faces but does not improve mood in healthy volunteers with high levels of depressive symptoms.

There is demand for new, effective and scalable treatments for depression, and development of new forms of cognitive bias modification (CBM) of negative emotional processing biases has been suggested as possible interventions to meet this need. We report two double blind RCTs, in which volunteers with high levels of depressive symptoms (Beck Depression Inventory ii (BDI-ii) > 14) completed a brief course of emotion recognition training (a novel form of CBM using faces) or sham training. In Study 1 (N = 36), participants completed a post-training emotion recognition task whilst undergoing functional magnetic resonance imaging to investigate neural correlates of CBM. In Study 2 (N = 190), measures of mood were assessed post-training, and at 2-week and 6-week follow-up. In both studies, CBM resulted in an initial change in emotion recognition bias, which (in Study 2) persisted for 6 weeks after the end of training. In Study 1, CBM resulted in increases neural activation to happy faces, with this effect driven by an increase in neural activity in the medial prefrontal cortex and bilateral amygdala. In Study 2, CBM did not lead to a reduction in depressive symptoms on the BDI-ii, or on related measures of mood, motivation and persistence, or depressive interpretation bias at either 2 or 6-week follow-ups. CBM of emotion recognition has effects on neural activity that are similar in some respects to those induced by Selective Serotonin Reuptake Inhibitors (SSRI) administration (Study 1), but we find no evidence that this had any later effect on self-reported mood in an analogue sample of non-clinical volunteers with low mood (Study 2).

Neurophysiological evidence for distinct biases in emotional face processing associated with internalizing and externalizing symptoms in children

Attentional bias to threat has been implicated in both internalizing and externalizing disorders. This study utilizes event-related potentials to examine early stages of perceptual attention to threatening (angry or fearful) versus neutral faces among a sample of 200 children ages 6–8 years from a low-income, urban community. Although both internalizing and externalizing symptoms were associated with processing biases, the nature of the bias differed between these two symptom domains. Internalizing symptoms were associated with heightened early attentional selection (P1) and later perceptual processing (P2) of fearful faces. In contrast, externalizing symptoms were associated with reduced early attentional selection (P1) of fearful faces and enhanced perceptual processing (P2) of neutral faces, possibly indicative of a hostile interpretation bias for ambiguous social cues. These results provide insight into the distinct cognitive-affective processes that may contribute to the etiology and maintenance of internalizing and externalizing psychopathology.

Factors associated with depression in people with inflammatory bowel disease: The relationship between active disease and biases in neurocognitive processing.

Depression is common among people with inflammatory bowel disease (IBD), though the causes remain unclear. We conducted a cross-sectional study to investigate the role of emotional processing biases in contributing to depression among people with IBD. One hundred and twenty outpatients with IBD were recruited and: (a) completed questionnaires to record: age, sex, social support, socioeconomic status, anxiety and depression (n=104), (b) underwent assessments of biases in emotional recognition (n=112), emotional memory and reinforcement learning (c) had recorded from clinical records: type of IBD, duration of IBD, IBD activity and (d) provided blood for high-sensitivity C-reactive protein levels (n=99). Sixty-eight participants had Crohn's disease and 49 had ulcerative colitis. Of these, 35 had active disease and 26 had depression. Those with depression were more likely to be female, lack social support, have active disease, be taking corticosteroids but not TNF-alpha inhibitors and exhibit less positive emotional recognition bias. On multivariable regression analysis, depression was associated independently with lack of social support (unstandardized regression coefficient (B)=-1.40, P=0.02) and increased disease activity (B=1.29, P=0.03). Causal steps analysis was consistent with less positive emotional recognition bias partially mediating the effects of disease activity on depression. This is the first study to demonstrate links between disease activity and less positive biases in emotional recognition that could explain higher rates of depression among people with active IBD. Future prospective studies are required to confirm the effects of emotional processing biases in depression and allow stronger causal inferences to be drawn.

Are hoarding symptoms associated with interpersonally relevant attentional biases? A preliminary investigation

According to cognitive-behavioral models of hoarding disorder, positive and negative emotional processing biases may contribute to the core symptoms of clutter, acquiring, and difficulty discarding. In disorders commonly comorbid with hoarding (e.g., depression; anxiety), studies have revealed specific patterns of attentional biases that relate to central symptoms. However, links between hoarding symptoms and biased attention, particularly involving interpersonal content, remain empirically untested. In the present study, we aimed to conduct the first investigation of hoarding symptoms and attentional biases. A sample of 57 young adults viewed images of positive and negative facial expressions paired with neutral facial expressions. During stimulus presentation eye tracking data captured four measures of early-stage and late-stage attentional biases toward emotional stimuli. Hoarding symptoms were measured dimensionally using the Saving Inventory-Revised. Results yielded an association between early orientation toward negative stimuli and severity of acquiring symptoms. Conversely, difficulty discarding/saving was associated with multiple measures of late-stage positive attentional biases. Findings reinforce the importance of examining both positive and negative emotional systems in relation to specific hoarding symptom clusters, even at the basic information processing level.

Biases in processing of mood-congruent facial expressions in depression

Cognitive models of depression suggest that depressed individuals exhibit a tendency to attribute negative meaning to neutral stimuli, and enhanced processing of mood-congruent stimuli. However, evidence thus far has been inconsistent. In this study, we sought to identify both differential interpretation of neutral information as well as emotion processing biases associated with depression. Fifty adult participants completed standardized mood-related questionnaires, a novel immediate mood scale questionnaire (IMS-12), and a novel task, Emotion Matcher, in which they were required to indicate whether pairs of emotional faces show the same expression or not. We found that overall success rate and reaction time on the Emotion Matcher task did not differ as a function of severity of depression. However, more depressed participants had significantly worse performance when presented with sad-neutral face pairs, as well as increased reaction times to happy-happy pairs. In addition, accuracy of the sad-neutral pairs was found to be significantly associated with depression severity in a regression model. Our study provides partial support for the mood-congruent hypothesis, revealing only a potential bias in interpretation of sad and neutral expressions, but not a general deficit in processing of facial expressions. The potential of such bias in serving as a predictor for depression should be further examined in future studies.

Subchronic treatment with St John's wort produces a positive shift in emotional processing in healthy volunteers.

The neurocognitive model of antidepressant treatment in depression states that antidepressants work by producing relatively immediate positive shifts in emotional processing, which translate into clinical improvement with time. St John's Wort has shown antidepressant potential in randomised controlled trials; however, its pharmacological actions are broad and it is unknown whether treatment also produces changes in emotional processing. We investigated whether short-term treatment with St John's wort has similar effects on emotional processing to those reported with other antidepressants such as selective serotonergic reuptake inhibitors. Forty-eight healthy participants were given St John's wort or placebo treatment for seven days. On day 7 they completed a battery of tasks to measure emotional processing and other elements of cognition. St John's wort treatment produced similar changes to other antidepressants, for example reducing recognition of disgusted faces and attention to fearful faces, while increasing memory for positive words. We failed to find evidence for an effect of St John's wort on other aspects of cognition including working memory. These findings lend support to the theory that the production of early positive biases in emotional processing may be a common feature of all clinically effective antidepressants with diverse pharmacological mechanisms.

Multi-unit relations among neural, self-report, and behavioral correlates of emotion regulation in comorbid depression and obesity

Depression is a leading cause of disability and is commonly comorbid with obesity. Emotion regulation is impaired in both depression and obesity. In this study, we aimed to explicate multi-unit relations among brain connectivity, behavior, and self-reported trait measures related to emotion regulation in a comorbid depressed and obese sample (N = 77). Brain connectivity was quantified as fractional anisotropy (FA) of the uncinate fasciculi, a white matter tract implicated in emotion regulation and in depression. Use of emotion regulation strategies was assessed using the Emotion Regulation Questionnaire (ERQ). We additionally measured reaction times to identifying negative emotions, a behavioral index of depression-related emotion processing biases. We found that greater right uncinate fasciculus FA was related to greater usage of suppression (r = 0.27, p = 0.022), and to faster reaction times to identifying negative emotions, particularly sadness (r = −0.30, p = 0.010) and fear (r = −0.35, p = 0.003). These findings suggest that FA of the right uncinate fasciculus corresponds to maladaptive emotion regulation strategies and emotion processing biases that are relevant to co-occurring depression and obesity. Interventions that consider these multi-unit associations may prove to be useful for subtyping and improving clinical outcomes for comorbid depression and obesity.

Functional outcome and social cognition in bipolar disorder: Is there a connection?

BackgroundInterest in social cognition in bipolar disorder (BD) has increased considerably over the past decade, with studies highlighting major impairments, especially in mental state reasoning, even during euthymia. A causal relationship between social cognition deficits and social functioning has already been established in individuals with schizophrenia, but there is still little information about links between social cognition and social functioning in BD. Our aim was therefore to review the relationship between functional outcome and social cognition in patients with BD. MethodsWe conducted a systematic review of the literature. Relevant articles were identified through literature searches in the MEDLINE/PubMed, EBSCOHost and Google Scholar databases for the years 2000–2017, using the keywords bipolar, social cognition, theory of mind, mentalizing, emotion recognition, emotion processing, and functioning. A total of 20 studies met our inclusion/exclusion criteria. ResultsWe found that functioning was significantly correlated with three domains of social cognition (ToM, emotion processing, and attribution bias). Twelve of 13 studies reported a correlation with emotion processing, but a correlation with ToM was only found in three of the 11 studies that assessed it. Six studies found an effect of depressive symptoms on emotion processing and no significant association was found with manic symptomatology. ConclusionsTo the best of our knowledge, the present review is the first to specifically explore the relationship between social cognition and social functioning in patients with BD. This exploration is of interest, as it enhances current understanding of this disorder and, by so doing, should improve patient outcomes.

Dissociable temporal effects of bupropion on behavioural measures of emotional and reward processing in depression.

Antidepressants remediate negative biases in emotional processing early in treatment, prior to mood improvement. However, the effects on reward processing potentially relevant to the treatment of anhedonia are less clear. Here we investigate the early and sustained effects of the dopamine and noradrenaline reuptake inhibitor bupropion on behavioural measures of emotional and reward processing in currently depressed individuals. Forty-six currently depressed patients and 42 healthy controls participated in a repeated measures study, during which open-label bupropion was administered to only the patient group over a six week period without a placebo group. All participants completed the Emotional Test Battery and a probabilistic instrumental learning task at week 0, week 2 and week 6. Currently depressed patients displayed negative biases in emotional processing and blunted response bias for high-probability wins compared to the healthy controls at baseline. Bupropion was found to reduce the negative biases in emotional processing early in treatment, including a significant decrease in the percentage misclassification of other face emotions as sad and the number of negative self-referent words falsely recalled between baseline and week 2. Conversely, bupropion was found to initially further reduce the response bias for high-probability wins between baseline and week 2. This effect reversed with six weeks' bupropion treatment and reward processing was normalized compared to the healthy controls. Early in treatment, bupropion acts to reduce negative biases in emotional processing but exacerbates impaired reward processing. The beneficial actions of bupropion on reward processing then occur later in treatment. Such dissociation in the temporal effects of bupropion on emotional and reward processing has implications for the treatment of the different symptom domains of negative affect and anhedonia in depression.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.

Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression

RationaleDepressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome.ObjectivesThe objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients’ emotional processing biases.MethodsSeventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin.ResultsWe found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010).ConclusionsPsilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings.

Interferon-α induces negative biases in emotional processing in patients with hepatitis C virus infection: a preliminary study.

Treatment of medical patients with the inflammatory cytokine, interferon-α (IFN-α), is frequently associated with the development of clinical depressive symptomatology. Several important biological correlates of the effect of IFN-α on mood have been described, but the neuropsychological changes associated with IFN-α treatment are largely unexplored. The aim of the present preliminary study was to assess the effect of IFN-α on measures of emotional processing. We measured changes in emotional processing over 6-8 weeks in 17 patients receiving IFN-α as part of their treatment for hepatitis C virus infection. Emotional processing tasks included those which have previously been shown to be sensitive to the effects of depression and antidepressant treatment, namely facial expression recognition, emotional categorisation and the dot probe attentional task. Following IFN-α, patients were more accurate at detecting facial expressions of disgust; they also showed diminished attentional vigilance to happy faces. IFN-α produced the expected increases in scores on depression rating scales, but there was no correlation between these scores and the changes in emotional processing. Our preliminary findings suggest that IFN-α treatment produces negative biases in emotional processing, and this effect is not simply a consequence of depression. It is possible that increased recognition of disgust may represent a neuropsychological marker of depressive disorders related to inflammation.

Negative bias in expression-related mismatch negativity(MMN) in remitted late-life depression: An event-related potential study

Negative bias in cognition is closely associated with susceptibility to recurrent episodes of depression. Given the high recurrence rate of depression, previous studies have focused on the attentive level in late-life depression (LLD), but depression relapse is difficult to detect as a lower chief complaint in elderly people. Facial expression mismatch negativity (EMMN) is a tool that can measure cognitive bias in pre-attentive processing. In this study, we sought to explore the cognitive bias in pre-attentive emotional information processing in LLD. Thirty patients with remitted LLD and 30 non-depressed, age- and gender-matched normal controls (NC) were enrolled in this study. Automatic emotional processing was elicited by using an expression-related oddball paradigm in all participants. There were no significant differences in N170 amplitude and latency between remitted LLD and NC. Compared with NC subjects, patients with remitted LLD demonstrated an attenuated mean amplitude of positive and negative EMMN, whereas the mean amplitude of negative EMMN in remitted LLD was much larger than that of positive EMMN. Our findings suggest that although basic processing of facial expressions is intact in remitted LLD, automatic processing of facial expressions in remitted LLD is impaired with a negative bias in cognition. Further investigation of the contributions of negative bias in EMMN to susceptibility to recurrence of LLD is warranted.

Cognition in depression: Can we THINC-it better?

BackgroundCognitive compromise is a common experience for patients with depression and other mood disorders. Depressed patients sustain deficits in working memory and attentional distortions in emotional processing and negative attention biases, which may contribute to maintaining their depressive state. MethodsThe Mood Assessment and Classification (MAC) Committee comprised academic psychiatrists with clinical expertise in the management of mood disorders. The independently convened committee met to discuss contentious aspects of mood disorders diagnosis and assessment with the express aim of informing clinical practice and future research. ResultsThe Committee specifically identified cognition as an important aspect for clinicians to consider in the context of depression and mood disorders. This article highlights some of the barriers to assessment and proposes tools that have the potential to be implemented in clinical practice. LimitationsThe conclusions drawn within this article are based on expert opinion. We have noted the limitations of the literature that informs this opinion. ConclusionsAs cognitive ability has been closely linked to patients’ ability to achieve functional recovery, it is imperative that clinicians are able to identify patients with cognitive deficits and are equipped with tools to conduct effective cognitive assessments. Examining cognitive factors may generate a deeper understanding of the pathogenesis of depression and mood disorders which can ultimately be used to inform treatment.

Brain responses to sound intensity changes dissociate depressed participants and healthy controls

Depression is associated with bias in emotional information processing, but less is known about the processing of neutral sensory stimuli. Of particular interest is processing of sound intensity which is suggested to indicate central serotonergic function. We tested weather event-related brain potentials (ERPs) to occasional changes in sound intensity can dissociate first-episode depressed, recurrent depressed and healthy control participants. The first-episode depressed showed larger N1 amplitude to deviant sounds compared to recurrent depression group and control participants. In addition, both depression groups, but not the control group, showed larger N1 amplitude to deviant than standard sounds. Whether these manifestations of sensory over-excitability in depression are directly related to the serotonergic neurotransmission requires further research. The method based on ERPs to sound intensity change is fast and low-cost way to objectively measure brain activation and holds promise as a future diagnostic tool.

Priming the Secure Attachment Schema Affects the Emotional Face Processing Bias in Attachment Anxiety: An fMRI Research.

Our study explored how priming with a secure base schema affects the processing of emotional facial stimuli in individuals with attachment anxiety. We enrolled 42 undergraduate students between 18 and 27 years of age, and divided them into two groups: attachment anxiety and attachment secure. All participants were primed under two conditions, the secure priming using references to the partner, and neutral priming using neutral references. We performed repeated attachment security priming combined with a dual-task paradigm and functional magnetic resonance imaging. Participants’ reaction times in terms of responding to the facial stimuli were also measured. Attachment security priming can facilitate an individual’s processing of positive emotional faces; for instance, the presentation of the partner’s name was associated with stronger activities in a wide range of brain regions and faster reaction times for positive facial expressions in the subjects. The current finding of higher activity in the left-hemisphere regions for secure priming rather than neutral priming is consistent with the prediction that attachment security priming triggers the spread of the activation of a positive emotional state. However, the difference in brain activity during processing of both, positive and negative emotional facial stimuli between the two priming conditions appeared in the attachment anxiety group alone. This study indicates that the effect of attachment secure priming on the processing of emotional facial stimuli could be mediated by chronic attachment anxiety. In addition, it highlights the association between higher-order processes of the attachment system (secure attachment schema priming) and early-stage information processing system (attention), given the increased attention toward the effects of secure base schema on the processing of emotion- and attachment-related information among the insecure population. Thus, the following study has applications in providing directions for clinical treatment of mood disorders in attachment anxiety.

Prefrontal cortex stimulation does not affect emotional bias, but may slow emotion identification.

Transcranial direct current stimulation (tDCS) has recently garnered attention as a putative depression treatment. However, the cognitive mechanisms by which it exerts an antidepressant effect are unclear: tDCS may directly alter ‘hot’ emotional processing biases, or alleviate depression through changes in ‘cold’ (non-emotional) cognitive function. Here, 75 healthy participants performed a facial emotion identification task during 20 minutes of anodal or sham tDCS over the left dorsolateral prefrontal cortex (DLPFC) in a double-blind, within-subject crossover design. A subset of 31 participants additionally completed a task measuring attentional distraction during stimulation. Compared to sham stimulation, anodal tDCS of the left DLPFC resulted in an increase in response latency across all emotional conditions. Bayesian analysis showed definitively that tDCS exerted no emotion-dependent effect on behaviour. Thus, we demonstrate that anodal tDCS produces a general, rather than an emotion-specific, effect. We also report a preliminary finding in the subset of participants who completed the distractibility task: increased distractibility during active stimulation correlated significantly with the degree to which tDCS slowed emotion identification. Our results provide insight into the possible mechanisms by which DLPFC tDCS may treat symptoms of depression, suggesting that it may not alter emotional biases, but instead may affect ‘cold’ cognitive processes.

Neurophysiological Processing of Emotion in Children of Mothers with a History of Depression: the Moderating Role of Preschool Persistent Irritability.

Research on emotion-processing biases in offspring of depressed parents has produced a variety of findings. Child persistent irritability may be a useful clinical feature that demarcates subgroups of offspring with distinct patterns of emotion processing. The present study examined whether early persistent irritability moderated the relationship between maternal lifetime history of a depressive disorder and appetitive- and aversive-emotion processing in 338 never-depressed pre-adolescent children (43.8% female). When children were 3, mothers were interviewed about children's persistent irritability. Six years later, EEG was recorded while children completed a task in which the late positive potential (LPP), a neural index of emotional reactivity, was measured in response to appetitive, aversive, and neutral images. At both assessments, mothers were interviewed about their own psychopathology. Among offspring of depressed mothers, children characterized by high levels of early persistent irritability showed an enhanced LPP to appetitive and aversive compared to neutral images (i.e., ΔLPP), whereas children with low levels of early irritability showed attenuated ΔLPPs. In offspring of mothers with no history of depression, there was no association between irritability and emotion processing. Findings suggest that persistent irritability influences the pattern of emotion-processing aberrations in offspring of depressed mothers.