Reduced electrocortical response to threatening faces in major depressive disorder

Background: There is growing support for the emotion context insensitivity hypothesis, which states that major depressive disorder (MDD) is associated with a deficit in emotional reactivity. Under this hypothesis, depressed individuals exhibit reduced behavioral and physiological responses to both appetitive and aversive stimuli. We sought to examine this possibility using the late positive potential, a neural response sensitive to aversive and threatening stimuli. Methods: Forty‐seven individuals participated in the study, 22 of whom met criteria for current MDD and 25 with no history of depression or other Axis I disorders. All individuals passively viewed emotional faces while event‐related potentials were recorded. Results: The vertex positive potential was significantly increased in response to fearful and angry faces across the entire sample. The late positive potential was also increased in response to threatening faces, but only among never‐depressed individuals. In the MDD group, this electrocortical response to emotional faces was absent. Conclusions: This study provides neural evidence in support of the view that MDD is associated with blunted emotional reactivity to negative stimuli, which until now has been examined primarily with measures of behavior, self‐report, and peripheral physiology. These results are also consistent with two prior studies showing reduced amygdala activation in response to fearful faces among depressed individuals. It remains to be determined whether abnormal activity in response to emotional stimuli is associated with trait risk for MDD or results from MDD. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

Dysfunctional distracter inhibition and facilitation for sad faces in depressed individuals

Depression is a commonly occurring mental disorder, which is characterized by dysfunctional inhibition and facilitation for emotional stimuli. The aim of the present study was to investigate distracter inhibition and facilitation for emotional faces in depressed individuals in a negative affective priming task. Control participants who had never suffered from depression (NC), sub-clinically depressed participants, and participants diagnosed with a current major depressive disorder (MDD), Anxiety Inventory, the Hamilton Depression Rating Score were recruited using the Beck Depression Inventory, the Beck and DSM-IV as tools. Twenty-four participants in each group completed a negative affective priming task. The main finding was that there were no significant differences among the three groups in the positive and negative priming effects of happy faces. However, there were significant differences for positive and negative priming effects of sad faces between each pair of groups, with the effects being lowest for MDD and highest for NC participants. It can be concluded that depressed individuals are characterized by enhanced facilitation and deficient inhibition for negative materials, which is a stable cognitive vulnerability risk, possibly associated with the occurrence of depression. There are differences in the cognitive dysfunction for negative stimuli between clinically depressed and sub-clinically depressed individuals.     

Effects of cortisol on the memory bias for emotional words? A study in patients with depression and healthy participants using the Directed Forgetting task

Mood congruent alterations in information processing such as an impaired memory bias for emotional information and impaired inhibitory functions are prominent features of a major depressive disorder (MDD). Furthermore, in MDD patients hypothalamic–pituitary–adrenal axis dysfunctions are frequently found. Impairing effects of stress or cortisol administration on memory retrieval as well as impairing stress effects on cognitive inhibition are well documented in healthy participants. In MDD patients, no effect of acute cortisol administration on memory retrieval was found.The current study investigated the effect of acute cortisol administration on memory bias in MDD patients (N = 55) and healthy controls (N = 63) using the Directed Forgetting (DF) task with positive, negative and neutral words in a placebo controlled, double blind design. After oral administration of 10 mg hydrocortisone/placebo, the item method of the DF task was conducted. Memory performance was tested with a free recall test.Cortisol was not found to have an effect on the results of the DF task. Interestingly, there was significant impact of valence: both groups showed the highest DF score for positive words and remembered significantly more positive words that were supposed to be remembered and significantly more negative words that were supposed to be forgotten. In general, healthy participants remembered more words than the depressed patients. Still, the depressed patients were able to inhibit intentionally irrelevant information at a comparable level as the healthy controls. These results demonstrate the importance to distinguish in experimental designs between different cognitive domains such as inhibition and memory in our study.     

Self-referential processing influences functional activation during cognitive control: an fMRI study

Rostral anterior cingulate cortex (rACC) plays a central role in the pathophysiology of major depressive disorder (MDD). As we reported in our previous study (Wagner et al., 2006), patients with MDD were characterized by an inability to deactivate this region during cognitive processing leading to a compensatory prefrontal hyperactivation. This hyperactivation in rACC may be related to a deficient inhibitory control of negative self-referential processes, which in turn may interfere with cognitive control task execution and the underlying fronto-cingulate network activation. To test this assumption, a functional magnetic resonance imaging study was conducted in 34 healthy subjects. Univariate and functional connectivity analyses in statistical parametric mapping software 8 were used. Self-referential stimuli and the Stroop task were presented in an event-related design. As hypothesized, rACC was specifically engaged during negative self-referential processing (SRP) and was significantly related to the degree of depressive symptoms in participants. BOLD signal in rACC showed increased valence-dependent (negative vs neutral SRP) interaction with BOLD signal in prefrontal and dorsal anterior cingulate regions during Stroop task performance. This result provides strong support for the notion that enhanced rACC interacts with brain regions involved in cognitive control processes and substantiates our previous interpretation of increased rACC and prefrontal activation in patients during Stroop task.     

The neural substrates of affective processing toward positive and negative affective pictures in patients with major depressive disorder

Previous studies examining neural responses to emotional stimuli in individuals with major depressive disorder (MDD) have indicated increased responses within the left amygdala to sad faces, and increased activity within the visual cortex and striatum to expressions of happiness. Using functional magnetic resonance imaging (fMRI), the current study measured neural responses to neutral, positive and negative pictures of the International Affective Picture System in 15 healthy individuals and 15 patients with MDD. Depressed individuals demonstrated lower activity in the right hippocampus and the right insula to negative affective pictures, whereas they showed lower activity in the right anterior cingulate cortex and the left insula to positive pictures. However, within the MDD group, the severity of depression correlated with the activity of the left amygdala, bilateral inferior orbitofrontal areas, and the left insula to negative pictures, whereas there were no clear indications of association between specific cerebral regions and positive pictures. Our findings indicate that preferential decreases in the left amygdala in response to negative pictures might be involved in the processing of emotional stimuli in depressed individuals. Also, these findings suggest that the bilateral inferior orbitofrontal cortices and left amygdala may be preferentially recruited in MDD patients, but not in healthy individuals.     

Brain activation to emotional words in depressed vs healthy subjects

Depression involves either enhanced processing of negative stimuli or diminished processing of positive stimuli. We used functional magnetic resonance imaging to assess brain activation in depressed vs healthy participants. Fifteen participants diagnosed with major depressive disorder and 15 controls were scanned during a lexical decision task involving neutral, happy, sad, and threat-related words. For happy words, depressed subjects exhibited less activation than did controls to happy words in fronto-temporal and limbic regions. For sad words, depressed subjects showed more activation than did controls in the inferior parietal lobule and less activation in the superior temporal gyrus and cerebellum, suggesting a complex activation pattern that varies for neural sub-circuits that may be associated with different cognitive or behavioral processes.     

Reduced sustained brain activity during processing of positive emotional stimuli in major depression.

BACKGROUND: This study examines the directionality and temporal specificity of brain activity during sustained processing of emotional stimuli in individuals with current major depressive disorder (MDD) and nondepressed control participants. METHODS: Slow wave (SW) components of the event-related brain potential (ERP) were recorded from 16 control participants and 15 participants with MDD during a working memory task. During the task, individuals were shown a positive, neutral, or negative word and were asked to maintain it in memory for 5 sec. Participants then saw a letter and had to decide whether it was a part of the previously presented word. The ERP components were measured from nine scalp sites (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4) during the encoding of emotional words. RESULTS: Compared with control individuals, MDD participants exhibited decreased brain responses to positive relative to negative or neutral stimuli. This decrease in brain activity during processing of positive information was evident across all sites and SW components. CONCLUSIONS: Our findings suggest that cognitive deficits in MDD may stem from diminished brain responses during processing of positive information and may not be associated with an augmented response to negative stimuli.     

Brief report: Overgeneral autobiographical memory in adolescent major depressive disorder

The current study examined whether overgeneral autobiographical memory (OGM) bias serves as a state-like marker of major depressive disorder (MDD) in adolescence or whether it would also be observed in currently nondepressed adolescents with a history of MDD. We examined differences in OGM to positive and negative cue words between adolescents (aged 11–18 years) with current MDD (n = 15), remitted MDD (n = 25), and no history of any depressive disorder (n = 25). Youth and their parents were administered a structured diagnostic interview and adolescents completed the autobiographical memory test. Compared to never depressed adolescents, adolescents with current or remitted MDD recalled less specific memories in response to positive and negative cue words. The difference between the two MDD groups was small and nonsignificant. These findings suggest that OGM is not simply a state-like marker in currently depressed adolescents, but is also evident in adolescents with remitted MDD, indicating that it may represent a trait-like vulnerability that increases risk for relapse.     

Appetite change profiles in depression exhibit differential relationships between systemic inflammation and activity in reward and interoceptive neurocircuitry

Appetite change is a defining feature of major depressive disorder (MDD), yet little neuroscientific evidence exists to explain why some individuals experience increased appetite when they become depressed while others experience decreased appetite. Previous research suggests depression-related appetite changes can be indicative of underlying neural and inflammatory differences among MDD subtypes. The present study explores the relationship between systemic inflammation and brain circuitry supporting food hedonics for individuals with MDD. Sixty-four participants (31 current, unmedicated MDD and 33 healthy controls [HC]) provided blood samples for analysis of an inflammatory marker, C-reactive protein (CRP), and completed a functional magnetic resonance imaging (fMRI) scan in which they rated the perceived pleasantness of various food stimuli. Random-effects multivariate modeling was used to explore group differences in the relationship between CRP and the coupling between brain activity and inferred food pleasantness (i.e., strength of the relationship between activity and pleasantness ratings). Results revealed that for MDD with increased appetite, higher CRP in blood related to greater coupling between orbitofrontal cortex and anterior insula activity and inferred food pleasantness. Compared to HC, all MDD exhibited a stronger positive association between CRP and coupling between activity in striatum and inferred food pleasantness. These findings suggest that for individuals with MDD, systemic low-grade inflammation is associated with differences in reward and interoceptive-related neural circuitry when making hedonic inferences about food stimuli. In sum, altered immunologic states may affect appetite and inferences about food reward in individuals with MDD and provide evidence for physiological subtypes of MDD.     

抑郁症患者情绪图片反应特征及杏仁核反应模式的研究

目的 探讨抑郁症患者对情感刺激的行为学反应模式及其相关的杏仁核时程反应过程.方法 12例首次发病、未经治疗的抑郁症患者(抑郁症组)和13名健康个体(健康对照组)对观看正性、中性和负性情绪图片的愉悦度等评分;并在被动注视任务下行功能磁共振成像,采用感兴趣区分析方法,比较两组杏仁核在不同情绪图片任务组块间的血氧水平依赖(BOLD)信号时间反应特征.结果 (1)抑郁症组情绪图片愉悦度评分[正性:(6.6 ±0.2)分;中性:(4.7 ±0.1)分]低于健康对照组[分别为(7.7 ±0.2)分和(5.1 ±0.1)分],负性情绪图片评分[(3.4 ±0.3)分]高于健康对照组[(2.2 ±0.2)分;P<0.01].(2)对正性情绪图片任务,两组间右侧杏仁核存在"组×时间"交互作用(P=0.002);抑郁症组杏仁核BOLD信号变化率为(0.02±0.09)%,激活时间后移至Block 2.对负性情绪图片任务,两组间左侧杏仁核有"组×时间"交互作用(P=0.008),右侧杏仁核存在组主效应(P=0.007)和时间主效应(P=0.016),抑郁症组BOLD信号变化率低于(-0.06 ±0.14)%.结论 杏仁核是抑郁症患者丧失愉悦体验和情绪低落的神经基础之一.     

Never-depressed females with a family history of depression demonstrate affective bias

According to cognitive theories of depression, individuals susceptible to depression attend selectively to negative information. The purpose of the study was to examine if such an affective processing bias is present in never-depressed individuals with a family history of major depressive disorder (MDD). Formerly depressed female patients having at least one first-degree relative with a history of MDD (n=23), their never-depressed female siblings (n=21) and never-depressed female controls (n=21) performed a conventional and an emotional Stroop task using negative, positive and neutral words. A significant effect was found of group on negative processing bias; post hoc comparisons indicated that never-depressed siblings showed a larger negative processing bias than never-depressed controls. No significant differences were observed in positive bias or conventional interference between the three groups. Our findings suggest that never-depressed females with a family history of depression, like depressed patients, have more difficulties to inhibit negative material and to direct their attention towards task-specific material. This adds to the existing evidence that affective processing bias is a trait characteristic that contributes to the onset of depression and that could be a useful endophenotype for MDD.     

Response conflict and frontocingulate dysfunction in unmedicated participants with major depression

Individuals with major depressive disorder (MDD) often exhibit impaired executive function, particularly in experimental tasks that involve response conflict and require adaptive behavioral adjustments. Prior research suggests that these deficits might be due to dysfunction within frontocingulate pathways implicated in response conflict monitoring and the recruitment of cognitive control. However, the temporal unfolding of conflict monitoring impairments in MDD remains poorly understood. To address this issue, we recorded 128-channel event-related potentials while 20 unmedicated participants with MDD and 20 demographically matched, healthy controls performed a Stroop task. Compared to healthy controls, MDD subjects showed larger Stroop interference effects and reduced N2 and N450 amplitudes. Source localization analyses at the time of maximal N450 activity revealed that MDD subjects had significantly reduced dorsal anterior cingulate cortex (dACC; Brodmann area 24/32) and left dorsolateral prefrontal cortex (Brodmann area 10/46) activation to incongruent relative to congruent trials. Consistent with the heterogeneous nature of depression, follow-up analyses revealed that depressed participants with the lowest level of conflict-related dACC activation 620 ms post-stimulus were characterized by the largest Stroop interference effects (relatively increased slowing and reduced accuracy for incongruent trials). Conversely, MDD participants with relatively stronger dACC recruitment did not differ from controls in terms of interference effects. These findings suggest that for some, but not all individuals, MDD is associated with impaired performance in trials involving competition among different response options, and reduced recruitment of frontocingulate pathways implicated in conflict monitoring and cognitive control.     

A review of fMRI studies during visual emotive processing in major depressive disorder

Objectives. This review synthesized literature on brain activity, indexed by functional magnetic resonance imaging (fMRI), during visual affective information processing in major depressive disorder (MDD). Activation was examined in regions consistently implicated in emotive processing, including the anterior cingulate cortex (ACC), prefrontal cortex (PFC), amygdala, thalamus/basal ganglia and hippocampus. We also reviewed the effects of antidepressant interventions on brain activity during emotive processing. Methods. Sixty-four fMRI studies investigating neural activity during visual emotive information processing in MDD were included. Results. Evidence indicates increased ventro-rostral ACC activity to emotive stimuli and perhaps decreased dorsal ACC activity in MDD. Findings are inconsistent for the PFC, though medial PFC hyperactivity tends to emerge to emotive information processing in the disorder. Depressed patients display increased amygdala activation to negative and arousing stimuli. MDD may also be associated with increased activity to negative, and decreased activity to positive, stimuli in basal ganglia/thalamic structures. Finally, there may be increased hippocampus activation during negative information processing. Typically, antidepressant interventions normalize these activation patterns. Conclusion. In general, depressed patients have increased activation to emotive, especially negative, visual stimuli in regions involved in affective processing, with the exception of certain PFC regions; this pattern tends to normalize with treatment.     

Variation in the corticotropin-releasing hormone receptor 1 (CRHR1) gene influences fMRI signal responses during emotional stimulus processing

The corticotropin-releasing hormone (CRH) system coordinates neuroendocrine and behavioral responses to stress and has been implicated in the development of major depressive disorder (MDD). Recent reports suggest that GG-homozygous individuals of a single nucleotide polymorphism (rs110402) in the CRH receptor 1 (CRHR1) gene show behavioral and neuroendocrine evidence of stress vulnerability. The present study explores whether those observations extend to the neuronal processing of emotional stimuli in humans. CRHR1 was genotyped in 83 controls and a preliminary sample of 16 unmedicated patients with MDD who completed a functional magnetic resonance imaging scan while viewing blocks of positive, negative, and neutral words. In addition, potential mediating factors such as early life stress, sex, personality traits, and negative memory bias were examined. Robust differences in blood oxygenation level-dependent (BOLD) signal were found in healthy controls (A allele carriers > GG-homozygotes) in the right middle temporal/angular gyrus while subjects were viewing negative versus neutral words. Among GG-homozygotes, BOLD signal in the subgenual cingulate was greater in MDD participants (n = 9) compared with controls (n = 33). Conversely, among A-carriers, BOLD signal was smaller in MDD (n = 7) compared with controls (n = 50) in the hypothalamus, bilateral amygdala, and left nucleus accumbens. Early life stress, personality traits, and levels of negative memory bias were associated with brain activity depending on genotype. Results from healthy controls and a preliminary sample of MDD participants show that CRHR1 single nucleotide polymorphism rs110402 moderates neural responses to emotional stimuli, suggesting a potential mechanism of vulnerability for the development of MDD.     

Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression.

BACKGROUND: Bipolar disorder (BD) is characterised by abnormalities in mood and emotional processing, but the neural correlates of these, their relationship to depressive symptoms, and the similarities with deficits in major depressive disorder (MDD) remain unclear. We compared responses within subcortical and prefrontal cortical regions to emotionally salient material in patients with BP and MDD using functional magnetic resonance imaging. METHODS: We measured neural responses to mild and intense expressions of fear, happiness, and sadness in euthymic and depressed BD patients, healthy control subjects, and depressed MDD patients. RESULTS: Bipolar disorder patients demonstrated increased subcortical (ventral striatal, thalamic, hippocampal) and ventral prefrontal cortical responses particularly to mild and intense fear, mild happy, and mild sad expressions. Healthy control subjects demonstrated increased subcortical responses to intense happy and mild fear, and increased dorsal prefrontal cortical responses to intense sad expressions. Overall, MDD patients showed diminished neural responses to all emotional expressions except mild sadness. Depression severity correlated positively with hippocampal response to mild sadness in both patient groups. CONCLUSIONS: Compared with healthy controls and MDD patients, BD patients demonstrated increased subcortical and ventral prefrontal cortical responses to both positive and negative emotional expressions.     

The neural basis of the abnormal self‐referential processing and its impact on cognitive control in depressed patients

Persistent pondering over negative self‐related thoughts is a central feature of depressive psychopathology. In this study, we sought to investigate the neural correlates of abnormal negative self‐referential processing (SRP) in patients with Major Depressive Disorder and its impact on subsequent cognitive control‐related neuronal activation. We hypothesized aberrant activation dynamics during the period of negative and neutral SRP in the rostral anterior cingulate cortex (rACC) and in the amygdala in patients with major depressive disorder. Additionally, we assumed abnormal activation in the fronto‐cingulate network during Stroop task execution. 19 depressed patients and 20 healthy controls participated in the study. Using an event‐related functional magnetic resonance imaging (fMRI) design, negative, positive and neutral self‐referential statements were displayed for 6.5 s and followed by incongruent or congruent Stroop conditions. The data were analyzed with SPM8. In contrast to controls, patients exhibited no significant valence‐dependent rACC activation differences during SRP. A novel finding was the significant activation of the amygdala and the reward‐processing network during presentation of neutral self‐referential stimuli relative to baseline and to affective stimuli in patients. The fMRI analysis of the Stroop task revealed a reduced BOLD activation in the right fronto‐parietal network of patients in the incongruent condition after negative SRP only. Thus, the inflexible activation in the rACC may correspond to the inability of depressed patients to shift their attention away from negative self‐related stimuli. The accompanying negative affect and task‐irrelevant emotional processing may compete for neuronal resources with cognitive control processes and lead thereby to deficient cognitive performance associated with decreased fronto‐parietal activation. Hum Brain Mapp 36:2781–2794, 2015. © 2015 Wiley Periodicals, Inc.     

A double dissociation of ventromedial prefrontal cortical responses to sad and happy stimuli in depressed and healthy individuals.

BACKGROUND: The ventromedial prefrontal cortex (VMPFC) is a region implicated in the assessment of the rewarding potential of stimuli and may be dysfunctional in major depressive disorder (MDD). The few studies examining prefrontal cortical responses to emotive stimuli in MDD have indicated increased VMPFC responses to pleasant images but decreased responses to sad mood provocation when compared with healthy individuals. We wished to corroborate these results by examining neural responses to personally relevant happy and sad stimuli in MDD and healthy individuals within the same paradigm. METHODS: Neural responses to happy and sad emotional stimuli (autobiographical memory prompts and congruent facial expressions) were measured using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in MDD (n = 12) and healthy (n = 12) individuals. RESULTS: Increased and decreased responses in VMPFC were observed in MDD and healthy individuals, respectively, to happy stimuli, whereas the pattern was reversed for MDD and healthy individual responses to sad stimuli. These findings were not explained by medication effects in depressed individuals. CONCLUSIONS: These findings indicate a double dissociation of the pattern of VMPFC response to happy and sad stimuli in depressed and healthy individuals and suggest abnormal reward processing in MDD.     

“Loser” or “Popular”?: Neural response to social status words in adolescents with major depressive disorder

Concerns about social status are ubiquitous during adolescence, with information about social status often conveyed in text formats. Depressed adolescents may show alterations in the functioning of neural systems supporting processing of social status information. We examined whether depressed youth exhibited altered neural activation to social status words in temporal and prefrontal cortical regions thought to be involved in social cognitive processing, and whether this response was associated with development. Forty-nine adolescents (ages 10–18; 35 female), including 20 with major depressive disorder and 29 controls, were scanned while identifying the valence of words that connoted positive and negative social status. Results indicated that depressed youth showed reduced late activation to social status (vs neutral) words in the superior temporal cortex (STC) and medial prefrontal cortex (MPFC); whereas healthy youth did not show any significant differences between word types. Depressed youth also showed reduced late activation in the dorsolateral prefrontal cortex and fusiform gyrus to negative (vs positive) social status words; whereas healthy youth showed the opposite pattern. Finally, age was positively associated with MPFC activation to social status words. Findings suggest that hypoactivation in the “social cognitive brain network” might be implicated in altered interpersonal functioning in adolescent depression.     

Episodic simulation of future events is impaired in patients with major depressive disorder

We examined future episodic simulation in patients with major depressive disorder (MDD) using a method that distinguishes between episodic and non-episodic details of events. Patients were impaired at generating specific episodic details concerning future events; non-episodic details were not affected. In addition, all participants generated more episodic details for positive than for negative stimulus words. These results suggest a deficit in autonoetic awareness among patients with MDD. Difficulties imagining future events may impact upon the success of therapeutic interventions aimed at altering biases in the prediction of positive and negative future happenings.     

More excited for negative facial expressions in depression: Evidence from an event-related potential study

Objective

This study aims to investigate the intensity evaluation of social stimuli in depression.

Methods

Twenty-four never-disordered control participants (NC), 24 sub-clinically depressed individuals and 24 participants diagnosed with a current major depressive disorder (MDD) were recruited. All participants completed an emotional intensity evaluation task, in which they were required to judge the intensity of the facial expressions by pressing response keys, with the event-related potential (ERP) being recorded during the process.

Results

The MDD participants had higher intensity scores for sad faces compared with the NC group, longer reaction times (RTs) for all faces compared with other groups and higher P1 and P2 amplitude for sad faces compared with other faces. The sub-clinically depressed individuals had lower intensity scores for happy and neutral faces compared with other groups, longer RTs for happy faces compared with other faces and higher P1 and P2 amplitudes for happy faces compared with sad faces.

Conclusion

The findings suggest that the MDD participants are more excited for negative facial expressions, while the sub-clinically depressed individuals might have a disturbed perception for happy stimuli, which suggests a different cognitive pattern for facial expressions between MDD and sub-clinical depression. Moreover, the deep perception for sad faces is correlated with increased suicidal ideation.

Significance

The intensity effect of social stimuli (facial expressions) was observed in sub-clinically and clinically depressed (MDD) individuals simultaneously, which might suggest that the more excited perception for negative facial expressions is a stable cognitive vulnerability possibly associated with the occurrence or recurrence of depression.