Processing In Major Depression Research Articles

Effective connectivity during face processing in major depression - distinguishing markers of pathology, risk, and resilience.

Aberrant brain connectivity during emotional processing, especially within the fronto-limbic pathway, is one of the hallmarks of major depressive disorder (MDD). However, the methodological heterogeneity of previous studies made it difficult to determine the functional and etiological implications of specific alterations in brain connectivity. We previously reported alterations in psychophysiological interaction measures during emotional face processing, distinguishing depressive pathology from at-risk/resilient and healthy states. Here, we extended these findings by effective connectivity analyses in the same sample to establish a refined neural model of emotion processing in depression. Thirty-seven patients with MDD, 45 first-degree relatives of patients with MDD and 97 healthy controls performed a face-matching task during functional magnetic resonance imaging. We used dynamic causal modeling to estimate task-dependent effective connectivity at the subject level. Parametric empirical Bayes was performed to quantify group differences in effective connectivity. MDD patients showed decreased effective connectivity from the left amygdala and left lateral prefrontal cortex to the fusiform gyrus compared to relatives and controls, whereas patients and relatives showed decreased connectivity from the right orbitofrontal cortex to the left insula and from the left orbitofrontal cortex to the right fusiform gyrus compared to controls. Relatives showed increased connectivity from the anterior cingulate cortex to the left dorsolateral prefrontal cortex compared to patients and controls. Our results suggest that the depressive state alters top-down control of higher visual regions during face processing. Alterations in connectivity within the cognitive control network present potential risk or resilience mechanisms.

Neural signature of error processing in major depression

The clinical presentation of major depression (MD) is heterogenous and comprises various affective and cognitive symptoms including an increased sensitivity to errors. Various electrophysiological but only few functional magnetic resonance imaging (fMRI) studies investigated neural error processing in MD with inconsistent findings. Thus, reliable evidence regarding neural signatures of error processing in patients with current MD is limited despite its potential relevance as viable neurobiological marker of psychopathology. We therefore investigated a sample of 16 young adult female patients with current MD and 17 healthy controls (HC). During fMRI, we used an established Erikson-flanker Go/NoGo-paradigm and focused on neural alterations during errors of commission. In the absence of significant differences in rates of errors of commission in MD compared to HC, we observed significantly (p < 0.05, FWE-corrected on cluster level) enhanced neural activations of the dorsal anterior cingulate cortex (dACC) and the pre-supplementary motor area (pre-SMA) in MD relative to HC and thus, in brain regions consistently associated to neural error processing and corresponding behavioral adjustments. Considering comparable task performance, in particular similar commission error rates in MD and HC, our results support the evidence regarding an enhanced responsivity of neural error detection mechanisms in MD as a potential neural signature of increased negative feedback sensitivity as one of the core psychopathological features of this disorder.

Fronto-parietal and temporal brain dysfunction in depression: A fMRI investigation of auditory mismatch processing.

Mismatch responses reflect neural mechanisms of early cognitive processing in the auditory domain. Disturbances of these mechanisms on multiple levels of neural processing may contribute to clinical symptoms in major depression (MD). A functional magnetic resonance imaging (fMRI) study was conducted to identify neurobiological foundations of altered mismatch processing in MD. Twenty-five patients with major depression and 25 matched healthy individuals completed an auditory mismatch paradigm optimized for fMRI. Brain activity during mismatch processing was compared between groups. Moreover, seed-based connectivity analyses investigated depression-specific brain networks. In patients, mismatch processing was associated with reduced activation in the right auditory cortex as well as in a fronto-parietal attention network. Moreover, functional coupling between the right auditory cortex and frontal areas was reduced in patients. Seed-to voxel analysis on the whole-brain level revealed reduced connectivity between the auditory cortex and the thalamus as well as posterior cingulate. The present study indicates deficits in sensory processing on the level of the auditory cortex in depression. Hyposensitivity in a fronto-parietal network presumably reflects altered attention mechanisms in depression. The observed impairments may contribute to psychopathology by reducing the ability of the affected individuals to orient attention toward important environmental cues.

Facing recovery: Emotional bias in working memory, rumination, relapse, and recurrence of major depression; an experimental paradigm conducted five years after first episode of major depression

Identifying vulnerability factors for relapse of depression is essential in planning preventive interventions. Emotional face processing in major depression (MDD) shows promise as a potential cognitive marker for depression. The current study investigates how working memory (WM) load in face processing relates to rumination and new episodes of MDD in a novel explorative paradigm. It was expected that history of MDD is associated with reduction of the ability to process sad stimuli in high WM load conditions and reduction of the ability to process happy stimuli in low WM conditions. It was further predicted that these relations are associated with rumination and risk for relapse. The experiment was included as a cross sectional part in a follow-up study of a population that previously experienced first episode (FE) depression. The FE (N = 23) and a healthy control group (N = 22) completed a WM face processing task. In the task, three happy or sad faces were presented, processed in either a high or low WM taxing manner, followed by a target stimulus consisting of one of the previous pictures. Response time and accuracy were dependent variables. Rumination and number of relapses or recurrences were measured. The FE group recalled the placement of significantly fewer happy faces in the low WM load condition, and significantly fewer sad faces in the high WM load condition compared to controls. Significantly different scores between groups predicted trait rumination. Poor accuracy in the sad high WM load condition correlated with high degree of rumination. Relapse or recurrence was predicted by rumination. The present study supports an emotional WM deficit in remitted MDD. This suggests that deficits in manipulation of sad faces could represent a trait bias related to rumination and depression.

Depression is associated with enhanced aversive Pavlovian control over instrumental behaviour

The dynamic modulation of instrumental behaviour by conditioned Pavlovian cues is an important process in decision-making. Patients with major depressive disorder (MDD) are known to exhibit mood-congruent biases in information processing, which may occur due to Pavlovian influences, but this hypothesis has never been tested directly in an unmedicated sample. To address this we tested unmedicated MDD patients and healthy volunteers on a computerized Pavlovian-Instrumental Transfer (PIT) task designed to separately examine instrumental approach and withdrawal actions in the context of Pavlovian appetitive and aversive cues. This design allowed us to directly measure the degree to which Pavlovian cues influence instrumental responding. Depressed patients were profoundly influenced by aversive Pavlovian stimuli, to a significantly greater degree than healthy volunteers. This was the case for instrumental behaviour both in the approach condition (in which aversive Pavlovian cues inhibited ‘go’ responses), and in the withdrawal condition (in which aversive Pavlovian cues facilitated ‘go’ responses). Exaggerated aversive PIT provides a potential cognitive mechanism for biased emotion processing in major depression. This finding also has wider significance for the understanding of disrupted motivational processing in neuropsychiatric disorders.

Neural Basis of the Emotional Conflict Processing in Major Depression: ERPs and Source Localization Analysis on the N450 and P300 Components.

Objects: Effective psychological function requires that cognition is not affected by task-irrelevant emotional stimuli in emotional conflict. Depression is mainly characterized as an emotional disorder. The object of this study is to reveal the behavioral and electrophysiological signature of emotional conflict processing in major depressive disorder (MDD) using event-related potentials (ERPs) and standardized low-resolution brain electromagnetic tomography (sLORETA) analysis.Method: We used a face–word Stroop task involving emotional faces while recording EEG (electroencephalography) in 20 patients with MDD and 20 healthy controls (HCs). And then ERPs were extracted and the corresponding brain sources were reconstructed using sLORETA.Results: Behaviorally, subjects with MDDs manifested significantly increased Stroop effect when examining the RT difference between happy incongruent trials and happy congruent trials, compared with HC subjects. ERP results exhibited that MDDs were characterized by the attenuated difference between P300 amplitude to sad congruent stimuli and sad incongruent stimuli, as electrophysiological evidence of impaired conflict processing in subjects with MDD. The sLORETA results showed that MDD patients had a higher current density in rostral anterior cingulate cortex (rostral ACC) within N450 time window in response to happy incongruent trials than happy congruent stimuli. Moreover, HC subjects had stronger activity in right inferior frontal gyrus (rIFG) region in response to incongruent stimuli than congruent stimuli, revealing successful inhibition of emotional distraction in HCs, which was absent in MDDs.Conclusion: Our results indicated that rostral ACC was implicated in the processing of negative emotional distraction in MDDs, as well as impaired inhibition of task-irrelevant emotional stimuli, relative to HCs. This work furnishes novel behavioral and neurophysiological evidence that are closely related to emotional conflict among MDD patients.

Aberrant working memory processing in major depression: evidence from multivoxel pattern classification.

Major depressive disorder (MDD) is often accompanied by severe impairments in working memory (WM). Neuroimaging studies investigating the mechanisms underlying these impairments have produced conflicting results. It remains unclear whether MDD patients show hyper- or hypoactivity in WM-related brain regions and how potential aberrations in WM processing may contribute to the characteristic dysregulation of cognition-emotion interactions implicated in the maintenance of the disorder. In order to shed light on these questions and to overcome limitations of previous studies, we applied a multivoxel pattern classification approach to investigate brain activity in large samples of MDD patients (N = 57) and matched healthy controls (N = 61) during a WM task that incorporated positive, negative, and neutral stimuli. Results showed that patients can be distinguished from healthy controls with good classification accuracy based on functional activation patterns. ROI analyses based on the classification weight maps showed that during WM, patients had higher activity in the left DLPFC and the dorsal ACC. Furthermore, regions of the default-mode network (DMN) were less deactivated in patients. As no performance differences were observed, we conclude that patients required more effort, indexed by more activity in WM-related regions, to successfully perform the task. This increased effort might be related to difficulties in suppressing task-irrelevant information reflected by reduced deactivation of regions within the DMN. Effects were most pronounced for negative and neutral stimuli, thus pointing toward important implications of aberrations in WM processes in cognition-emotion interactions in MDD.

Other race effect on amygdala response during affective facial processing in major depression.

The other race effect, also known as own race bias, refers to the enhanced ability to recognize faces belonging to one's own race relative to faces from another race. The other race effect is associated with increased amygdala response in healthy individuals. The amygdala is a key node in emotion processing which shows impaired functioning in depression and has been proposed to be a marker of depressive state. We investigated the impact of the other race effect on amygdala responses in depression. Participants were 30 individuals with major depression (mean age 39.4 years) and 23 healthy individuals (mean age: 38.8 years) recruited from the community. Participants were Asian, Black/African American and Caucasian. During a functional MRI scan, participants viewed Caucasian faces which displayed a range of sad expressions. A region of interest analysis of left and right amygdala responses was performed. Increased bilateral amygdala responses were observed in response to the Caucasian face stimuli in participants who were Asian or Black/African American as compared to Caucasian participants in both healthy individuals and individuals with major depression. There was no significant group by race interaction effect. Increased amygdala responses associated with the other race effect were evident in both individuals with major depression and in healthy participants. Increased amygdala responses with the other race effect is a potential confound of the neural correlates of facial processing in healthy participants and in mental health disorders. The implications of the other race effect on impairments in interpersonal functioning in depression require further investigation.

P.2.f.020 - One-week administration of escitalopram decreases neural responses to self-referential processing in major depression

To examine age group differences in the identification, engagement, clinical outcomes, and monitoring of older, relative to middle aged and younger, veterans with behavioral health needs enrolled in an integrated care management programCross-sectional and longitudinalPrimary care clinics affiliated with two Veterans Affairs Medical CentersA total of9,087 veterans were referred to the Behavioral Health Laboratory (BHL) for a behavioral health assessment and 7,251 completed an initial assessmentData on consult source and reason for the referral, clinical assessment outcomes, and engagement were collected during a 3-year period. Variations in process and patient-level factors were examined as a function of age group.Although all age groups evidenced high rates of engagement in clinical assessment calls, older adults were slightly more likely to complete the assessments than young/middle-aged veterans. Clinical assessment outcomes revealed that although older adults were less likely to meet criteria for more complex, severe conditions, rates of disorder remained clinically significant, and comorbidity was common. Finally, older veterans receiving treatment monitoring for a newly prescribed antide- pressant consistently reported high rates of antidepressant adherence during the course of the monitoring calls and showed significant reductions in depressive symptomatology during the course of monitoring.Results indicate age-related variability in processes and outcomes among veterans referred to the BHL and suggest that older veterans are just as likely to benefit from a program designed to facilitate the identification, engagement, monitoring, and care management of primary care patients experiencing behavioral health issues.

Impact of electroconvulsive therapy on magnetoencephalographic correlates of dysfunctional emotional processing in major depression

In major depressive disorder (MDD), electrophysiological and imaging studies provide evidence for a reduced neural activity in parietal and dorsolateral prefrontal regions. In the present study, neural correlates and temporal dynamics of visual affective perception have been investigated in patients with unipolar depression in a pre/post treatment design using magnetoencephalography (MEG). Nineteen in-patients and 19 balanced healthy controls passed MEG measurement while passively viewing pleasant, unpleasant and neutral pictures. After a 4-week treatment with electroconvulsive therapy or 4-week waiting period without intervention respectively, 16 of these patients and their 16 corresponding controls participated in a second MEG measurement. Before treatment neural source estimations of magnetic fields evoked by the emotional scenes revealed a general bilateral parietal hypoactivation in depressed patients compared to controls predominately at early and mid-latency time intervals. Successful ECT treatment, as reflected by a decline in clinical scores (Hamilton Depression Scale; HAMD) led to a normalization of this distinct parietal hypoactivation. Effective treatment was also accompanied by relatively increased neural activation at right temporo-parietal regions. The present study indicates dysfunctional parietal information processing and attention processes towards emotional stimuli in MDD patients which can be returned to normal by ECT treatment. Since convergent neural hypoactivations and treatment effects have recently been shown in MDD patients before and after pharmacological therapy, this electrophysiological correlate might serve as a biomarker for objective treatment evaluation and thereby potentially advance treatment options and support the prediction of individual treatment responses.

Antidepressant short-term and long-term brain effects during self-referential processing in major depression

Acute depression is associated with impaired self-referential processing. Antidepressant effects on the neural bases of self-referential processing in depression are unknown. This study aimed to assess short- and long-term effects of agomelatine on these neural bases in depressed patients and the association between pre-treatment brain activation and remission of depression 6 months later. We conducted a randomized double-blind, placebo-controlled, functional magnetic resonance imaging (fMRI) study during an emotional self-referential task, including three scanning sessions (baseline, after 1 week, and after 7 weeks). Twenty-five depressed outpatients were included, all treated with agomelatine or placebo for 1 week. Then, all patients received agomelatine for 24 weeks. Fourteen matched healthy volunteers (HV) who received placebo for 1 week were also included. After 7 days, only depressed patients receiving agomelatine significantly deactivated the ventrolateral prefrontal cortex during self-referential processing, as observed in HV at baseline. After 7 weeks, depressed patients significantly increased the activation of the ventral anterior cingulate cortex. Finally dorsomedial prefrontal cortex and precuneus activations at baseline significantly separated remitters from non-remitters at 24 weeks. In depressed patients, agomelatine had short- and long-term effects on brain structures involved in anhedonia and emotional regulation during self-referential processing. Activation of the dorsomedial prefrontal cortex and precuneus could be informative in the development of biomarker-based treatment of major depression.

Retinal dysfunction of contrast processing in major depression also apparent in cortical activity.

Depressive disorder is often associated with the subjective experience of altered visual perception. Recent research has produced growing evidence for involvement of the visual system in the pathophysiology of depressive disorder. Using the pattern electroretinogram (PERG), we found reduced retinal contrast response in patients with major depression. Based on this observation, the question arises whether this change has a cortical correlate. To evaluate this, we analyzed the visual evoked potential (VEP) of the occipital cortex in 40 patients with depressive disorder and 28 healthy controls. As visual stimuli, checkerboard stimuli of 0.51° check size, 12.5 reversals per second and a contrast of 3-80% was used. In addition to the PERG, we recorded the VEP with an Oz versus FPz derivation. The amplitude versus contrast transfer function was compared across the two groups and correlated with the severity of depression, as measured by the Hamilton Depression Rating Scale and the Beck Depression Inventory. Patients with major depression displayed significantly reduced VEP amplitudes at all contrast levels compared to control subjects (p = 0.029). The VEP amplitude correlated with psychometric measures for severity of depression. The degree of depression reduced the contrast transfer function in the VEP to a lesser extent than in the PERG: While the PERG is reduced to ≈50%, the VEP is reduced to 75%. Our results suggest that depression affects the cortical response in major depression, but less so than the retinal responses. Modified contrast adaptation in the lateral geniculate nucleus or cortex possibly moderates the increased losses in the retina.

Genetic variation in CACNA1C affects neural processing in major depression

Genetic studies found the A allele of the single nucleotide polymorphism rs1006737 in the CACNA1C gene, which encodes for the alpha 1C subunit of the voltage-dependent, L-type calcium ion channel Cav1.2, to be overrepresented in patients with major depressive disorder (MDD). Altered prefrontal brain functioning and impaired semantic verbal fluency (SVF) are robust findings in these patients. A recent functional magnetic resonance imaging (fMRI) study found the A allele to be associated with poorer performance and increased left inferior frontal gyrus (IFG) activation during SVF tasks in healthy subjects. In the present study, we investigated the effects of rs1006737 on neural processing during SVF in MDD. In response to semantic category cues, 40 patients with MDD and 40 matched controls overtly generated words while brain activity was measured with fMRI. As revealed by whole brain analyses, genotype significantly affected brain activity in patients. Compared to patients with GG genotype, patients with A allele demonstrated increased task-related activation in the left middle/inferior frontal gyrus and the bilateral cerebellum. Patients with A allele also showed enhanced functional coupling between left middle/inferior and right superior/middle frontal gyri. No differential effects of genotype on SVF performance or brain activation were found between diagnostic groups. The current data provide further evidence for an impact of rs1006737 on the left IFG and demonstrate that genetic variation in CACNA1C modulates neural responses in patients with MDD. The observed functional alterations in prefrontal and cerebellar areas might represent a mechanism by which rs1006737 influences susceptibility to MDD.

Effect of Antidepressant Medication Use on Emotional Information Processing in Major Depression

Acute administration of antidepressant medication increases emotional information processing for positive information in both depressed and healthy persons. This effect is likely relevant to the therapeutic actions of these medications, but it has not been studied in patients with major depressive disorder taking antidepressants as typically prescribed in the community. The authors used eye tracking to examine the effects of antidepressant medication on selective attention for emotional stimuli in a sample of 47 patients with major depressive disorder (21 medicated and 26 unmedicated) and 47 matched comparison subjects without depression. Participants completed a passive-viewing eye-tracking task assessing selective attention for positive, dysphoric, threatening, and neutral stimuli in addition to providing medication information and self-report measures of depression and anxiety severity. Depressed participants currently taking antidepressants and nondepressed comparison subjects demonstrated greater total gaze duration and more fixations for positive stimuli compared with unmedicated depressed participants. Depressed participants on medication also had fewer fixations for dysphoric stimuli compared with depressed participants not on medication. Antidepressants, as prescribed in the community to patients with depression, appear to modify emotional information processing in the absence of differences in depression severity. These results are consistent with previous work and indicate a robust effect for antidepressants on positive information processing. They also provide further evidence for modification of information processing as a potential mechanism of action for antidepressant medication.

Abnormal proactive and reactive cognitive control during conflict processing in major depression.

According to the Dual Mechanisms of Control framework, cognitive control consists of two complementary components: proactive control refers to anticipatory maintenance of goal-relevant information, whereas reactive control acts as a correction mechanism that is activated when a conflict occurs. Possibly, the well-known diminished inhibitory control in response to negative stimuli in Major Depressive Disorder (MDD) patients stems from a breakdown in proactive control, and/or anomalies in reactive cognitive control. In our study, MDD patients specifically showed increased response latencies when actively inhibiting a dominant response to a sad compared with a happy face. This condition was associated with a longer duration of a dominant ERP topography (800-900 ms poststimulus onset) and a stronger activity in the bilateral dorsal anterior cingulate cortex, reflecting abnormal reactive control when inhibiting attention to a negative stimulus. Moreover, MDD patients showed abnormalities in proactive cognitive control when preparing for the upcoming imperative stimulus (abnormal modulation of the contingent negative variation component), accompanied by more activity in brain regions belonging to the default mode network. All together, deficits to inhibit attention to negative information in MDD might originate from an abnormal use of both proactive resources and reactive control processes.

Comparison of neuropsychological functioning and emotional processing in major depression and social anxiety disorder subjects, and matched healthy controls

Few studies of neuropsychological function in major depression have examined emotional processing or the impact of gender. Patients have also been compared with highly selected control participants and rarely with other patient groups. The objective of this study was to compare neuropsychological function in a major depressive episode (MDE) with a group of patients with an anxiety disorder, social anxiety disorder (SAD), and healthy controls, to include measures of emotional processing and to analyse the effects of gender on neuropsychological function and emotional processing in these groups. One hundred and one medication-free patients with MDE, 30 patients with SAD and 76 healthy control participants were recruited. The groups were matched for age and estimated premorbid intelligence and education. Subjects performed a battery of neuropsychological tests assessing; verbal learning and memory, visuospatial learning and memory, attention, executive function and psychomotor performance. They also performed a task measuring the accuracy of recognition of facial emotional expressions. Compared with healthy participants and those with SAD, patients with MDE were significantly impaired in verbal learning and spatial working memory. The SAD group misclassified significantly more neutral expressions as angry and fewer as sad, compared with the MDE group and healthy controls, but there were no significant differences between the MDE group and healthy controls. The profile of performance was the same regardless of gender. The study confirms a significant impairment in neuropsychological function in a clinical sample of outpatients with MDE, which is likely to have important implications for day-to-day functioning and treatment.

Emotive interference during cognitive processing in major depression: An investigation of lower alpha 1 activity

Individuals with Major Depressive Disorder (MDD) tend to be more susceptible to distraction by negative emotional material than their non-depressed counterparts. This extends to an enhanced vulnerability to interference from mood-congruent stimuli during cognitive processing. The current study investigated the electrophysiological correlates of competing cognitive and emotional processing demands in MDD. Event-related alpha activity within the lower alpha 1 band was examined during the online information retention phase of a non-emotive WM task with extraneous emotional stimuli (positive, negative and neutral) presented as background images. EEG activity over posterior parietal cortex was compared between 15 acutely depressed and 16 never depressed right-handed women. A valence specific dissociation in lower alpha 1 activity was observed between the two groups, consistent with greater attentional resource allocation to positive distracters in control participants and to negative distracters in MDD participants. No group differences were seen when neutral distracters were displayed. These results demonstrate that activity within the lower alpha 1 band is sensitive to competing emotional and cognitive processing demands and highlight the importance of posterior parietal regions in depression-related susceptibility to affective distractibility during cognitive processing.

Facial emotion processing in major depression: a systematic review of neuroimaging findings

BackgroundCognitive models of depression suggest that major depression is characterized by biased facial emotion processing, making facial stimuli particularly valuable for neuroimaging research on the neurobiological correlates of depression. The present review provides an overview of functional neuroimaging studies on abnormal facial emotion processing in major depression. Our main objective was to describe neurobiological differences between depressed patients with major depressive disorder (MDD) and healthy controls (HCs) regarding brain responsiveness to facial expressions and, furthermore, to delineate altered neural activation patterns associated with mood-congruent processing bias and to integrate these data with recent functional connectivity results. We further discuss methodological aspects potentially explaining the heterogeneity of results.MethodsA Medline search was performed up to August 2011 in order to identify studies on emotional face processing in acutely depressed patients compared with HCs. A total of 25 studies using functional magnetic resonance imaging were reviewed.ResultsThe analysis of neural activation data showed abnormalities in MDD patients in a common face processing network, pointing to mood-congruent processing bias (hyperactivation to negative and hypoactivation to positive stimuli) particularly in the amygdala, insula, parahippocampal gyrus, fusiform face area, and putamen. Furthermore, abnormal activation patterns were repeatedly found in parts of the cingulate gyrus and the orbitofrontal cortex, which are extended by investigations implementing functional connectivity analysis. However, despite several converging findings, some inconsistencies are observed, particularly in prefrontal areas, probably caused by heterogeneities in paradigms and patient samples.ConclusionsFurther studies in remitted patients and high-risk samples are required to discern whether the described abnormalities represent state or trait characteristics of depression.

Failure to segregate emotional processing from cognitive and sensorimotor processing in major depression

Most functional neuroimaging studies of major depressive disorder (MDD) employ univariate methods of statistical analysis to localize abnormalities of neural activity. Less has been done to investigate functional relations between these regions, or with regions not usually implicated in depression. Examination of intraneuronal and interneural network relations is important for the advancement of emerging network models for MDD. Principal component analysis (PCA), a multivariate statistical method, was used to examine differences in functional connectivity between 10 unmedicated patients with MDD and 12 healthy subjects engaged in a positive word viewing task. In healthy subjects, principal component (PC) 1 (33% variance) revealed functional connectivity of task-specific sensory, linguistic, and motor regions, along with functional anticorrelations in the default mode network; PC2 (10% variance) displayed functional connectivity of areas involved in emotional processing. This segregation of functions did not occur in the depressed group, where regions involved in emotional functions appeared in PC1 (34% variance) co-varying with those involved in linguistic, motor, and default mode network processing. The lack of segregation of emotional processing from cognitive and sensorimotor functions may represent a systems level neural substrate for a core phenomenon of depression: the interconnection of affective disturbance with experience, cognition, and behavior.

S20-03 - Neurogenetics of emotion processing in major depression

Converging lines of research suggest that major depression is characterized by abnormalities in different stages of emotion processing (e.g., automatic emotion processing, emotion regulation, or reward processing). Using functional neuroimaging, the neurobiological correlates of these emotion processing biases have been intensively investigated during the last decade. Depressed patients appear to be characterized by a hyper-responsive amygdala to negative stimuli, dysfunctional prefrontal activity during emotion regulation and blunted activity of the ventral striatum in response to positive cues or reward.We present a series of studies investigating genetic underpinnings of these neurobiological abnormalities frequently observed in depression. We demonstrate a consistent pattern of serotonergic and neuropeptide genes that bias automatic amygdala responsiveness towards subliminally presented negative stimuli. Other genes were shown to impact prefrontal engagement during conscious emotion processing, e.g. genetic variants in the interleukin 1 beta gene. Further polymorphisms, e.g. in the endocannabinoid system rather seem to influence striatal responsiveness to positive social cues.We conclude that the neurobiological abnormalities in major depression which are linked to biased emotional processes are strongly under genetic influence. The investigation of neurogenetic pathways to different aspects of depression psychopathology might help to better characterize patients according to their neurobiological dysfunctions and might ultimately lead to individualized therapy plans.