rMDD Patients Research Articles

Classification of recurrent major depressive disorder using a residual denoising autoencoder framework: Insights from large-scale multisite fMRI data

Background and objectiveRecurrent major depressive disorder (rMDD) has a high recurrence rate, and symptoms often worsen with each episode. Classifying rMDD using functional magnetic resonance imaging (fMRI) can enhance understanding of brain activity and aid diagnosis and treatment of this disorder. MethodsWe developed a Residual Denoising Autoencoder (Res-DAE) framework for the classification of rMDD. The functional connectivity (FC) was extracted from fMRI data as features. The framework addresses site heterogeneity by employing the Combat method to harmonize feature distribution differences. A feature selection method based on Fisher scores was used to reduce redundant information in the features. A data augmentation strategy using a Synthetic Minority Over-sampling Technique algorithm based on Extended Frobenius Norm measure was incorporated to increase the sample size. Furthermore, a residual module was integrated into the autoencoder network to preserve important features and improve the classification accuracy. ResultsWe tested our framework on a large-scale, multisite fMRI dataset, which includes 189 rMDD patients and 427 healthy controls. The Res-DAE achieved an average accuracy of 75.1 % (sensitivity = 69 %, specificity = 77.8 %) in cross-validation, thereby outperforming comparison methods. In a larger dataset that also includes first-episode depression (comprising 832 MDD patients and 779 healthy controls), the accuracy reached 70 %. ConclusionsWe proposed a deep learning framework that can effectively classify rMDD and 33 identify the altered FC associated with rMDD. Our study may reveal changes in brain function 34 associated with rMDD and provide assistance for the diagnosis and treatment of rMDD.

Trait and state effects of different modes of thinking on salivary cortisol in daily life in patients with recurrent major depression and healthy individuals

Habitual modes of thinking such as repetitive negative thinking (RNT), but also momentary cognitive processes such as mindwandering could be vulnerability factors for the course of Major Depressive Disorder (MDD). On the physiological level, cortisol represents an important biological stress marker of the hypothalamic-pituitary-adrenal (HPA) axis. Being a dynamic and non-invasive measure, salivary cortisol can be assessed in daily life via Ambulatory Assessment (AA). So far, consensus exists on a dysregulation of the HPA axis in MDD. However, findings are ambiguous and AA-studies examining both trait and state level effects of cognitive processes on cortisol release in daily life in patients with recurrent major depression (rMDD) and healthy controls (HCs) are lacking. A sample of 119 (nrMDD=57, nHCs=62) participants underwent a baseline session, including self-rated questionnaires (RNT, mindfulness) followed by a 5-day AA, where participants indicated the occurrence of mindwandering and levels of mentalshift problems ten times per day via smartphone, and collected saliva cortisol samples five times per day. Via multilevel models, we found habitual RNT, but not mindfulness, to predict higher cortisol levels, with the effects being stronger in rMDD patients. State mindwandering and mentalshift problems predicted increased cortisol 20 min later across groups. State cognitions did not mediate the effects of habitual RNT on cortisol release. Our results suggest independent mechanisms of action for trait and state cognitions on cortisol activity in daily life and indicate a greater physiological vulnerability toward trait RNT and the tendency to experience mentalshift problems in patients with recurrent major depression.

Effects of an experimentally induced inflammatory stimulus on motivational behavior in remitted depressed patients

BackgroundAcute inflammation is associated with sickness behavior characterized by reduced motivation for pleasurable activities in humans. The current study investigated the effect of an experimentally induced inflammatory stimulus on motivational reward in people who remitted from depression. MethodsThis randomized, double-blind crossover study involved 12 participants, 5 with remitted major depressive disorder (rMDD) and 7 healthy controls (HC), who received an injection of typhoid vaccine and placebo (or vice-versa) intramuscularly at least one week apart. At baseline and between 4 and 6 h post-injection on both days, participant mood was measured using the profile of mood states (POMS), and injection blood samples were collected for cytokines measurement. All participants completed the Effort Expenditure for Rewards Task (EEfRT), a behavioral paradigm measuring effort-based decision-making before and 4 h post-both injections. Generalized linear mixed modeling was used to evaluate group differences in choosing the hard over easy task to obtain a monetary reward. ResultsTyphoid vaccine increased IL-6 in all participants. On the EEfRT, a significant interaction between treatment condition (typhoid vs. placebo) and participant group (HC vs. rMDD) was found (p = .004). Analyses of simple effects within treatment conditions found that after placebo, HCs were more likely to choose the harder task than rMDD (OR = 3.21; p = .013). However, after the typhoid vaccine, no differences were found between rMDD and HC (p = .397). Analyses within participant groups found that the probability of choosing a hard task was higher after placebo for HC (OR = 1.37; p = .045), but not different within rMDD (p = .241). For HC at baseline, mood was significantly lower following injection with typhoid vaccine, relative to placebo (b = −1.03, p < .001); however, this effect should be considered coincidental, given that mood rating was taken prior to injection. For rMDD patients 4–6 h post-injection, mood was significantly lower following typhoid vaccine, relative to placebo (b = −0.981, p < .001 b = −0.77, p < .001). Finally, for HC receiving placebo, mood was significantly lower 4–6 h post-injection, relative to baseline (b = −1.76, p < .001). ConclusionsOur preliminary findings suggest persistent deficits in motivational reward processing function despite clinical improvement in remitted depressed patients.

Reciprocal Prospective Effects of Momentary Cognitions and Affect in Daily Life and Mood Reactivity Toward Daily Events in Remitted Recurrent Depression

Major depressive disorder is a recurrent condition. Potential risk factors for future episodes are maladaptive cognitions, such as rumination and unfavorable reactivity toward negative daily events. Positive thoughts and positive daily events, in contrast, could act as a buffer against mood deterioration. The aim of the present study is to (a) examine differences in daily affect and cognitions in remitted depressed patients with a history of recurrent episodes (rMDD) and healthy controls, (b) analyze reciprocal prospective effects of momentary cognitions and affect, and (c) investigate effects of daily events on affect and cognitions in both groups. A sample of N = 102 participants underwent an ecological momentary assessment (EMA) phase of 5 consecutive days, where rMDD patients (n = 51) and healthy controls (n = 51) indicated their momentary rumination, positive thoughts, affect, and the occurrence of daily events 10 times per day. Via multilevel lag models, we found higher rumination to predict a decrease of positive affect (PA) in the rMDD group, but no effect of rumination on subsequent negative affect (NA) in either group. Higher positive thoughts predicted an increase in PA and a decrease in NA, similarly strong in both groups. Regarding daily events, rMDD patients reported a stronger increase in NA and rumination following negative daily events compared to controls, whereas an observed subsequent decrease of PA and positive thoughts was not moderated by group. Following positive daily events, rMDD patients showed a stronger increase in PA and positive thoughts and a stronger decrease in NA and rumination than controls. For interventions targeting relapse prevention, our results indicate the implementation of strategies fostering the responsiveness to positive events and the up-regulation of positive affect.

Lateralized subgenual ACC metabolic connectivity patterns in refractory melancholic depression: does it matter?

Although treatment resistance to antidepressant pharmacotherapy is quite common, the phenomenon of refractory major depressive disorder (rMDD) is not well understood. Nevertheless, the metabolic activity of the subgenual anterior cingulate cortex (sgACC) has been put forward as a possible metabolic biomarker of clinical prediction and response, albeit sgACC lateralization differences in functional connectivity have not yet been extensively examined. Also not in the refractory depressed state. To examine sgACC lateralization differences in metabolic connectivity, we recruited 43 right-handed antidepressant-free unipolar melancholic rMDD patients and 32 right-handed healthy controls to participate in this 18FDG PET study and developed a searchlight-based interregional covariance connectivity approach. Compared to non-depressed individuals, sgACC covariance analysis showed stronger metabolic connections with frontolimbic brain regions known to be affected in the depressed state. Furthermore, whereas the left sgACC showed stronger metabolic connections with ventromedial prefrontal cortical regions, implicated in anhedonia, suicidal ideation, and self-referential processes, the right sgACC showed significantly stronger metabolic connections with posterior hippocampal and cerebellar regions, respectively specialized in memory and social processing. Overall, our results substantiate earlier research that the sgACC is a metabolic key player when clinically depressed and that distinct lateralized sgACC metabolic connectivity patterns are present.

Functional connectivity patterns of the subgenual anterior cingulate cortex in first-episode refractory major depressive disorder.

Although accumulating evidence has been elucidating the neuronal basis of refractory/nonrefractory major depressive disorder (rMDD/nrMDD), the results are inconsistent, and little is known about the distinct neural mechanisms underlying rMDD. Here, we explored the convergent/divergent brain networks between first-episode MDD subtypes using the resting-state functional connectivity (RSFC) approach. In total, 33 healthy controls (HCs), 31 first-episode rMDD patients and 33 first-episode nrMDD patients were enrolled and underwent MRI scanning. The left subgenual anterior cingulate cortex (sgACC) was selected as the seed region, and RSFC was employed to evaluate associations between the seed and other regions in the whole brain. Both MDD subtypes exhibited convergent left sgACC-based neural networks, including increased RSFC with the dorsal prefrontal cortex (DPFC) and decreased RSFC with the bilateral orbitofrontal cortex (OFC) and right parahippocampus. rMDD patients exhibited increased left sgACC-OFC RSFC relative to nrMDD patients, and RSFC with the bilateral OFC in rMDD patients was negatively correlated with HAMD scores. These findings confirmed our speculation that convergent and divergent neural networks exist between rMDD and nrMDD. Cortical-limbic circuits, especially the prefrontal-limbic circuit, may serve as the convergent dysfunctional neural circuitry in MDD subtypes. As an important biomarker, a unique OFC-sgACC circuit abnormality was identified in rMDD patients, which might help elucidate the underlying mechanism regarding treatment responses in rMDD patients.

The alteration of cognitive function networks in remitted patients with major depressive disorder: an independent component analysis

IntroductionDysfunctional connectivity of resting-state functional networks has been observed in patients with major depressive disorder (MDD), particularly in cognitive function networks including the central executive network (CEN), default mode network (DMN) and salience network (SN). Findings from studies examining how aberrant functional connectivity (FC) changed after antidepressant treatment, however, have been inconsistent. Thus, the purpose of the present study was to explore potential mechanisms of altered cognitive function networks during resting-state between remitted major depressive disorder (rMDD) patients and healthy controls (HCs) and furthermore, the relationship between dysfunctional connectivity patterns in rMDD and clinical symptoms. MethodologyIn this study, 19 HCs and 19 rMDD patients were recruited for resting-state functional magnetic resonance imaging (fMRI) scanning. FC was evaluated with independent component analysis for CEN, DMN and SN. Two sample t tests were conducted to compare differences between rMDD and HCs. A Pearson correlation analysis was also performed to examine the relationship between connectivity of networks and cognitive function scores and clinical symptoms. ResultsCompared to healthy controls, remitted patients showed lower connectivity in CEN, mostly in the superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior parietal lobule (IPL) and part of the supramarginal gyrus (SMG). Conversely, the bilateral insula, part of the SMG (a key node of the CEN) and dorsal anterior cingulate cortex (dACC) of the DMN showed higher connectivity in rMDD patients. Pearson correlation results demonstrated that connectivity of the right IPL in CEN was positively correlated with cognitive function scores, and connectivity of the left insula was negatively correlated with BDI scores. ConclusionsThough rMDD patients reached the standard of clinal remission, unique impairments of FC in cognitive function networks remained. Aberrant FC between cognitive function networks responsible for executive control was observed in rMDD and may be associated with residual clinical symptoms.

Neurobiological predictors for clinical trajectories in fully remitted depressed patients.

BackgroundSerious long term health and economic detriment accompany residual depressive symptoms even in fully remitted depressed patients (rMDD). Neurobiological predictors for rMDD patients’ illness trajectory are absent.MethodsrMDD patients (n = 39, female = 26) underwent magnetic resonance imaging. Baseline analyses of brain structure via voxel‐based morphometry and brain function via functional connectivity (FC) at rest were correlated with changes in the Hamilton Depression Rating Scale between baseline and follow‐up, and incidence of a recurrent major depressive episode (MDE) within a 2‐year period.ResultsGray matter increases in default mode (DN) regions in the posterior cingulate cortex (PCC) and increased resting‐state FC within the DN both predicted change of depressive symptoms. Patients with recurrent MDE had larger bilateral nucleus accumbens and left insula volumes. Post hoc exploratory analysis of nucleus accumbens and insula conceptualized as part of the brain's reward circuit demonstrated reduced connectivity in patients with recurrent MDE.ConclusionsHigher DN connectivity and PCC volume coinciding with a more favorable course of symptoms suggest neural mechanisms of self‐recovery beyond the phase of active medical treatment. Alterations in the brain's reward circuit might be a starting point for designing maintenance treatments that prevent recurrent MDEs in rMDD patients.

Abnormal Cerebellar Volume in Patients with Remitted Major Depression with Persistent Cognitive Deficits

Cerebellar involvement in major depressive disorder (MDD) has been demonstrated by a growing number of studies, but it is unknown whether cognitive functioning in depressed individuals is related to cerebellar gray matter volume (GMV) abnormalities. Impaired attention and executive dysfunction are characteristic cognitive deficits in MDD, and critically, they often persist despite remission of mood symptoms. In this study, we investigated cerebellar GMV in patients with remitted MDD (rMDD) that showed persistent cognitive impairment. We applied cerebellum-optimized voxel-based morphometry in 37 patients with rMDD and with cognitive deficits, in 12 patients with rMDD and without cognitive deficits, and in 36 healthy controls (HC). Compared with HC, rMDD patients with cognitive deficits had lower GMV in left area VIIA, crus II, and in vermal area VIIB. In patients with rMDD, regression analyses demonstrated significant associations between GMV reductions in both regions and impaired attention and executive dysfunction. Compared with HC, patients without cognitive deficits showed increased GMV in bilateral area VIIIB. This study supports cerebellar contributions to the cognitive dimension of MDD. The data also point towards cerebellar area VII as a potential target for non-invasive brain stimulation to treat cognitive deficits related to MDD.

Connectivity patterns of cognitive control network in first episode medication-naive depression and remitted depression

BackgroundCognitive dysfunctions, such as impaired cognitive control, are frequently observed in patients with major depressive disorder (MDD). Although the cognitive control network (CCN) is widely considered a core feature of major depressive disorder (MDD), the relationship between cognitive dysfunction and symptom dimensions remains unclear. This study investigated differences in resting-state functional connectivity of the cognitive control network (CCN) between first-episode medication-naive MDD patients and remitted MDD. MethodsWe collected resting-state functional MRI (rs-fMRI) data from 22 first-episode medication-naive major depressive disorder (fMDD) patients, 20 patients previously diagnosed with MDD in the remitted phase of depression (rMDD), and 20 healthy controls (HC). The CCN was derived from fMRI images using independent component analysis (ICA), a data-driven image analysis method. ResultsChanges in functional connectivity (FC) within the CCN was mainly attenuated in the right dorsolateral prefrontal cortex and the left inferior parietal lobule, while strengthened in the right dorsal anterior cingulate cortex and the right insula in both fMDD and rMDD groups. Compared with the fMDD group, the rMDD group had decreased FC in the bilateral insula and the right dorsolateral prefrontal cortex. Further analysis explored that the FC in the bilateral insula, the right dorsal anterior cingulate cortex and the right inferior parietal lobule were correlated positively cognitive disturbance factor scores in both patients groups. ConclusionsThese findings are in agreement with the previous findings that the cognitive control network are impaired in MDD. Furthermore, our results suggest that the alteration of CCN might underpin the cognitive disturbance and the distinct patterns of the CCN between fMDD and rMDD patients may be an important target for effective cognitive remediation in MDD.

State-Related Alterations of Spontaneous Neural Activity in Current and Remitted Depression Revealed by Resting-State fMRI.

Purpose: Although efforts have been made to identify neurobiological characteristic of major depressive disorder (MDD) in recent years, trait- and state-related biological characteristics of MDD still remains unclear. Using functional magnetic resonance imaging (fMRI), the aim of this study was to explore whether altered spontaneous neural activities in MDD are trait- or state- related.Materials and Methods: Resting-state fMRI data were analyzed for 72 current MDD (cMDD) patients (first-episode, medication-naïve), 49 remitted MDD (rMDD) patients, and 78 age- and sex- matched healthy control (HC) subjects. The values of amplitude of low-frequency fluctuation (ALFF) were compared between groups.Results: Compared with the cMDD group, the rMDD group had increased ALFF values in the left middle occipital gyrus, left middle temporal gyrus and right cerebellum anterior lobe. Besides, compared with the HC group, the cMDD group had decreased ALFF values in the left middle occipital gyrus. Further analysis explored that the mean ALFF values in the left middle occipital gyrus, left middle temporal gyrus and right cerebellum anterior lobe were correlated positively with BDI scores in rMDD patients.Conclusion: Abnormal activity in the left middle occipital gyrus, left middle temporal gyrus and right cerebellum anterior lobe may be state-specific in current (first-episode, medication-naïve) and remitted (medication-naïve) depression patients. Furthermore, the state-related compensatory effect was found in these brain areas.

Associations Between Daily Affective Instability and Connectomics in Functional Subnetworks in Remitted Patients with Recurrent Major Depressive Disorder.

Remitted patients with major depressive disorder (rMDD) often report more fluctuations in mood as residual symptomatology. It is unclear how this affective instability is associated with information processing related to the default mode (DMS), salience/reward (SRS), and frontoparietal (FPS) subnetworks in rMDD patients at high risk of recurrence (rrMDD). Sixty-two unipolar, drug-free rrMDD patients (⩾2 MDD episodes) and 41 healthy controls (HCs) were recruited. We used experience sampling methodology to monitor mood/cognitions (10 times a day for 6 days) and calculated affective instability using the mean adjusted absolute successive difference. Subsequently, we collected resting-state functional magnetic resonance imaging data and performed graph theory to obtain network metrics of integration within (local efficiency) the DMS, SRS, and FPS, and between (participation coefficient) these subnetworks and others. In rrMDD patients compared with HCs, we found that affective instability was increased in most negative mood/cognition variables and that the DMS had less connections with other subnetworks. Furthermore, we found that rrMDD patients, who showed more instability in feeling down and irritated, had less connections between the SRS and other subnetworks and higher local efficiency coefficients in the FPS, respectively. In conclusion, rrMDD patients, compared with HCs, are less stable in their negative mood and these dynamics are related to differences in information processing within- and between-specific functional subnetworks. These results are a first step to gain a better understanding of how mood fluctuations in real life are represented in the brain and provide insights into the vulnerability profile of MDD.

Facial emotion recognition, theory of mind and the role of facial mimicry in depression

BackgroundThis study examined whether acutely (aMDD) and remitted depressed patients (rMDD) show deficits in the two aspects of social cognition – facial emotion recognition (FER) and reasoning – when using ecologically valid material. Furthermore, we examined whether reduced facial mimicry mediates the association between depressive symptoms and FER, and whether FER deficits and reasoning deficits are associated. MethodIn 42 aMDD, 43 rMDD, and 39 healthy controls (HC) FER was assessed using stimuli from the Amsterdam Dynamic Facial Expression Set, reasoning by the Movie for the Assessment of Social Cognition. Furthermore, the activity of Zygomaticus Major and Corrugator supercilii were recorded. ResultsaMDD recognized happy faces less accurately, were less confident recognizing happiness and anger and found it more difficult to recognize happiness, anger and fear than HC. rMDD were less confident recognizing anger and found it more difficult to recognize happiness, anger and fear than HC. Reduced mimicry did not explain FER deficits. aMDD but not rMDD showed impaired reasoning. LimitationsThe stimulus material was comparably easy to decode. Therefore, it is possible that the FER deficits of aMDD and rMDD patients are more pronounced than demonstrated in this study. ConclusionsaMDD show deficits in FER and reasoning, whereas rMDD only show mild impairments in the recognition of emotional expressions. There must be other processes – besides mimicry – that serve the accurate recognition of emotional facial expressions.

Subgenual Cingulate-Amygdala Functional Disconnection and Vulnerability to Melancholic Depression.

The syndromic heterogeneity of major depressive disorder (MDD) hinders understanding of the etiology of predisposing vulnerability traits and underscores the importance of identifying neurobiologically valid phenotypes. Distinctive fMRI biomarkers of vulnerability to MDD subtypes are currently lacking. This study investigated whether remitted melancholic MDD patients, who are at an elevated lifetime risk for depressive episodes, demonstrate distinctive patterns of resting-state connectivity with the subgenual cingulate cortex (SCC), known to be of core pathophysiological importance for severe and familial forms of MDD. We hypothesized that patterns of disrupted SCC connectivity would be a distinguishing feature of melancholia. A total of 63 medication-free remitted MDD (rMDD) patients (33 melancholic and 30 nonmelancholic) and 39 never-depressed healthy controls (HC) underwent resting-state fMRI scanning. SCC connectivity was investigated with closely connected bilateral a priori regions of interest (ROIs) relevant to MDD (anterior temporal, ventromedial prefrontal, dorsomedial prefrontal cortices, amygdala, hippocampus, septal region, and hypothalamus). Decreased (less positive) SCC connectivity with the right parahippocampal gyrus and left amygdala distinguished melancholic rMDD patients from the nonmelancholic rMDD and HC groups (cluster-based familywise error-corrected p⩽0.007 over individual a priori ROIs corresponding to approximate Bonferroni-corrected p⩽0.05 across all seven a priori ROIs). No areas demonstrating increased (more positive) connectivity were observed. Abnormally decreased connectivity of the SCC with the amygdala and parahippocampal gyrus distinguished melancholic from nonmelancholic rMDD. These results provide the first resting-state neural signature distinctive of melancholic rMDD and may reflect a subtype-specific primary vulnerability factor given a lack of association with the number of previous episodes.

Facial emotion recognition in remitted depressed women

Although major depressive disorder (MDD) is primarily characterized by mood symptoms, depressed patients have impairments in facial emotion recognition in many of the basic emotions (anger, fear, happiness, surprise, disgust and sadness). On the other hand, the data in remitted MDD (rMDD) patients is inconsistent and it is not clear that if those impairments persist in remission. To extend the current findings, we applied facial emotion recognition test to a group of remitted depressed women and compared to those of controls. Analyses of variance results showed a significant emotion and group interaction, and in the post hoc analyses, rMDD patients had higher accuracy rate for recognition of sadness compared to those of controls. There were no differences in the reaction time among the patients and controls across the all the basic emotions. The higher recognition rates for sad faces in rMDD patients might contribute to the impairments in social communication and the prognosis of the disease.

Altered anatomical patterns of depression in relation to antidepressant treatment: Evidence from a pattern recognition analysis on the topological organization of brain networks

BackgroundAccumulated evidence has illuminated the topological infrastructure of major depressive disorder (MDD). However, the changes of topological properties of anatomical brain networks in remitted major depressive disorder patients (rMDD) remain an open question. The present study provides an exploratory examination of pattern changes among current major depressive disorder patients (cMDD), rMDD patients and healthy controls (HC) by means of a pattern recognition analysis. MethodsTwenty-eight cMDD patients (age range: 22–54, mean age: 39.57), 15 rMDD patients (age range: 23–53, mean age: 38.40) and 30 HC (23–54, mean age: 35.57) were enrolled. For each subject, we computed five kinds of weighted white matter (WM) networks via employing five physiological parameters (i.e. fractional anisotropy, mean diffusivity, λ1, λ2 and λ3) and then calculated three network measures of these weighted networks. We treated these measures as features and fed into a feature selection mechanism to choose the most discriminative features for linear support vector machine (SVM) classifiers. ResultsLinear SVM could excellently distinguish the three groups with the 100% classification accuracy of recognizing cMDD/rMDD from HC, and 97.67% classification accuracy of recognizing cMDD from rMDD. The further pattern analysis found two types of discriminative patterns among cMDD, rMDD and HC. (i) Compared with HC, both cMDD and rMDD exhibited the similar deficit patterns of node strength primarily involving the salience network (SN), default mode network (DMN) and frontoparietal network (FPN). (ii) Compared with cMDD and rMDD showed the altered pattern of intra-communicability within DMN and inter-communicability between DMN and the other sub-networks including the visual recognition network (VRN) and SN. LimitationsThe present study had a limited sample size and a lack of larger independent data set to validate the methods and confirm the findings. ConclusionsThese findings implied that the impairment of MDD was closely associated with the alterations of connections within SN, DMN and FPN, whereas the remission of MDD was benefitted from the network compensatory of intra-communication within DMN and inter-communication between DMN and the other sub-networks (i.e., VRN and SN).

Reduced default mode network suppression during a working memory task in remitted major depression

Insufficient default mode network (DMN) suppression was linked to increased rumination in symptomatic Major Depressive Disorder (MDD). Since rumination is known to predict relapse and a more severe course of MDD, we hypothesized that similar DMN alterations might also exist during full remission of MDD (rMDD), a condition known to be associated with increased relapse rates specifically in patients with adolescent onset. Within a cross-sectional functional magnetic resonance imaging study activation and functional connectivity (FC) were investigated in 120 adults comprising 78 drug-free rMDD patients with adolescent- (n = 42) and adult-onset (n = 36) as well as 42 healthy controls (HC), while performing the n-back task. Compared to HC, rMDD patients showed diminished DMN deactivation with strongest differences in the anterior-medial prefrontal cortex (amPFC), which was further linked to increased rumination response style. On a brain systems level, rMDD patients showed an increased FC between the amPFC and the dorsolateral prefrontal cortex, which constitutes a key region of the antagonistic working-memory network. Both whole-brain analyses revealed significant differences between adolescent-onset rMDD patients and HC, while adult-onset rMDD patients showed no significant effects. Results of this study demonstrate that reduced DMN suppression exists even after full recovery of depressive symptoms, which appears to be specifically pronounced in adolescent-onset MDD patients. Our results encourage the investigation of DMN suppression as a putative predictor of relapse in clinical trials, which might eventually lead to important implications for antidepressant maintenance treatment.

Abnormal prefrontal activity subserving attentional control of emotion in remitted depressed patients during a working memory task with emotional distracters

Patients with major depressive disorder (MDD) show deficits in processing of facial emotions that persist beyond recovery and cessation of treatment. Abnormalities in neural areas supporting attentional control and emotion processing in remitted depressed (rMDD) patients suggests that there may be enduring, trait-like abnormalities in key neural circuits at the interface of cognition and emotion, but this issue has not been studied systematically. Nineteen euthymic, medication-free rMDD patients (mean age 33.6 years; mean duration of illness 34 months) and 20 age- and gender-matched healthy controls (HC; mean age 35.8 years) performed the Emotional Face N-Back (EFNBACK) task, a working memory task with emotional distracter stimuli. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure neural activity in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC), orbitofrontal cortex (OFC), ventral striatum and amygdala, using a region of interest (ROI) approach in SPM2. rMDD patients exhibited significantly greater activity relative to HC in the left DLPFC [Brodmann area (BA) 9/46] in response to negative emotional distracters during high working memory load. By contrast, rMDD patients exhibited significantly lower activity in the right DLPFC and left VLPFC compared to HC in response to positive emotional distracters during high working memory load. These effects occurred during accurate task performance. Remitted depressed patients may continue to exhibit attentional biases toward negative emotional information, reflected by greater recruitment of prefrontal regions implicated in attentional control in the context of negative emotional information.

P02-38 - Biological alterations during remission of major depressive disorder

IntroductionThe natural course of Major Depressive Disorder (MDD) encompasses the occurrence of alternating intervals of major depressive episodes and remission. While several abnormalities in neural circuits related to acute MDD have been identified, the neural mechanisms underlying stable remission remain obscure.ObjectivesAcute MDD is characterized by increased amygdala and subgenual anterior cingulate cortex (sACC) activation and decreased connectivity between the amygdala and the sACC. Consequently, we expect those regions to be affected during remission.AimsTo determine whether active counter-regulatory mechanisms are implicated in the maintenance of full remission once antidepressant treatment has been discontinued.MethodsFunctional and structural magnetic resonance imaging was used to measure brain activation and volume of the amygdala and the sACC. Images were obtained from 38 healthy subjects without any psychiatric life-time diagnosis and 38 gender-matched drug-free remitted MDD patients. Furthermore, correlation analyses were performed with clinical variables.ResultsPatients with rMDD exhibited lower activation in the amygdala and the sACC and increased functional coupling between the amygdala and sACC compared to controls. This connectivity was particularly pronounced in patients characterized by a long cumulated time of depressive episodes. Similarly, structural connectivity results showed increased association between the amygdala and sACC volume in rMDD patients compared to controls.ConclusionsRemitted MDD is related to neural alterations within a neural circuit encompassing the amygdala and the sACC compared to controls. These findings suggest active counter-regulatory mechanisms likely contributing to the maintenance of remission once treatment has been discontinued.

Health related quality of life in recurrent depression: A comparison with a general population sample

Background In the acute phase major depressive disorder (MDD) is a disabling disease. We compared HRQOL in patients with remitted MDD (rMDD) with a community sample and longitudinally assessed the relation between depressive symptoms and HRQOL in recurrently depressed patients. Methods We used 12-month data of patients from the Depression Evaluation Longitudinal Therapy Assessment (DELTA) study. HRQOL was assessed with the Medical Outcome Short Form (SF-36). Remission was determined with the Structured Clinical Interview for DSM-IV and depressive symptoms were assessed with the Beck Depression Inventory. Patients' mean SF-36 scores were compared with those of an age- and sex-matched Dutch reference population. The longitudinal relation between levels of SF-36 and levels of depressive symptomatology was assessed with a repeated measures linear regression analysis using the mixed models module. Results In patients with rMDD in the remitted phase, especially in women, both physical and mental HRQOL was lower than in a Dutch population sample. An increase in the level of depressive symptoms corresponded to a decrease in all scales of the SF-36. Conclusion Also in remitted rMDD patients, especially in women, HRQOL is lower than in the general population which emphasizes that also in this phase of recurrent depression HRQOL deserves attention. Furthermore, in patients with rMDD a higher depressive symptom severity level is associated with a lower HRQOL. These findings imply that residual symptoms should be treated aggressively and HRQOL enhancement therapies should be developed.