Maintenance Of Major Depressive Disorder Research Articles

Aberrant degree centrality profiles during rumination in major depressive disorder.

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.

The Fake IQ Test: a novel measure of self-reflection in major depressive disorder.

Excessive negative self-referential processing plays an important role in the development and maintenance of major depressive disorder (MDD). Current measures of self-reflection are limited to self-report questionnaires and invoking imagined states, which may not be suitable for all populations. The current study aimed to pilot a new measure of self-reflection, the Fake IQ Test (FIQT). Participants with MDD and unaffected controls completed a behavioural (experiment 1, n = 50) and functional magnetic resonance imaging version (experiment 2, n = 35) of the FIQT. Behaviourally, those with MDD showed elevated negative self-comparison with others, higher self-dissatisfaction and lower perceived success on the task, compared with controls; however, FIQT scores were not related to existing self-report measures of self-reflection. In the functional magnetic resonance imaging version, greater activation in self-reflection versus control conditions was found bilaterally in the inferior frontal cortex, insula, dorsolateral prefrontal cortex, motor cortex and dorsal anterior cingulate cortex. No differences in neural activation were found between participants with MDD and controls, nor were there any associations between neural activity, FIQT scores or self-report measures of self-reflection. Our results suggest the FIQT is sensitive to affective psychopathology, but a lack of association with other measures of self-reflection may indicate that the task is measuring a different construct. Alternatively, the FIQT may measure aspects of self-reflection inaccessible to current questionnaires. Future work should explore relationships with alternative measures of self-reflection likely to be involved in perception of task performance, such as perfectionism.

Negative Stressful Life Events and Social Support Are Associated With White Matter Integrity in Depressed Patients and Healthy Control Participants: A Diffusion Tensor Imaging Study

BackgroundNegative stressful life events and deprivation of social support play critical roles in the development and maintenance of major depressive disorder (MDD). The present study aimed to investigate in a large sample of patients with MDD and healthy control participants (HCs) whether these effects are also reflected in white matter (WM) integrity. MethodsIn this diffusion tensor imaging study, 793 patients with MDD and 793 age- and sex-matched HCs were drawn from the Marburg-Münster Affective Disorders Cohort Study (MACS) and completed the Life Events Questionnaire (LEQ) and Social Support Questionnaire (SSQ). Generalized linear models were performed to test voxelwise associations between fractional anisotropy (FA) and diagnosis (analysis 1), LEQ (analysis 2), and SSQ (analysis 3). We examined whether SSQ interacts with LEQ on FA or is independently associated with improved WM integrity (analysis 4). ResultsPatients with MDD showed lower FA in several frontotemporal association fibers compared with HCs (pTFCE-FWE = .028). Across both groups, LEQ correlated negatively with FA in widely distributed WM tracts (pTFCE-FWE = .023), while SSQ correlated positively with FA in the corpus callosum (pTFCE-FWE = .043). Modeling the combined association of both variables on FA revealed significant—and antagonistic—main effects of LEQ (pTFCE-FWE = .031) and SSQ (pTFCE-FWE = .037), but no interaction of SSQ × LEQ. ConclusionsOur results indicate that negative stressful life events and social support are both related to WM integrity in opposing directions. The associations did not differ between patients with MDD and HCs, suggesting more general, rather than depression-specific, mechanisms. Furthermore, social support appears to contribute to improved WM integrity independent of stressful life events.

Reducing default mode network connectivity with mindfulness-based fMRI neurofeedback: a pilot study among adolescents with affective disorder history

Adolescents experience alarmingly high rates of major depressive disorder (MDD), however, gold-standard treatments are only effective for ~50% of youth. Accordingly, there is a critical need to develop novel interventions, particularly ones that target neural mechanisms believed to potentiate depressive symptoms. Directly addressing this gap, we developed mindfulness-based fMRI neurofeedback (mbNF) for adolescents that aims to reduce default mode network (DMN) hyperconnectivity, which has been implicated in the onset and maintenance of MDD. In this proof-of-concept study, adolescents (n = 9) with a lifetime history of depression and/or anxiety were administered clinical interviews and self-report questionnaires, and each participant’s DMN and central executive network (CEN) were personalized using a resting state fMRI localizer. After the localizer scan, adolescents completed a brief mindfulness training followed by a mbNF session in the scanner wherein they were instructed to volitionally reduce DMN relative to CEN activation by practicing mindfulness meditation. Several promising findings emerged. First, mbNF successfully engaged the target brain state during neurofeedback; participants spent more time in the target state with DMN activation lower than CEN activation. Second, in each of the nine adolescents, mbNF led to significantly reduced within-DMN connectivity, which correlated with post-mbNF increases in state mindfulness. Last, a reduction of within-DMN connectivity mediated the association between better mbNF performance and increased state mindfulness. These findings demonstrate that personalized mbNF can effectively and non-invasively modulate the intrinsic networks associated with the emergence and persistence of depressive symptoms during adolescence.

The Neural Correlates of the Abnormal Implicit Self-Esteem in Major Depressive Disorder: An Event-Related Potential Study.

Implicit self-esteem (ISE) has been considered a critical factor in the development and maintenance of major depressive disorder (MDD). Further investigating the event-related potential (ERP) characteristics underlying abnormal ISE in MDD would be helpful for understanding the neural mechanism of MDD. For this purpose, 32 MDD patients and 31 age- and sex-matched healthy controls (HCs) were enrolled in this study. The Rosenberg Self-Esteem Scale (RSES) was used to evaluate explicit self-esteem (ESE), and a self-esteem go/no-go association task (GNAT) was used to assess ISE. Electroencephalograms were synchronously recorded when performing the self-esteem GNAT. Behavioral data and ERP characteristics under different conditions were analyzed and compared within and across groups. The results showed that compared to HCs, MDD patients had significantly lower RSES scores and self-D scores of GNAT, which reflected lower levels of ESE and ISE, respectively. No significant correlation was found between RESE and self-D scores, and only RESE scores were significantly negatively correlated with the Hamilton Depression Rating Scale (HAMD) score. The averaged centroparietal go-P3 amplitude under the self-positive condition was significantly smaller in MDD than in HCs. Moreover, HCs had a significantly larger average centroparietal go-P3 amplitude in self-positive than in self-negative conditions, while this pattern was opposite in the MDD group. The neural activity patterns for other conditions were similar between MDD and HCs. Our results suggested that patients with MDD have a decreased level of both ESE and ISE, and ISE might be more independent of clinical symptoms. Decreased neural processing that implicitly associate self with positive conditions (and relatively increased implicit association between self and negative conditions) might be important neural correlates for abnormal ISE in MDD.

Cumulative lifetime acute stressor exposure interacts with reward responsiveness to predict longitudinal increases in depression severity in adolescence.

Life stress and blunted reward processing each have been associated with the onset and maintenance of major depressive disorder. However, much of this work has been cross-sectional, conducted in separate lines of inquiry, and focused on recent life stressor exposure, despite the fact that theories of depression posit that stressors can have cumulative effects over the lifespan. To address these limitations, we investigated whether acute and chronic stressors occurring over the lifespan interacted with blunted reward processing to predict increases in depression over time in healthy youth. Participants were 245 adolescent girls aged 8-14 years old (Mage = 12.4, s.d. = 1.8) who were evaluated at baseline and two years later. The reward positivity (RewP), an event-related potential measure of reward responsiveness, was assessed at baseline using the doors task. Cumulative lifetime exposure to acute and chronic stressors was assessed two years later using the Stress and Adversity Inventory for Adolescents (Adolescent STRAIN). Finally, depressive symptoms were assessed at both baseline and follow-up using the Children's Depression Inventory. As hypothesized, greater lifetime acute stressor exposure predicted increases in depressive symptoms over two years, but only for youth exhibiting a blunted RewP. This interaction, however, was not found for chronic stressors. Lifetime acute stressor exposure may be particularly depressogenic for youth exhibiting a blunted RewP. Conversely, a robust RewP may be protective in the presence of greater acute lifetime stressor exposure.

Parasympathetic cardiac control during attentional focus and worry in major depressive disorder

Worry, which refers to uncontrollable chains of thoughts and images with negative affective load, is a transdiagnostic symptom of various mental disorders including major depressive disorder (MDD). Current theories relate excessive worry to deficient top-down control of automatically occurring perseverative thinking. This study investigated parasympathetic cardiac control in MDD in the context of worry and cognitive control. Heart rate variability (HRV) was recorded, in the high frequency (HF) and low frequency (LF) bands, in 36 MDD patients and 36 healthy controls while they performed a breathing focus task. The task included two phases during which participants' ability to concentrate on their breathing was assessed before and after an instructed worry phase. In addition to higher self-reported worry, MDD patients exhibited lower HF and LF HRV at rest, and lower LF HRV during the task than controls. MDD was also associated with impaired breathing concentration ability, more negative and neutral thought intrusions, more negative mood during breathing focus and increased stress during instructed worry. In the total sample, LF HRV correlated negatively with self-reported worry and negative thought intrusions, and positively with mood ratings. The reduction of HRV confirms the notion of low parasympathetic cardiac control in MDD. Moreover, low HRV represents a correlate of blunted prefrontal activity and impaired cognitive control that characterize the disorder. Impaired cognitive control may exacerbate worry, which is in turn involved in the genesis of aversive emotional states and maintenance of MDD.

Noradrenergic system and cognitive flexibility: Disentangling the effects of depression and childhood trauma

Stress plays a fundamental role in the development and maintenance of major depressive disorder (MDD). Importantly, maladaptive changes in the physiological stress regulation systems have been demonstrated. In the locus coeruleus-noradrenergic (LC-NA) system, up-regulated central alpha2-adrenergic receptors in patients with MDD affect cognitive functions. Although cognitive deficits are core symptoms of MDD, the relationship between the LC-NA system and cognitive processes has rarely been investigated in depressed patients. The aim of our study was to investigate whether noradrenergic stimulation affects cognitive flexibility in MDD. In addition, we aimed to further disentangle the effects of MDD and adverse childhood experiences (ACE), such as physical or sexual abuse on cognitive function. In a double-blind placebo-controlled study, MDD patients with ACE, MDD patients without ACE, healthy participants with ACE and healthy control participants without MDD or ACE were tested with a task switching task (total N = 125). Participants were tested twice after treatment with either 10 mg yohimbine or a placebo. Switch costs (differences between switch and repetition trials) in reaction times and accuracy served as the independent variables. We found higher switch costs in MDD patients as compared with controls, while ACE did not affect task performance. Yohimbine administration had no effect on task switching. The results of this study contribute to a better understanding of the role of the LC-NA system as a neurobiological mechanism of cognitive processes in patients with MDD.

The cytokine network in the pathogenesis of major depressive disorder. Close to translation?

Major depressive disorder (MDD) is a common condition that afflicts the general population across a broad spectrum of ages and social backgrounds. MDD has been identified by the World Health Organization as a leading cause of disability worldwide. Approximately 30% of patients are poor responsive to standard of care (SOC) treatment and novel therapeutic approaches are warranted. Since chronic inflammation, as it is often observed in certain cancers, type 2 diabetes, psoriasis and chronic arthritis, are accompanied by depression, it has been suggested that immunoinflammatory processes may be involved in the pathogenesis of MDD. Cytokines are a group of glycoproteins secreted from lymphoid and non-lymphoid cells that orchestrate immune responses. It has been suggested that a dysregulated production of cytokines may be implicated in the pathogenesis and maintenance of MDD. On the basis of their functions, cytokines can be subdivided in pro-inflammatory and anti-inflammatory cytokines. Since abnormal blood and cerebrospinal fluid of both pro and anti-inflammatory cytokines are altered in MDD, it has been suggested that abnormal cytokine homeostasis may be implicated in the pathogenesis of MDD and possibly to induction of therapeutic resistance. We review current data that indicate that cytokines may represent a useful tool to identify MDD patients that may benefit from tailored immunotherapeutic approaches and may represent a potential tailored therapeutic target.

An Integrated Sleep and Reward Processing Model of Major Depressive Disorder

Major depressive disorder with comorbid sleep disturbance has been associated with negative outcomes, including lower rates of treatment response and a greater likelihood of depressive relapse compared to those without sleep disturbance. However, little, if any, research has been conducted to understand why such negative treatment outcomes occur when sleep disturbance is present. In this conceptual review, we argue that the relationship of sleep disturbance and negative treatment outcomes may be mediated by alterations in neural reward processing in individuals with blunted trait-level reward responsivity. We first briefly characterize sleep disturbance in depression, discuss the nature of reward processing impairments in depression, and summarize the sleep/reward relationship in healthy human subjects. We then introduce a novel Integrated Sleep and Reward model of the course and maintenance of major depressive disorder and present preliminary evidence of sleep and reward interaction in unipolar depression. Finally, we discuss limitations of the model and offer testable hypotheses and directions for future research.

Pro-inflammatory monocyte profile in patients with major depressive disorder and suicide behaviour and how ketamine induces anti-inflammatory M2 macrophages by NMDAR and mTOR

BackgroundDepression is a highly prevalent disorder that is one of the leading causes of disability worldwide. Despite an unknown aetiology, evidence suggests that the innate and adaptive immune systems play a significant role in the development and maintenance of major depressive disorder (MDD). The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), has demonstrated rapid and robust efficacy as an antidepressant when administered at sub-anaesthetic doses.MethodsOur goal was to characterize the pro-inflammatory profile of patients with MDD by measuring pro-inflammatory cytokines in plasma and circulating monocyte subsets and to understand how ketamine induces an anti-inflammatory program in monocyte and macrophages in vitro and vivo.FindingOur results show that patients with MDD without other comorbidities (N = 33) exhibited significantly higher levels of pro-inflammatory IL-12 and IL-6 in plasma and that these cytokines were associated with increased numbers of non-classical (CD11b+CD16brightCD14neg) monocytes and increased activation state (CD40+CD86+) of classical monocytes in circulation. Remarkably, we have demonstrated that sub-anaesthetic doses of ketamine programs human monocytes into M2c-like macrophages by inducing high levels of CD163 and MERTK with intermediate levels of CD64 and stimulating mTOR-associated gene expression in vitro. The NMDAR antagonist MK-801, but not the α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonist, NBQX, also polarizes macrophages to an M2c-like phenotype, but this phenotype disappears upon mTOR pathway inhibition. Sub-anaesthetic doses (10 mg/kg) of ketamine administration in mice both promote reduction of circulating classical pro-inflammatory monocytes and increase of alternative M2 macrophage subtypes in the spleen and CNS.InterpretationOur results suggest an anti-inflammatory property of ketamine that can skew macrophages to an M2-like phenotype, highlighting potential therapeutic implications not only for patients with MDD but also other inflammatory-based diseases.FundingThis study was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT-FONCYT).

Effectiveness of trauma-focused treatment for adolescents with major depressive disorder

ABSTRACT Background: Major Depressive Disorder (MDD) in adolescence has a high prevalence and risk of disability, but current treatments show limited effectiveness and high drop-out and relapse rates. Although the role of distressing experiences that relate to the development and maintenance of MDD has been recognized for decades, the efficacy of a trauma-focused treatment approach for MDD has hardly been studied. Objective: To determine the effectiveness of eye movement desensitization and reprocessing (EMDR) therapy as a stand-alone intervention in adolescents diagnosed with MDD. We hypothesized that reprocessing core memories related to the onset and maintenance of MDD using EMDR therapy would be associated with a significant decrease in depressive and comorbid symptoms. Method: We recruited 32 adolescents (12–18 years) fulfilling DSM-IV criteria for mild to moderate-severe MDD from an outpatient youth mental health care unit. Treatment consisted of six weekly 60-min individual sessions. Presence or absence of MDD classification (ADIS-C), symptoms of depression (CDI), symptoms of posttraumatic stress (UCLA), anxiety (SCARED), somatic complaints (CSI), and overall social-emotional functioning (SDQ) were assessed pre and post-treatment and 3 months after treatment. Results: 60.9% of the adolescents completing treatment no longer met DSM-IV criteria for MDD after treatment anymore, and 69.8% at follow-up. Multilevel analyses demonstrated significant posttreatment reductions of depressive symptoms (CDI: Cohen’s d = 0.72), comorbid posttraumatic stress, anxiety and somatic complaints, while overall social-emotional functioning improved. These gains were maintained at 3-month follow-up (Cohen’s d = 1.11). Severity of posttraumatic stress reactions significantly predicted the posttreatment outcome; however, duration of MDD, number of comorbid disorders, or having a history of emotional abuse, emotional neglect or physical neglect were not predictive for outcome. Conclusions: This is the first study suggesting that EMDR therapy is associated with a significant reduction of depressive symptoms and comorbid psychiatric problems in adolescents with mild to moderate-severe MDD.

Decision-making of patients with major depressive disorder in the framework of action control

ABSTRACTIntroduction: Patients with major depressive disorder (MDD) experience dysfunctional emotional states and cognitive impairments, leading to behavioural, social, and functional issues. Neurocognitive theory proposes that the initiation and maintenance of MDD is primarily the result of a deficit of action control which in turn would lead to decision-making impairments.Methods: We assessed 27 medicated outpatients with MDD who were demographically matched with 16 healthy participants on decision-making (DM) processes (Iowa Gambling Task (IGT) and Reversal Learning Task (RLT)), clinical variables (depressive symptoms and self-efficacy), and volition (Lille Apathy Rating Scale).Results: Patients with MDD displayed deficits on the IGT but not on the RLT. Correlational analysis of patients with MDD revealed no significant associations between IGT or RLT performance and volition, depressive symptom severity, and self-efficacy. However, differences on the IGT between patients with MDD and controls became non-significant when controlling for the variance of these scores.Conclusions: MDD appears to have an impact on dynamic DM processes, while basic processes are preserved. Limitations as well as directions for future research are discussed with regard to the neurocognitive model of depression.

A Hot-Cold Cognitive Model of Depression: Integrating the Neuropsychological Approach Into the Cognitive Theory Framework

In the 50 years following Beck’s cognitive theory, empirical research has consistently supported the role of dysfunctional, ‘hot’ cognition in the onset and maintenance of major depressive disorder. Compromised ‘cold’ cognition in attention, memory, and executive control abilities, independent of the affective state, has attracted much clinical interest for its role throughout the course of illness and into remission. We propose integrating cold cognition into Beck’s cognitive theory framework to account for the complementary roles of both hot and cold cognition in depression onset and maintenance. A critical review of cognitive research was conducted to inform an integrated hot-cold cognitive model of depression. Cold cognitive deficits likely act as a gateway to facilitate the activation and expression of the hot cognitive biases through a weakened ability to attend, retrieve, and critically assess information. Cold deficits become exacerbated by the negative mood state, essentially ‘becoming hot’, lending to maladaptive emotion regulation through ruminative processes. Depleted cognitive resources contribute to the manifestation of further deficit in problem-solving ability in everyday life, which in itself, may act as a stressor for the onset of recurrent episodes, perpetuating the depressive cycle. We discuss the interaction between hot and cold cognition within the cognitive theory framework and the potential of complementary hot-cold pathways to elucidate novel means of prevention and treatment for depression. Dysfunction in hot (emotion-dependent) and cold (emotion-independent) cognition has been demonstrated in depression, but psychological treatment has largely focused on hot cognition only. Hot and cold cognition are complementary processes throughout the activation and maintenance of depressive schemas and biases, necessitating the consideration of both hot and cold cognitive aspects to disrupt the depressive cycle. The proposed hot-cold cognitive model shows promise to stimulate new research avenues for the prevention and treatment of depression. Dysfunction in hot (emotion-dependent) and cold (emotion-independent) cognition has been demonstrated in depression, but psychological treatment has largely focused on hot cognition only. Hot and cold cognition are complementary processes throughout the activation and maintenance of depressive schemas and biases, necessitating the consideration of both hot and cold cognitive aspects to disrupt the depressive cycle. The proposed hot-cold cognitive model shows promise to stimulate new research avenues for the prevention and treatment of depression.

Dissociable Neural Responses to Monetary and Social Gain and Loss in Women With Major Depressive Disorder

Neuroimaging studies have revealed aberrant reward and loss processing in patients with major depressive disorder (MDD). While most studies use monetary stimuli to study these processes, it is important to consider social stimuli given that the social environment plays a significant role in the development and maintenance of MDD. In the present study, we examined whether monetary gain/loss and social acceptance/rejection would elicit dissociable salience-related neural responses in women diagnosed with MDD compared to healthy control (HC) women. Twenty women diagnosed with MDD and 20 matched HC women performed the monetary incentive delay task (MID) and the social feedback task (SFT) during functional magnetic resonance imaging (fMRI). This study focused on women since women have a higher rate of MDD, higher frequency of relapse, and are more likely to develop MDD as a consequence of negative interpersonal relationships compared to men. We found that during the MID, HCs but not MDD patients demonstrated strong overlapping activations in the right anterior insula (AI) in response to both monetary gain and loss. During the SFT, MDD patients but not HCs showed overlapping activations in the AI in response to social acceptance and rejection. Our results may suggest a dissociation such that MDD patients show decreased sensitivity to monetary stimuli whether gain or loss, and increased sensitivity to social stimuli whether acceptance or rejection, although this will need to be verified in larger samples with direct comparisons between groups and stimuli. These data demonstrate distinct abnormalities in reward and loss processing that converge within the AI. Our findings also highlight the critical need to assess across both non-social and social domains when examining reward and loss systems in MDD to broaden our understanding of the disorder and identify novel targets for treatment.

Neuroimmune Advance in Depressive Disorder.

Major depressive disorder (MDD) or depression is one of the most highly prevalent, chronic, and recurrent disorders, which is associated with a high burden of disease and substantial impairment in social functions. Both immune molecules and cells have been implicated in the pathophysiology and maintenance of MDD. Findings in animals and MDD patients have suggested that both pro- and anti-inflammatory cytokines are activated in the neuroinflammation which contribute to behavioral symptoms and changes in the course of depression. There is a growing body of evidence to support that neuroinflammation is a mediator for the communication among stress response, neuroendocrine, neurotransmission, neurogenesis, and gut microbiota. These communications have been known as risk factors in the pathogenesis of MDD. In the meantime, accumulating evidence has suggested that some interventions targeting the inflammatory processes may play an important role in the treatment of MDD.

Emotion Regulation in Current and Remitted Depression: A Systematic Review and Meta-Analysis.

Background: Major Depressive Disorder (MDD) is a highly prevalent, recurrent, and potentially chronic disorder. Identifying risk factors and underlying mechanisms to inform preventive and therapeutic interventions is therefore imperative. Emotion regulation is a proposed factor in the development and maintenance of MDD. The aim of the present review was to summarize and synthesize research on self-reported emotion regulation strategy use and emotion regulation abilities in adults diagnosed with current and remitted MDD.Methods: Seventy-two eligible studies were retrieved from databases through a systematic literature search. Group differences between individuals with current MDD, remitted MDD, and healthy controls were calculated using meta-analytic procedures. Meta-regression analyses investigated potential moderator effects on emotion regulation difficulties.Results: Results indicated that individuals with current MDD report higher maladaptive emotion regulation strategy use for avoidance (Hedges' g = 1.3), rumination (g = 2.1), and suppression (g = 1.1) compared to healthy controls. Also, they reported lower adaptive emotion regulation strategy use for acceptance (g = −1.0), problem solving (g = −1.0), and reappraisal (g = −0.7). Individuals with current MDD reported limited general emotion regulation abilities, indicated by higher alexithymia (g = 1.45), lower emotional awareness (g = −0.95), emotional clarity (g = −1.50) and emotional tolerance (g = −1.89). Similar results were found in individuals with remitted MDD for avoidance (g = 1.0), rumination (g = 1.1), suppression (g = 0.6), and general emotion regulation abilities. However, no difference was found between individuals with remitted MDD and healthy controls for adaptive emotion regulation strategies. Meta-regression analyses suggest that age of illness onset, comorbid anxiety and duration of remission influence emotion regulation.Conclusion: The present review and meta-analysis indicates that individuals with current and remitted MDD have difficulties with emotion regulation compared to individuals who have never been depressed. Although depressive symptoms improve, emotion regulation difficulties may continue, and could be a contributing factor to relapse. Our findings inform future research on emotion regulation and psychotherapeutic interventions.

Attentional biases in patients suffering from unipolar depression: results of a dot probe task investigation

Cognitive models of depression emphasize the relevance of cognitive biases for development, onset and maintenance of major depressive disorder (MDD). Attentional biases consisting of increased attention to negative, mood congruent stimuli and reduced attention to positive, mood-incongruent stimuli are postulated but have rarely been tested for early attentional processing. Furthermore, the role of concurrent depressive mood as a moderating factor has not been studied to date. Participants comprised 30 patients suffering from MDD and 30 healthy control subjects. All participants performed a dot-probe task with pictorial stimuli displaying affective facial expressions, presented either for 100ms or for 500ms. Attentional biases towards faces displaying joy in both MDD patients and control subjects and towards faces displaying pain in MDD subjects were found at presentation times of 100ms. In the MDD sample, the bias indices at 100ms were correlated with concurrent depressive mood. In patients with pronounced depressive mood, significant biases towards happy and angry faces were observed that exceed the biases obtained in control subjects and patients with less depressive mood. The results provide first evidence that MDD patients with pronounced depressive mood show an increased early attentional engagement towards emotional salient stimuli, independent from valence.

The influence of REM sleep and SWS on emotional memory consolidation in participants reporting depressive symptoms

Negative emotional memory bias is thought to play a causal role in the onset and maintenance of major depressive disorder. Rapid Eye Movement (REM) sleep has been shown to selectively consolidate negative emotional memories in healthy participants, and is greater in quantity and density in depressed patients. Slow-Wave Sleep (SWS) is typically associated with the consolidation of non-emotional memories. However, the effects of REM sleep and SWS on emotional memory consolidation have not been investigated in participants reporting depressive symptoms. In this study, we recruited two groups of healthy participants; one reporting mild-to-moderate depressive symptoms, and another reporting minimal depressive symptoms (assessed using the Beck Depression Inventory; BDI-II). Using a within-subjects split-night design, we measured consolidation of positive, neutral and negative images across a 3 h retention interval rich in either REM sleep or SWS. We found a significant sleep condition x image valence interaction in participants reporting depressive symptoms [F (2, 20) = 4.73, p = .021], but not participants reporting minimal depressive symptoms [F (2, 22) = .17, p = .845]. Participants reporting depressive symptoms consolidated significantly more neutral memories during SWS, and marginally more negative memories during REM sleep, than those reporting minimal depressive symptoms [t (21) = 2.44, p = .023; t (21) = 1.96, p = .064, respectively]. Our preliminary results demonstrate that REM sleep and SWS have differential effects on the consolidation of emotional and neutral images in participants reporting depressive symptoms. Further studies including larger sample sizes are required to investigate whether REM sleep alterations promote the development of negative memory bias in major depressive disorder.

Altered DNA methylation of glucose transporter 1 and glucose transporter 4 in patients with major depressive disorder

Alterations in brain glucose metabolism and in peripheral glucose metabolism have frequently been observed in major depressive disorder (MDD). The insulin independent glucose transporter 1 (GLUT1) plays a key role in brain metabolism while the insulin-dependent GLUT4 is the major glucose transporter for skeletal and cardiac muscle. We therefore examined methylation of GLUT1 and GLUT4 in fifty-two depressed inpatients and compared data to eighteen healthy comparison subjects. DNA methylation of the core promoter regions of GLUT1 and GLUT4 was assessed by bisulfite sequencing. Further factors determined were fasting glucose, cortisol, insulin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). We found significantly increased methylation of the GLUT1 in depressed inpatients compared to healthy comparison subjects (CG). Further findings comprise increased concentrations of fasting cortisol, glucose, insulin, and increased IL-6 and TNF-α. After six weeks of inpatient treatment, significantly lower GLUT1 methylation was observed in remitted patients compared to non-remitters. GLUT4 methylation was not different between depressed patients and CG, and did not differ between remitted and non-remitted patients. Although preliminary we conclude from our results that the acute phase of major depressive disorder is associated with increased GLUT1 methylation and mild insulin resistance. The successful treatment of depression is associated with normalization of GLUT1 methylation in remitters, indicating that this condition may be reversible. Failure of normalization of GLUT1 methylation in non-remitters may point to a possible role of impeded brain glucose metabolism in the maintenance of MDD.