Aspects Of Major Depressive Disorder Research Articles

Gender differences in risk factors for suicide attempts among young, first-episode and drug-naive major depressive disorder patients with anxiety symptoms.

Suicide attempts and anxiety are common commodities in patients with major depressive disorder (MDD), and suicide attempts are often associated with anxiety symptoms. Studies have found gender differences in several aspects of MDD; however, gender differences in suicide attempts in young first-episode and drug-naive (FEDN) MDD patients with anxiety remain unknown. This study aimed to investigate potential gender differences in the prevalence of suicide attempts and associated risk factors among young FEDN MDD patients with anxiety in a Chinese Han population. A cross-sectional study was conducted on 1289 young patients with FEDN MDD. Demographics, clinical characteristics, and biochemical parameters of patients were collected. Suicide attempters accounted for 23.80% and 26.12% of male and female FEDN MDD patients with anxiety, respectively, with no significant gender differences. Binary logistic regression analyses showed that anxiety, clinical global impression severity, and thyroid peroxidase antibody significantly predicted suicide attempts in both male and female FEDN MDD patients with anxiety, while body mass index significantly predicted suicide attempts only in males, and psychotic symptoms predicted suicide attempts only in females. The present study represents the first large-scale investigation of gender differences in the prevalence of suicide attempts and related risk factors among young FEND MDD patients with anxiety in the Chinese Han population. The results indicate that risk factors associated with suicide attempts vary by gender among young FEND MDD patients with anxiety, although a comparable rate of suicide attempts was observed in both female and male patients.

Major depressive disorder and bistability in an HPA-CNS toggle switch.

Major depressive disorder (MDD) is the most common psychiatric disorder. It has a complex and heterogeneous etiology. Most treatments take weeks to show effects and work well only for a fraction of the patients. Thus, new concepts are needed to understand MDD and its dynamics. One of the strong correlates of MDD is increased activity and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which produces the stress hormone cortisol. Existing mathematical models of the HPA axis describe its operation on the scale of hours, and thus are unable to explore the dynamic on the scale of weeks that characterizes many aspects of MDD. Here, we propose a mathematical model of MDD on the scale of weeks, a timescale provided by the growth of the HPA hormone glands under control of HPA hormones. We add to this the mutual inhibition of the HPA axis and the hippocampus and other regions of the central nervous system (CNS) that forms a toggle switch. The model shows bistability between euthymic and depressed states, with a slow timescale of weeks in its dynamics. It explains why prolonged but not acute stress can trigger a self-sustaining depressive episode that persists even after the stress is removed. The model explains the weeks timescale for drugs to take effect, as well as the dysregulation of the HPA axis in MDD, based on gland mass changes. This understanding of MDD dynamics may help to guide strategies for treatment.

Assessment of patient life engagement in major depressive disorder using items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR)

BackgroundPatient-reported outcomes can measure domains that are personally meaningful, such as life engagement, which reflects motivation, pleasure, and well-being. This study explored whether certain items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR) can capture patient life engagement in major depressive disorder (MDD). MethodsIDS-SR life engagement items were identified by a) a panel of expert psychiatrists (n = 4), b) patient interviews (n = 20), and c) a principal component analysis (PCA) to explore clustering of items. Psychometric analyses were performed on potential subscales, and a minimal clinically important difference (MCID) was estimated by anchor- and distribution-based methods. IDS-SR data were obtained from three randomized controlled trials of adjunctive brexpiprazole in MDD. ResultsExpert psychiatrists selected 10 items by consensus from the IDS-SR that might capture patient life engagement (Cronbach's alpha, 0.82; item–total correlations, 0.36–0.58). Patient interviews identified 13 items as moderately to very relevant to life engagement (Cronbach's alpha, 0.85; item–total correlations, 0.35–0.61). The PCA revealed a cluster that included all 10 items selected by psychiatrists and 11 items identified by patients. Expert psychiatrists intentionally distinguished life engagement and core depressive symptoms, although patient insights and the PCA indicated that these aspects of MDD are strongly linked. The 10-item IDS-SR life engagement subscale had an MCID of 3–5 points. ConclusionsDifferent approaches consistently identified a subset of 10 IDS-SR items that can measure life engagement in MDD, which may be suitable to group into an IDS-SR life engagement subscale.

Multi-modal MRI measures reveal sensory abnormalities in major depressive disorder patients: A surface-based study

BackgroundMulti-modal magnetic resonance imaging (MRI) measures are supposed to be able to capture different brain neurobiological aspects of major depressive disorder (MDD). A fusion analysis of structural and functional modalities may better reveal the disease biomarker specific to the MDD disease. MethodsWe recruited 30 MDD patients and 30 matched healthy controls (HC). For each subject, we acquired high-resolution brain structural images and resting-state fMRI (rs-fMRI) data using a 3 T MRI scanner. We first extracted the brain morphometric measures, including the cortical volume (CV), cortical thickness (CT), and surface area (SA), for each subject from the structural images, and then detected the structural clusters showing significant between-group differences in each measure using the surface-based morphology (SBM) analysis. By taking the identified structural clusters as seeds, we performed seed-based functional connectivity (FC) analyses to determine the regions with abnormal FC in the patients. Based on a logistic regression model, we performed a classification analysis by selecting these structural and functional cluster-wise measures as features to distinguish the MDD patients from the HC. ResultsThe MDD patients showed significantly lower CV in a cluster involving the right superior temporal gyrus (STG) and middle temporal gyrus (MTG), and lower SA in three clusters involving the bilateral STG, temporal pole gyrus, and entorhinal cortex, and the left inferior temporal gyrus, and fusiform gyrus, than the controls. No significant difference in CT was detected between the two groups. By taking the above-detected clusters as seeds to perform the seed-based FC analysis, we found that the MDD patients showed significantly lower FC between STG/MTG (CV’s cluster) and two clusters located in the bilateral visual cortices than the controls. The logistic regression model based on the structural and functional features reached a classification accuracy of 86.7% (p < 0.001) between MDD and controls. ConclusionThe present study showed sensory abnormalities in MDD patients using the multi-modal MRI analysis. This finding may act as a disease biomarker distinguishing MDD patients from healthy individuals.

The cerebellum as a moderator of negative bias of facial expression processing in depressive patients

• Negative bias (NB) in emotion processing is an important aspect of MDD. • Neural basis of NB in facial expression processing in MDD was assessed. • Higher activation in posterior cerebellum was found to relate to higher NB in MDD. • Higher activation in the same area was related to a lower NB in the HC group. • This area might mediate biasing emotion processing by reflecting self-mood. Negative bias—a mood-congruent bias in emotion processing—is an important aspect of major depressive disorder (MDD), and such a bias in facial expression recognition has a significant effect on patients’ social lives. Neuroscience research shows abnormal activity in emotion-processing systems regarding facial expressions in MDD. However, the neural basis of negative bias in facial expression processing has not been explored directly. Sixteen patients with MDD and twenty-three healthy controls (HC) who underwent an fMRI scan during an explicit facial emotion task with happy to sad faces were selected. We identified brain areas in which the MDD and HC groups showed different correlations between the behavioral negative bias scores and functional activities. Behavioral data confirmed the existence of a higher negative bias in the MDD group. Regarding the relationship with neural activity, higher activity of happy faces in the posterior cerebellum was related to a higher negative bias in the MDD group, but lower negative bias in the HC group. The sample size was small, and the possible effects of medication were not controlled for in this study. We confirmed a negative bias in the recognition of facial expressions in patients with MDD. fMRI data suggest the cerebellum as a moderator of facial emotion processing, which biases the recognition of facial expressions toward their own mood.

Therapeutic effect of Thymoquinone on behavioural response to UCMS and neuroinflammation in hippocampus and amygdala in BALB/c mice model.

Major depressive disorder is the leading cause of disability worldwide. The corticolimbic system plays a critical role in the emotional and cognitive aspects of major depressive disorder. Owing to the unsatisfactory efficacy of conventional antidepressants, there is a need to explore novel therapies. The current study aimed to explore the antidepressant potential of thymoquinone, a natural compound with anti-inflammatory activity, and propose its underlying mechanism of action in the unpredictable chronic mild stress (UCMS) mouse model. Coat state, forced swim test, elevated plus maze test, novelty suppressed feeding test and social interaction test were performed to quantify the behavioural shift induced by UCMS and the effect of thymoquinone and fluoxetine treatment. In addition, messenger RNA (mRNA) expression levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) and BDNF and NeuN were analysed by a quantitative real-time polymerase chain reaction in the hippocampus and amygdala of experimental and control groups. UCMS significantly deteriorated coat state. Thymoquinone reinstated the resignation behaviour and latency to feed affected by UCMS. UCMS induced an increase in inflammatory cytokines (IL-1β, IL-6 and TNF-α) in the hippocampus and amygdala, which was decreased by thymoquinone. UCMS caused an increase in BDNF and NeuN mRNA levels in the amygdala while a decrease in the hippocampus. This opposite effect on BDNF was also compensated by thymoquinone; however, thymoquinone did not significantly change Ki67 and NeuN mRNA levels in the hippocampus. Thymoquinone restored the behavioural changes induced by UCMS. In addition, the antidepressant effect of thymoquinone is in line with changes in inflammatory parameters and changes in BDNF in the hippocampus and amygdala.

The Health-Related Quality of Life, Work Productivity, Healthcare Resource Utilization, and Economic Burden Associated with Levels of Suicidal Ideation Among Patients Self-Reporting Moderately Severe or Severe Major Depressive Disorder in a National Survey

BackgroundSuicidal ideation (SI) is a cardinal aspect of major depressive disorder (MDD); however, patient-reported outcomes data from large-scale surveys are limited concerning SI in the context of MDD. This study aims to understand the association between varying levels of SI and health-related quality of life (HRQoL), work productivity, healthcare resource utilization (HRU), and associated costs in patients with moderately severe/severe MDD.MethodsThis was a retrospective, cross-sectional analysis of 2013 national survey data. Patients who self-reported moderately severe or severe MDD and completed the Short Form Survey Version 2 (SF-36v2), Work Productivity Loss and Activity Impairment questionnaire (WPAI), and questions related to HRU were analyzed. Direct and indirect costs were calculated. Patients were categorized and analyzed by the level of SI (no SI, low, moderate, and high) based on their response to Item 9 of the Patient Health Questionnaire-9.ResultsAmong 75,000 respondents, 15.3% self-reported receiving a physician diagnosis of moderately severe or severe MDD and 2.8% of the total sample endorsed some level of SI. Patients with high SI showed a higher burden than patients with no SI, reporting lower mean SF-36v2 mental component summary scores (p<0.001), higher work productivity loss (p=0.039), and higher numbers of per patient per month hospitalizations (p=0.002) and emergency room visits (p=0.011). High SI was associated with greater per patient per month direct costs ($1220 vs $796; p=0.002) and indirect costs ($1449 vs $1058; p=0.001) compared with no SI. When patients with low or moderate SI were compared with patients with no SI, the results were mixed.ConclusionHigher levels of SI were associated with lower HRQoL, greater HRU, and more work impairment resulting in higher direct and indirect costs compared with patients with MDD but no SI. These results highlight the need to implement effective treatment models and interventions in the employed population.

Serum insulin-like growth factor-1 as a potential marker for MDD diagnosis, its clinical characteristics, and treatment efficacy validation: data from an open-label vortioxetine study

BackgroundIGF-1 is an essential neurotrophin produced peripherally and in the brain. Impairments in the brain IGF-1 concentrations might be responsible for some aspects of major depressive disorder (MDD) pathogenesis, whereas peripheral IGF-1 could have the marker value. We aimed: 1) to compare serum IGF-1 levels in MDD patients and healthy controls (HC); 2) to elucidate possible associations between changes in IGF-1 expression and crucial characteristics of the current depressive episode, MDD course; 3) to evaluate IGF-1 dynamics after 8 weeks` vortioxetine treatment.MethodsSeventy-eight MDD patients (according to DSM-5) and 47 HC were enrolled. Serum IGF-1, psychopathological (MADRS, CGI) and neuropsychological parameters (PDQ-5, RAVLT, TMT-B, DSST) were analyzed in all subjects at admission and 48 patients after 8 weeks` vortioxetine treatment. AUC-ROCs were calculated to determine if the value of serum IGF-1 could separate MDD patients from HC. Multiple regression models were performed to explore relationships between IGF-1 and depressive episode’s symptoms.ResultsMDD patients had significantly higher serum IGF-1 levels than HC (228 (183–312) ng/ml vs 153 (129–186) ng/ml, p < 0.0001). IGF-1 had a good diagnostic value for predicting MDD in the whole sample with AUC of 0.820 (p < 0.0001). For a cutoff of 178.00 ng/ml, the sensitivity and specificity were 83 and 71%, respectively, and the number needed to misdiagnose was 5, indicating that only 1 of 5 tests give an invalid result. Among MADRS items, only reported sadness, inner tension, and concentration difficulties were significantly positively associated with serum IGF-1 concentrations. Vortioxetine treatment significantly attenuated IGF-1 levels and improved all psychopathological, neuropsychological parameters.ConclusionsSignificant associations between IGF-1 levels and hypothymia, anxiety, and cognitive disturbances may indicate a pathogenic role of IGF-1 for the mentioned symptoms. We assume that the activity of the cerebral-hepatic axis increases in response to insufficient IGF-1 brain expression in MDD patients, whereas, vortioxetine treatment restores cerebral IGF-1 concentrations and, consequently, decreases its compensatory production by the liver.Trial registrationregistered at ClinicalTrials.gov (NCT03187093). First posted on 14th June 2017.

Lithium treatment for unipolar major depressive disorder: Systematic review.

The potential value of lithium treatment in particular aspects of unipolar major depressive disorder remains uncertain. With reports of controlled trials identified by systematic searching of Medline, Cochrane Library, and PsycINFO literature databases, we summarized responses with lithium and controls followed by selective random-effects meta-analyses. We identified 36 reports with 39 randomized controlled trials: six for monotherapy and 12 for adding lithium to antidepressants for acute major depression, and 21 for long-term treatment. Data for monotherapy of acute depression were few and inconclusive. As an adjunct to antidepressants, lithium was much more effective than placebo ( p<0.0001). For long-term maintenance treatment, lithium was more effective than placebo in monotherapy ( p=0.011) and to supplement antidepressants ( p=0.038), and indistinguishable from antidepressant monotherapy. The findings indicate efficacy of lithium as a treatment for some aspects of major depressive disorder, especially as an add-on to antidepressants and for long-term prophylaxis. It remains uncertain whether some benefits of lithium treatment occur with many major depressive disorder patients, or if efficacy is particular to a subgroup with bipolar disorder-like characteristics or mixed-features.

Is low cognitive functioning a predictor or consequence of major depressive disorder? A test in two longitudinal birth cohorts.

Cognitive impairment has been identified as an important aspect of major depressive disorder (MDD). We tested two theories regarding the association between MDD and cognitive functioning using data from longitudinal cohort studies. One theory, the cognitive reserve hypothesis, suggests that higher cognitive ability in childhood decreases risk of later MDD. The second, the scarring hypothesis, instead suggests that MDD leads to persistent cognitive deficits following disorder onset. We tested both theories in the Dunedin Study, a population-representative cohort followed from birth to midlife and assessed repeatedly for both cognitive functioning and psychopathology. We also used data from the Environmental Risk Longitudinal Twin Study to test whether childhood cognitive functioning predicts future MDD risk independent of family-wide and genetic risk using a discordant twin design. Contrary to both hypotheses, we found that childhood cognitive functioning did not predict future risk of MDD, nor did study members with a past history of MDD show evidence of greater cognitive decline unless MDD was accompanied by other comorbid psychiatric conditions. Our results thus suggest that low cognitive functioning is related to comorbidity, but is neither an antecedent nor an enduring consequence of MDD. Future research may benefit from considering cognitive deficits that occur during depressive episodes from a transdiagnostic perspective.

Cortisol response patterns in depressed women and their healthy daughters at risk: Comparison with healthy women and their daughters

A dysfunctional hypothalamic pituitary adrenal (HPA) axis is widely accepted as a significant pathophysiological aspect of Major Depressive Disorder (MDD). Despite studies suggesting that a dysfunctional HPA axis might be present before the clinical syndrome becomes apparent, the functioning of the HPA axis in high–risk populations has not been well defined. The aim of the present study was to investigate the HPA axis functioning of mothers suffering from MDD and their healthy daughters compared to age- and sex-matched healthy controls. This design allowed a comparison of HPA axis functional differences among daughter and mother groups. HPA axis function was evaluated with a modified dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, which was performed after obtaining the diurnal adrenocorticotropic hormone (ACTH) and cortisol values at 8:00, 16:00, and 23:00 h. We found that MDD mothers and their daughters had low morning cortisol and the MDD mothers additionally had low-morning ACTH compared with controls. Dexamethasone suppressed both cortisol and ACTH in all groups and subsequent HPA axis stimulation by CRH-evoked a lower cortisol response but a higher ACTH response among subjects with MDD mothers. Although high-risk daughters had comparable cortisol levels after CRH infusion, the AUC for ACTH was greater than those of controls. These patterns of results suggest that multiple level HPA dysfunctions are present in both MDD patients and their high-risk carrying daughters. However, insufficient cortisol secretion was only present in MDD mothers, while the daughters could compensate cortisol levels during CRH challenge.

Mindfulness-based cognitive therapy for relapse prophylaxis in mood disorders.

Relapse and recurrence are common and debilitating aspects of major depressive disorder. Furthermore, the risk of developing a chronic course of illness increases with each successive episode and, even among patients who achieve clinical remission, residual depressive symptoms are commonly reported. Maintenance antidepressant monotherapy is effective as long as it is continued, yet in practice side effect burden, tachyphylaxis, safety concerns and premature discontinuation can combine to push non‐compliance rates as high as 40%1. Alternatives to long‐term antidepressant monotherapy, especially those addressing mood outcomes in a broader context of well‐being, may appeal to patients wary of continued intervention.

Altered spontaneous neural activity in first-episode, unmedicated patients with major depressive disorder

Abnormal brain function is presumed to be a pathophysiological aspect of major depressive disorder (MDD). However, the underlying patterns of spontaneous neural activity have been poorly characterized and replicated to date. In this study, we applied a novel approach of fractional amplitude of low-frequency fluctuation (fALFF) to investigate the alteration of spontaneous neural activity in MDD. Sixteen first-episode, unmedicated patients with MDD and 16 healthy controls were recruited and subjected to resting-state fMRI scans to measure the fALFF across the whole brain. Compared with healthy controls, MDD patients exhibited decreased fALFF in the right angular gyrus, left middle temporal gyrus, left superior temporal gyrus, right putamen, right precuneus, and the right superior temporal gyrus. Differences in fALFF between MDD patients and controls indicated that altered spontaneous neural activity was distributed across a number of specific brain regions among MDD patients. These atypical functional regions may help explain some of the neural processes underlying the clinical symptoms accompanying MDD.

Altered brain network modules induce helplessness in major depressive disorder

ObjectiveThe abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. MethodsResting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. ResultsSmall-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. LimitationThe limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. ConclusionsThe results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness.

Emotion Regulation in Depression

Sustained negative affect and difficulties experiencing positive affect are hallmark features of major depressive disorder. Recent research has suggested that difficulties in emotion regulation are at the core of these cardinal symptoms of major depressive disorder; depressed patients exhibit more frequent use of maladaptive emotion regulation and difficulties effectively implementing adaptive strategies. It remains unclear, however, what underlies these difficulties in emotion regulation. Cognitive theories of depression have a long tradition of focusing on cognitive factors that increase depression risk and maintain depressive episodes, but the link between cognitive and affective aspects of major depressive disorder remains to be explored. We propose that cognitive biases and deficits in cognitive control putatively associated with depression affect emotion regulation in critical ways, thereby setting the stage for maintained negative affect and diminished levels of positive affect. We close with a discussion of implications for treatment and future directions for research in this area.

Sex differences of gray matter morphology in cortico-limbic-striatal neural system in major depressive disorder

Sex differences are observed in both epidemiological and clinical aspects of major depressive disorder (MDD). The cortico-limbic-striatal neural system, including the prefrontal cortex, amygdala, hippocampus, and striatum, have shown sexually dimorphic morphological features and have been implicated in the dysfunctional regulation of mood and emotion in MDD. In this study, we utilized a whole-brain, voxel-based approach to examine sex differences in the regional distribution of gray matter (GM) morphological abnormalities in medication-naïve participants with MDD. Participants included 29 medication-naïve individuals with MDD (16 females and 13 males) and 33 healthy controls (HC) (17 females and 16 males). Gray matter morphology of the cortico-limbic-striatal neural system was examined using voxel-based morphometry analyzes of high-resolution structural magnetic resonance imaging scans. The main effect of diagnosis and interaction effect of diagnosis by sex on GM morphology were statistically significant (p < 0.05, corrected) in the left ventral prefrontal cortex, right amygdala, right hippocampus and bilateral caudate when comparing the MDD and HC groups. Posthoc analyzes showed that females with MDD had significant GM decreases in limbic regions (p < 0.05, corrected), compared to female HC; while males with MDD demonstrated significant GM reduction in striatal regions, (p < 0.05, corrected), compared to HC males. The observed sex-related patterns of abnormalities within the cortico-limbic-strial neural system, such as predominant prefrontal-limbic abnormalities in MDD females vs. predominant prefrontal-striatal abnormalities in MDD males, suggest differences in neural circuitry that may mediate sex differences in the clinical presentation of MDD and potential targets for sex-differentiated treatment of the disorder.

Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review.

Cognitive impairments are now widely acknowledged as an important aspect of major depressive disorder (MDD), and it has been proposed that executive function (EF) may be particularly impaired in patients with MDD. However, the existence and nature of EF impairments associated with depression remain strongly debated. Although many studies have found significant deficits associated with MDD on neuropsychological measures of EF, others have not, potentially due to low statistical power, task impurity, and diverse patient samples, and there have been no recent, comprehensive, meta-analyses investigating EF in patients with MDD. The current meta-analysis uses random-effects models to synthesize 113 previous research studies that compared participants with MDD to healthy control participants on at least one neuropsychological measure of EF. Results of the meta-analysis demonstrate that MDD is reliably associated with impaired performance on neuropsychological measures of EF, with effect sizes ranging from 0.32 to 0.97. Although patients with MDD also have slower processing speed, motor slowing alone cannot account for these results. In addition, some evidence suggests that deficits on neuropsychological measures of EF are greater in patients with more severe current depression symptoms, and those taking psychotropic medications, whereas evidence for effects of age was weaker. The results are consistent with the theory that MDD is associated with broad impairment in multiple aspects of EF. Implications for treatment of MDD and theories of EF are discussed. Future research is needed to establish the specificity and causal link between MDD and EF impairments.

Experience Sampling Methodology studies of depression: the state of the art

Experience Sampling Methodology (ESM) is ideally suited to test the predictions, and inform the development of contemporary cognitive models of depression. Yet there has been no systematic examination of ESM in depression research. A search of databases (PsychARTICLES, PsycINFO, AMED, Ovid Medline and CINAHL) was conducted to identify studies published within the last 25 years investigating major depressive disorder (MDD) using ESM. Altogether, 19 studies using ESM, or comparable methodologies, with clinically depressed individuals were identified and critically reviewed. The identified studies examined six aspects of MDD: methodological issues; positive and negative affect; cortisol secretion; antidepressant treatment; work performance; genetic risk factors. Despite some methodological limitations of existing studies, ESM has made a significant contribution to our current understanding of depression by consolidating existing theories, uncovering new and clinically relevant findings and identifying questions for future research. This review concludes by introducing the possibility of using ESM as an intervention tool in clinical practice and proposing that ESM could be useful for furthering knowledge of the causes of MDD.

Emotional reactivity to daily events in major and minor depression.

Although emotional dysfunction is an important aspect of major depressive disorder (MDD), it has rarely been studied in daily life. Peeters, Nicolson, Berkhof, Delespaul, and deVries (2003) observed a surprising mood-brightening effect when individuals with MDD reported greater reactivity to positive events. To better understand this phenomenon, we conducted a multimethod assessment of emotional reactivity to daily life events, obtaining detailed reports of appraisals and event characteristics using the experience-sampling method and the Day Reconstruction Method (Kahneman, Krueger, Schkade, Schwarz, & Stone, 2004) in 35 individuals currently experiencing a major depressive episode, 26 in a minor depressive (mD) episode, and 38 never-depressed healthy controls. Relative to healthy controls, both mood-disordered groups reported greater daily negative affect and lower positive affect and reported events as less pleasant, more unpleasant, and more stressful. Importantly, MDD and mD individuals reported greater reductions in negative affect following positive events, an effect that converged across assessment methods and was not explained by differences in prevailing affect, event appraisals, or medications. Implications of this curious mood-brightening effect are discussed.

Sleep state instabilities in major depressive disorder: Detection and quantification with electrocardiogram‐based cardiopulmonary coupling analysis

Sleep disruption is an important aspect of major depressive disorder but lacks an objective and inexpensive means of assessment. We evaluated the utility of electrocardiogram (ECG)-based cardiopulmonary coupling analysis to quantify physiologic sleep stability in patients with major depression. Relative to controls, unmedicated depressed patients had a reduction in high-frequency coupling, an index of stable sleep, an increase in low-frequency coupling, an index of unstable sleep, and an increase in very-low-frequency coupling, an index of wakefulness/REM sleep. The medicated depressed group showed a restoration of stable sleep to a level comparable with that of the control group. ECG-based cardiopulmonary coupling analysis may provide a simple, cost-efficient point-of-care method to quantify sleep quality/stability and to objectively evaluate the severity of insomnia in patients with major depression.