Major Depressive Disorder Population Research Articles

Impact of yoga-based interventions on cognitive and autonomic functions in major depressive disorder population.

Cognitive and autonomic dysfunction is increasingly being recognized as an important clinical dimension in major depressive disorder. The aim of this study is to evaluate the effect of a combined approach of yoga and diet intervention on cognitive and autonomic functions in individuals with major depressive disorders. This experimental observational study was conducted at RUHS College of Medical Sciences and Associated Hospitals, Jaipur, on the major depressive disorder population of either sex cognitive function (mini-mental score, Montreal cognitive protocol A and B, P300 latency and amplitude) and autonomic function parameters (frequency and time domain) were recorded at baseline and after three months of a combined approach of yoga and diet intervention. This study compared cognitive and autonomic function parameters at baseline and after three months of yoga and diet intervention in a major depressive disorder population. Analysis revealed a significant decrease in body mass index (<0.05), systolic blood pressure (<0.001), Hamilton rating scale for depression (<0.001), P300 latency (<0.001), standard deviation of NN interval (SDNN) (<0.001), and mean heart rate (<0.001), whereas there was a significant increase in mini-mental score (<0.001), Montreal cognitive protocol A and B (<0.001), high frequency (HF) (<0.001), root mean square standard deviation (RMSSD) (<0.001), and PNN50 (<0.001) after a combined approach of yoga and diet in the study group as compared to control group participants. Yoga and diet combined may be an effective adjunct therapy for improving brain health and mental performance, lowering the risk of depression by affecting the neurotransmitter system and raising vagal tone which contributes to learning and memory.

Characterizing Major Depressive Disorder (MDD) using alpha-band activity in resting-state electroencephalogram (EEG) combined with MATRICS Consensus Cognitive Battery (MCCB)

BackgroundThe diagnosis of major depressive disorder (MDD) is commonly based on the subjective evaluation by experienced psychiatrists using clinical scales. Hence, it is particularly important to find more objective biomarkers to aid in diagnosis and further treatment. Alpha-band activity (7-13 Hz) is the most prominent component in resting electroencephalogram (EEG), which is also thought to be a potential biomarker. Recent studies have shown the existence of multiple sub-oscillations within the alpha band, with distinct neural underpinnings. However, the specific contribution of these alpha sub-oscillations to the diagnosis and treatment of MDD remains unclear. MethodsIn this study, we recorded the resting-state EEG from MDD and HC populations in both open and closed-eye state conditions. We also assessed cognitive processing using the MATRICS Consensus Cognitive Battery (MCCB). ResultsWe found that the MDD group showed significantly higher power in the high alpha range (10.5–11.5 Hz) and lower power in the low alpha range (7–8.5 Hz) compared to the HC group. Notably, high alpha power in the MDD group is negatively correlated with working memory performance in MCCB, whereas no such correlation was found in the HC group. Furthermore, using five established classification algorithms, we discovered that combining alpha oscillations with MCCB scores as features yielded the highest classification accuracy compared to using EEG or MCCB scores alone. ConclusionsOur results demonstrate the potential of sub-oscillations within the alpha frequency band as a potential distinct biomarker. When combined with psychological scales, they may provide guidance relevant for the diagnosis and treatment of MDD.

Non-invasive brain stimulation and cognitive function in patients with major depressive disorder or bipolar depression: systematic review and meta-analysis

IntroductionNon-invasive brain stimulation protocols are effective treatments for depressive episodes. Although the cognitive adverse effects of electroconvulsive therapy (ECT) are well documented, evidence regarding the cognitive effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) is mixed.ObjectivesThe aim of this study was to synthesize research on the cognitive effects of non-invasive brain stimulation protocols and to differentiate between studies of major depressive disorder (MDD), bipolar depression and mixed populations.MethodsFollowing a systematic literature search of multiple electronic databases, a series of meta-analyses were conducted to estimate standardized mean differences (SMD) between pre- and post-treatment cognitive functioning across nine cognitive domains. Where possible, SMDs were estimated separately for MDD, bipolar depression and mixed populations. In studies that included both patients with MDD and bipolar depression, the percentage of patients with a diagnosis of bipolar depression was tested as a potential moderator.ResultsMore than 150 treatment arms were included in the analyses. For ECT, we observed a small decline in language functioning and a decrease in autobiographical memory scores. There was no evidence of pre-post differences across other cognitive domains. For rTMS and tDCS, small to moderate cognitive improvements were observed for several cognitive domains, for example for executive functioning. Across most analyses, between-study heterogeneity was high and could not be accounted for by differences between MDD, bipolar depression or mixed populations.ConclusionsThere was limited evidence that differentiation between studies of MDD, bipolar depression and mixed populations accounted for between-study heterogeneity in analyses of pre-post differences in cognitive functioning. Given that most studies included both patients with MDD and bipolar depression, this finding should be treated as preliminary. Across all the treatment protocols examined, more data are needed to investigate the cognitive effects of non-invasive brain stimulation in patients with bipolar depression.Disclosure of InterestNone Declared

Alcohol use as a predictor of the course of major depressive disorder: a prospective population-based study.

There are indications that problematic alcohol use may negatively impact the course of major depressive disorder (MDD). However, most studies on alcohol use and adverse MDD outcomes are conducted amongst MDD populations with (severe) alcohol use disorder in psychiatric treatment settings. Therefore, it remains unclear whether these results can be generalised to the general population. In light of this, we examined the longitudinal relationship between alcohol use and MDD persistence after a 3-year follow-up amongst people with MDD from the general population. Data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a psychiatric epidemiological prospective study comprising four waves amongst the adult Dutch general population (n = 6.646). The study sample (n = 642) consisted of those with 12-month MDD who participated at the follow-up wave. The outcome was 12-month MDD persistence after the 3-year follow-up, which was assessed via the Composite International Diagnostic Interview version 3.0. Weekly alcohol consumption was operationalised as non-drinking (0 drinks), low-risk drinking (⩽7 drinks; reference), at-risk drinking (women 8-13 drinks, men 8-20 drinks) and high-risk drinking (women ⩾14, men ⩾21 drinks). We performed univariate and multiple logistic regression analyses, which were adjusted for various socio-demographic and health-related factors. The majority (67.4%) of the MDD sample were female, while the mean age was 47.1 years. Amongst these, 23.8% were non-drinkers, 52.0% were low-risk drinkers and 14.3% and 9.4% were at-risk and high-risk drinkers, respectively. Around one-quarter of the sample (23.6%) met the criteria for a persistent MDD after 3-year follow-up. No statistically significant association was found between alcohol use and MDD persistence, either for the crude model or the adjusted models. In comparison to low-risk drinking, the full adjusted model showed no statistically significant associations between MDD persistence and non-drinking (odds ratio (OR) = 1.15, p = 0.620), at-risk drinking (OR = 1.25, p = 0.423), or high-risk drinking (OR = 0.74, p = 0.501). Contrary to our expectations, our findings showed that alcohol use was not a predictor of MDD persistence after 3-year follow-up amongst people with MDD from the general population.

Biomarkers of intestinal permeability and blood-brain barrier permeability in adolescents with major depressive disorder

BackgroundThe etiology in major depressive disorder (MDD) has not been fully understood. Accumulating evidence suggests an association between altered intestinal and blood-brain barrier (BBB) permeability and psychiatric disorders, while its changes in adolescent MDD populations have been received less attention. In this study, our aim was to explore the differences in plasma levels of intestinal and blood-brain barrier permeability markers in adolescents with MDD compared with healthy controls (HCs). MethodsWe enrolled MDD (n = 50), and HCs (n = 40) with the age of 13–18 years old. The plasma level of zonulin, I-FABP, LPS, and claudin-5 were quantified. The Hamilton Depression Scale 17 items (HAMD-17) and Hamilton Anxiety Scale 14 items (HAMA-14) were used for symptom assessments. ResultsThe plasma levels of zonulin, I-FABP, LPS, and claudin-5 in the MDD group were significantly higher than those in the HCs. Plasma I-FABP levels in MDD with moderate to severe anxiety were significantly higher than those in MDD without moderate to severe anxiety and HCs. In addition, these four biomarkers (alone or combined) can be used as diagnostic markers for MDD in adolescents. LimitationsThe key limitation of this study is the blood measurements at a single time point with a relatively small sample size. ConclusionsThese findings advance our understanding of the pathophysiology of intestinal barrier injury, bacterial translocation, and blood-brain barrier injury involved in adolescents with MDD.

Translational control by ketamine and its implications for comorbid cognitive deficits in depressive disorders.

Ketamine has shown antidepressant effects in patients with major depressive disorder (MDD) resistant to first-line treatments and approved for use in this patient population. Ketamine induces several forms of synaptic plasticity, which are proposed to underlie its antidepressant effects. However, the molecular mechanism of action directly responsible for ketamine's antidepressant effects remains under active investigation. It was recently demonstrated that the effectors of the mammalian target of rapamycin complex 1 (mTORC1) signalling pathway, namely, eukaryotic initiation factor 4E (eIF4E) binding proteins 1 and 2 (4E-BP1 and 4E-BP2), are central in mediating ketamine-induced synaptic plasticity and behavioural antidepressant-like effect. 4E-BPs are a family of messenger ribonucleic acid (mRNA) translation repressors inactivated by mTORC1. We observed that their expression in inhibitory interneurons mediates ketamine's effects in the forced swim and novelty suppressed feeding tests and the long-lasting inhibition of GABAergic neurotransmission in the hippocampus. In addition, another effector pathway that regulates translation elongation downstream of mTORC1, the eukaryotic elongation factor 2 kinase (eEF2K), has been implicated in ketamine's behavioural effects. We will discuss how ketamine's rapid antidepressant effect depends on the activation of neuronal mRNA translation through 4E-BP1/2 and eEF2K. Furthermore, given that these pathways also regulate cognitive functions, we will discuss the evidence of ketamine's effect on cognitive function in MDD. Overall, the data accrued from pre-clinical research have implicated the mRNA translation pathways in treating mood symptoms of MDD. However, it is yet unclear whether the pro-cognitive potential of subanesthetic ketamine in rodents also engages these pathways and whether such an effect is consistently observed in the treatment-resistant MDD population.

Efficacy and safety of vortioxetine in treatment of patients with major depressive disorder and common co-morbid physical illness

BackgroundThe multimodal antidepressant vortioxetine is effective in reducing somatic symptoms in patients with major depressive disorder (MDD), but little is known about its effects in reducing depressive symptoms in patients with common comorbid physical illnesses. MethodsThis was a pooled analysis of 13 randomized, placebo-controlled trials which evaluated the efficacy (using the Montgomery–Åsberg Depression Rating Scale [MADRS]) and safety of vortioxetine (5-20 mg/day) in adult patients with MDD. We evaluated stable somatic comorbid conditions that were verified by a diagnosis and had sufficient database representation. ResultsOf the 5982 patients included in the database, 963 (16.1%) patients had a diagnosis of cardiovascular disease, 152 (2.5%) had diabetes mellitus and 26 (0.4%) had chronic obstructive pulmonary disorder (COPD). At Week 8, adjusted mean[95%CI] treatment differences (vortioxetine vs. placebo) on MADRS total scores were −2.7[−4.2, −1.3] (p = 0.0002) points for the cardiovascular disease, −4.0[−7.7, −0.4] (p = 0.03) for the diabetes, and −6.2[−21.3, 8.9] (p = 0.36) for the COPD groups. The rate and pattern of adverse events were similar across the sub-groups with comorbidities and was consistent with that expected for vortioxetine treatment. LimitationsThe primary studies were not designed to investigate the relationship between vortioxetine and comorbidities, nor were the post hoc analyses powered to detect group differences. ConclusionsPatients with MDD and comorbid cardiovascular disease or diabetes respond to vortioxetine in a similar way to the broader MDD population. Vortioxetine was generally safe and well tolerated and without unexpected adverse events in these subpopulations, most of whom are taking multiple concomitant medications.

Mindfulness-Based Cognitive Therapy in Recurrent MDD Patients With Residual Symptoms: Alterations in Resting-State Theta Oscillation Dynamics Associated With Changes in Depression and Rumination.

Many patients with major depressive disorder (MDD) suffer from residual symptoms. Rumination is a specific known risk factor for the onset, severity, prolongation, and relapse of MDD. This study aimed to examine the efficacy and EEG substrates of mindfulness-based cognitive therapy (MBCT) in alleviating depression and rumination in an MDD population with residual symptoms. We recruited 26 recurrent MDD individuals who had residual symptoms with their current antidepressants to participate in the 8-week MBCT intervention. We evaluated the efficacy and changes in the dynamics of resting-state theta rhythm after the intervention, as well as the associations between theta alterations and improvements in depression and rumination. The participants showed reduced depression, enhanced adaptive reflective rumination, and increased theta power and phase synchronization after MBCT. The increased theta-band phase synchronizations between the right occipital regions and the right prefrontal, central, and parietal regions were associated with reduced depression, while the increase in theta power in the left parietal region was associated with improvements in reflective rumination. MBCT could alleviate depression and enhance adaptive, reflective rumination in recurrent MDD individuals with residual symptoms through the modulation of theta dynamics in specific brain regions.

Treatment patterns of patients diagnosed with major depressive disorder and suicidal ideation or attempt: a U.S. population-based study utilizing real-world data

BackgroundThere is a knowledge gap regarding the treatment patterns of patients with major depressive disorder (MDD) who experience suicidal ideation or a suicide attempt (SI/SA).MethodsPatients with SI/SA were identified from a large US-based claims database covering 84 million lives, during 1/1/2014–3/31/2020. Patients with MDD were indexed at their first diagnosis for SI/SA and followed up to 365 days. Treatment patterns were captured at the class level and included procedures of electroconvulsive therapy and transcranial magnetic stimulation, and pharmacotherapy including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, other antidepressants, anxiolytics, hypnotics/sedatives, antipsychotics, psychostimulants, and lithium.ResultsThere were 42,204 MDD + SI/SA patients identified. In the year prior to the index event > 40% of individuals received an SSRI and more than one-third received an anxiolytic. Within 1 year following, 84.4% received ≥1 of the treatments of interest. Of those, 70.2% went on to a subsequent class-based regimen, 46.3% received a third, and 28.1% received ≥4. More than three-quarters of patients received multiple treatment classes simultaneously. SSRIs were the most common treatments during follow-up (61.9%), followed by other antidepressants (51.3%), anxiolytics (50.8%) and anticonvulsants (43.6%).ConclusionsThere was a large amount of variability and polypharmacy in the treatments received by MDD patients with SI/SA, and is much more complex than what has been previously observed in the general MDD population. Within one-year, many patients received four or more unique class-based regimens and most patients received treatments from multiple classes simultaneously, indicating the high unmet medical need and therapy refractoriness of this patient population.

A preliminary study on the relationship between sleep, depression and cardiovascular dysfunction in a 4 sample population

BackgroundMajor Depressive Disorder (MDD) has been linked in the literature to poorer prognosis in patients with cardiovascular dysfunction, although the mechanisms of this relationship remain unclear. Underlying Sleep Disordered Breathing (SDB) serves as a potential candidate to explain this effect due to its downstream effects on inflammatory activation and decreased nitric oxide (NO) bioavailability, both of which have been shown to contribute to the pathophysiology of both MDD and cardiovascular disease (CVD).MethodsThis study utilizes overnight polysomnography and an inflammation panel to examine the links between cardiovascular dysfunction and sleep difficulties in control participants and patients diagnosed with SDB only, MDD only, and both SDB and MDD.ResultsResults demonstrate a strong positive relationship between sleep dysfunction and the nitric oxide synthesis inhibitor Symmetric Dimethyl Arginine (SDMA) in the MDD-only cohort, suggesting a link between SDMA-mediated NO dysregulation and CVD pathogenesis in individuals with MDD. Additionally, hypopneas, a form of sleep impairment characterized by partial reduction of airflow, were found to play a significant role in the relationship between SDB and cardiovascular dysfunction in MDD-only patients.ConclusionsResults of this study demonstrate the need for widespread screening for SDB in MDD populations to detect predisposition to CVD, and also offer SDMA as a new potential target for CVD treatment in individuals with MDD.

Face tuning in female and male individuals with depression

IntroductionThe current COVID-19 pandemic brings social isolation to our daily lives that may elevate depression. The impact of major depressive disorder (MDD) on social cognitive functioning is far from understood, but essential for prevention and treatment of this neuropsychiatric condition.ObjectivesOur aim was to examine (i) whether face tuning is lower in depression; and (ii) how it is related to other cognitive abilities (such as perceptional organization). Furthermore, we intended to clarify gender impact on face tuning in MDD, as twice more females are affected.MethodsUsing a recently developed paradigm, the Face-n-Food task, we examined face tuning in 26 patients with MDD and 26 person-by-person matched controls. The advantage of non-face images is that its single elements do not promote face processing.ResultsStrikingly, MDD individuals showed intact face tuning. As sex ratio in our patient sample was about 2:1 (as in MDD population in general), we recruited additional male patients and found that MDD male patients were as good as female patients. Yet, while face tuning in MDD patients showed a significant correlation with perceptual organization abilities, in controls, it was linked with social cognition.ConclusionsThe outcome suggests that the origins of aberrant social functioning in MDD lie in maladaptive cognitive schemas rather than in a lack of sensitivity towards social signals per se. To elucidate neural circuits involved in face tuning in MDD, a magnetoencephalography (MEG) study with the Face-n-Food images is currently under progress.DisclosureNo significant relationships.

Multiscale neural modeling of resting-state fMRI reveals executive-limbic malfunction as a core mechanism in major depressive disorder

Major depressive disorder (MDD) represents a grand challenge to human health and society, but the underlying pathophysiological mechanisms remain elusive. Previous neuroimaging studies have suggested that MDD is associated with abnormal interactions and dynamics in two major neural systems including the default mode - salience (DMN-SAL) network and the executive - limbic (EXE-LIM) network, but it is not clear which network plays a central role and which network plays a subordinate role in MDD pathophysiology. To address this question, we refined a newly developed Multiscale Neural Model Inversion (MNMI) framework and applied it to test whether MDD is more affected by impaired circuit interactions in the DMN-SAL network or the EXE-LIM network. The model estimates the directed connection strengths between different neural populations both within and between brain regions based on resting-state fMRI data collected from normal healthy subjects and patients with MDD. Results show that MDD is primarily characterized by abnormal circuit interactions in the EXE-LIM network rather than the DMN-SAL network. Specifically, we observe reduced frontoparietal effective connectivity that potentially contributes to hypoactivity in the dorsolateral prefrontal cortex (dlPFC), and decreased intrinsic inhibition combined with increased excitation from the superior parietal cortex (SPC) that potentially lead to amygdala hyperactivity, together resulting in activation imbalance in the PFC-amygdala circuit that pervades in MDD. Moreover, the model reveals reduced PFC-to-hippocampus excitation but decreased SPC-to-thalamus inhibition in MDD population that potentially lead to hypoactivity in the hippocampus and hyperactivity in the thalamus, consistent with previous experimental data. Overall, our findings provide strong support for the long-standing limbic-cortical dysregulation model in major depression but also offer novel insights into the multiscale pathophysiology of this debilitating disease.

Procognitive Effects of Antidepressants and Other Therapeutic Agents in Major Depressive Disorder: A Systematic Review.

To review the efficacy of antidepressants and other therapeutic agents for the treatment of cognitive impairment in adults with major depressive disorder (MDD). We conducted a database search of MEDLINE, PsycINFO, and Embase through Ovid on May 7, 2019. The year of publication was not restricted. The search terms "Major Depressive Disorder," "depress*," "cognit*," and "therapeutics" were used. The studies included in this review were clinical trials of antidepressants and other therapeutic agents in MDD populations. Participants were aged between 18 and 65 years and had a DSM-III, -IV, or -5 diagnosis of MDD. In total, 2,045 research papers were screened, 53 full-text articles were assessed, and 26 articles were eligible to be included in this systematic review. The data and quality of research papers were assessed and screened by 2 independent reviewers. Discrepancies were resolved through a third reviewer. Overall, studies demonstrated that tricyclic antidepressants do not have procognitive effects, while vortioxetine and bupropion have demonstrated procognitive effects in MDD populations relative to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Several non-antidepressant agents, such as modafinil, amphetamines, and erythropoietin, have also demonstrated significant positive effects on cognition in depression. Present-day antidepressants and other agents have demonstrated procognitive effects in MDD, but the findings between various agents are mixed. Further research looking at objective measures of cognitive performance would be helpful to obtain more definitive results regarding the efficacy of therapeutics for cognitive impairment in MDD.

A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy of SAGE-217 in the Treatment of Adult Patients With Major Depressive Disorder

Major depressive disorder (MDD) is a disabling episodic condition, with a lifetime prevalence of 16.6% in the United States. Decreased gamma-aminobutyric acid (GABA) signaling has been linked to MDD. SAGE-217 is an investigational, oral neuroactive steroid and GABAA receptor positive allosteric modulator. A pivotal study of SAGE-217 in MDD (NCT03000530) demonstrated significant reductions in depressive symptoms. Here, we evaluate the efficacy and safety of two doses of SAGE-217 in a Phase 3, multicenter, double-blind, randomized, placebo-controlled trial (NCT03672175) in a larger MDD population.

The Potential Procognitive Effects of Modafinil in Major Depressive Disorder: A Systematic Review.

To assess the efficacy of modafinil, a wakefulness-promoting drug, in major depressive disorder (MDD), with a specific focus on the putative procognitive effects of modafinil. A database search of MEDLINE, PsycINFO, and Embase was conducted. No date limits were applied (the end date of the search was October 26, 2018), and only articles in English were included. The following search terms were used: modafinil, depression, depress*, major depressive disorder, cognition, cognitive dysfunction, and cogniti*. Studies included were placebo-controlled or open-label trials of modafinil in MDD populations. Participants had to be diagnosed with MDD via DSM-IV or DSM-5 criteria, and no other interventions other than standard antidepressant treatment could be used in the trial. Overall, 540 articles were screened, 22 full-text research articles for inclusion criteria were assessed, and 12 studies were included in this review. Two independent reviewers extracted data and assessed the quality of publications. Modafinil was associated with improvements in executive functioning after 4 weeks of open-label adjunctive treatment in currently depressed participants. Furthermore, in a placebo-controlled study of remitted MDD participants, modafinil led to rapid improvements in episodic and working memory after a single dose. There were contradictory findings on the subjective effects of modafinil on concentration. Modafinil shows preliminary evidence of alleviating specific cognitive symptoms in MDD patients, especially in the short term. However, more research using placebo-controlled longitudinal designs is needed to assess the benefits of modafinil, as there are very few studies addressing modafinil and cognition in MDD.

The burden of suicidal ideation across Europe: a cross-sectional survey in five countries.

BackgroundSuicidal ideation (SI) is an associated risk of depression, affecting 30–40% of the depressed population. However, there is a paucity of studies investigating the impact of SI in Europe. This retrospective observational study examined the burden of SI among adults with major depressive disorder (MDD) in the 2017 National Health and Wellness Survey in five European countries: France, Germany, Italy, Spain, and the UK.MethodsBivariate analyses evaluated group differences between respondents with MDD with and without SI according to demographic characteristics, self-reported health-related quality of life, work productivity and activity impairment (WPAI), and healthcare resource utilization (HRU). Generalized linear models examined group differences country-wise, after controlling for relevant confounders.ResultsAmong 52,060 respondents, 3,308 individuals were diagnosed with MDD, comprising SI (n=905) and non-SI (nSI) (n=2403) patients. Adjusted differences (ADs), compared to the general population, were observed using the Medical Outcomes Study Short Form Survey (SF-12v2) mental component summary scores (AD: SI=−20.02, nSI=−10.77), physical component summary scores (AD: SI=−4.49, nSI=−2.50), and EuroQoL-5 Dimensions (AD: SI=−0.34, nSI=−0.15) (for all, p<0.001). Significantly greater WPAI and higher HRU were associated with SI compared to nSI.ConclusionThe results illustrate the unique impact of SI within the MDD population and the need to reduce the burden.

Prevalence of suicide attempt in individuals with major depressive disorder: a meta-analysis of observational surveys.

Suicide attempt (SA), which is one of the strongest predictors of completed suicide, is common in major depressive disorder (MDD) but its prevalence across epidemiological studies has been mixed. The aim of this comprehensive meta-analysis was to examine the pooled prevalence of SA in individuals with MDD. A systematic literature search was conducted in PubMed, Embase, PsycINFO, Web of Science and Cochrane Library from their commencement date until 27 December 2017. Original studies containing data on prevalence of SA in individuals with MDD were analyzed. In all, 65 studies with a total of 27 340 individuals with MDD were included. Using the random effects model, the pooled lifetime prevalence of SA was 31% [95% confidence interval (CI) 27-34%], 1-year prevalence was 8% (95% CI 3-14%) and 1-month prevalence was 24% (95% CI 15-34%). Subgroup analyses revealed that the lifetime prevalence of SA was significantly associated with the patient setting, study region and income level, while the 1-month prevalence of SA was associated with only the patient setting. This meta-analysis confirmed that SA was common in individuals with MDD across the world. Careful screening and appropriate interventions should be implemented for SA in the MDD population.

The measurement of cognitive reactivity to sad mood in patients remitted from major depressive disorder.

ObjectivesCognitive reactivity (CR) to sad mood is a risk factor for major depressive disorder (MDD). CR is usually measured by assessing change on the Dysfunctional Attitudes Scale (DAS‐change) after sad mood‐induction. It has, however, been suggested that the versions of the DAS (A/B) are not interchangeable, impacting the reliability and validity of the change score. The Leiden Index of Depression Sensitivity‐Revised (LEIDS‐R) is an alternative self‐report measure of CR. Studies examining the relationship between LEIDS‐R and DAS‐change have shown mixed results. We examined whether scores of these CR measures differed between remitted MDD and controls, the relationship between these CR measures, and the effect of order of DAS administration on DAS‐change.DesignCross‐sectional design with two groups (remitted MDD and controls).MethodsSixty‐eight MDD patients remitted from ≥2 previous episodes, not taking antidepressants, and 43 never‐depressed controls participated in a mood‐induction and filled in the DAS‐A/B in randomized order before and after mood‐induction, and LEIDS‐R separately.Results LEIDS‐R scores and pre‐mood‐induction DAS scores were significantly higher in remitted MDD than controls (p < .001, Cohen's d = 1.48; p = .001, Cohen's d = 0.66, respectively). DAS‐change did not differ between these groups (p = .67, Cohen’s d = 0.08). LEIDS‐R correlated with DAS‐change (r = .30, p = .042), but only in the group that filled in DAS‐B before DAS‐A. In remitted MDD, DAS‐change was dependent on the order of DAS versions before and after mood‐induction (10.6 ± 19.0 vs. −1.2 ± 10.5, for order B‐A and A‐B, respectively), with a significant group × order interaction (p = .012).ConclusionsExisting DAS versions are not interchangeable, which compromises the usefulness of mood‐inductions in clinical practice. The LEIDS‐R seems a valid measure of cognitive vulnerability to depression.Practitioner points Clinical implications: Cognitive reactivity (CR) is a risk factor of depressive recurrence. The current measurement of CR, by assessing change on the Dysfunctional Attitudes Scale (DAS) after mood‐induction, is not reliable.The Leiden Index Depression Sensitivity‐Revised (LEIDS‐R) is an alternative CR measure. In contrast to mood‐induction, it reliably assesses depression vulnerability.The use of mood‐inductions for clinical/research purposes is unnecessary. Limitations of the study: We were not able to examine the effect of previous treatment, which could have affected results as psychological treatments probably have differential effects on CR.Examining un‐medicated patients may have led to selection of a sample not completely representative for the general MDD population.We did not administer both parallel versions of the DAS (A/B) before and after mood‐induction. This might have provided better understanding of their differential sensitivity to change.

The Limbic System in Youth Depression: Brain Structural and Functional Alterations in Adolescent In-patients with Severe Depression.

Adolescent-onset major depressive disorder (MDD) is associated with an increased risk of recurrent depressive episodes, suicidal behaviors, and psychiatric morbidity throughout the lifespan. The objective of the present study was to investigate brain structural and functional changes in adolescent patients with MDD. Furthermore, we aimed to clarify the influence of early-life stress on brain function and structure. The study investigated adolescent patients with severe MDD (n=20, mean age=16.0, range=15-18 years) and a control sample of matched healthy adolescents (n=21, mean age=16.6, range=15-18 years). Functional MRI data were obtained using a face-matching paradigm to investigate emotion processing. Structural MRI data were analyzed using voxel-based morphometry (VBM). In line with previous studies on adult MDD, adolescent patients showed elevated amygdala activity to negative and reduced amygdala activity to positive emotional stimuli. Furthermore, MDD patients showed smaller hippocampal volumes compared to healthy adolescents. Higher levels of childhood maltreatment were associated with smaller hippocampal volumes in both depressed patients and healthy controls, whereby no associations between amygdala reactivity and childhood maltreatment were found. Our results suggest that hippocampal alterations in youth MDD patients may at least partly be traced back to higher occurrence of early-life adverse experiences. Regarding the strong morphometric impact of childhood maltreatment and its distinctly elevated prevalence in MDD populations, this study provides an alternative explanation for frequently observed limbic structural abnormalities in depressed patients.

Comparative evaluation of vortioxetine as a switch therapy in patients with major depressive disorder

Switching antidepressant therapy is a recommended strategy for depressed patients who neither respond to nor tolerate an initial pharmacotherapy course. This paper reviews the efficacy and tolerability of switching to vortioxetine. All three published studies of patients with major depressive disorder (MDD) switched from SSRI/SNRI therapy to vortioxetine due to lack of efficacy or tolerability were selected. Vortioxetine was evaluated versus agomelatine directly (REVIVE) and versus sertraline, venlafaxine, bupropion, and citalopram in an indirect treatment comparison (ITC) from switch studies retrieved in a literature review. Vortioxetine׳s impact on SSRI-induced treatment-emergent sexual dysfunction (TESD) was assessed directly versus escitalopram (NCT01364649) in stable patients with MDD. Vortioxetine׳s tolerability in the switch population was compared to the overall MDD population. Vortioxetine showed significant benefits over agomelatine on efficacy, functioning, and quality-of-life outcomes, with fewer withdrawals due to adverse events (AEs) (REVIVE). Vortioxetine had numerically higher remission rates versus all therapies included (ITC). Withdrawal rates due to AEs were significantly lower for vortioxetine versus sertraline, venlafaxine, and bupropion, and numerically lower versus citalopram. Switching to vortioxetine was statistically superior to escitalopram in improving TESD (NCT01364649). Tolerability was similar in the switch and overall MDD populations. These findings suggest that vortioxetine is an effective switch therapy for patients with MDD whose response to SSRI/SNRI therapy is inadequate. Vortioxetine was well tolerated and, for patients with a history of TESD, showed significant advantages versus escitalopram. Vortioxetine appears to be a valid option for patients with MDD who have not been effectively treated with first-line pharmacotherapies.