Cognitive dysfunction is a recognized feature of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). Cognitive impairment is associated with poor overall functional ...outcome and is therefore an important feature of illness to optimize for patients’ occupational and academic outcomes. While generally people with BD appear to have a greater degree of cognitive impairment than those with MDD, direct comparisons of both patient groups within a single study are lacking. There are a number of methods for the assessment of cognitive function, but few are currently used in clinical practice. Current symptoms, past course of illness, clinical features, such as the presence of psychosis and comorbid conditions, may all influence cognitive function in mood disorders. Despite the general lack of assessment of cognitive function in clinical practice, clinicians are increasingly targeting cognitive symptoms as part of comprehensive treatment strategies. Novel pharmacological agents may improve cognitive function, but most studies of standard mood stabilizers, such as lithium and the anticonvulsants, have focused on whether or not the medications impair cognition. Non‐pharmacological strategies, such as cognitive remediation and exercise, are increasingly studied in patients with mood disorders. Despite the growing interest in strategies to manage cognitive function, there is a paucity of high‐quality trials examining either pharmacological or non‐pharmacological modes of intervention.
IMPORTANCE: Despite the prevalence of antenatal depression and the fact that only one-third of pregnant women with depression consider it acceptable to take antidepressants, the effect of untreated ...depression on neonatal outcomes remains to be addressed thoroughly. OBJECTIVE: To undertake a systematic review and meta-analysis to understand the effect of untreated depression on neonatal outcomes. DATA SOURCES: We executed our search strategy, with emphasis on its exhaustiveness, in MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials, and Web of Science. The search was conducted in July, 2015. STUDY SELECTION: We included randomized and nonrandomized studies that examined neonatal outcomes in women with depression receiving neither pharmacological nor nonpharmacological treatment compared with women without depression. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened titles and abstracts, assessed full-text articles, extracted data, and assessed their quality using a modified version of the Newcastle-Ottawa Scale. We pooled data using random-effects meta-analyses, quantified heterogeneity using the I2 statistic, and explored it with subgroup analyses by type of assessment of depression, severity, reported conflicts of interest, and study quality. MAIN OUTCOMES AND MEASURES: Primary outcomes were preterm birth before 37 weeks and before 32 weeks, small and large for gestational age, low birth weight, and neonatal intensive care unit admission. RESULTS: Of the 6646 titles initially identified, 23 studies met inclusion criteria, all observational, with a total of 25 663 women. Untreated depression was associated with significantly increased risks of preterm birth (odds ratio OR, 1.56; 95% CI, 1.25-1.94; 14 studies; I2, 39%) and low birth weight (OR, 1.96; 95% CI, 1.24-3.10; 8 studies; I2, 48%), with a trend toward higher risks for exposure to more severe depression. While the odds of preterm birth more than doubled in studies reporting conflicts of interest (OR, 2.50; 95% CI, 1.70-3.67; 5 studies; I2, 0%), studies not reporting such conflicts showed more moderate results (OR, 1.34; 95% CI, 1.08-1.66; 9 studies; I2, 30%). CONCLUSIONS AND RELEVANCE: Our results contrast with what is, to our knowledge, the only previous systematic review that examined the question of untreated depression because we found significant risks of 2 key perinatal outcomes, preterm birth and low birth weight. These are important results for pregnant women and clinicians to take into account in the decision-making process around depression treatment.
Current practice for selecting pharmacological and non-pharmacological antidepressant treatments has yielded low response and remission rates in Major Depressive Disorder (MDD). Neuroimaging ...biomarkers of brain structure and function may be useful in guiding treatment selection by predicting response vs. non-response outcomes.
In this review, we summarize data from studies examining predictors of treatment response using structural and functional neuroimaging modalities, as they pertain to pharmacotherapy, psychotherapy, and stimulation treatment strategies. A literature search was conducted in OVID Medline, EMBASE, and PsycINFO databases with coverage from January 1990 to January 2017.
Several imaging biomarkers of therapeutic response in MDD emerged: frontolimbic regions, including the prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, and insula were regions of interest. Since these sub-regions are implicated in the etiology of MDD, their association with response outcomes may be the result of treatments having a normalizing effect on structural or activation abnormalities.
The direction of findings is inconsistent in studies examining these biomarkers, and variation across ‘biotypes’ within MDD may account for this. Limitations in sample size and differences in methodology likely also contribute.
The identification of accurate, reliable neuroimaging biomarkers of treatment response holds promise toward improving treatment outcomes and reducing burden of illness for patients with MDD. However, before these biomarkers can be translated into clinical practice, they will need to be replicated and validated in large, independent samples, and integrated with data from other biological systems.
•Neuroimaging response predictors for antidepressant therapies are proposed.•Frontolimbic structural and functional indices may have predictive potential.•Frontolimbic regions are also involved in depression etiology.•Inconsistency of findings may result from variation across depression ‘biotypes’.•Data replication, validation, and integration are required for clinical translation.
The role of antidepressants in the acute treatment of bipolar depression remains a contentious issue. A previous meta-analysis of randomized controlled trials (RCTs) concluded that antidepressants ...were effective and safe for bipolar depression. Several trials published since then suggest that antidepressants may not be as beneficial as previously concluded. The current systematic review and meta-analyses reexamine the efficacy and safety of antidepressant use for the acute treatment of bipolar depression.
EMBASE, MEDLINE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials databases were searched for double-blind RCTs published from 2003 to 2009 using the following diagnostic medical subject heading (MESH) terms: bipolar disorder, bipolar depression, bipolar I disorder, bipolar II disorder, bipolar III disorder, bipolar mania, cyclothymia, manic depressive psychosis, mixed mania and depression, and rapid cycling and bipolar disorder. Databases of trial registries were also searched for unpublished RCTs. These searches were supplemented by hand searches of relevant articles and review articles.
Trials that compared acute (< 16 wk) antidepressant treatment with either an active drug or a placebo comparator in adult bipolar patients, depressive phase were eligible for inclusion. Main outcome measures were clinical response, remission, and affective switch.
Six RCTs (N = 1,034) were identified since publication in 2004 of the first meta-analysis that assessed antidepressant use in the acute treatment of bipolar depression. These studies were combined with earlier studies for a total of 15 studies containing 2,373 patients. Antidepressants were not statistically superior to placebo or other current standard treatment for bipolar depression. Antidepressants were not associated with an increased risk of switch. Studies that employed more sensitive criteria to define switch did report elevated switch rates for antidepressants.
Although antidepressants were found to be safe for the acute treatment of bipolar depression, their lack of efficacy may limit their clinical utility. Further high-quality studies are required to address the existing limitations in the literature.
OBJECTIVE: A number of studies have used magnetic resonance imaging to examine volumetric differences in temporal structures in subjects suffering from major depressive disorder. Studies have ...reported lower hippocampal and amygdala volume, but results have been inconsistent. The authors were interested, therefore, in examining these studies in the aggregate in order to determine whether hippocampal volume is lower in major depressive disorder. They also examined factors that may contribute to the disparate results in the literature. METHOD: A meta-analysis was conducted of studies that used magnetic resonance imaging to assess the volume of the hippocampus and related structures in patients with major depressive disorder. RESULTS: Patients were seen to have lower hippocampal volume relative to comparison subjects, detectable if the hippocampus was measured as a discrete structure. CONCLUSIONS: Although the effect of major depressive disorder on amygdala volume remains to be conclusively established, inclusion of the amygdala with the hippocampus appears to have decreased the likelihood of detecting volumetric differences in either structure. Slice thickness or other scan parameters did not account for a substantive amount of the variance in results, whereas clinical variables of the populations studied, such as duration of illness or presence of abuse, may account for much of the discrepancy between findings.
Antidepressants (ADs) are the most common treatment for major depressive disorder (MDD). However, only ∼30% of patients experience adequate response after a single AD trial, and this variability ...remains poorly understood. Here, we investigated microRNAs (miRNAs) as biomarkers of AD response using small RNA-sequencing in paired samples from MDD patients enrolled in a large, randomized placebo-controlled trial of duloxetine collected before and 8 weeks after treatment. Our results revealed differential expression of miR-146a-5p, miR-146b-5p, miR-425-3p and miR-24-3p according to treatment response. These results were replicated in two independent clinical trials of MDD, a well-characterized animal model of depression, and post-mortem human brains. Furthermore, using a combination of bioinformatics, mRNA studies and functional in vitro experiments, we showed significant dysregulation of genes involved in MAPK/Wnt signalling pathways. Together, our results indicate that these miRNAs are consistent markers of treatment response and regulators of the MAPK/Wnt systems.
Background: Some, although not all, studies report small hippocampal volume in patients with major depressive disorder (MDD) relative to healthy controls. Here, we explore the contribution of key ...demographic and clinical variables to this difference. Methods: We used meta-analytic techniques to provide an updated analysis of data from 32 magnetic resonance imaging studies of hippocampal volume in patients with MDD. Results: Our analysis confirmed the difference in hippocampal volume, but only among patients with MDD whose duration of illness was longer than 2 years or who had more than 1 disease episode. We found no such effect in studies that included patients who did not fit these criteria. The effect was limited to children and middle-aged or older adults. Analyzed collectively, studies including young adult patients showed equivalent hippocampal volumes across MDD patients and controls, a result that may be attributable to a reduced burden of illness in this population. Age at onset of disease, severity of depression at the time of scanning, sex and slice thickness did not contribute to differences in hippocampal volume between patients with MDD and controls. Limitations: The small size of many of the clinical and demographic subgroups may have limited statistical power to detect between-group differences. Conclusion: Although all studies were cross-sectional, our results suggest that hippocampal volume reductions generally occur after disease onset in patients with MDD. These findings have implications for the timing of clinical interventions aimed at reducing the impact of MDD on neuronal structure and function.
Background This review integrates neuroimaging studies of 2 domains of social cognition — emotion comprehension and theory of mind (ToM) — in patients with major depressive disorder and bipolar ...disorder. The influence of key clinical and method variables on patterns of neural activation during social cognitive processing is also examined. Methods Studies were identified using PsycINFO and PubMed (January 1967 to May 2011). The search terms were “fMRI,” “emotion comprehension,” “emotion perception,” “affect comprehension,” “affect perception,” “facial expression,” “prosody,” “theory of mind,” “mentalizing” and “empathy” in combination with “major depressive disorder,” “bipolar disorder,” “major depression,” “unipolar depression,” “clinical depression” and “mania.” Results Taken together, neuroimaging studies of social cognition in patients with mood disorders reveal enhanced activation in limbic and emotion-related structures and attenuated activity within frontal regions associated with emotion regulation and higher cognitive functions. These results reveal an overall lack of inhibition by higher-order cognitive structures on limbic and emotion-related structures during social cognitive processing in patients with mood disorders. Critically, key variables, including illness burden, symptom severity, comorbidity, medication status and cognitive load may moderate this pattern of neural activation. Limitations Studies that did not include control tasks or a comparator group were included in this review. Conclusion Further work is needed to examine the contribution of key moderator variables and to further elucidate the neural networks underlying altered social cognition in patients with mood disorders. The neural networks underlying higher-order social cognitive processes, including empathy, remain unexplored in patients with mood disorders.
Background:
The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines ...remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.
Methods:
Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Neurostimulation Treatments” is the fourth of six sections of the 2016 guidelines.
Results:
Evidence-informed responses were developed for 31 questions for 6 neurostimulation modalities: 1) transcranial direct current stimulation (tDCS), 2) repetitive transcranial magnetic stimulation (rTMS), 3) electroconvulsive therapy (ECT), 4) magnetic seizure therapy (MST), 5) vagus nerve stimulation (VNS), and 6) deep brain stimulation (DBS). Most of the neurostimulation treatments have been investigated in patients with varying degrees of treatment resistance.
Conclusions:
There is increasing evidence for efficacy, tolerability, and safety of neurostimulation treatments. rTMS is now a first-line recommendation for patients with MDD who have failed at least 1 antidepressant. ECT remains a second-line treatment for patients with treatment-resistant depression, although in some situations, it may be considered first line. Third-line recommendations include tDCS and VNS. MST and DBS are still considered investigational treatments.
Neuroimaging studies assessing neurobiological differences between patients with major depressive disorder (MDD) and healthy controls (HC) are often hindered by small sample sizes and heterogeneity ...of the patient sample. We performed a comprehensive literature search for studies assessing cortical thickness between patient and control groups, including studies investigating treatment effects on cortical thickness. We identified 34 studies meeting criteria for the systematic review and used Seed-based d Mapping to meta-analyze 24 of those that met additional criteria. Analysis of the full sample of subjects (MDD = 1073; HC = 936) revealed significant thinning in the MDD group in the bilateral orbitofrontal gyrus (BA 11), left pars opercularis (BA 45) and left calcarine fissure/lingual gyrus (BA 17), as well as an area of significant thickening in the left supramarginal gyrus (BA 40). These results support other imaging modalities that report disruptions in various frontal and temporal areas in MDD and identify additional areas in all major cerebral lobes likely to be significant when parsing for biomarkers of treatment or relapse.
•We need informative neurobiological markers for major depressive disorder.•Recent neuroimaging studies found differences in cortical thickness between groups.•In MDD, we found cortical thinning in frontal and occipital regions (BA 11, 45, 17).•There was cortical thickening in one parietal area (BA 40).•Assessing multiple neurobiological parameters is recommended for future studies.
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