Subgroup Of Depressed Patients Research Articles

Blood cell ratios in mood and cognitive outcomes following electroconvulsive therapy

Systemic inflammation is commonly reported in depression, with dysregulation of both the innate and adaptive arms of the immune system documented. Obtaining ratios of neutrophils, platelets, and monocytes to counts of lymphocytes (NLR, PLR, MLR, respectively) represents a low-cost and easily reproducible measure of an individual's inflammatory burden that can be calculated effortlessly from routine clinical full white blood cell counts. Electroconvulsive therapy (ECT) remains the most effective acute antidepressant treatment for depression but is often limited by its cognitive side-effects. Here, we examined differences in blood cell ratios in subgroups of depressed patients (unipolar/bipolar, psychotic/non-psychotic, early-onset/late-onset) and ECT-related subgroups (responder/non-responder, remitter/non-remitter). We also explored the relationships between blood cell ratios and depression severity and immediate cognitive outcomes post-ECT. Our results show baseline NLR was raised in patients with psychotic depression. In the entire group of patients, significant negative correlations were noted between the PLR and SII and baseline HAM-D24 score, signifying that lower systemic inflammation is associated with more severe depressive symptoms. Significant positive correlations were noted between various blood cell ratios and mean time to recovery of orientation in the entire group of patients and in depression subgroups, indicating that increased peripheral inflammation is linked to worse cognitive outcomes post-ECT. Overall, our results suggest that assessment of blood cell ratios could be useful for predicting mood changes in patients at risk of developing depressive episodes or relapse following successful treatment or for identifying those at risk for cognitive side-effects following ECT.

Effects of adjunctive brexpiprazole on sleep-wake and circadian parameters in youth with depressive disorders: study protocol for a clinical trial

IntroductionSleep-wake and circadian disturbance is a key feature of mood disorders with a potential causal role and particular relevance to young people. Brexpiprazole is a second-generation antipsychotic medication with demonstrated...

Affective and somatic symptom clusters in depression and their relationship to treatment outcomes in the STAR*D sample

BackgroundThe heterogenous nature of depression continues to stymie efforts to identify biomarkers or predict treatment response. Efforts leveraging large datasets to define more uniform subtypes of depression or subgroups of depressed patients have considered only small subsets of symptoms. We aimed to understand how inclusion of more diverse complaints would impact data-emergent symptom and patient clusters. MethodsWe applied principal components analysis to baselineInventory of Depressive Symptomatology data from 1491 patients with major depressive disorder to derive naturally co-occurring symptom subsets before utilizing k-means clustering to divide patients into groups based on standardized residuals of each symptom subset score. We evaluated the clinical utility of our approach by comparing how cluster membership impacted response to citalopram. ResultsPrinicpal components analysis identified nine naturally co-occurring symptom subsets: core affective symptoms, appetite/weight loss, anxiety, somatic symptoms, insomnia, negative intrusive thoughts, leaden paralysis/mood quality, diurnal mood variation, and irritability. Cluster analysis identified two patient groups, differing significantly in 7 of 9 c symptom subsets. Patients distinguished by the prominence of somatic versus core affective symptoms exhibited less reduction in depression severity with citalopram treatment. LimitationsResults depend not only on raw data, but also parameter selection, and interpretation. Replication is indicated. ConclusionsFindings are consistent with previous reports linking somatic symptoms to treatment resistance and demonstrating that SSRIs are most effective in treating affective symptoms. A novel distinction between physical somatic symptoms and psychic anxiety highlights the utility of assessing a broad spectrum of symptoms when exploring heterogeneity in depression and the need for treatments targeting physical somatic symptoms specifically.

Assessing the links between childhood trauma, C-reactive protein and response to antidepressant treatment in patients with affective disorders

Adverse Childhood Experiences (ACE) are a well-known risk-factor for depression. Additionally, (high-sensitive) C-reactive Protein (hsCRP) is elevated in subgroups of depressed patients and high following ACE. In this context the literature considers hsCRP and ACE to be associated with treatment resistant depression. With the data being heterogenous, this study aimed to explore the associations of ACE, hsCRP levels and response to antidepressant treatment in uni- and bipolar depression. N = 76 patients diagnosed with uni- or bipolar depression and N = 53 healthy controls were included. Treatment was over 6 weeks in an inpatient psychiatric setting within an observatory study design. Depressive symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), ACE were assessed by the Childhood Trauma Questionnaire (CTQ); the body-mass-index (BMI) and hsCRP were measured. HsCRP levels did not differ between the study population and the healthy controls. While the depressive symptoms decreased, the hsCRP levels increased. Sexual abuse was associated with significant higher and emotional abuse with lower levels of hsCRP after 6 weeks. The baseline hsCRP levels and the ACE subgroups did not show significant associations with the treatment response in unipolar depressed patients. The long-lasting effects of specific forms of ACE may have relevant impact on inflammation, supporting hsCRP to be a suitable biomarker. With ACE and hsCRP not showing any significant associations with treatment response in the unipolar depressed subgroup, a more differentiate research concerning biomarkers and treatment regimens is needed when talking about treatment response.

Features of EEG Spectral Parameters in Depressive Patients with Different Efficiencies of Decision-making

We analyzed the relationships between the EEG spectral parameters in depressed patients reflecting the functional state of the brain, and the efficiency of their decision-making based on both logic and emotional learning in order to clarify the neurophysiological mechanisms underlying decision-making impairments. As a result of multivariate cluster analysis based on 96 EEG spectral power parameters, two subgroups of depressive patients were identified. The groups differ in the EEG amplitude-frequency and spatial characteristics, but do not differ either in age or in severity of depression. The subgroup of depressive patients who formed cluster 2 and had higher spectral powers of the EEG ∆ (2–4 Hz), θ1 (4–6 Hz), θ2 (6–8 Hz), α1 (8–9 Hz) and α2 (9–11 Hz) subbands, as compared with the patients who formed cluster 1, had a higher level of cognitive test performance that requires decision-making: the Wisconsin Card Sorting Test (WCST), which evaluates logic-based decision-making, and the Iowa Gambling Task (IGT), which evaluates decision-making based on emotional learning. Cluster 2 patients also exhibited a better long-term memorization (in the ten-word long-term memory test) compared with those who formed cluster 1. Judging by the EEG parameters, the neurophysiological mechanisms of inhibition are more intact in patients forming cluster 2 than in cluster 1 patients who have lower spectral power values of the EEG ∆ (2–4 Hz), θ1 (4–6 Hz), θ2 (6–8 Hz), α1 (8–9 Hz), and α2 (9–11 Hz) subbands. The impairment of decision-making functions in depressive patients may, at least partially, be due to the deficit of the brain inhibition mechanisms that ensure normal integrative brain activity, including such higher mental functions as memory, attention, and decision-making.

Which patients benefit specifically from short-term psychodynamic psychotherapy (STPP) for depression? Study protocol of a systematic review and meta-analysis of individual participant data

IntroductionShort-term psychodynamic psychotherapy (STPP) is an empirically supported treatment that is often used to treat depression. However, it is largely unclear if certain subgroups of depressed patients can benefit specifically...

Eating styles in major depressive disorder: Results from a large-scale study

Depressed persons have been found to present disturbances in eating styles, but it is unclear whether eating styles are different in subgroups of depressed patients. We studied the association between depressive disorder, severity, course and specific depressive symptom profiles and unhealthy eating styles. Cross-sectional and course data from 1060 remitted depressed patients, 309 currently depressed patients and 381 healthy controls from the Netherlands Study of Depression and Anxiety were used. Depressive disorders (DSM-IV based psychiatric interview) and self-reported depressive symptoms (Inventory of Depressive Symptomatology) were related to emotional, external and restrained eating (Dutch Eating Behavior Questionnaire) using analyses of covariance and linear regression. Remitted and current depressive disorders were significantly associated with higher emotional eating (Cohen's d = 0.40 and 0.60 respectively, p < 0.001) and higher external eating (Cohen's d = 0.20, p = 0.001 and Cohen's d = 0.32, p < 0.001 respectively). Little differences in eating styles between depression course groups were observed. Associations followed a dose-response association, with more emotional and external eating when depression was more severe (both p-values <0.001). Longer symptom duration was also associated to more emotional and external eating (p < 0.001 and p = 0.001 respectively). When examining individual depressive symptoms, neuro-vegetative depressive symptoms contributed relatively more to emotional and external eating, while mood and anxious symptoms contributed relatively less to emotional and external eating. No depression associations were found with restrained eating. Intervention programs for depression should examine whether treating disordered eating specifically in those with neuro-vegetative, atypical depressive symptoms may help prevent or minimize adverse health consequences.

Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy.

Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30–50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic–pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants.

Associations of number and severity of depressive episodes with C-reactive protein and Interleukin-6.

Many researchers have found that the inflammatory process in the body and the brain may result in psychiatric disorders. Meta-analyses of cross-sectional studies have reported increase in inflammatory markers in depression. However, the direction of the association remains unclear. To compare the levels of C-reactive protein (CRP) and Interleukin-6 (IL-6) in depressed and healthy controls. To study the associations of these biomarkers with severity and number of depressive episodes. A total of 72 subjects with major depression and 60 healthy controls were studied. CRP and IL-6 were measured in all subjects. No significant differences were noted between depressed patients and healthy controls with regard to CRP (p=0.29) and IL-6 (p=0.50). Those who were suffering from severe depression based on Beck's Depressive Inventory (BDI), were positively correlated with raised CRP (p=0.011) in comparison to patients with mild to moderate depression. Single and recurrent depressive disorder (RDD) were not associated with significant rise in CRP (p=0.866) and IL-6 (p=0.531). Severity of depression is correlated with elevated CRP but not with IL-6. No association found between number of depressive episodes and levels of CRP and IL-6. It is possible that immune dysregulation is not generally present in depression, but might be restricted to particular subgroups of depressed patients. Several factors that could influence the depression and inflammation relationship need further investigation.

Why do stimulants not work in typical depression?

Stimulants have been suggested as therapeutics in depression for 80 years now, but there is still no evidence from randomized controlled trials that stimulants, in general, possess specific antidepressant effects. Also, several recent large randomized controlled trials which tried to establish an indication for stimulants as add-on in depression failed, and the companies no longer proceed with regulatory filings. One reason why the common belief of an antidepressant effect has survived over decades is a lack of clarity in psychopathology. Tiredness in the sense of sleepiness (downregulation of arousal) and lack of drive are mixed up with tiredness in the sense of exhaustion with high inner tension (upregulation of arousal) and inhibition of drive. The latter is found in typical depression, and according to the recently introduced arousal regulation model of affective disorders, upregulation of arousal is considered to be an important pathogenetic factor. Psychostimulants are unlikely to have beneficial effects in those patients with upregulated arousal. However, there might be subgroups of depressed patients, such as atypical depression, which suffer from sleepiness and lack of drive and might respond to stimulants. Arousal, a dimension included in the Research Domain Criteria project of the National Institute of Mental Health, can be assessed with an electroencephalography-based algorithm (the Vigilance Algorithm Leipzig) and is a promising biomarker to identify subgroups of patients, which might respond to stimulants.

Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat

The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gut microbiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.

Role of Neuro-Immunological Factors in the Pathophysiology of Mood Disorders: Implications for Novel Therapeutics for Treatment Resistant Depression.

Mood disorders are associated with persistently high rates of morbidity and mortality, despite the widespread availability of antidepressant treatments. One limitation to extant therapeutic options has been that nearly all approved antidepressant pharmacotherapies exert a similar primary action of blocking monoamine transporters, and few options exist for transitioning treatment resistant patients to alternatives with distinct mechanisms. An emerging area of science that promises novel pathways to antidepressant and mood-stabilizing therapies has followed from evidence that immunological factors play major roles in the pathophysiology of at least some mood disorder subtypes. Here we review evidence that the compounds that reduce the release or signaling of neuroactive cytokines, particularly IL-1β, IL-6, and TNF-α, can exert antidepressant effects in subgroups of depressed patients who are identified by blood-based biomarkers associated with inflammation. Within this context we discuss the role of microglia in central neuroinflammation, and the interaction between the peripheral immune system and the central synaptic microenvironment during and after neuroinflammation. Finally we review data using preclinical neuroinflammation models that produce depression-like behaviors in experimental animals to guide the discovery of novel neuro-immune drug targets.

Sharp-wave EEG abnormalities and neural complexity in depressive patients: preliminary report

According to recent findings cognitive and emotional dysregulation in depression and psychiatric disorders may be related to deficits in inhibitory functions and temporo-limbic seizure-like activity due to specific changes in neural dynamics and complexity of neural networks. In order to evaluate the clinical utility of nonlinear analysis of EEG complexity (measured by Lyapunov exponents) and to assess underlying epileptiform changes, we studied a sample of 19 depressive patients including nine depressive patients with episodic sharp-wave EEG abnormalities and ten depressive patients without any abnormalities, and compared also subgroups of these patients who used benzodiazepine medication to assess its influence on EEG complexity. The results show that the depressive patients with episodic sharp-wave EEG abnormalities had significantly lower EEG complexity than the control groups of patients. The data also indicate that benzodiazepines significantly influence neural complexity and increase it in the subgroup of patients with sharp wave abnormalities, and on the other hand decrease the level of complexity in the control subgroup of depressive patients. In agreement with other findings results of this study suggest that sharp waves or other underlying epileptiform EEG abnormalities related to abnormal neural excitability and disturbances in brain inhibitory systems may be reflected in specific changes of EEG complexity. These specific changes in EEG complexity may be related to treatment resistance to usual medications in several depressive patients and might represent clinical indicators for anticonvulsant treatment.

Comorbid anxiety disorders in late-life depression: results of a cohort study.

Comorbid anxiety disorders are common in late-life depression and negatively impact treatment outcome. This study aimed to examine personality characteristics as well as early and recent life-events as possible determinants of comorbid anxiety disorders in late-life depression, taking previously examined determinants into account. Using the Composite International Diagnostic Interview (CIDI 2.0), we established comorbid anxiety disorders (social phobia (SP), panic disorder (PD), generalized anxiety disorder (GAD), and agoraphobia (AGO)) in 350 patients (aged ≥60 years) suffering from a major depressive disorder according to DSM-IV-TR criteria within the past six months. Adjusted for age, sex, and level of education, we first examined previously identified determinants of anxious depression: depression severity, suicidality, partner status, loneliness, chronic diseases, and gait speed in multiple logistic regression models. Subsequently, associations were explored with the big five personality characteristics as well as early and recent life-events. First, multiple logistic regression analyses were conducted with the presence of any anxiety disorder (yes/no) as dependent variable, where after analyses were repeated for each anxiety disorder, separately. In our sample, the prevalence rate of comorbid anxiety disorders in late-life depression was 38.6%. Determinants of comorbid anxiety disorders were a lower age, female sex, less education, higher depression severity, early traumatization, neuroticism, extraversion, and conscientiousness. Nonetheless, determinants differed across the specific anxiety disorders and lumping all anxiety disorder together masked some determinants (education, personality). Our findings stress the need to examine determinants of comorbid anxiety disorder for specific anxiety disorders separately, enabling the development of targeted interventions within subgroups of depressed patients.

Cytokine Antagonists May Help Some Depression Patients

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessCytokine Antagonists May Help Some Depression PatientsAaron LevinAaron LevinSearch for more papers by this authorPublished Online:16 Jun 2014https://doi.org/10.1176/appi.pn.2014.6b17AbstractStudying the relationship of inflammatory cytokines to depression may open doors to the origins of the disorder and possible treatments.A few years ago, some researchers were hypothesizing that inflammatory cytokines were a cause of depression.The evidence seemed initially persuasive, said Andrew Miller, M.D., at APA’s 2014 annual meeting in New York in May.Inflammatory cytokines may play a role in depression, but not the only role, says psychiatric oncologist Andrew Miller, M.D.David HathcoxLevels of IL-6, tumor necrosis factor-α (TNF-α), and c-reactive protein (CRP) are indeed often elevated in patients with depression and are associated with treatment resistance, said Miller, a professor of psychiatry and behavioral sciences and director of psychiatric oncology at the Winship Cancer Institute at Emory University School of Medicine.Experimentally, inflammatory cytokines induce depressive symptoms in healthy volunteers, as does therapeutic use of interferon in hepatitis-C patients, he said. Furthermore, inhibition of inflammatory cytokines reduces depressive symptoms in patients with cancer, depression, or psoriasis, among other illnesses.“It all adds up to a good case, but one size does not fit all,” cautioned Miller. Only subgroups of depressed patients have elevated levels of cytokines, and cytokines are also higher in patients with other psychiatric disorders (such as bipolar disorder, schizophrenia, and anxiety) and in general medical conditions (such as cancer or heart disease).“Cytokines are not about disorders but about the symptoms and the circuits that are related to those symptoms within those disorders,” he said.Studies in humans and in nonhuman primates suggest that interferon-α (an antiviral/antiproliferative cytokine used to treat viral infections or cancers) taps into pathways known to be involved in depression, said Miller.“Interferon-α alters glucose metabolism in the basal ganglia and leads to reduced prefrontal cortical metabolic activity,” he said. At the same time, there is increased activity in the globus pallidus and putamen, mimicking a pattern seen in Parkinson’s disease. “Neurons fire at a high rate because they are not being inhibited by dopamine.”fMRI studies of patients taking interferon-α for hepatitis-C showed that in the ventral striatum, being on the drug correlated highly with reduced motivation and anhedonia. Other studies showed similar effects with a variety of inflammatory stimuli.Miller then tested the effects of a TNF-α antagonist (infliximab) in patients with treatment-resistant depression. This was not a clinical trial, he emphasized, but a way to better understand the cytokine hypothesis of depression.Even getting to that point wasn’t simple, he said. “It took us a tremendously long time to convince the drug companies to even test the drugs in a depressed population, because the FDA automatically issues a black-box warning that treatment with a potential new drug could precipitate suicide.”Ultimately, they found that use of the drug reduced HAM-D scores overall equal to those found with placebo. However, the subset of patients with higher baseline CRP (>5 mg/L) levels demonstrated a greater treatment response, 62 percent among treated patients compared with 33 percent of those on placebo.This information might ultimately guide diagnosis or measurement of treatment effects. Plasma CRP has a readily available test and correlates well with CRP in cerebrospinal fluid, he said.“There are cells in the brain producing CRP, so we’re getting a sense of what’s going on in the brain in terms of neuroinflammation.”Within six hours of an infliximab infusion, gene expression arrays reflected down-regulation of the TNF-α and NF-κB pathways and predicted who would respond and who would not, he said. “Also, symptoms like motivation, psychomotor retardation, suicidality, and anxiety all got better,” as did the brain regions he anticipated would get better after blocking cytokines.Miller again cautioned that cytokine antagonists are not a panacea for depression and about the need to stratify patients: “Using cytokine antagonists in patients who have low inflammation actually causes them to do worse.” ■ ISSUES NewArchived

EPA-1600 - Celecoxib add-on to sertraline in the therapy of major depression: cytokines and kynurenine metabolites

A proinflammatory state in a subgroup of depressed patients has been reported repeatedly (e.g. increased interleukin-6 and tumour necrosis factor-alpha). COX-2 inhibitors down-regulate increased inflammatory markers and are therefore investigated as an add-on therapy in depression. Proinflammatory cytokines and/or kynurenine metabolites may predict the outcome of treatment with COX-2 inhibitors. To prove or disapprove the hypothesis of a better therapy response in the group of add-on celecoxib to sertraline, particularly in patients with a more pronounced proinflammatory state at baseline. The aim is to find a biological predictor (cytokines and/or kynurenine metabolites) for treatment outcome. This is a dual-center, randomized, double-blind, placebo-controlled, parallel group phase IIa study. It investigates the mean change in clinical outcome and in serum cytokine and kynurenine levels from baseline to endpoint (week 6) in patients with major depression (HAMD-17 ≥ 22) treated with sertraline plus celecoxib versus sertraline plus placebo for six weeks. 51 depressed patients of both gender, aged between 18 and 60 years without any recent inflammatory disease were enrolled. The study comprises six study visits (6x ratings, 3x blood collections) during six weeks of treatment and a follow-up visit 10 weeks after baseline. Cytokines were measured by Enzyme-linked Immunosorbent Assay (ELISA), kynurenine and its metabolites by High Performance Liquid Chromatography (HPLC). The study was completed quite recently and the results are in progress.

EPA-1586 - Celecoxib add-on to sertraline in the therapy of major depression: clinical outcome

A proinflammatory state in a subgroup of depressed patients has been reported repeatedly, for example an increase in interleukin-6 and tumour necrosis factor-a is well documented. Treatment with COX-2 inhibitors down-regulate increased inflammatory markers. Therefore an adjunctive treatment of depression with COX-2 in combination with an antidepressant might lead to a better clinical outcome. To prove or disapprove the hypothesis of a better clinical outcome in the group with add-on celecoxib to sertraline in terms of improvement of HamD-17 and MADRS scores from baseline to endpoint. This is a dual-center, randomized, double-blind, placebo-controlled, parallel group phase IIa study to investigate the mean change in clinical outcome and in serum expression of inflammation markers from baseline to endpoint (week 6) in patients with major depression (HAMD-17 ≥ 22) treated with celecoxib in combination with sertraline compared to sertraline combined with placebo. 51 depressed patients of both gender, aged between 18 and 60 without any recent inflammatory related disease were enrolled. The study comprises six study visits (6x ratings including HAMD-17 and MADRS, 3x blood collections) during six weeks of treatment and a follow-up visit 10 weeks after baseline. The study was completed quite recently and the results are in progress.

Effects of 1-Year Treatment With Highly Purified Omega-3 Fatty Acids on Depression After Myocardial Infarction

The effects of supplementation of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on prevalence and severity of depression were evaluated in patients after a myocardial infarction. A cross-sectional evaluation (posttest-only design) within the prospective, randomized, controlled, multicenter OMEGA trial was performed in patients after myocardial infarction at 12 months' follow-up (N = 2,081; age, mean = 64 years; men, 76.7%; women, 21.8%) from April 2005 to June 2007. Patients received supplementation with ethyl esters 90 (460-mg EPA and 380-mg DHA) or placebo for 12 months. Depression was assessed with the Beck Depression Inventory-II (BDI-II); a BDI-II cutoff score of ≥ 14 was used as diagnosis of depression. When the total population was evaluated, no effects of EPA/DHA supplementation on depressive symptoms according to BDI-II score (mean [SD]) could be demonstrated: EPA/DHA (n = 1,046), 7.1 (6.9); placebo (n = 1,035), 7.1 (7.0); P = .7. The post hoc analyses of depressed patients with and without antidepressants revealed a tendency toward an antidepressant effect in patients with EPA/DHA supplementation as monotherapy: EPA/DHA (n = 125), 19.4 (5.8); placebo (n = 113), 19.9 (5.1); P = .07. However, in depressed patients with EPA/DHA supplementation as adjunctive to conventional antidepressants, a clinically relevant antidepressant effect was demonstrated: EPA/DHA (n = 33), 20.9 (7.1); placebo (n = 29), 24.9 (8.5); P < .05. EPA/DHA supplementation in the total sample of patients after myocardial infarction had no effect on depressive symptoms. The clinically relevant antidepressant effect in the subgroup of depressed patients with EPA/DHA supplementation as adjunctive to conventional antidepressants that was revealed in the post hoc analysis might provide a basis for a controlled, prospective trial of omega-3 augmentation of antidepressants in patients after myocardial infarction. ClinicalTrials.gov identifier: NCT00251134.

Interpersonal psychotherapy (IPT) in major depressive disorder

In this article, we will introduce interpersonal psychotherapy as an effective short-term treatment strategy in major depression. In IPT, a reciprocal relationship between interpersonal problems and depressive symptoms is regarded as important in the onset and as a maintaining factor of depressive disorders. Therefore, interpersonal problems are the main therapeutic targets of this approach. Four interpersonal problem areas are defined, which include interpersonal role disputes, role transitions, complicated bereavement, and interpersonal deficits. Patients are helped to break the interactions between depressive symptoms and their individual interpersonal difficulties. The goals are to achieve a reduction in depressive symptoms and an improvement in interpersonal functioning through improved communication, expression of affect, and proactive engagement with the current interpersonal network. The efficacy of this focused and structured psychotherapy in the treatment of acute unipolar major depressive disorder is summarized. This article outlines the background of interpersonal psychotherapy, the process of therapy, efficacy, and the expansion of the evidence base to different subgroups of depressed patients.

Circadian rhythms and treatment implications in depression

In humans almost all physiological and behavioural functions occur on a rhythmic basis. Therefore the possibility that delays, advances or desynchronizations of circadian rhythms may play a role in the pathophysiology of psychiatric disorders is an interesting field of research. In particular mood disorders such as seasonal affective disorder and major depression have been linked to circadian rhythms alterations. Furthermore, the antidepressant efficacy of both pharmacological and non-pharmacological strategies affecting endogenous circadian rhythms, such as new antidepressant medications, light-therapy and sleep deprivation, is consistent with the idea that circadian alterations may represent a core component of depression, at least in a subgroup of depressed patients. This paper briefly describes the molecular and genetic mechanisms regulating the endogenous clock system, and reviews the literature supporting the relationships between depression, antidepressant treatments and changes in circadian rhythms.