ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression

The ATP-binding cassette family of transporter proteins, subfamily B (MDR/TAP), member 1 (ABCB1) (P-glycoprotein) transporter is a key component of the blood–brain barrier. Many antidepressants are subject to ABCB1 efflux. Functional polymorphisms of ABCB1 may influence central nervous system bioavailability of antidepressants subject to efflux. Single-nucleotide polymorphisms (SNPs) at rs1045642 (C3435T) of ABCB1 have been associated with efflux pump efficiency. This may explain part of the interindividual variation in antidepressant dose needed to remit. Individuals (N=113) with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) major depressive disorder (MDD) were treated with escitalopram (ESC) or venlafaxine (VEN) over 8 weeks. The17-item Hamilton Depression Rating Scale was assessed serially, blind to genotype. SNP rs1045642 of ABCB1 along with two SNPs previously reported to be in linkage disequilibrium with it (rs2032582 and rs1128503) were genotyped. Demographic features, clinical features, P450 metabolizer status and 5-HTTLPR (serotonin-transporter-linked promoter region) genotype were controlled for. Carriers of rs1045642 TT needed on average 11 mg of ESC to remit, whereas TC and CC carriers required 24 and 19 mg, respectively (P=0.0001). This equates to a 2.0- (95% confidence interval=1.5–3.4; P<0.001) fold greater ESC dose needed to remit for C carriers compared with TT carriers at rs1045642. Of VEN-treated subjects carrying TT genotype at rs1045642, 73.3% remitted compared with 12.5% for CC genotype (odds ratio=6.69; 95% confidence interval=1.72–25.9, P=0.006). These data suggest that antidepressant dose needed to remit can be predicted by an ABCB1 SNP. This has the potential clinical translation implications for dose selection and remission from MDD.

Preventive strategies in depression : gathering evidence for risk factors and potential interventions

This editorial critiques the recent literature concerning both vitamin D deficiency in major depression and supplementation as a treatment strategy, and contextualises it within a broader approach to the prevention of depression, based on the recent evidence for lifestyle as a risk factor for depression and anxiety.

Towards automated detection of depression from brain structural magnetic resonance images

Introduction : Depression is a major issue worldwide and is seen as a significant health problem. Stigma and patient denial, clinical experience, time limitations, and reliability of psychometrics are barriers to the clinical diagnoses of depression. Thus, the establishment of an automated system that could detect such abnormalities would assist medical experts in their decision-making process. This paper reviews existing methods for the automated detection of depression from brain structural magnetic resonance images (sMRI).Methods : Relevant sources were identified from various databases and online sites using a combination of keywords and terms including depression, major depressive disorder, detection, classification, and MRI databases. Reference lists of chosen articles were further reviewed for associated publications.Results : The paper introduces a generic structure for representing and describing the methods developed for the detection of depression from sMRI of the brain. It consists of a number of components including acquisition and preprocessing, feature extraction, feature selection, and classification.Conclusion : Automated sMRI-based detection methods have the potential to provide an objective measure of depression, hence improving the confidence level in the diagnosis and prognosis of depression.

Barriers to the detection and management of depression by palliative care professional carers among their patients : perspectives from professional carers and patients' family members

Introduction: Clinical depression is highly prevalent yet underdetected and poorly managed within palliative care settings.

Objectives: This qualitative study explored the identification, monitoring, and management of symptoms of depression in patients receiving palliative care from 2 juxtaposed perspectives that are of care providers and care recipients' family members. Examining the barriers that restrict professional carers detecting and managing depression in their patients was a central focus of the study.

Methods: Focus groups were held with 18 professional carers, including 8 holding managerial positions, across 2 palliative care services, 1 regional and 1 metropolitan, which provided both inpatient and community-based care. Individual interviews were conducted with 10 family members of patients who had received or were receiving palliative care through these services.

Results: Thematic analysis of these data identified that both professional carers and family members perceived that depression is a wide-spread concern for patients receiving palliative care; however, numerous barriers were identified that affect professional carers’ ability to identify depression. These included knowledge and training deficits, low self-efficacy, prioritization of physical concerns and time constraints, patient/family characteristics, and system/process issues. These themes (and related subthemes) are discussed in this article.

Conclusions: Specialized training in depression is recommended for professional carers in order to improve their depression-related knowledge, detection skills, and self-efficacy. The ultimate goal of such training is to increase the rate of recognition of depression that in turn will lead to appropriate treatment for depressed patients.

Validity of the Beck Depression Inventory as a screening tool for a clinical mood disorder in Bariatric surgery candidates

Background : The Beck Depression Inventory (BDI) is one of the most commonly used instruments to assess depression in persons with obesity. While it has been validated in normal and psychiatric populations, in obese populations, its validity remains uncertain. This study aimed to investigate the validity and reliability of the BDI-IA and BDI-II in severely obese bariatric surgery candidates.

Methods : Consecutive new candidates at a bariatric surgery clinic were invited to participate in the study by their consulting surgeon. All candidates were assessed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I); 118 completed the BDI-IA and 83 completed the BDI-II. Two hundred one patients (response rate, 88 %) participated in the study. The current sample (82 % female) had an average body mass index of 42.83 ± 6.34 and an average age of 45 ± 12 years.

Results : Based on the SCID-I, 54 candidates (26.9 %) met the criteria for a mood disorder, with 37 meeting the criteria for current major depressive disorder. Individuals diagnosed with a clinical mood disorder had significantly higher scores on the BDI (BDI-IA, 23.59 ± 9.69 vs. 12.76 ± 8.29; BDI-II, 22.93 ± 5.22 vs. 11.25 ± 8.44). Our results indicated that, as a screening tool for a clinical mood disorder, the BDI-II had an optimal cutoff of 13, with a sensitivity of 100 and specificity of 67.75.

Conclusions : Results indicated that the BDI-IA should not be used as a tool to measure depressive symptomatology in obese bariatric surgery candidates. No cutoff was identified with adequate sensitivity and specificity, and over 20 % of patients were misclassified. As a screening tool for a clinical mood disorder, the BDI-II was adequate; however, prevalence rates were significantly overestimated.

Confirmatory factor analysis of the Beck Depression inventory in obese individuals seeking surgery

Background : The Beck Depression Inventory (BDI) is frequently employed as measure of depression in studies of obesity. The aim of the study was to assess the factorial structure of the BDI in obese patients prior to bariatric surgery.

Methods : Confirmatory factor analysis was conducted on the current published factor analyses of the BDI. Three published models were initially analysed with two additional modified models subsequently included. A sample of 285 patients presenting for Lap-Band® surgery was used.

Results : The published bariatric model by Munoz et al. was not an adequate fit to the data. The general model by Shafer et al. was a good fit to the data but had substantial limitations. The weight loss item did not significantly load on any factor in either model. A modified Shafer model and a proposed model were tested, and both were found to be a good fit to the data with minimal differences between the two. A proposed model, in which two items, weight loss and appetite, were omitted, was suggested to be the better model with good reliability.

Conclusions : The previously published factor analysis in bariatric candidates by Munoz et al. was a poor fit to the data, and use of this factor structure should be seriously reconsidered within the obese population. The hypothesised model was the best fit to the data. The findings of the study suggest that the existing published models are not adequate for investigating depression in obese patients seeking surgery.

Raised CRP levels in obese patients : symptoms of depression have an independent positive association

Background: Depression and obesity, the two common ailments of modern society, are associated with increased risk of coronary artery disease and raised C-reactive protein (CRP) levels. Are the effects of depression and obesity related or do they influence CRP levels independently?

Objective: In 493 consecutive patients presenting for obesity surgery, we explored the relationship between symptoms of depression and raised CRP levels after controlling for confounding factors.

Methods and Procedures: Depression was measured using the Beck Depression Inventory (BDI). Confounding variables were age, gender, BMI, waist and hip measures, smoking and alcohol habits, medications, biochemical measures of the metabolic syndrome, and indirect measures of insulin resistance. General linear regression sought variables independently associated with CRP levels.

Results: These patients had a BMI range from 31 to 91 kg/m2, participants age ranged from 14 to 71 years, and 76% were women. The median CRP concentration was 7.7 mg/l (interquartile range: 3.9–14), 40% had an abnormally raised concentration (>10 mg/l). The mean BDI score was 17.0 ± 9.0, indicating symptoms of moderate depression. We found five independent factors associated with raised CRP levels. In order of strength of association, these were: higher BMI (β = 0.36, P < 0.001), female gender (β = −0.19, P < 0.001), estrogen therapy (β = 0.18, P < 0.001), higher BDI score (β = 0.11, P = 0.01), and insulin resistance index (β = 0.11, P = 0.01), and with a combined R 2 = 0.24, (P < 0.001). Discussion: In obese patients, symptoms of depression were associated with raised CRP levels after controlling for confounding variables. Obese women on estrogen therapy are at risk of high CRP levels.

Lifestyle management of unipolar depression

Objective To be used in conjunction with ‘Pharmacological management of unipolar depression’ [Malhi et al. Acta Psychiatr Scand 2013;127(Suppl. 443):6–23] and ‘Psychological management of unipolar depression’ [Lampe et al. Acta Psychiatr Scand 2013;127(Suppl. 443):24–37]. To provide clinically relevant recommendations for lifestyle modifications in depression, derived from a literature review.

Method A search of pertinent literature was conducted up to August 2012 in the area of lifestyle factors and depression. A narrative review was then conducted.

Results There is evidence that level of physical activity plays a role in the risk of depression, and there is a large and validated evidence base for exercise as a therapeutic modality. Smoking and alcohol and substance misuse appear to be independent risk factors for depression, while the new epidemiological evidence supports the contention that diet is a risk factor for depression; good quality diets appear protective and poor diets increase risk.

Conclusion Lifestyle modification, with a focus on exercise, diet, smoking and alcohol, may be of substantial value in reducing the burden of depression in individuals and the community.

In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS) and autoimmune responses directed against O&NS- damaged neoepitopes

Objective: Depression is accompanied by activation of immuno-inflammatory and oxidative and nitrosative stress (IO&NS) pathways, and increased IgM/IgA responses to lipopolysaccharide (LPS) of gram-negative commensal bacteria. The latter suggests that bacterial translocation has caused IgM/IgA responses directed against LPS. Bacterial translocation may drive IO&NS responses.

Method: To examine the associations between IgM/IgA responses to LPS and IO&NS measurements, including plasma/serum interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin, lysozyme, oxidized LDL (oxLDL) antibodies, peroxides, and IgM (auto)immune responses against malondialdehyde (MDA), azelaic acid, phophatidyl inositol (Pi), NO-tryptophan and NO-tyrosine in depressed patients and controls.

Results: We found significant positive associations between IgM/IgA responses to LPS and oxLDL antibodies, IgM responses against MDA, azelaic acid, Pi, NO-tryptophan, and NO-tyrosine. The IgA responses to LPS were correlated with lysozyme. There were no significant positive correlations between the IgM/IgA responses to LPS and IL-1 and neopterin.

Conclusion: The findings show that in depression there is an association between increased bacterial translocation and lysozyme production, an antibacterial compound, O&NS processes, and autoimmune responses directed against O&NS generated neoantigenic determinants. It is suggested that bacterial translocation may drive IO&NS pathways in depression and thus play a role in its pathophysiology.