Depression and inflammation fuel one another. Inflammation plays a key role in depression's pathogenesis for a subset of depressed individuals; depression also primes larger cytokine responses to stressors and pathogens that do not appear to habituate. Accordingly, treatment decisions may be informed by attention to questions of how (pathways) and for whom (predispositions) these links exist, which are the focus of this article. When combined with predisposing factors (moderators such as childhood adversity and obesity), stressors and pathogens can lead to exaggerated or prolonged inflammatory responses. The resulting sickness behaviors (e.g., pain, disturbed sleep), depressive symptoms, and negative health behaviors (e.g., poor diet, a sedentary lifestyle) may act as mediating pathways that lead to further, unrestrained inflammation and depression. Depression, childhood adversity, stressors, and diet can all influence the gut microbiome and promote intestinal permeability, another pathway to enhanced inflammatory responses. Larger, more frequent, or more prolonged inflammatory responses could have negative mental and physical health consequences. In clinical practice, inflammation provides a guide to potential targets for symptom management by signaling responsiveness to certain therapeutic strategies. For example, a theme across research with cytokine antagonists, omega-3 fatty acids, celecoxib, and exercise is that anti-inflammatory interventions have a substantially greater impact on mood in individuals with heightened inflammation. Thus, when inflammation and depression co-occur, treating them in tandem may enhance recovery and reduce the risk of recurrence. The bidirectional links between depression, inflammation, and disease suggest that effective depression treatments could have a far-reaching impact on mood, inflammation, and health.

http://pni.osumc.edu/KG%20Publications%20(pdf)/255.pdf

Inflammation: Depression Fans the Flames and Feasts on the Heat

Importance Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants. Objective To assess the efficacy, safety, and dose-response of intranasal esketamine hydrochloride in patients with treatment-resistant depression (TRD). Design, Setting, and Participants This phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study was conducted in multiple outpatient referral centers from January 28, 2014, to September 25, 2015. The study consisted of 4 phases: (1) screening, (2) double-blind treatment (days 1-15), composed of two 1-week periods, (3) optional open-label treatment (days 15-74), and (4) posttreatment follow-up (8 weeks). One hundred twenty-six adults with a DSM-IV-TR diagnosis of MDD and history of inadequate response to 2 or more antidepressants (ie, TRD) were screened, 67 were randomized, and 60 completed both double-blind periods. Intent-to-treat analysis was used in evaluation of the findings. Interventions In period 1, participants were randomized (3:1:1:1) to placebo (n = 33), esketamine 28 mg (n = 11), 56 mg (n = 11), or 84 mg (n = 12) twice weekly. In period 2, 28 placebo-treated participants with moderate-to-severe symptoms were rerandomized (1:1:1:1) to 1 of the 4 treatment arms; those with mild symptoms continued receiving placebo. Participants continued their existing antidepressant treatment during the study. During the open-label phase, dosing frequency was reduced from twice weekly to weekly, and then to every 2 weeks. Main Outcomes and Measures The primary efficacy end point was change from baseline to day 8 (each period) in the Montgomery-Asberg Depression Rating Scale (MADRS) total score. Results Sixty-seven participants (38 women, mean [SD] age, 44.7 [10.0] years) were included in the efficacy and safety analyses. Change (least squares mean [SE] difference vs placebo) in MADRS total score (both periods combined) in all 3 esketamine groups was superior to placebo (esketamine 28 mg: −4.2 [2.09], P  = .02; 56 mg: −6.3 [2.07], P  = .001; 84 mg: −9.0 [2.13], P P Conclusions and Relevance In this first clinical study to date of intranasal esketamine for TRD, antidepressant effect was rapid in onset and dose related. Response appeared to persist for more than 2 months with a lower dosing frequency. Results support further investigation in larger trials. Trial Registration clinicaltrials.gov identifier:NCT01998958

/pdf/efficacy-and-safety-of-intranasal-esketamine-adjunctive-to-t3xyboq3fq.pdf

Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial

With depression being the psychiatric disorder incurring the largest societal costs in developed countries, there is a need to gather evidence on the role of nutrition in depression, to help develop recommendations and guide future psychiatric health care. The aim of this systematic review was to synthesize the link between diet quality, measured using a range of predefined indices, and depressive outcomes. Medline, Embase and PsychInfo were searched up to 31st May 2018 for studies that examined adherence to a healthy diet in relation to depressive symptoms or clinical depression. Where possible, estimates were pooled using random effect meta-analysis with stratification by observational study design and dietary score. A total of 20 longitudinal and 21 cross-sectional studies were included. These studies utilized an array of dietary measures, including: different measures of adherence to the Mediterranean diet, the Healthy Eating Index (HEI) and Alternative HEI (AHEI), the Dietary Approaches to Stop Hypertension, and the Dietary Inflammatory Index. The most compelling evidence was found for the Mediterranean diet and incident depression, with a combined relative risk estimate of highest vs. lowest adherence category from four longitudinal studies of 0.67 (95% CI 0.55-0.82). A lower Dietary Inflammatory Index was also associated with lower depression incidence in four longitudinal studies (relative risk 0.76; 95% CI: 0.63-0.92). There were fewer longitudinal studies using other indices, but they and cross-sectional evidence also suggest an inverse association between healthy diet and depression (e.g., relative risk 0.65; 95% CI 0.50-0.84 for HEI/AHEI). To conclude, adhering to a healthy diet, in particular a traditional Mediterranean diet, or avoiding a pro-inflammatory diet appears to confer some protection against depression in observational studies. This provides a reasonable evidence base to assess the role of dietary interventions to prevent depression. This systematic review was registered in the PROSPERO International Prospective Register of Systematic Reviews under the number CRD42017080579.

/pdf/healthy-dietary-indices-and-risk-of-depressive-outcomes-a-t844sze0q6.pdf

Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies

Physical activity and sedentary behavior in people with major depressive disorder: A systematic review and meta-analysis.

https://scholarlypublications.universiteitleiden.nl/access/item%3A3004308/view

Diet quality and depression risk: A systematic review and dose-response meta-analysis of prospective studies.

Diet, a modifiable lifestyle factor, may influence the development of depression. We performed a systematic review of observational studies examining the relationship between dietary patterns and depression in healthy adults. A literature research was conducted searching various electronic databases up to May 2013. Study selection was based on predefined inclusion and exclusion criteria. Included studies were reviewed, and relevant data were extracted by two independent researchers. Due to a high level of heterogeneity, no meta-analysis was conducted. Therefore, main results are presented in a descriptive way. In total, 16 studies met the inclusion criteria and are part of this review. Dietary patterns most commonly found were traditional/healthy patterns, Western/unhealthy patterns and Mediterranean patterns. The available literature suggests a protective effect of healthy and Mediterranean patterns, as well as a potential positive association of Western patterns and depression. However, comparison of the included studies was difficult, due to differences in relevant study characteristics and methodological limitations. There are indications that dietary patterns may have influence on the onset of depression, but no firm conclusion can be drawn at this point. Further research is needed to clarify the diet–depression relationship, preferably in the form of methodological strong prospective studies using more homogeneous methods.

Dietary patterns and the risk of depression in adults: a systematic review of observational studies.

Associations between poor sleep quality and different measures of obesity.

Depression is supposed to be associated with an unhealthy lifestyle including poor diet. The objective of this study was to investigate differences in diet quality between patients with a clinical diagnosis of depression and population-based controls. Additionally, we aimed to examine effects of specific depression characteristics on diet by analyzing if diet quality varies between patients with distinct depression subtypes, and if depression severity is associated with diet quality.

https://link.springer.com/content/pdf/10.1186%2Fs12888-015-0426-9.pdf

Associations between depression subtypes, depression severity and diet quality: cross-sectional findings from the BiDirect Study

Objective The accessibility of green space is an important aspect of the urban residential environment and has been found to be beneficial for health and well-being. This study investigates the association between different indicators of green space and the outcomes body mass index (BMI) and prevalent type 2 diabetes in an urban population. Design Population-based cross-sectional study. Setting Dortmund, a city located in the industrial Ruhr area in Western Germany. Participants 1312 participants aged 25–74 years from the Dortmund Health Study. Methods The participants’ addresses were geocoded and shapefiles of statistical districts, road network and land use, as well as data on neighbourhood characteristics were obtained at baseline. Three indicators of green space were constructed using geographical information systems: proportion of green space, recreation location quotient (RLQ) weighted by population and distance to the next park or forest. Multilevel linear and logistic regression analyses on the association of green space with BMI and type 2 diabetes were performed, adjusted by individual-level characteristics and neighbourhood unemployment rate. Results The multilevel regression analyses showed no association between green space and BMI. In contrast, the three indicators of green space were significantly associated with type 2 diabetes. Residents of neighbourhoods with a low RLQ had a 2.44 (95% CI 1.01 to 5.93) times higher odds to have type 2 diabetes compared with residents of high RLQ neighbourhoods. Likewise, residing more than 0.8 km away from the nearest park or forest increased the odds of type 2 diabetes (OR 1.71, 95% CI 1.05 to 2.77). Conclusions This study indicates that green space and its spatial accessibility might play a role in the development of type 2 diabetes. Further research is needed to clarify this association.

https://bmjopen.bmj.com/content/bmjopen/8/1/e019062.full.pdf

Corinna Rahe

Papers

Dietary patterns and the risk of depression in adults: a systematic review of observational studies.

Associations between poor sleep quality and different measures of obesity.

Associations between depression subtypes, depression severity and diet quality: cross-sectional findings from the BiDirect Study

Inner-city green space and its association with body mass index and prevalent type 2 diabetes: a cross-sectional study in an urban German city

Association between major depressive disorder and odor identification impairment.