An Inflammatory Biomarker as a Differential Predictor of Outcome of Depression Treatment With Escitalopram and Nortriptyline

Uher, Rudolf; Tansey, Katherine E.; Dew, Tracy; Maier, Wolfgang; Mors, Ole; Hauser, Joanna; Dernovšek, Mojca Zvezdana; Henigsberg, Neven; Souery, Daniel; Farmer, Anne; McGuffin, Peter

doi:10.1176/appi.ajp.2014.14010094

Cited by 350 publications

(283 citation statements)

References 55 publications

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“…Although the promise of anti-inflammatory pharmacological agents for the treatment of chronic psychopathology has gained traction based on the work done with regard to depression (Raison et al, 2013;Uher et al, 2014), other forms of intervention could prove efficacious in dampening inflammatory processes in fear-and anxiety-based disorders. Cognitive and behavioral interventions, including prolonged exposure, are effective treatments for fear-and anxiety-based disorders (Butler et al, 2006;Powers et al, 2010), but it still remains unclear whether these treatments also reduce inflammation.…”

Section: Treatment Implications and Future Directionsmentioning

confidence: 99%

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

Michopoulos

Powers

Gillespie

et al. 2016

Neuropsychopharmacol

544

376

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The study of inflammation in fear-and anxiety-based disorders has gained interest as growing literature indicates that proinflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein, have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a positive association between inflammation and fear-and anxiety-based symptoms, suggesting that other factors are important in future assessments of inflammation's role in the maintenance of these disorders (ie, sex, co-morbid conditions, types of trauma exposure, and behavioral sources of inflammation). The most parsimonious explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the activation of the stress response and central and peripheral immune cells to release cytokines. Dysregulation of the stress axis in the face of increased sympathetic tone and decreased parasympathetic activity characteristic of anxiety disorders could further augment inflammation and contribute to increased symptoms by having direct effects on brain regions critical for the regulation of fear and anxiety (such as the prefrontal cortex, insula, amygdala, and hippocampus). Taken together, the available data suggest that targeting inflammation may serve as a potential therapeutic target for treating these fear-and anxiety-based disorders in the future. However, the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions.

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Section: Treatment Implications and Future Directionsmentioning

confidence: 99%

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

Michopoulos

Powers

Gillespie

et al. 2016

Neuropsychopharmacol

544

376

View full text Add to dashboard Cite

show abstract

“…In mood disorders, several studies have suggested that the chronic mild inflammation indicated by elevated C-reactive protein (Courtet et al, 2015;Rapaport et al, 2015;Uher et al, 2014) as well as the quantification of the levels of inflammatory cytokines such as IL-6, IL-10 and TNF (de Witte et al, 2014;Ducasse et al, 2015b;Haapakoski et al, 2015;Halaris et al, 2015;Rethorst et al, 2013) could prove to be useful biomarkers for improved diagnosis and the detection of treatment refractoriness (Strawbridge et al, 2015), as well as indicators of the risk of suicide. As an increasing number of inflammatory factors are tested, an emerging picture supports the idea that a complex network of cytokines is involved in the pathophysiology of disease such as major depression (Dahl et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays

Belzeaux

Lefebvre

Lazzari

et al. 2017

Psychoneuroendocrinology

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Cytokines produced by both immune and non-immune cells are likely to play roles in the development and/or progression of psychiatric disorders. Indeed, many investigators have compared the blood cytokine levels in psychiatric patients with those of healthy controls or monitored their levels in patients during disease progression to identify biomarkers. Nevertheless, very few studies have confirmed that such cytokines remain stable in healthy individuals through periods of weeks and months. This is an important issue to consider before using blood cytokine levels as biomarkers of disease traits, disease state, or treatment response. Although multiplex assay technology represents an advance in identifying biomarkers because it allows simultaneous examination of large panels of analytes from a small volume of sample, it is necessary to verify whether these assays yield enough sensitivity and reproducibility when applied to the blood from neuropsychiatric patients. Therefore, we compared two multiplex immunoassays, the bead-based Luminex® (Bio-Rad) and the electro-chemiluminescence-based V-plex® (MesoScaleDiscovery), for the detection and quantification of 31 cytokines, chemokines and growth factors in both the sera and plasma of patients with major depressive episodes (MDE) and age-and sex-matched healthy control subjects during a 30-week period. Although both platforms exhibited low coefficients of variability (CV) between the duplicates in the calibration curves, the linearity was better in general for the V-PLEX® platform. However, neither platform was able to detect the absolute values for all of the tested analytes. Among the 16 analytes that were detected by both assays, the intra-assay reproducibility was in general better with the V-PLEX® platform. Although it is not a general rule that the results from sera and plasma will be correlated, consistent results were more frequent with the V-PLEX® platform. Furthermore, the V-PLEX® results were more consistent with the gold standard ELISA simplex assay for IL-6 in both sera and plasma. The intra-individual variability of the measurements, among the sera and plasma for the 4 samples harvested from each healthy individual, was low for Eotaxin, G-CSF, IL-4, IL-7, IL-9, IL-12p40, IL-12p70, IL-15, MIP-1β, PDGF-BB, TNF, TNF-β and VEGF, but intermediate or high for IFN-γ, IL-6, IL-8, IL-10, and IP10. Together, these data suggest that extreme caution is needed in translating the results of multiplex cytokine profiling into biomarker discovery in psychiatry. Dear Editor,We thank you and the Editor in chief, Robert Dantzer, for reaching the conclusion to ultimately publish our manuscript. Following your suggestion, we changed the tiltle to: "How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays".We were concerned by the persistent negative comments of Reviewer#3, stressing out that our comparison between the two platforms we have worked with suffers a number of theoretical and technical limitations because...

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“…Interestingly and importantly, the depressed patients who are non responders to antidepressant therapies or who are treatment resistant show higher plasma concentrations of several proinflammatory cytokines as compared to responders 35,36 . To add to the conclusions, cytokine expression in the leukocytes from depressed patients are reduced following escitalopram and nortriptyline treatment with a significant correlation between these changes and treatment response.…”

Section: Cytokine Hypothesis and Depressionmentioning

confidence: 99%

Depression: An Immuno-Inflammatory Cascade

Sharma¹,

Sharma²,

Sharma³

et al. 2016

Arşiv Kaynak Tarama Dergisi

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Major depressive disorder also known as clinical depression, unipolar depression or depression is associated with significant morbidity, mortality, high suicidal tendencies and deaths. Preclinical and clinical studies suggest that psychiatric illnesses like major depression are associated with inflammatory processes. While it is unlikely that major depression is a primary inflammatory disorder, there is now evidence to suggest that inflammation play a subtle role in the pathophysiology of major depression. The inflammation in depression cascade pin points to the origin from immune hyperactivity and thus a new theory that explains role of immune system mediated inflammation has been accepted and researched upon. widely. This theory states that depression is accompanied by altered immune function and activation of the inflammatory response system. This theory is strengthened form the fact that the current therapeutic options which mainly target neurotransmitters, are not effective in many patients and these patients has been found to be associated with elevated levels of inflammatory mediators specifically cytokines. It is reported more recently that other risk factors for depression, including psychosocial stress, psychological trauma, sleep disturbance and pain, also increases inflammatory processes. Thus the intervention in the immune system originated from inflammatory cytokines seems a therapeutically viable option in the field of depression research.

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An Inflammatory Biomarker as a Differential Predictor of Outcome of Depression Treatment With Escitalopram and Nortriptyline

Abstract: An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice.

Cited by 350 publications

References 55 publications

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays

Depression: An Immuno-Inflammatory Cascade

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