A dynamic course of T cell defects in individuals at risk for mood disorders

Snijders, Gijsje; Schiweck, Carmen; Mesman, Esther; Grosse, Laura; Wit, Harm de; Nolen, Willem A.; Drexhage, Hemmo A.; Hillegers, Manon H. J.

doi:10.1016/j.bbi.2016.05.007

Cited by 59 publications

(49 citation statements)

References 30 publications

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“…Snijders et al (12) took the monocyte data on the DBO adolescents of Mesman et al (5) further and showed that the DBO 16-year-old adolescents had deficits in the number of circulating lymphocytes, particularly of total CD3 + T cells and within this population particularly in the Treg cell subset. Interestingly, she found that the lower the level of the anti-inflammatory Treg cells in the DBO adolescents, the higher the monocyte inflammatory gene activation.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, Th1 (IFN-γ + ), Th2 (IL4 + ), and Th17 (IL17A + ) subsets were assessed and described relative to the total number of leukocytes. All used procedures including the gating strategy are extensively described in Snijders et al (12). The researcher was blind to the identity of the sample during the FACS measurement and analysis of the data.…”

Section: Methodsmentioning

confidence: 99%

“…In all cohorts, there was a deficit in the number of T cells, while within the T cell population there were abnormal fluctuations over time in the circulating levels of anti-inflammatory T regulatory (Treg) cells and T-helper 2 (Th2) cells and of pro-inflammatory T-helper 1 (Th1) and T-helper 17 (Th17) cells (7, 11, 12). …”

Section: Introductionmentioning

confidence: 99%

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T Cell Deficits and Overexpression of Hepatocyte Growth Factor in Anti-inflammatory Circulating Monocytes of Middle-Aged Patients with Bipolar Disorder Characterized by a High Prevalence of the Metabolic Syndrome

et al. 2017

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BackgroundWe previously reported T cell deficits and pro-inflammatory gene activation in circulating monocytes of two cohorts of bipolar disorder (BD) patients, a cohort of postpartum psychosis patients and in bipolar offspring. Pro-inflammatory gene activation occurred in two clusters of mutually correlating genes, cluster 1 for inflammation-related cytokines/factors, cluster 2 for motility, chemotaxis, and metabolic factors.AimTo verify these cellular immune abnormalities in yet another cohort [the bipolar stress study (BiSS) cohort] of relative old (52 years, median) BD patients and to relate immune abnormalities to hair cortisol levels, measured in this cohort and representing long-term systemic cortisol levels, and to the presence of the metabolic syndrome (MetS), which was prevalent in 29% of the BiSS patients.MethodsMonocyte immune gene activation (quantitative polymerase chain reaction) and T cell deficits (fluorescence-activated cell sorting analysis) were determined in 97 well-controlled, largely euthymic BiSS BD patients. Monocyte genes included the cluster 1 and 2 genes, the genes for the glucocorticoid receptor (GR) α and GRβ, and the gene for hepatocyte growth factor [HGF, a marker of monocyte-derived circulating angiogenic cells (CACs)]. CACs serve vessel repair. Abnormal numbers are found in patients with MetS and vascular damage.ResultsAs compared to healthy controls: (1) the pro-inflammatory cluster 1 genes were downregulated, and the GRα and the HGF gene were upregulated in the monocytes of the BiSS patients and (2) T cell deficits were shown (reduced numbers of lymphocytes in particular of T cells). Within the reduced T cell population, a shift had taken place in the T-helper populations: T-helper 17 and T-helper 2 increased and T regulatory cells decreased. Correlations between hair cortisol, the MetS, monocyte gene activation, and T cell deficits were not found.ConclusionT cell deficits most likely are a trait phenomenon of BD, since they have also been found in the other cohorts of BD patients and in bipolar offspring. Monocytes of this cohort showed an anti-inflammatory set point, suggesting that pro- and anti-inflammation are state characteristics of BD. The monocyte gene profile indicated an increased CAC activity; the question arises whether this is due to putative vessel damage in these relatively old patients with a high prevalence of the MetS.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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T Cell Deficits and Overexpression of Hepatocyte Growth Factor in Anti-inflammatory Circulating Monocytes of Middle-Aged Patients with Bipolar Disorder Characterized by a High Prevalence of the Metabolic Syndrome

et al. 2017

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“…In patients with mood disorders, a dynamic pattern of T cell defects, flares of inflammation, and compensatory increases of immune cells subset is observed during their lifetime (Drexhage et al., ; Snijders et al., ). The interpretation of these findings is still under debate, and several different mechanisms have been proposed, including an inborn dysregulation of the immune system, leading to auto‐inflammatory reactivity, stress and exposure to infectious agents (Anderson & Maes, ; Bergink, Gibney, & Drexhage, ; Dantzer, ; Leonard & Maes, ; Raison, Capuron, & Miller, ).…”

Section: What Are the Perspectives?mentioning

confidence: 99%

Perspectives in affective disorders: Clocks and sleep

Wirz‐Justice

Benedetti

2019

Eur J of Neuroscience

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Mood disorders are often characterised by alterations in circadian rhythms, sleep disturbances and seasonal exacerbation. Conversely, chronobiological treatments utilise zeitgebers for circadian rhythms such as light to improve mood and stabilise sleep, and manipulations of sleep timing and duration as rapid antidepressant modalities. Although sleep deprivation (“wake therapy”) can act within hours, and its mood‐elevating effects be maintained by regular morning light administration/medication/earlier sleep, it has not entered the regular guidelines for treating affective disorders as a first‐line treatment. The hindrances to using chronotherapeutics may lie in their lack of patentability, few sponsors to carry out large multi‐centre trials, non‐reimbursement by medical insurance and their perceived difficulty or exotic “alternative” nature. Future use can be promoted by new technology (single‐sample phase measurements, phone apps, movement and sleep trackers) that provides ambulatory documentation over long periods and feedback to therapist and patient. Light combinations with cognitive behavioural therapy and sleep hygiene practice may speed up and also maintain response. The urgent need for new antidepressants should hopefully lead to reconsideration and implementation of these non‐pharmacological methods, as well as further clinical trials. We review the putative neurochemical mechanisms underlying the antidepressant effect of sleep deprivation and light therapy, and current knowledge linking clocks and sleep with affective disorders: neurotransmitter switching, stress and cortico‐limbic reactivity, clock genes, cortical neuroplasticity, connectomics and neuroinflammation. Despite the complexity of multi‐system mechanisms, more insight will lead to fine tuning and better application of circadian and sleep‐related treatments of depression.

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“…MDD is often associated with alterations in the immune system, including increased circulating levels of biomarkers of inflammation [3,4], reduced blood lymphocyte counts, and reduced proliferative responses of lymphocytes to mitogens [5][6][7][8]. Inflammatory mediators induce depression in patients treated with recombinant cytokines.…”

Section: Introductionmentioning

confidence: 99%

Resolution of inflammation-induced depression requires T lymphocytes and endogenous brain interleukin-10 signaling

Laumet

Edralin

Chiang

et al. 2018

Neuropsychopharmacol

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In humans, depression is often associated with low-grade inflammation, activation of the tryptophan/kynurenine pathway, and mild lymphopenia. Preclinical research confirms that inflammation induces depression-like behavior through activation of the tryptophan/kynurenine pathway. However, the mechanisms governing recovery from depression are unknown. Understanding the pathways leading to resolution of depression will likely lead to identification of novel targets for treatment. We investigated the contribution of T lymphocytes to the resolution of lipopolysaccharide-induced depression-like behavior. Duration of depression-like behavior was markedly prolonged in mice without mature T or B lymphocytes (Rag1 mice). This prolonged depression-like behavior was associated with persistent upregulation of the tryptophan-metabolizing enzyme indoleamine-2,3-dioxygenase (Ido)1 in the prefrontal cortex (PFC). Reconstitution of Rag1 mice with T lymphocytes normalized resolution of depression-like behavior and expression of Ido1 in the PFC. During resolution of inflammation-induced depression-like behavior, T lymphocytes accumulated in the meninges and were required for induction of interleukin (IL)-10 in the meninges and the PFC. Inhibition of IL-10 signaling by nasal administration of neutralizing anti-IL-10 antibody to WT mice led to persistent upregulation of Ido1 in the PFC and prolonged depression-like behavior. Conversely, nasal administration of recombinant IL-10 in Rag1 mice normalized Ido1 expression and resolution of depression-like behavior. In conclusion, the present data show for the first time that resolution of inflammation-induced depression is an active process requiring T lymphocytes acting via an IL-10-dependent pathway to decrease Ido1 expression in the brain. We propose that targeting the T lymphocyte/IL-10 resolution pathway could represent a novel approach to promote recovery from major depressive disorder.

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A dynamic course of T cell defects in individuals at risk for mood disorders

Cited by 59 publications

References 30 publications

T Cell Deficits and Overexpression of Hepatocyte Growth Factor in Anti-inflammatory Circulating Monocytes of Middle-Aged Patients with Bipolar Disorder Characterized by a High Prevalence of the Metabolic Syndrome

T Cell Deficits and Overexpression of Hepatocyte Growth Factor in Anti-inflammatory Circulating Monocytes of Middle-Aged Patients with Bipolar Disorder Characterized by a High Prevalence of the Metabolic Syndrome

Perspectives in affective disorders: Clocks and sleep

Resolution of inflammation-induced depression requires T lymphocytes and endogenous brain interleukin-10 signaling

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