Deficiencies of the T and natural killer cell system in major depressive disorder

Grosse, Laura; Hoogenboezem, Thomas; Ambrée, Oliver; Bellingrath, Silja; Jörgens, Silke; Wit, Harm J. de; Wijkhuijs, Annemarie J.M.; Arolt, Volker; Drexhage, Hemmo A.

doi:10.1016/j.bbi.2015.12.003

Cited by 142 publications

(57 citation statements)

References 28 publications

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“…Our finding of increased T reg levels in MDD differs from a number of studies that have reported reduced T reg counts in depressed populations (Grosse et al, 2016b; Li et al, 2010). In contrast, our results are consistent with data from a study of elderly subjects that reported that an elevated percentage of T reg cells was associated with worse physical and mental health status, as well as higher levels of depressive symptomatology (Ronaldson et al, 2016).…”

Section: Discussioncontrasting

confidence: 99%

Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance

Suzuki

Savitz

Teague

et al. 2017

Brain, Behavior, and Immunity

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A subset of individuals with major depressive disorder (MDD) have impaired adaptive immunity characterized by a greater vulnerability to viral infection and a deficient response to vaccination along with a decrease in the number and/or activity of T cells and natural killer cells (NKC). Nevertheless, it remains unclear which specific subsets of lymphocytes are altered in MDD, a shortcoming we address here by utilizing an advanced fluorescence-activated cell sorting (FACS) method that allows for the differentiation of important functionally-distinct lymphocyte sub-populations. Furthermore, despite evidence that sleep disturbance, which is a core symptom of MDD, is itself associated with alterations in lymphocyte distributions, there is a paucity of studies examining the contribution of sleep disturbance on lymphocyte populations in MDD populations. Here, we measured differences in the percentages of 13 different lymphocytes and 6 different leukocytes in 54 unmedicated MDD patients (partially remitted to moderate) and 56 age and sex-matched healthy controls (HC). The relationship between self-reported sleep disturbance and cell counts was evaluated in the MDD group using the Pittsburgh Sleep Quality Index (PSQI). The MDD group showed a significantly increased percentage of CD127low/CCR4+ Treg cells, and memory Treg cells, as well as a reduction in CD56+CD16− (putative immunoregulatory) NKC counts, the latter, prior to correction for body mass index. There also was a trend for higher effector memory CD8+ cell counts in the MDD group versus the HC group. Further, within the MDD group, self-reported sleep disturbance was associated with an increased percentage of effector memory CD8+ cells but with a lower percentage of CD56+CD16− NKC. These results provide important new insights into the immune pathways involved in MDD, and provide novel evidence that MDD and associated sleep disturbance increase effector memory CD8+ and Treg pathways. Targeting sleep disturbance may have implications as a therapeutic strategy to normalize NKC and memory CD8+ cells in MDD.

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Section: Discussioncontrasting

confidence: 99%

Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance

Suzuki

Savitz

Teague

et al. 2017

Brain, Behavior, and Immunity

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“…The DOWN genes were affiliated with modules of the transcriptome partially specialized for adaptive immune function, and smaller clusters of strongly coexpressed DOWN genes were enriched in T cells, B cells, and NK cells. These results are compatible with prior data implicating relative suppression of the cellular immune system in (some people with) depression, including evidence for decreased NK cell cytotoxicity and decreased proliferation of lymphocytes challenged with mitogens in vitro (44) , and with recent data suggesting that deficiencies of NK and T cells co-occur with inflammatory monocyte activation as related phenomena in the same patients with MDD 21 , 22 , 45 , 46 .…”

Section: Discussionsupporting

confidence: 91%

“…Focusing on a consensus set of 165 genes, we investigated the functional significance of the genes that were differentially (over- or under-) expressed in cases compared with controls. We also explored the secondary hypothesis that innate immune system activation is coupled to relative inactivation of the adaptive immune system in patients with MDD 21 , 22 , 23 .…”

mentioning

confidence: 99%

Replicable and Coupled Changes in Innate and Adaptive Immune Gene Expression in Two Case-Control Studies of Blood Microarrays in Major Depressive Disorder

Leday

Vértes

Richardson

et al. 2018

Biological Psychiatry

171

131

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BackgroundPeripheral inflammation is often associated with major depressive disorder (MDD), and immunological biomarkers of depression remain a focus of investigation.MethodsWe used microarray data on whole blood from two independent case-control studies of MDD: the GlaxoSmithKline–High-Throughput Disease-specific target Identification Program [GSK-HiTDiP] study (113 patients and 57 healthy control subjects) and the Janssen–Brain Resource Company study (94 patients and 100 control subjects). Genome-wide differential gene expression analysis (18,863 probes) resulted in a p value for each gene in each study. A Bayesian method identified the largest p-value threshold (q = .025) associated with twice the number of genes differentially expressed in both studies compared with the number of coincidental case-control differences expected by chance.ResultsA total of 165 genes were differentially expressed in both studies with concordant direction of fold change. The 90 genes overexpressed (or UP genes) in MDD were significantly enriched for immune response to infection, were concentrated in a module of the gene coexpression network associated with innate immunity, and included clusters of genes with correlated expression in monocytes, monocyte-derived dendritic cells, and neutrophils. In contrast, the 75 genes underexpressed (or DOWN genes) in MDD were associated with the adaptive immune response and included clusters of genes with correlated expression in T cells, natural killer cells, and erythroblasts. Consistently, the MDD patients with overexpression of UP genes also had underexpression of DOWN genes (correlation > .70 in both studies).ConclusionsMDD was replicably associated with proinflammatory activation of the peripheral innate immune system, coupled with relative inactivation of the adaptive immune system, indicating the potential of transcriptional biomarkers for immunological stratification of patients with depression.

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“…The immunological hypothesis in ND and CMD has many direct contributors, such as the TORCH (Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes simplex virus)[80] and PANDAS models in ND disorders, serological studies, for example in schizophrenia (see above), leucocyte counts in depression[87], gastrointestinal inflammation in psychosis[29], the autoantibodies link[88], the inflammation topic in mood disorders[89], and, finally, evidence for upregulated proinflammatory mediators such as IL-1β, IL-6 and TNF-α[90]. However, in some instances such as UTI or ulcer the categorization of immune processes is less clear and may involve different basic mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Infectious, atopic and inflammatory diseases, childhood adversities and familial aggregation are independently associated with the risk for mental disorders: Results from a large Swiss epidemiological study

Ajdacic-Gross¹,

Aleksandrowicz²,

Rodgers³

et al. 2016

WJP

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AIMTo examine the associations between mental disorders and infectious, atopic, inflammatory diseases while adjusting for other risk factors.METHODSWe used data from PsyCoLaus, a large Swiss Population Cohort Study (n = 3720; age range 35-66). Lifetime diagnoses of mental disorders were grouped into the following categories: Neurodevelopmental, anxiety (early and late onset), mood and substance disorders. They were regressed on infectious, atopic and other inflammatory diseases adjusting for sex, educational level, familial aggregation, childhood adversities and traumatic experiences in childhood. A multivariate logistic regression was applied to each group of disorders. In a complementary analysis interactions with sex were introduced via nested effects.RESULTSAssociations with infectious, atopic and other chronic inflammatory diseases were observable together with consistent effects of childhood adversities and familial aggregation, and less consistent effects of trauma in each group of mental disorders. Streptococcal infections were associated with neurodevelopmental disorders (men), and measles/mumps/rubella-infections with early and late anxiety disorders (women). Gastric inflammatory diseases took effect in mood disorders (both sexes) and in early disorders (men). Similarly, irritable bowel syndrome was prominent in a sex-specific way in mood disorders in women, and, moreover, was associated with early and late anxiety disorders. Atopic diseases were associated with late anxiety disorders. Acne (associations with mood disorders in men) and psoriasis (associations with early anxiety disorders in men and mood disorders in women) contributed sex-specific results. Urinary tract infections were associated with mood disorders and, in addition, in a sex-specific way with late anxiety disorders (men), and neurodevelopmental and early anxiety disorders (women).CONCLUSIONInfectious, atopic and inflammatory diseases are important risk factors for all groups of mental disorders. The sexual dimorphism of the associations is pronounced.

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Deficiencies of the T and natural killer cell system in major depressive disorder

Cited by 142 publications

References 28 publications

Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance

Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: Association with sleep disturbance

Replicable and Coupled Changes in Innate and Adaptive Immune Gene Expression in Two Case-Control Studies of Blood Microarrays in Major Depressive Disorder

Infectious, atopic and inflammatory diseases, childhood adversities and familial aggregation are independently associated with the risk for mental disorders: Results from a large Swiss epidemiological study

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