Immunologische Veränderungen in einer Kohorte hochgradig adipöser Patienten mit komorbider Depression

Prevalence of Major Depressive Disorder (MDD) and obesity are ever-increasing and a major public health concern. The two conditions are strongly linked on an epidemiological level, with both disorders favouring development of the other by approximately 50 % and increasing overall morbidity in the general population. This comorbidity could be in part driven by converging biological pathways, including inflammatory processes. As chronic low-grade inflammation is present in both MDD and obesity, the study of potential immunogenic shifts in patients with obesity and comorbid depressive symptoms may shed light on putative shared mechanisms. Multicolour flow cytometry of peripheral blood mononuclear cells (PBMC) was used for characterization of immune phenotypes. Immune cell population frequencies of patients with severe obesity and comorbid depression (n = 10) were compared to obese (n = 17) and lean controls (n = 20) without psychiatric symptoms and correlated with clinical characteristics. The Patient Health Questionnaire (PHQ-9) was used for assessment of depressive symptoms and depression defined by a cut-off ≥ 10. Patients with obesity and comorbid depressive symptoms showed reduced amounts of cytotoxic natural killer cells, CD8+ effector memory T cells and dendritic cells in comparison to normal-weight controls. Frequencies of regulatory T cells were increased in patients with obesity and comorbid depression, compared to obese patients without depression. The amount of circulating CD4+ central memory T cells was elevated in obese patients with comorbid depression compared to lean controls. Furthermore, frequencies of cytotoxic natural killer cells, dendritic cells and CD4+ central memory T cells significantly correlated with PHQ scores in the total sample. A higher waist-hip-ratio (WHR) was associated with lower frequencies of dendritic cells. Together, these results are suggestive of a possible depression-specific immune dysregulation in patients with obesity.Depression und Adipositas sind hochprävalent in der Allgemeinbevölkerung und stellen eine starke Belastung für die Betroffen, Angehörigen und das allgemeine Gesundheitssystem dar. Epidemiologisch wurde eine stabile, bidirektionale Assoziation von Depression und Adipositas nachgewiesen, beide Erkrankungen erhöhen das Risiko für das Auftreten der jeweils anderen um circa 50 %. Dieser Zusammenhang könnte eventuell durch konvergierende pathophysiologische Vorgänge erklärt werden, da beide Krankheitsbilder mit chronischen, systemischen Entzündungsvorgängen assoziiert sind. Besonders Patienten mit atypischer Depressionssymptomatik, welche gesteigerten Appetit, Gewichtszunahme, Fatigue und Hypersomnie umfasst, zeigen signifikante Assoziationen mit erhöhten Entzündungsparametern im Blut. Die Immunphänotypisierung von Patienten mit hochgradiger Adipositas und komorbider Depression bietet eine Möglichkeit, diese Mechanismen genauer zu erforschen. Ziel dieser Arbeit war die Untersuchung der relativen Verteilung verschiedener Immunzellpopulationen im Blut adipöser Patienten mit depressiver Symptomatik (n = 10) im Vergleich zu einer adipösen (n = 17) und einer normalgewichtigen Kohorte (n = 20). Depression wurde durch eine Punktzahl von ≥ 10 des Patient Health Questionnaire (PHQ-9) Fragebogens definiert. Mittels Durchflusszytometrie wurden die zellulären Komponenten des angeborenen und des adaptiven Immunsystems analysiert, auf Gruppenunterschiede getestet und die Ergebnisse mit klinischen Parametern korreliert. Im Blut adipöser Patienten mit komorbider Depression fanden sich signifikant reduzierte Zahlen zytotoxischer natürlichen Killerzellen und dendritischer Zellen, sowie eine Zunahme von CD4+ zentralen T-Gedächtniszellen und regulatorischen T Zellen im Vergleich zur gesunden Kontrollgruppe. Die Menge zytotoxischer natürlicher Killerzellen und CD4+ zentraler T-Gedächtniszellen korrelierte signifikant mit dem Schweregrad der Depression, aber nicht mit Taille-Hüft-Verhältnissen. Die Reduktion dendritischer Zellen zeigte einen Zusammenhang mit Depression und Taille-Hüft-Verhältnissen. Diese Ergebnisse suggerieren potenziell depressionsspezifische Auswirkungen auf das Immunsystem bei Patienten mit hochgradiger Adipositas

Immunological substrates of depressive symptoms in patients with severe obesity: An exploratory study

In this pilot study, we explored the immune phenotype of patients with severe obesity and comorbid depressive symptoms compared to non-depressed patients with obesity and normal-weight controls. Immune cell subsets were analysed by flow cytometry and depressive symptoms assessed using the Patient Health Questionnaire (PHQ-9). Cell frequencies were correlated with depressive symptom scores and waist-to-hip ratio (WHR). Patients with obesity and comorbid depression showed significantly lower numbers of circulating cytotoxic natural killer cells, dendritic cells and CD8(+) effector memory T cells, compared to normal-weight controls. Regulatory T cells and CD4(+) central memory T cells were increased compared to non-depressed patients with obesity and compared to normal-weight controls, respectively. Frequencies of cytotoxic natural killer cells and CD4(+) central memory T cells significantly correlated with PHQ-9 scores, but not with WHR. Reduced numbers of dendritic cells were observed in both patient groups with obesity and correlated with PHQ-9 scores and WHR. These findings provide evidence for an altered immune composition in comorbid obesity and depression, supporting a pathobiological overlap between the two disorders

SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of multiple sclerosis patients

We aimed to evaluate SIGLEC1 (CD169) as a biomarker in multiple sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the presence of SIGLEC1(+) myeloid cells in demyelinating diseases. We performed flow cytometry-based measurements of SIGLEC1 expression on monocytes in 86 MS patients, 41 NMOSD patients and 31 healthy controls. Additionally, we histologically evaluated the presence of SIGLEC1(+) myeloid cells in acute and chronic MS brain lesions as well as other neurological diseases. We found elevated SIGLEC1 expression in 16/86 (18.6%) MS patients and 4/41 (9.8%) NMOSD patients. Almost all MS patients with high SIGLEC1 levels received exogenous interferon beta as an immunomodulatory treatment and only a small fraction of MS patients without interferon treatment had increased SIGLEC1 expression. In our cohort, SIGLEC1 expression on monocytes was-apart from those patients receiving interferon treatment-not significantly increased in patients with MS and NMOSD, nor were levels associated with more severe disease. SIGLEC1(+) myeloid cells were abundantly present in active MS lesions as well as in a range of acute infectious and malignant diseases of the central nervous system, but not chronic MS lesions. The presence of SIGLEC1(+) myeloid cells in brain lesions could be used to investigate the activity in an inflammatory CNS lesion