Serum Inflammatory Markers and Their Associations with the Integrity of the Cingulum Bundle in Schizophrenia, from Prodromal Stages to Chronic Psychosis

Abstract

Peripheral cytokines may affect the brain through chronic activation of microglia and, as a result, can potentially lead to decreased integrity of white matter of cingulum bundle (CB). Therefore, the aim of the study was to analyze the relationships between peripheral inflammatory markers and the integrity of the CB in various states: from healthy controls, through prodromal states and first-episode psychosis, to long-term schizophrenia. The integrity of the CB was measured using diffusion tensor imaging. We analyzed six parameters: CRP, IL-6, IL-8, IL-10, TNF-α, and IFN-γ. We found that levels of IL-6 and IFN-γ differed significantly between groups. Initial analysis showed some correlations between the inflammatory markers and CB integrity, in particular a correlation with IL-6 that was present in several groups. However, none of the analyzed parameters were associated with the integrity of the CB after correction for multiple comparisons. Conclusions: Our results supported our hypothesis that there are increased levels of inflammatory markers in psychotic disorders, but did not allow to confirm our hypothesis that there is a link between increased peripheral inflammatory markers and decreased integrity of the CB. However, we found some interesting trend levels that need to be verified in larger studies.

Serum Inflammatory Markers and Integrity of the Superior Longitudinal Fasciculus and the Inferior Longitudinal Fasciculus in Schizophrenia, from Prodromal Stages to Chronic Psychosis—A Cross-Sectional Study

“…Our previous study showed that the levels of some IM parameters ([ 15 ], supplementary table) and some DTI parameters of SLF and ILF (data not shown) are correlated with age and BMI. We also found some associations between IM and smoking, disease duration, exacerbations, types, and doses (chlorpromazine equivalent) of antipsychotics ([ 15 ], supplementary table).…”

“…Our previous study showed that the levels of some IM parameters ([ 15 ], supplementary table) and some DTI parameters of SLF and ILF (data not shown) are correlated with age and BMI. We also found some associations between IM and smoking, disease duration, exacerbations, types, and doses (chlorpromazine equivalent) of antipsychotics ([ 15 ], supplementary table). Therefore, for each analyzed IM and DTI parameter, an additional multiple linear regression analysis was performed in two variants: (a) taking into account age and BMI (in every study group); and (b) taking into account age, BMI, smoking, disease duration, exacerbations, types, and doses of antipsychotics (in UHR (without smoking), FEP, and SCH).…”

“…It should be emphasized, however, that the profile of disrupted cytokines varies between studies, and these differences are not so greatr that it is possible to use them to determine the presence of the disorder in a given individual. Our previous studies have also found associations between peripheral inflammatory markers, especially interleukin 6 (IL-6) and interferon gamma (IFN-γ), and psychotic disorders [ 14 , 15 ]. Other evidence implicating inflammation in the etiology of schizophrenia includes, inter alia: (1) results of postmortem studies indicating activated microglia and elevated expression of inflammatory markers in the brains of schizophrenia patients; (2) genetic associations between schizophrenia and some polymorphisms in regions of DNA coding for immune-related genes; (3) increased risk of schizophrenia in patients with autoinflammatory diseases; (4) the observed influence of non-steroidal anti-inflammatory drugs on reducing the severity of psychotic symptoms; (5) associations between cytokine levels and disease severity and treatment response; and (6) the influence of antipsychotic treatments on levels of certain cytokines [ 7 , 10 , 16 , 17 , 18 , 19 , 20 ].…”

“…Our previous study analyzing the corpus callosum region found correlations between reduced integrity and increased levels of IL-6 in healthy controls and IFN-γ in chronic schizophrenia [ 14 ]. We have also found some correlations between increased IL-6 and reduced integrity of the cingulum bundle, but they did not remain significant after correction for multiple comparisons [ 15 ]. Focusing on the SLF and ILF, associations between reduced integrity of these brain regions and increased peripheral inflammatory markers (IM) have been found in the general population [ 42 ] and in patients with bipolar disorder [ 39 ].…”

Oligodendrocyte Progenitors in Schizophrenia: The Role in Pathogenesis and Potential Treatment Target

“…Однако результаты исследований достаточно противоречивы. Не удалось, например, выявить связи между повышением концентраций таких цитокинов, как CRP, IL-6, IL-8, IL-10, TNF-α и IFN-γ, в плазме крови пациентов и структурой белого вещества поясного пучка в их мозге [92]. Этот тракт, связывающий лобную, теменную и височную кору, является по данным ДТТ одной из областей с наиболее выраженными нарушениями структуры миелина как у больных шизофренией, так и у лиц с высоким риском психоза [93].…”