Cerebral Structural Abnormalities and Their Associations With Peripheral Cytokine Levels in a Group of Untreated Patients With Nasopharyngeal Carcinoma.

Xinmei Luo,Guannan Zhu,Xin Wu,Siyi Li,Qiyong Gong,Yu Jiang,Wenjing Zhang,Jie Liu,Su Lui,Yan Wang

doi:10.3389/fonc.2021.740033

Abstract

The current study is to characterize the alterations of peripheral cytokines and anatomical brain changes, and their relationships in untreated nasopharyngeal carcinoma (NPC) patients with depressive symptoms. Twenty-nine newly diagnosed NPC patients without any treatment and 46 matched healthy comparisons were recruited, scanned with high-resolution T1 images and assessed psychologically using Hamilton Rating Scale for Depression (HAMD). Serum levels of interleukin-1 beta (IL-1β), IL-2, IL-6, IL-8, IL-10, interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-β) were measured by quantitative chemiluminescence assay. Inter-group comparisons of anatomical brain measures were performed, and regions with significant inter-group differences were correlated to HAMD scores and cytokines in NPC patients. A subgroup analysis especially within NPC patients with depression was conducted to precisely characterize the associations among serum cytokines, brain changes and depressive symptoms. Relative to healthy subjects, NPC patients showed significantly decreased cortical thickness in the left parahippocampal gyrus, increased surface area in the right superior parietal lobule and precentral gyrus, and increased gray matter volume in the right postcentral gyrus, bilateral caudate nucleus and right thalamus, as well as significantly elevated IL-1β, IL-2 and IL-10. The elevated IL-2 and IL-10 were negatively correlated with surface area in right superior parietal lobule, whilst IL-1β level was positively correlated to HAMD scores. In patients with depression, specific brain changes and evaluated IL-1β were identified, and the IL-1β interacted with right precentral gyrus to significantly affect the depressive symptoms. Our findings provide novel evidence indicating potential effects of inflammation on brain structure and behavior in NPC patients.

Highlights

Nasopharyngeal carcinoma (NPC) is a malignant cancer which originates from the nasopharynx epithelium
Our findings revealed that patients had elevated levels of pro-inflammatory and anti-inflammatory cytokines after they were diagnosed with nasopharyngeal carcinoma (NPC), and abnormal cortical and subcortical gray matter changes mainly involving limbic-striatal-thalamocortical circuits
In subgroup analysis among patients with clinically-defined depression, the severity of depressive symptoms was significantly correlated to the levels of elevated cytokines and the subtle anatomical abnormalities simultaneously, and a multivariate regression analysis indicated that serum cytokines and brain structural changes might interact in some way to affect the depressive symptoms

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is a malignant cancer which originates from the nasopharynx epithelium. Recent research reported that early-stage NPC patients who received intensive modulated radiotherapy (IMRT) could achieve excellent 5-year survival rate>90% [3]. To improve the well-being and life quality of NPC survivors in the long-term recovery in cancer caring, growing attention is focused on the psychological status of patients, which is a key factor that may affect life quality. Being depressive is one of the most common comorbid psychiatric symptoms in cancer patients, among which the incidence is approximately three to five times greater than that in the general population [4, 5]. Previous studies found that depressive symptoms were related to decreased survival rate among patients with renal carcinoma [9] and gastric cancer [10]. It is essential to identify psychopathological alterations and elucidate the underlying mechanisms in patients with NPC, which may extend our knowledge in such aspect and help develop effective psychological interventions

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Results

Conclusion