Glioma is the most common primary central nervous system tumor, with high aggressiveness and excessive mortality (1, 2). At present, the main treatment for glioma is surgical resection, and other treatments include radiation therapy, chemotherapy, and emerging immunotherapy (3–5). Even with these treatments, the prognosis of glioma patients is still unfavorable (6, 7). According to previous studies, the median survival time for patients with low-grade glioma (LGG) (World Health Organization (WHO) I-II grade) is 5.6–13.3 years, while for patients with high-grade glioma (HGG) (WHO III-IV grade), it is only 12.2–15.4 months (7–10). Poor survival of glioma patients may lead to a heavy mental burden (11, 12). Apart from that, glioma patients face some other problems: for example, areas of brain impairment could cause a high risk of mental disorders (13, 14). Moreover, treatments of glioma (such as surgery, chemotherapy, etc.) may impose negative influences on their mental health, too (15, 16). Therefore, the mental health of glioma patients is a major issue currently.

In order to better manage the mental health of glioma patients, many studies have recognized potential factors that are associated with anxiety and depression in these patients (11, 12, 17). One previous study indicates blood inflammatory cytokines could be predictors of depression in glioma patients (17). Moreover, another study suggests that decreased IL-2 levels and elevated IFN-γ levels were positively associated with anxiety and depression in glioma patients, respectively (11). Significantly, a recent study has indicated that female gender, single, divorced, or widowed marital status, increased WHO classification, shorter education duration, chronic kidney disease (CKD), and hyperlipidemia are risk factors for anxiety and depression in glioma patients (12). However, this study has a small sample size (N = 190) and does not evaluate the longitudinal variation of anxiety and depression in glioma patients; at the same time, some important factors affecting anxiety and depression are not included in its study (such as Karnofsky performance status (KPS) score, postoperative complications, etc.) and the prognostic role of anxiety and depression is not adjusted by multivariate regression analysis in glioma patients. Our study hypothesized that anxiety and depression were at high prevalence in postoperative glioma patients and had important impacts on their prognosis. In addition, there might be some risk factors obviously related to anxiety and depression in postoperative glioma patients, such as gender and postoperative complications, etc. These risk factors might be beneficial to the management of postoperative glioma patients. In addition, the Glioma Outcomes (GO) Project provides high-standard care for postoperative glioma patients (18).

Therefore, the present study included 270 glioma patients who received surgical resection and collected sufficient characteristics and treatment information, aiming to comprehensively evaluate the risk factors and prognostic value of anxiety and depression, as well as to assess the change in anxiety and depression longitudinally in those patients.

Anxiety and depression are common clinical symptoms in glioma patients who received surgical resection, which should be paid high attention since they have many negative influences, for example, reducing the quality of life, worsening the performance status of glioma patients, etc (21, 22).. However, only a small number of studies have reported the risk factors of anxiety and depression in glioma patients. For instance, one study finds that elevated IFN-γ levels are positively related to depression in glioma patients (11). Another literature states that anxiety is more common in younger glioma patients than in older glioma patients (23). Additionally, a recent article illustrates several factors for anxiety and depression in glioma patients, including gender, marital status, WHO classification, hyperlipidemia, education duration, and CKD (12). However, this previous study has some shortages as described in this introduction section. In our study, it was revealed that gender, marital status, KPS score, WHO classification, tumor location, and postoperative complications were independent risk factors for anxiety in glioma patients. Furthermore, marital status, KPS score, WHO classification, and postoperative complications were independent risk factors for depression in glioma patients. These findings could be explained by that: (a) Estrogen imbalance could induce the females-specific risk of mental disorders (24), so females might be more prone to anxiety than males in glioma patients. However, this is a conjecture and needs to be verified in further study. (b) Single/divorced/widowed glioma patients might feel lonelier and more emotionally compared with those with married status (25, 26). Therefore, glioma patients with single/divorced/widowed marital status might be at a high risk of anxiety and depression. (c) Glioma patients with KPS score ≤ 70 had poor performance status and were unable to take care of themselves, both events could cause anxiety and depression. (d) The recurrence risk is higher in HGG patients than in LGG patients (27), and thus they might feel more fear of recurrence than LGG patients (which was positively correlated with anxiety and depression (28)), so WHO classification was a risk factor for anxiety and depression in glioma patients. (e) The parietal was an important region for anxious arousal, whose impairment of function might cause mental disorders in glioma patients (29, 30), and thus parietal tumor was a risk factor for anxiety in glioma patients. (f) The postoperative complications (including epilepsy and cognitive impairment, etc.) might directly cause anxiety and depression in glioma patients (31–33). Therefore, postoperative complications appear to be risk factors for anxiety and depression in glioma patients.

Anxiety and depression could have serious negative consequences on the prognosis of cancer patients. Evidence shows that anxiety and depression are positively associated with mortality in patients with cancers, including glioma (12, 34, 35).. For example, one study suggests that glioma patients with depression have worse OS than those without depression (36). Another research indicates a worse OS in glioma patients with depression, especially in HGG glioma patients (35). In addition, a recent study has also shown that anxiety and depression are related to worse survival in glioma patients (12). The findings of these previous studies are in part consistent with the results of our study, which revealed that anxiety or depression at baseline was associated with poorer OS in glioma patients. The explanations for these results are as follows: (a) Depression might affect the endocrine system of the patients, thereby indirectly accelerating the deterioration of the condition, which caused a worse OS (37). (b) Anxiety and depression might make patients reluctant to cooperate with post-operative recovery treatment and even lead to suicide (38).

Clearly, the longitudinal progress of mental disorders in cancer patients is also a notable issue. For instance, a previous study reports the prevalence of depression has been continuously high during a 1-year period in cancer patients (39). It is partly consistent with our results. Our study performed longitudinal assessments and found that anxiety and depression remained high during a 3-year period in glioma patients, while they did not rise significantly. This might be because: Glioma patients with anxiety and depression were at a high risk of death (12, 35, 36), implying that patients with high anxiety and depression died possibly at the follow-up period over time. In our study, the deaths of these patients might lead to the underestimation of anxiety and depression during the follow-up period in glioma patients.

In addition, several study designs should be pointed out as well in the current study: (1) Our study chose HADS because of its simplicity, convenience, and heterogeneity. Our study needed to evaluate anxiety and depression in glioma patients at multiple time points, so it was easier to implement the study design by using simple scales to evaluate anxiety and depression in glioma patients, such as HADS. (2) In fact, some factors might be potentially related. For example, we thought that the WHO grade and A/D were likely to interfere with each other. However, their interference was not direct. Therefore, if the WHO grade had been excluded, the results of our study might be misjudged. In order to reflect the prognosis role of anxiety and depression in postoperative glioma patients in an objective manner as much as possible, we considered including WHO grade as a variable.

This study, however, still presents some limitations: (a) It is a single-center study, which leads to selection bias. (b) It only includes adult patients with glioma, however, the situation of children with glioma is unclear, and further research should be conducted to evaluate risk factors and prognostic potency of anxiety and depression in children with glioma. (c) It only assesses anxiety and depression in glioma patients by HADS, and future studies should use multiple assessment scales to further investigate their anxiety and depression.

In conclusion, our study discovers multiple independent risk factors for anxiety and depression in glioma patients who receive surgical resection. Moreover, anxiety and depression have a high prevalence and are connected with poorer survival in those patients. These findings may improve the management of mental health and prognosis of glioma patients.