Prevalence and Risk Factors for Anxiety and Depression in Chinese Unruptured Intracranial Aneurysms Patients Treated by Endovascular Intervention

Background : Studies on anxiety and depression after treatment via endovascular intervention for unruptured intracranial aneurysm (UIA) patients are rare and controversial. We aimed to explore the prevalence of anxiety and depression among Chinese UIA patients treated by endovascular intervention and to identify which factors contribute to the development of these symptoms. Methods : We performed a cross-sectional study of anxiety and depression in patients who underwent endovascular treatment for UIAs using the Hospital Anxiety and Depression Scale (HADS). The demographic, clinical and radiological data for all patients were retrospectively collected from the aneurysm database and medical records. Moreover, we utilized a large sample data and logistic regression analysis to investigate the risk factors for the anxiety and depression for these patients. Results : Two hundred patients returned a completed questionnaire in this study. Of the 200 patients, 34 (17.0%) suffered from anxiety, and 31 (15.5%) suffered from depression after being discharged for 30.67±8.6 months. The multivariate analysis results indicated that treatment cost exceeding the annual household income was statistically significantly associated with anxiety (OR= 2.42, p= 0.03). Patients with shorter sleep time was statistically significantly associated with anxiety (OR= 1.51, p= 0.02) and depression (OR= 1.62, p= 0.007). Conclusion : The prevalence of anxiety and depression in the UIA patients treated by endovascular intervention was 17.0% and 15.5% respectively. Treatment cost exceeding the annual household income was statistically significantly associated with anxiety. Patients with shorter sleep time was statistically significantly associated with anxiety and depression. Our findings provide valuable evidence for the clinical and psychological management of these patients. depression. The multivariate analysis results indicated that a treatment cost exceeding the annual household income was statistically significantly associated with anxiety (OR= 2.42, p= 0.03). Patients with shorter sleep time was statistically significantly associated with anxiety (OR= 1.51, p= 0.02) and depression (OR= 1.62, p= 0.007).


Conclusion:
The prevalence of anxiety and depression in the UIA patients treated by endovascular intervention was 17.0% and 15.5% respectively. Treatment cost exceeding the annual household income was statistically significantly associated with anxiety. Patients with shorter sleep time was statistically significantly associated with anxiety and depression. Our findings provide valuable evidence for the clinical and psychological management of these patients.

Background
Unruptured intracranial aneurysm (UIA) is a common disease with a prevalence approximately 7% in Chinese adults aged 35 to 75 years [1]. In addition, advances in and the increasing availability of highresolution imaging technologies have led to a higher rate of incidentally detected UIAs [1,2]. Once aneurysm ruptured, its typically cause subarachnoid hemorrhage (SAH) and sequelae, resulting in significant morbidity and mortality [3,4]. Anxiety and depression are common in aneurysm disease and both are important determinants of quality of life in patients [5,6]. The threat of rupture becomes most obvious cause on the preoperative anxiety and depression in patients with UIA [5,7,8].
However, studies on anxiety and depression after treatment via endovascular intervention for UIA patients are rare and controversial [5,9,10]. We aimed to explore the prevalence of anxiety and depression among Chinese UIA patients treated by endovascular intervention and to identify which factors contribute to the development of these symptoms.

Study Design and participants
A cross-sectional study was performed. We retrospectively reviewed the hospital database for all

Assessment Instrument
The Hospital Anxiety and Depression Scale (HADS) is a promising tool for identifying and quantifying depression and anxiety in physically ill patients [11,12]. Therefore, the HADS was used to evaluate anxiety and depression in UIA patients. The HADS is composed of seven items related to anxiety symptoms and seven related to the depression symptoms, with 14 items in total [12,13]. All of the 14 items are answered by patients using a four-point Likert scale. These scores were calculated based on the sum of the questions used to evaluate the anxiety and depression domains. In this study, scores ≥8 were considered positive for both the anxiety and depression domains. The content of the questionnaire is mainly composed of the HADS. In addition, it includes important items such as average daily sleep time, educational level, ratio of treatment costs and annual household income and physical exercise level within the last month, etc. A combined online questionare will be sent to those patients willing to respond.

Data Collection
We conducted a telephone follow-up of the 300 patients who met the inclusion and exclusion criteria, 270 of which were successfully followed up, for a follow-up rate of 90.0%. We sent the combined online questionnaire to those 228 patients who are willing to respond. Eventually, 200 patients

Statistical Methods
Categorical variables were compared between the 2 groups using the Pearson χ2 test, continuity correction, and Fisher's exact 2-tailed test. Continuous variables were compared between groups using Student's t test. Interval data are reported as the mean±standard deviation, and nominal data are expressed as absolute numbers and valid percentages. Data were tested for normal distribution by making P-P and Q-Q plots. A logistic regression analysis was used to identify the association of the described variables with the anxiety and depression of patients. Candidate variables with P values less than 0.20 in univariate analyses were considered in the logistic regression analysis. Statistical significance was defined as p < 0.05. Statistical analysis was performed using SPSS Statistics version 24.0 software (IBM Corp., Armonk, New York, USA).

Demographic, Clinical and Radiological Characteristics
Two hundred patients returned a completed questionnaires in this study. The information regarding all patients were shown in Table 1 and Table 2. Of the 200 patients, 117 were female and 83 were male; their mean age was 55.2±9.48 years (range 23-74 years). They had a total of 245 aneurysms (161 patients had one aneurysm, 34 had two, 4 had three, and one had four), and the majority of aneurysms occurred in the anterior circulation (81.5%) ( Table 2). All patients included in the study had a good preoperative mRS score (mRS 0-2), and 160 (80%) patients undwent stenting or flow diversion (FD) rather than 40 patients (20%) underwent simple coiling. Based on the results of neurological or radiological examination, treatment-related complications occurred in 8 patients due to ischemia. No technical failures were observed in our cohort; one patient with severe postoperative ischemic complications had an mRS of 5 at discharge, and the other patients exhibited good postoperative neurological outcomes (mRS=0-2). All patients presented a good neurological outcome (mRS=0-2) at follow-up. In our study, radiological follow-up was available for 167 patients, with a mean radiological follow-up period of 30.76±8.43 months; 7 patients experienced recurrence and had not received further treatment at follow-up. A complete summary of the demographic, clinical and radiological characteristics is shown in Table 1 and Table 2.

Prevalence and Risk Factors of Anxiety and Depression
As shown in Table 2, of the 200 UIA patients, 34 (17.0%) suffered from anxiety, and 31 (15.5%) suffered from depression after being discharged for 30.67±8.6 months. Table 3

Discussion
A pattern of significant psychological impairment was found to be associated with harboring an identified but untreated UIA [5,14,15]. For example, Towgood K et al [14] reported that 36% of untreated UIA patients presented with a pattern of significant psychosocial impairment 6 months post-treatment. Su SH et al [5] reported that 84% patients were found to be have mild to severe anxiety at 1 year after discovering the UIA. In additon, even 5 years after detection of the UIA, 39% patients were mildly to severely depressed and 32% patients had mild to severe anxiety. When an aneurysm was detected, many patients presented with complex psychological changes due to the confusion of disease-related knowledge and sudden changes in the physical role and physical function. As a result, the anxiety or depression emerge.
Studies reported that patients with a longer post-treatment time typically showed a lower anxiety and depression level than those of post-treatment time shorter [5,9]. This phenomenon indicated that patients may still feel anxiety or depression for a short term after treatments, for fearing of bleeding or recurrence of the aneurysms, then gets better over time. Nevertheless, there are still a considerable number of UIA patients who underwent microsurgery or endovascular treatment suffered from anxiety or depression. For example, Li Y et al [9] reported that 18.2% (n=8) of the clipping group had anxiety and 27.3% (n=12) had depression, 17.6% (n=13) of the coiling group had anxiety and 24.3% (n=18) han depression. Solheim et al [10] reported that 26.9% (n=7) of the open surgery group suffered from anxiety and 19.2% (n=5) suffered from depression, 31.6% (n=6) of the endovascular coiling group suffered from anxiety and 10.5% (n=2) suffered from depression. Unfortunately, the results of these research are limited by many factors such as little sample size, different assessment instrument and the cooperation of patients. Therefore, such issues need further study.
Nowadays, endovascular treatment of UIAs was considered a first-line strategy because of its superiority to microsurgical clipping in terms of both morbidity and mortality [16,17]. However, as we mentioned above, studies on anxiety and depression of UIA patients treated by endovascular intervention are rare and controversial. In addition, the risk factors of anxiety and depression for these patients need to be identified. This large cross-sectional study that took place over an average period of 30.67±8.6 months evaluated the anxiety and depression outcomes in UIA patients who underwent endovascular treatment. In our study, we found that 34 (17.0%) patients suffered from anxiety, and 31 (15.5%) suffered from depression, which means that many patients are still in a state of psychological impairment after an average recovery period of 30.67±8.6 months.The multivariate analysis results indicated that treatment cost exceeding the annual household income was statistically significantly associated with anxiety. Obviously, excessive financial burden tends to put patients in a state of anxiety. Therefore, corresponding policies and measures should be implemented to relieve the financial burden on these patients. Patients with shorter sleep time was statistically significantly associated with anxiety and depression. For these patients, we recommend that they should ensure adequate sleep and a healthy lifestyle The main limitation of this study was its retrospective design. The anxiety and depression of patients has not been assessed before treatment, so it is not possible to compare the anxiety and depression before and after treatment. It is necessary to conduct a prospective and multicenter study in the future.

Conclusion
In summary, the prevalence of anxiety and depression in the UIA patients treated by endovascular intervention was 17.0% and 15.5% respectively. A treatment cost exceeding the annual household income was statistically significantly associated with anxiety. Patients with shorter sleep time was statistically significantly associated with anxiety and depression. Our findings provide valuable evidence for the clinical and psychological management of these patients.

Declarations
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable requests.

Authors' contributions
ZX and ZH designed questionnaires and study protocol, analysis of data, and write up of article. MY, YJ, LG, HC and HP analyzed data and contributed in write-up of the different sections of the manuscript. XS and WJ contributed in data analysis. All authors read and approved the final manuscript.

Ethics approval and consent to participate
The ethic approval for this study was issued by the Institutional Review Board of the Xuanwu Hospital of Capital Medical University. The nature and purpose of this study was illustrated and full confidentiality guaranteed. A written informed consent was obtained from all participants. They were permitted to withdraw from the study at any time without negative consequences

Consent for publication
Not applicable. 1 ICVD represents "Ischemic cerebrovascular disease", 2 Ratio represents "Ratio of treatment cost and annual household income"  1 ICVD represents "Ischemic cerebrovascular disease", 2 Ratio represents "Ratio of treatment cost to annual household income" 1 ICVD represents "Ischemic cerebrovascular disease", 2 Ratio represents "Ratio of treatment cost to annual household income"