The Prevalence of Insomnia Symptoms and Its Association With Quality of Life Among Clinically Stable Older Patients With Psychiatric Disorders in China During the COVID-19 Outbreak

Aims: The negative impact of the COVID-19 outbreak on sleep quality of clinically stable psychiatric patients is unknown. This study examined the prevalence of insomnia symptoms and its association with quality of life (QOL) in clinically stable older psychiatric patients during the COVID-19 outbreak. Methods: This multicenter, cross-sectional study involved older patients attending maintenance-treatment at the outpatient departments of four major psychiatric hospitals in China. Patients’ basic socio-demographic and clinical characteristics were collected. Insomnia symptoms, depressive symptoms, and QOL were assessed with the Insomnia Severity Index (ISI), Patient Health Questionnaire (PHQ-9), and two items of the World Health Organization Quality of Life-brief version (WHOQOL-BREF), respectively. Binary logistic regression analysis was conducted to examine the independent associations of socio-demographic and clinical variables with insomnia symptoms, while the association between insomnia symptoms and QOL was examined with analysis of covariance. Results: A total of 941 patients were recruited. The prevalence of insomnia symptoms was 57.1% (95% CI: 53.9-60.2%). Analysis of covariance revealed that QOL was signicantly lower in patients with insomnia symptoms compared to those without them (P<0.01). Multivariate logistic regression analysis showed that insomnia symptoms were positively and independently associated with more severe depressive symptoms (P<0.01, OR=1.31, 95%CI: 1.26-1.37). Compared to patients with major depressive disorder, those with other psychiatric diagnoses had signicantly higher prevalence of insomnia symptoms (P=0.03, OR=1.47, 95%CI: 1.02-2.12). Conclusions: Insomnia symptoms were common among clinically stable older psychiatric patients during the COVID-19 outbreak. Considering their negative impact on QOL, regular assessment and treatment of insomnia symptoms need to be addressed in this population.


Introduction
The Coronavirus Disease 2019 (COVID- 19) was rst reported in Wuhan, China at the end of 2019, and subsequently was found in over 200 countries (1). Compared to the general population, psychiatric patients are arguably one of the most vulnerable subpopulations affected by the COVID-19 outbreak. Psychiatric patients have a higher risk of contagion due to their sedentary lifestyle, limited awareness of self-protection, and non-adherence to preventive public health measures (2). In addition, psychiatric patients, such as major depressive disorder (MDD), schizophrenia, and bipolar disorder, require long-term treatment. Due to the under-developed community mental health services in China, clinically stable patients need to regularly visit psychiatric outpatient departments located in urban hospitals for maintenance treatment (3,4). Travelling during the outbreak of any infectious disease inevitably increases the risk of infection. A signi cant proportion of patients have di culties to attend their psychiatric outpatient appointments due to quarantine and tra c restrictions for prevention and control of the COVID-19 outbreak (5). These public health preventive measures interrupt treatment leading to relapse and undesirable behaviors including self-harm and aggression.
Among those individuals affected by the COVID-19 outbreak, special attention should be given to older psychiatric patients. Compared with other age groups, older adults infected with COVID-19 have poor treatment outcomes and higher mortality rates (6,7). Older adults are scared about COVID-19, which could worsen their pre-existing mental health problems (8). Patients with MDD and anxiety disorder, in particular, are exceptionally vulnerable (9). Besides, most mental health services and education related to the COVID-19 (e.g., psycho-education and psychological counseling) are primarily delivered online (10). Many older psychiatric patients could not bene t from these online services due to their limited access to smartphones and broadband internet, and poor digital health literacy (8).
Insomnia symptoms are a major health problem worldwide (11). During the COVID-19 outbreak, insomnia symptoms were found to be very common in the general population (12) and subpopulations, such as frontline clinicians (13) and patients with COVID-19 (14). However, to the best of our knowledge, no study has focused on older adults, especially those with psychiatric disorders. Insomnia symptoms are associated with treatment with psychotropic medications (15), impaired cognitive function (16), increased risk of psychiatric disorders (17) and cardiovascular and metabolic diseases (18), poor quality of life (QOL) (19), increased consumption of health care services and economic burden (20). Insomnia symptoms are also risk factor for deterioration and relapse of psychiatric disorders (17). In order to reduce the negative impact of insomnia symptoms on health outcomes and daily life, it is important to understand their patterns and associated factors.
QOL is a widely used health outcome, which re ects individuals' general perception over their physical and mental health (21,22). The impact of insomnia symptoms on QOL in older psychiatric patients during the COVID-19 outbreak has not been explored. Thus, the aim of this study was to examine the prevalence of insomnia symptoms and its association with QOL in a sizeable cohort of clinically stable older psychiatric patients.

Participants
This was a cross-sectional study conducted between May 22 and June 23, 2020 in four major tertiary psychiatric hospitals located in the northern (Beijing), southern (Fujian province), eastern (Jiangsu province), and western parts (Gansu province) of China that represent a range of clinical settings. Older patients attending outpatient departments of the four psychiatric hospitals for maintenance treatment were consecutively invited to participate in this study. To be eligible, participants should be: 1) aged 50 years and above; 2) had a principal diagnosis of any types of psychiatric disorders diagnosed according to the International Statistical Classi cation of Diseases and Related Health Problems, 10th Revision (ICD-10) and con rmed by their treating psychiatrists; 3) were clinically stable judged by their treating psychiatrists. Following previous studies (23,24), those with changes in doses of psychotropic medications of less than 50% in the past three months were considered "clinically stable patients". This criterion has been used in clinical practice in the participating hospitals; and 4) they were able to give written informed consent. The study protocol was approved by the Ethical Committees of the respective hospitals.

Measurements
Patients' basic socio-demographic and clinical data were collected including age, gender, education, marital status, current severe medical conditions affecting the cardiovascular, respiratory, digestive, hematological, endocrine, urinary, connective tissue, and nervous systems (25). One additional COVID-19 related question was also asked, namely, whether they were concerned about the COVID-19 outbreak during the past months.
The severity of depressive symptoms was evaluated with the Chinese version of the 9-item Patient Health Questionnaire (PHQ-9) (26,27). Each item of the PHQ-9 is scored from 0 (not at all) to 3 (nearly every day). This psychometrically validated scale is widely used in Chinese populations (28). The total score of PHQ-9 that ranged between 0 and 27 was calculated by adding up all its item scores. The PHQ-9 total score of < 5, ≥5, and ≥ 10 indicated "no depressive symptoms", "mild depressive symptoms", and "moderate to severe depressive symptoms", respectively (29). Severity of insomnia symptoms was assessed with the 7-item Insomnia Severity Index (ISI), a Likert scale with each item ranging from 0 to 4 (30). The ISI has satisfactory psychometric properties in China (31). The ISI total score ranges from 0 to 28, with higher total scores representing more severe insomnia symptoms. The cut-off value of ≥ 8 was considered as "having insomnia symptoms" (32). The total score of the two items on the overall QOL of the World Health Organization Quality of Life-brief version (WHOQOL-BREF) (33)(34)(35) were used to assess patients' QOL, The QOL score ranged between 0 and 10, with a higher score representing higher QOL.

Data analysis
All data analyses were performed with the Statistic Package for Social Science (SPSS), Version 24.0. The normality of continuous variables was examined with the P-P Plot. Social-demographic (e.g., age, gender, marital status, education years) and clinical characteristics (e.g., severe medical diseases, concerns about the COVID-19 outbreak, principal psychiatric diagnoses, and severity of depressive symptoms) were compared between patients with and without insomnia symptoms. Normally distributed continuous variables were compared using the two independent samples ttests, while those that did not follow normal distribution were compared using Mann-Whitney U tests. Categorical variables were compared using χ 2 tests. Independent associations of socio-demographic and clinical variables with insomnia symptoms were examined applying binary logistic regression analysis with the "enter" method. All sociodemographic and clinical variables were entered as independent variables, and the presence of insomnia symptoms was the dependent variable. The QOL between patients with and without insomnia symptoms was compared using analysis of covariance (ANCOVA) after controlling for variables with signi cant group differences in univariate analyses. The level of signi cance was set at P < 0.05 (two-tailed).
Univariate analyses revealed that patients with insomnia symptoms were younger (P = 0.02) and had shorter education (P < 0.01) and higher PHQ-9 total scores (P < 0.01). In addition, the prevalence of insomnia symptoms was signi cantly different across principal psychiatric diagnoses (P < 0.01). There was no signi cant difference in the prevalence of insomnia symptoms between male and female patients (58.0% (95%CI: 52.4%-63.6%) vs. 56.6% (95%CI: 52.7%-60.4%), χ 2 = 0.17, P = 0.68). Binary logistic regression analysis found that the presence of insomnia symptoms was positively and independently associated with more severe depressive symptoms (P < 0.01, OR = 1.31, 95%CI: 1.26-1.37). Compared to MDD patients, those with other psychiatric diagnoses were more likely to have insomnia symptoms (P = 0.03, OR = 1.47, 95%CI: 1.02-2.12) ( Table 1). ANCOVA revealed that patients with insomnia symptoms had a signi cantly lower overall QOL compared to those without them (F (1, 941) = 19.37, P < 0.01). The reasons for frequent insomnia symptoms in older psychiatric patients are complex. Psychiatric disorders and insomnia symptoms often co-exist, because sleep rhythm often changes in many psychiatric disorders as well as with the use of psychotropic medications (43,44). Besides, age is a risk factor for insomnia (45). In older adults, sleep and circadian rhythm changes occur along with the physiologic changes, which presents as gradually decreased sleep e ciency and total sleep time. Unrealistic expectations about sleep duration and quality could elevate the risk of insomnia (46). Moreover, increased prevalence of medical problems (e.g., nocturia and physical disability) (47) and treatments (e.g., beta-blockers, glucocorticoids, and nonsteroidal anti-in ammatory drugs) (46) could contribute to the occurrence of insomnia. Aging women including those with psychiatric disorders are more likely to suffer from insomnia symptoms (44,50) than men. However, no gender difference was found in the current study. This discrepancy between the current and previous studies may be due to the increased prevalence of insomnia symptoms in both genders during the COVID-19 outbreak, which may offset the gender difference found earlier.
The COVID-19 outbreak could further trigger insomnia symptoms and related problems in older psychiatric patients for a number of reasons. First, more severe consequences and higher mortality rates in older adults with COVID-19 could spread fear and mental distress. Second, mass quarantine measures lead to loneliness, fatigue, and daytime sleepiness (48,49) and thus affect sleep and circadian rhythm. Third, older psychiatric patients have frequent comorbid chronic medical conditions and require long-term medication treatment. Di culties in attending hospitals during the COVID-19 outbreak further aggravate patients' distress about discontinuation of treatment contributing to the development of insomnia symptoms.
As expected, patients with insomnia symptoms reported more severe depressive symptoms in this study. The association between insomnia symptoms and depressive disorders is bidirectional. On one hand, insomnia symptoms are a risk factor of depressive disorders (50,51); on the other hand, depressive disorders increase the likelihood of insomnia symptoms (52). In meta-analyses insomnia symptoms signi cantly predicted the onset of depressive episodes (51,53,54) with an overall odds ratio (OR) of up to 2.83 (95%CI: 1.55-5.17) (51). This could be partly explained by the impairment of emotional processing caused by insomnia, which could lead to depressive symptoms (55). Furthermore, the association between insomnia and depressive symptoms might be related to common pathomechanisms, e.g., similar alterations of arousal states (56)(57)(58) and level of in ammatory markers (59). In this study, patients with other psychiatric diagnoses, mainly schizophrenia and organic mental disorders, were more likely to suffer from insomnia symptoms than those with MDD. The diagnostic heterogeneity makes it di cult to interpret the reasons for the unexpectedly signi cant group difference. Head-to-head comparative studies between different psychiatric diagnoses are warranted to replicate or refute this nding.
Patients with insomnia symptoms had a lower overall QOL than those without, which is consistent with previous ndings (60,61). According to the distress/protection QOL model (62), QOL is determined by the interaction between protective (e.g., good social support and economic status) and distressing factors (e.g., poor health). Insomnia symptoms are associated with impaired daytime functioning (63), de cits of attention, working memory, and executive function (64), poor physical health (18), and psychiatric symptoms (65), all of which could lower QOL.
The strengths of this study include the multicenter study-design and the large sample size, which increase the overall representativeness of the study sample. However, several methodological limitations need to be addressed. First, the study only included clinically stable patients, which limits the generalizability of the ndings to patients in different illness stage. Second, due to logistical reasons during the COVID-19 outbreak, clinical stability was judged by the treating psychiatrists, rather assessed by the aid of standardized rating instruments. Third, the causal relationships between demographic and clinical characteristics and insomnia symptoms could not be examined due to the crosssectional study design. Fourth, factors potentially associated with of insomnia symptoms (e.g., social support and economic status) were not examined in this study.

Conclusion
In conclusion, insomnia symptoms were common in clinically stable, older psychiatric patients during the COVID-19 outbreak. Given the negative impact of insomnia symptoms on QOL and daily functioning, regular assessment of sleep duration and quality should be included in the routine clinical care of this vulnerable population. and a variety of treatment modalities, such as cognitive-behavioral therapy (66), repetitive transcranial magnetic stimulation (67) Committee of participating hospitals for the release of the data.

Con ict of Interest
The authors have no con icts of interest to declare.

Funding
The study was supported by the National Science and Technology Major Project for investigational new drug