Prevalence of Psychological Symptoms and Its Impact on the Quality of Life of Sickle Cell Disease Patients in Makkah, Saudi Arabia

Background Patients with sickle cell disease (SCD), which is an inherited autosomal recessive disorder, experience a broad range of symptoms and complications such as acute chest syndrome, infections, strokes, seizures, etc. The main objective of this study was to assess the prevalence of depressive symptoms among SCD patients and determine the impact of sociodemographic factors and genotypes on depressive symptoms in Makkah City, Saudi Arabia. Methods A cross-sectional study was conducted among SCD patients aged 18 and above in the outpatient clinics in Makkah’s four main hospitals (Al Noor Specialist Hospital, King Faisal Hospital, King Abdulaziz Hospital, and Hera General Hospital) from December 2021 to April 2022. A total of 222 patients used a self-administrative questionnaire with an Arabic version of Patient Health Questionnaire-9 (PHQ-9) to assess for depression. Data were analyzed using IBM SPSS Statistics, version 26, and the chi-square (χ2) test was applied to examine the relationship between the variables. A p-value of less than 0.05 was regarded as statistically significant. Results The overall prevalence of depression was 85.6%, and multivariate analysis showed that age between 18 and 30 had a significant statistical value for the prevalence of depression (p-value = 0.029). Univariate analysis also indicated that low levels of education (p-value = 0.037) and low monthly income (p-value = 0.017) had a significant association with depression prevalence. Conclusion There is a high prevalence of depression among SCD patients in the Makkah region. Therefore, we recommend establishing a regular regional screening program and psychiatry referral for this patient population.


Introduction
Sickle cell disease (SCD) is an inherited autosomal recessive disorder caused by a mutation in the β-globin gene that tends to polymerize the red blood cells into sickle-shaped cells leading to chronic hemolytic anemia [1]. SS hemoglobinopathy (HbSS) is the most frequent and severe form of SCD while SC hemoglobinopathy (HbSC) is usually milder [2]. Patients with SCD experience a broad range of symptoms and complications such as acute chest syndrome, infections, strokes, seizures, priapism, pulmonary hypertension and embolism, deep venous thromboses and retinopathy; many other serious complications can also affect patients' quality of life, thus increasing morbidity and mortality [3,4].
In Saudi Arabia, numerous studies have been conducted to trace the natural history of SCD. There is a relatively common genetic disorder in this region of the world that is more prevalent in the eastern and southwestern regions [5]. The carrier status for SCD in Saudi Arabia ranges from 2% to 27%, and up to 1.4% have SCD [6]. In this context, the Saudi Ministry of Health introduced the National Premarital Screening Program (NPSP) as a means of prevention of inherited hemoglobinopathies, for all Saudi couples, to reduce the overall disease burden resulting from having affected children [5]. 1 2 2 2 2 2 3 4 Similar to other chronic medical conditions, SCD is commonly complicated by psychological symptoms that can be attributed to the chronic nature of the disease and other illness-related symptoms [5]. The prevalence of depression in SCD patients has been estimated to be between 21.6% and 44% worldwide and is associated with increased hospitalizations, pain crises, and poor quality of life [3,7]. These findings highlight the significance of detecting and treating psychological symptoms in adults with SCD, especially anxiety and depression.
Previous studies conducted in the southern and eastern regions of Saudi Arabia have found a high prevalence of depressive symptoms of 85.9% and 48.2%, respectively [5,8]. Therefore, in this study, we assessed the prevalence of depression among patients with SCD in four centers in Makkah City in western Saudi Arabia between December 2021 and April 2022, and then studied its relationship with sociodemographic factors.

Sample size and inclusion criteria
The targeted sample size was calculated to be 370 using the Raosoft sample size calculator (Raosoft, Inc., Seattle, WA) available online with a margin error determined as 5%, confidence level determined as 95% and an estimated total population of 10,000. The convenience sampling technique was used and a total of 222 patients were enrolled in the study. Patients with adult sickle cell disease, based on hemoglobin electrophoresis, aged 18 years and older were included in the study. Pregnant women, patients with SCD traits, and those who had already been diagnosed with depression were excluded.

Data collection
Data were collected with a self-administered online questionnaire, and patients' consent was required to start the questionnaire. The questionnaire contained three sections. The first section was general questions regarding patients' sociodemographic data including age, gender, nationality, marital status, level of education, occupation, monthly income, and residential state. The second section assessed sickle cell disease and consisted of nine questions including the age of onset, sickle cell genotype, medication used, number of vaso-occlusive crises (VOCs), hematology clinic visits, and hospitalizations per month. In the last section, the Patient Health Questionnaire-9 (PHQ-9) was used to identify and measure depression severity [9]. A patient's overall score indicated whether they were depressed or not: a score of 0-4 indicated no depression, a score of 5-9 indicated mild depression, a score of 10-14 indicated moderate depression, a score of 15-19 indicated moderate-severe depression, and a score of 20-27 indicated severe depression.

Statistical analysis
Data were analyzed using IBM SPSS Statistics, version 26 (IBM Corp., Armonk, NY). The chi-square (χ 2 ) test was used for qualitative data and expressed as numbers and percentages to examine the relationship between the variables. The odds ratio was calculated at a confidence interval (CI) of 95% to assess the risk factors (independent predictors) of depression. A p-value of less than 0.05 was considered statistically significant.

Results
This study included 222 participants and the majority (63.5%) were in the age range of 18-30 years. Of these, 55% were females, and 92.3% were Saudi nationals; 65.3% of them were single, 49.5% had a bachelor's degree, 27.9% were employed, and 26.6% had a monthly income <5000 Saudi Riyal, or SR ( Table 1).   Almost half of the participants (49.8%) reported that it was somewhat difficult to work, take care of things at home, and/or interact with others due to these problems. Of these, 80.6% received support from family or friends after being diagnosed with SCD, and 31.2% reported that they often needed assistance with daily activities. Housework (27.7%) and transportation (18.1%) were the most common forms of regular support patients needed from their caregivers. Many participants (47.1%) believed that their monthly income would be higher if they did not suffer from SCD ( Table 3).

Variable No. (%)
How difficult has it been for you to take care of your work, take care of things at home, and interact with others due to these problems?  The prevalence of depression among studied patients was 85.6%. We found that 34.2% had mild depression, 20.3% had moderate, 13.5% had moderately severe, and 12.2% had severe depression (Figure 1).

SR, Saudi Riyal
On the other hand, a non-significant relationship was found between depression prevalence and patients' clinical data, disease burden, support, and patients' opinion about the effect of the disease on their monthly income (p≥0.05) ( Tables 5, 6).   Multivariate logistic regression analysis was done to determine the risk factors (independent predictors) of depression among studied participants. The age of 18-30 years was an independent predictor (risk factor) of depression. While other variables were significant in the univariate analysis, they did not show significance after the multivariate analysis ( Table 7).

Discussion
Sickle cell disease is one of the most common diseases that cause chronic pain. It can also lead to a change in behavior and depressive symptoms [5]. Here, we assessed the prevalence of depression among SCD patients and determined the impact of sociodemographic factors and genotype on depressive symptoms in Makkah.
In this study, most participants (85.6%) were found to have depression. Our finding is consistent with studies by Alsubaie et al. and Aljumah et al. with depression rates of 85.9% in the southeastern Saudi Arabia and 61.1% in eastern Saudi Arabia, respectively [8,10]. The regional distribution of SCD was more prevalent in the eastern region with a prevalence of 145 per 10,000 followed by the southern region with a prevalence of 24 per 10,000, western region at 12 per 10,000, and central region at 6 per 10,000 [11]. Several factors could have contributed to these results, and these were evaluated as a secondary objective. First, younger patients (aged 18-30 years) had a higher depression prevalence than older patients (aged 30-51 years). The previous literature, however, did not show that age played a significant role. However, Adzika et al. reported significantly higher depression scores among 40-to 49-year-olds than any other age group [12]. In our study sample, 63.5% of study participants were aged 18-30 years, while 36.5% were 31-50 years of age, which may account for this difference. Second, depression is more prevalent among patients with lower levels of education, which is consistent with the study by Schaeffer et al. in which depressed SCD patients were found to be threefold more likely to have less than a secondary level of education [13]. This could be related to their recurrent pain crisis, which results in poor academic performance and missed school days. Third, patients with low incomes are more likely to be depressed. This concurs with the previous literature as Aljumah et al. reported low incomes were significantly associated with depression, at a p-value of 0.019 [14].
Also, as a secondary objective of the study, we determined the prevalence of depressive symptoms among various SCD genotypes. In light of the fact that HbSS is a more severe genotype of SCD, it is assumed to confer a much higher risk of psychological problems than HbSC, which is a less severe genotype. Here, a total of 55 (80%) of HbSS patients and 121 (86%) of HbSC patients were found to have depressive symptoms, thus suggesting that higher psychological distress levels are also associated with milder genotypes of SCD, that is, the HbSC. This result is inconsistent with that of Anim et al. who demonstrated that HbSS patients exceeded HbSC patients in the number and severity of their psychological symptoms [2].
This study supports other previous studies' findings that disease severity is not necessarily correlated with psychological distress [7,13,15]. Despite worsening health-related quality of life in two domains (general health and role-physical), more severe genotypes did not impact mental health [10]. Our study also showed that patients experiencing frequent VOCs and frequent hospitalizations and clinic visits had a higher risk of depression. These results support the findings of prior studies [3,5,7]. These results are reasonable because a VOC is the major cause of painful events with significant morbidities affecting the course of the disease. Furthermore, most patients (81%) attempted to manage their crises at home, mainly because they believed that medical assistance was not necessary (44.6%). The same belief was also expressed in previous studies by patients (76.6%) in their ability to cope with crises at home [16]. There are a number of potential explanations for these results including inadequate patient education regarding VOC management as well as depression leading to social withdrawal and isolation.
We found that nearly half of the participants (47.1%) believed their monthly income would be higher if they did not have SCD, which is also consistent with the survey by Osunkwo et al. where half of the patients (54%) reported the same [17]. People with SCD often miss work likely due to frequent and unpredictable pain crises and fatigue, which interfere with their ability to work.
A research showed that the number and severity of VOCs negatively impacted work performance, particularly for patients who had four or more crises in the previous year and reported a lack of attendance at work [16]. However, we did not find any statistically significant difference for SCD impacting the monthly income of patients.
This study does have some limitations. First, it is a descriptive study, and thus causal inferences cannot be made. Second, we used a convenient sample from four centers in Makkah, which might be too small to explore factors associated with depressive symptoms among patients with SCD. Third, self-administered surveys may introduce recall and social desirability bias. Fourth, while the PHQ-9 is a common and validated screening tool, a structured clinical interview would have yielded an accurate diagnosis of depression.

Conclusions
We conclude that there was a high prevalence of depressive symptoms among SCD patients in Makkah, Saudi Arabia. The most important risk factors for depression in SCD patients are young age, high frequency of VOCs, poor educational background, and low monthly income. Future studies on the current problem should focus on utilizing regular screening models, early psychiatric referrals, and follow-up visits for depression. The community should consider psycho-behavioral and/or pharmacological interventions to mitigate the consequences among SCD patients.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Ministry of Health, Makkah, Institutional Review Board issued approval H-02-K-076-0921-573. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.