The current study reports firstly on the prevalence rates and risk factors for anxiety and depression among school-age patients with SMA in China. Anxiety and depression were observed in 40.0% and 25.2% of SMA patients, respectively, in our study. We also found that the prevalence of depression and anxiety in SMA patients differed significantly across school type, academic delay, household economic level, clinical characteristics of disease, caregivers’ mental health, and caregivers’ expectations for patients.
Our findings indicated that the prevalence of anxiety and depression in school-age SMA patients were not significantly different between female and male children with SMA. Whether gender has a differential influence on the prevalence of anxiety and depression remains controversial. The WHO reported that depression is more common among females (5.1%) than males (3.6%). As with depression, anxiety disorders are more common among females than males. Linden et al. identified a large gender gap in depression and anxiety among patients with cancer, where the prevalence in women was two to three times higher than seen for men. In a Canadian study, Marrie et al. found that women experienced a higher level of depression in multiple sclerosis. Females also had significantly higher rates of anxiety than males among children and adolescents with cerebral palsy. In contrast to these findings, a study comparing women and men with chronic urticaria patient found no significant differences in total anxiety and depression scores. Inconsistent conclusions about the relationship between gender and anxiety and depression may be explained by the different incidence of diseases between genders. The lack of a significant difference in the prevalence of anxiety and depression between genders in our study might be explained by the fact that SMA morbidity is unrelated to gender.
In the present study, patients with type III and type I SMA had the highest and the lowest prevalence rates of anxiety, respectively, although this difference did not attain statistical significance. By contrast, the highest and lowest prevalence rates of depression were found in type I and type III patients, respectively, also with no statistically significant difference. A possible explanation for these observations is that type III patients retain more mobility than type I patients and can therefore maintain normal contacts, but that type III patients cannot enjoy the same activity levels as their normal peers, which leads to anxiety. On the other hand, type I patients are more likely to suffer from depression because of their limited mobility and therefore inability to socialize normally. Our results also indicated that the prevalence rates of depression and anxiety in patients with SMA showed no significant difference with age, although anxiety and depression occurred more frequently in adolescent patients aged 13–18 years. These results are consistent with to the WHO report that anxiety and depression are more likely to occur in older than younger people.
Our research found that patients with respiratory dysfunction had significantly higher anxiety and depression rates than patients without respiratory dysfunction. Given the association between psychological distress and poorer respiratory outcomes, this result is in agreement with studies on other respiratory diseases, previously reported. For example, one study found that 50% and 39% of patients with chronic obstructive pulmonary disease showed clinically significant anxiety and depression, respectively. Moreover, a nationwide population-based survey in Korea reported that allergic rhinitis and rhinosinusitis synergistically compromise the mental health and health-related quality of life of patients. Patients with asthma also have a high prevalence of depression, and we can hypothesize that the long-term course of the disease in SMA increases the patients’ anxious and depressive symptoms.
SMA patients often have digestive system complications such as constipation and gastroesophageal reflux. In the current study, the patients with digestive system dysfunction had a significantly higher anxiety and depression rate than those without digestive system complications. Studies have found that constipation and diarrhea often aggravate the anxiety of patients, and anxiety may affect the course of the disease through the neuroendocrine regulatory system, further aggravating the clinical symptoms of patients and exacerbating constipation[31, 32]. A study on Parkinson’s disease (PD) patients showed that severe constipation and motor symptoms were closely related to depression; the researchers explained that involvement of the enteric plexus of the gastrointestinal tract and dorsal motor nucleus of the vagus (DMV) initially causes constipation in PD patients, and subsequent spread to the raphe nuclei and locus coeruleus leads to depressive mood. Furthermore, gastroesophageal reflux reduces the quality of life of patients, so that the long-term course of disease promotes an increase in psychological pressure and damage to mental health, leading to anxiety and depression.
Skeletal deformities can lead to motor dysfunction in patients. As the disease progresses, the majority of SMA patients experience skeletal system dysfunctions such as hip joint dislocation, wrist joint deformity, ankle joint deformity, scoliosis, etc., leading to claudication, limitation in mobility, and reduced outdoor activities[34, 35]. Our study found that patients with skeletal deformities had significantly higher rates of anxiety and depression than those without skeletal deformities, which is in agreement with the results of psychological surveys on other musculoskeletal disorders. For example, the anxiety score in fracture patients was significantly higher than in healthy people. An investigation of depression rates in patients with hereditary paraplegia showed that their anxiety rate reached the survey 58% of the population is considered to be related to the patient’s mobility level. Pedras et al. also found a high prevalence of anxiety and depression symptoms among patients after a lower limb amputation. A further study suggested that patients with rheumatoid arthritis (RA) tend to experience anxiety, because RA is a chronic disease that causes pain, stiffness, swelling, and limitations in the motion and function of multiple joints.
The collective evidence shows that patients with motor functional disorders are more likely to have anxiety and depression. Psychological factors can also affect the treatment of physical diseases as it may decrease the treatment compliance (i.e. rehabilitation) in patients. Skeletal deformity affects the patient’s motor function, reduces quality of life, and increases anxiety. Further, skeletal deformities are often accompanied by changes in body shape and abnormal walking posture, affecting appearance and causing pain and anxiety for the patient. According to our research, we suggest that patients with skeletal deformities should undergo corrective surgery or wear orthoses to correct or prevent the deformity from worsening. Patients without skeletal deformities should be managed as early as possible, through attending regular physician appointments to properly maintain reasonable rehabilitation exercises.
SMA is a neuromuscular degenerative disease characterized by progressive muscle atrophy and muscle weakness. Progressive motor regression is the most notable characteristic of the disease. Rehabilitation exercise, as one of the most important treatment strategies, can significantly improve the condition of the disease and the quality of life of patients. Our results show that the anxiety rate of SMA patients who perform rehabilitation exercise is significantly lower than in those without rehabilitation training. The possible explanation for this difference is that rehabilitation exercise can improve patients' motor function and quality of life to a certain extent, thereby reducing the incidence of patients' anxiety and depression. At present, there is no detailed research to explain how exercise relieves anxiety and depression, but it is hypothesized that the mechanism of action is similar to that of antidepressants, with effects including increased expression of brain-derived neurotrophic factor (BDNF), increased availability of serotonin and norepinephrine, regulation of hypothalamic–pituitary–adrenal axis activity, and reduced systemic inflammatory signaling. Additionally, Schuch et al. contend that physical activity can confer protection against the emergence of anxiety. In particular, higher physical activity levels protect against agoraphobia and post-traumatic stress disorder. Therefore, reinforcing rehabilitation exercise is not only conducive to improving patients’ physical motor function, but may also support mental health by reducing the occurrence of anxiety and depression.
School education is very important to the physical and mental development of children. Education consists not only in teaching academic subjects but also in cultivating other skills in children, especially in morality, social interaction, and gradually improving their own personality. Many children with SMA cannot participate normally in school, leading to academic delay. Our study found that the anxiety and depression rates of children with academic delay were significantly higher than in those without academic delay. We further assessed the association between academic delay and anxiety and depression by adjusting covariates such as household income level and caregivers’ mental state, statistical significance remained (anxiety OR 2.23, 95%CI: 1.109 to 4.867; p = 0.025; depression OR 3.696, 95%CI: 1.556 to 7.855; p = 0.002, data not shown), which suggests that academic delay is an independent risk factor for the prevalence of anxiety and depression in SMA patients. This is probably because academic delay further limits social interaction, in addition with the loss of benefits from school, leading to increased psychological stress, anxiety, and depression. Moreover, anxiety and depression rates of SMA patients varied significantly between different types of schooling, with lower rates among patients enrolled in personalized schools compared with those attending traditional schools. Jacobsen et al. found that school type has an important impact on cognitive stimulation, when private schools provide more personalized methods. The reason for the significant differences in anxiety and depression in our study may be that personalized schools provide special support for SMA children, such as special desks and suitable classroom locations and recovery equipment. Therefore, in response to this situation, we encourage children with SMA to participate in school education, and call for schools to provide reasonable campus support, to optimize learning programs, and thereby to reduce the incidence of anxiety and depression in SMA patients.
Economic income determines the level of medical services and the quality of treatment for patients. We therefore investigated the prevalence rates of anxiety and depression in SMA patients with different household income levels. The results showed that the anxiety and depression rates of patients in high-income families were significantly lower than those in low-income families. Our results provide similar conclusions to studies on the prevalence of anxiety and depression in multiple sclerosis patients, which showed that patients with good economic status had the lowest levels of depression and anxiety[44, 45]. In addition, despite the continuous improvement in country and social support are gradually increasing in China, drug treatment for SMA is still not included in medical insurance which indicates the treatment needs of SMA patients has not been met yet. Hence, we conclude that economic status is one of the most important factors of anxiety and depression in school-age SMA patients. Economic support for the diagnosis and treatment of SMA patients needs to be greatly expanded in China, in addition to developing medical policies based on the capacity of SMA families to pay, reducing the economic burden on patients, improving the quality of nursing, and lowering the incidence of anxiety and depression.
Daily self-management refers to the ability to plan and arrange one's daily life, to control oneself and to deal with interpersonal relations. SMA patients have poor self-management ability and need caregivers to take care of daily life over an extended period. As we all know, emotional resonance is a psycho-social phenomenon, and personal mood is usually affected by the people surrounding us. Therefore, our research investigated the mental state of SMA caregivers and their expectations for disease treatment. The results showed that the mental state of caregivers can have a significant impact on anxiety and depression in SMA patients. A positive correlation was found between caregivers’ anxiety or depression and patients’ anxiety or depression, except there was no relation between caregivers’ depression and patients’ depression. In addition, our study found that caregivers’ expectations for diagnosis and treatment of SMA patients can significantly affect patients’ anxiety and depression. Anxiety and depression rates were significantly lower in caregivers with high expectations than in those with low expectations. Considering that caregivers have certain self-judgment and emotional control capabilities, it can be expected that guiding and resolving the caregiver’s psychology to reduce their subjective feelings of anxiety and depression may indirectly improve the anxiety and depression in SMA patients. Hence, it is important to encourage caregivers to maintain a positive attitude towards life and increase their confidence in the treatment of patients, which can reduce the possibility of anxiety and depression in the patients.
The consensus statement for standard of care (SOC) in SMA promotes multidisciplinary approaches, including pulmonary care, gastrointestinal and nutritional care, and orthopedic care and rehabilitation, which are helpful to improve SMA patients’ clinical symptoms, delay disease progression, and prolong survival. It is remarkable, however, that psychological care is not included in the SOC of SMA, as previous studies have shown that SMA patients always suffer from mental problems. Our study also demonstrates that there are high prevalence rates of anxiety and depression in SMA patients of school age. Together, these findings highlight the need for the SOC in SMA to include professional psychological support.
A major strength of our study was, first, to measure the prevalence rates of anxiety and depression in SMA patients. There are currently very few articles studying the psychology of SMA patients, and no systematic reports on the evaluation of anxiety and depression in children with SMA. Our study therefore represents an advance in assessing the anxiety and depression state of SMA patients. In addition, our research analyzes the factors that may affect the mental state of children with SMA, including the patient’s sociodemographic and clinical characteristics, and analyzes the influence of the caregiver’s subjective mental state and expectations on the anxiety and depression of SMA patients. Our findings emphasize the importance of increased focus on the psychological aspects of SMA care, including the indirect regulation of the psychological state of SMA patients by influencing the outlook of caregivers.
The present study also has several limitations. First, the low sample size could limit study precision. The small number of patients also affects the subgroup analyses for many of the potential moderators, which should be considered in light of a lack of statistical power to draw definitive conclusions. Our study was also cross-sectional, so it was not possible to determine the cause and effect relationship between the variables. Thirdly, the evaluation scales used are universal tools for assessing the mental state of children. At present, there is no psychological evaluation scale dedicated to SMA disease.
Further research is warranted using a larger survey sample at the individual level. In the meantime, psychological intervention measures to treat anxiety and depression require exploration in further follow-up observations. Finally, more research should be devoted to the development of a psychological scale dedicated to SMA disease.