Psychological symptoms in individuals with Spinal Muscular Atrophy (SMA) and their caregivers – results from a nation-wide study in Germany

Psychological symptoms in individuals with Spinal Muscular Atrophy (SMA) and their caregivers – results from a nation-wide study in Germany | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Psychological symptoms in individuals with Spinal Muscular Atrophy (SMA) and their caregivers – results from a nation-wide study in Germany Justine Hussong, Berenike Leibrock, Tabea Huelle, Hannah Mattheus, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8086836/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background This study investigates the prevalence and associations of psychological symptoms in individuals with Spinal Muscular Atrophy (SMA) and their caregivers, utilizing data from a cross-sectional, observational assessment conducted in Germany. Participants were recruited through the national German SMA registry (June – September 2021), and psychological symptoms were assessed using validated measures such as the Strengths and Difficulties Questionnaire (SDQ) in children with SMA (n = 21) and the German Mini-Symptom-Checklist (Mini-SCL) in adults with SMA (n = 82) and caregivers (n = 67). Results Results indicate that children with SMA exhibit lower rates of psychological symptoms compared to adults (9.5% vs. 13.4%), with internalizing symptoms (emotional problems, depression, anxiety) being the most prevalent in both age groups. Caregivers also demonstrate psychological symptoms in 14.9%, particularly those of individuals with SMA type 1. Symptom rates did not differ between groups with different motor function level. Significant correlations between caregiver and patient psychological symptoms were observed, while pharmacological treatment showed no significant impact on symptom rates. Conclusions In conclusion, the well-established access to medical care and social support systems appeared to influence the manifestation of psychological symptoms. Additionally, the correlation of patient and caregiver symptoms highlight the interplay between the mental health of both. These findings underscore the importance of integrating psychosocial care for both individuals with SMA and their caregivers to alleviate stress and promote well-being. Trial registration: German clinical trial register (DRKS), DRKS00022876. Registered 19 October 2020. Spinal Muscular Atrophy (SMA) Psychological symptoms Caregivers Internalizing symptoms Mental health Psychosocial care Figures Figure 1 Figure 2 Figure 3 Background Persons with rare diseases or chronic illnesses have a higher risk of developing mental health problems, especially anxiety and depression ( 1 , 2 ). Affected children and adolescents often develop symptoms due to maladjustment, school problems, or reduced social participation. Their parents and caregivers usually report higher perceived stress and lower quality of life which increase the risk of own psychological problems ( 1 , 3 ). A recent systematic analysis of the psychosocial situation of caregivers of children with spinal muscular atrophy (SMA) identified multiple stressors that may cause mental health problems in the long term, e.g. parental distress or insufficient supportive care ( 4 ). The present paper focuses on psychological symptoms in persons with SMA and their caregivers, as little is known about the associations between symptoms of caregiver and patient, as well as about the impact of motor function and new pharmacological treatments on mental health of both. Spinal muscular atrophy Spinal muscular atrophy (SMA) is a rare autosomal recessive disease causing degeneration and loss of motor neurons of the spinal cord leading to a progressive impairment of motor skills, physical disability and in severe cases to a reduced life expectancy ( 5 ). Prevalence of SMA in Europe is about 13–14 per 100,000 live births ( 6 ) and is caused by mutations in the survival motor neuron ( SMN1 ) gene ( 5 ). The severity of SMA is variable and can be classified into different phenotypes according to age of symptom onset and highest achieved motor function ( 5 ). In severe SMA type 1 (SMA1) symptoms begin in the first half year of life, children never learn to sit and have a reduced life expectancy (< 2 years) when untreated. Persons affected by SMA type 2 (SMA2) show motor regression before the age of 18 months. Sitting is the highest achievable motor function but can be lost over the time. Without therapy life expectancy is reduced. In SMA type 3 (SMA3), children learn to walk on his own but muscle weakness appear beyond the age of 18 months, and without therapy some of them are over the time wheel chair bound. Individuals with SMA type 4 (SMA4) show muscle weakness in the adulthood but they don’t lose the ability to walk. This existence and frequency of this type is controversial, as in many patients, first mild (less disabling) symptoms may appear in young adulthood ( 7 ). In the last years, new gene therapy treatments became available (i.e., nusinersen, onasemnogene abeparvovec, and risdiplam) leading to major improvements of the motor function and thus improving dramatically the prognosis of SMA ( 7 ). Therefore the prevalence of SMA is increasing and new phenotypes are appearing, thus a classification by the current level of current motor function (non-sitters, sitters, walkers) help clinicians to adjust and allow the appropriate medical care ( 8 ). Mental health problems in individuals with SMA and their caregivers Psychological symptoms in children with SMA are reported in 12%-40% ( 9 – 11 ). Externalizing symptoms (e.g. attention-deficit, hyperactivity, aggressive behavior) are rather uncommon (in 0–2%) and not higher than in control groups, whereas slightly higher rates (in 7%-19%) of internalizing symptoms (e.g. depression, anxiety) are reported ( 9 , 10 , 12 ), except for one Chinese study that found even higher rates of anxiety (40%) and depression (25%) in children with SMA ( 11 ). Less is known about psychological symptoms in adults with SMA. In a symptom list assessed in 70 adult German patients with SMA2 + 3 compared to 59 healthy controls, frequency of self-reported anxiety (17%), loss of interest (9%), concentration difficulties (20%), and insomnia (31%) was not significantly increased in SMA patients and did not differ between SMA2 and SMA3 ( 13 ). Further evaluations from Germany and Malaysia reported anxiety and depressive symptoms in 29–38% of adults with SMA ( 14 , 15 ). Regarding caregivers, studies report clinical depression symptoms in 21–36%, and clinical anxiety symptoms in 26–76% ( 14 , 16 – 19 ). Parental depression symptoms were associated with higher children’s and parental age, patient living at home and medical treatment (with nursinersen), and absence of rehabilitation management was associated with caregivers’ anxiety symptoms ( 18 , 19 ). The association of parental emotional symptoms and SMA type were inconsistent ( 16 , 19 ). The effect of modern SMA medical treatment on psychological symptoms in patients is scarcely examined so far. One study evaluated 26 patients (14 adults, 12 children) before and after nursinersen treatment and showed no change of depressive symptoms after 6 months of treatment ( 15 ). Another study from Turkey found even higher depression scores in caregivers of treated SMA children compared to untreated children ( 19 ). The aim of our study was to explore psychological symptoms in children and adults with SMA, as well as in their caregivers. Methods The present study is part of a cross-sectional, observational assessment of individuals with SMA and their caregivers on health-related quality of life and psychological symptoms (20,21). Sample Patients were recruited trough the national German SMA registry (www.sma-register.dewww.sma-register.de), which is part of the ‘Translational Research in Europe for the Assessment and Treatment of Neuromuscular Disease’ (TREAT-NMD) network. TREAT-NMD aims to facilitate recruitment of patients to neuromuscular research, in order to raise awareness and improve treatment methods. The enrollment in the SMA registry is voluntary and free of charge. To be recruited for the present study, participants had to meet all of the following criteria: (1) genetically confirmed diagnosis of SMA, (2) ≥ 4 years of age, and (3) currently residing in Germany. A study invitation and information sheet was sent via email by the SMA registry to all listed individuals meeting the study criteria. In children (participants < 18 years), parents/caregivers were contacted. After given informed consent, patients and one of their caregivers were invited to complete a questionnaire administered online via the study website www.soscisurvey.de. The study was approved by the local Ethics Committee of the Saarland Medical Association (February 4, 2020, protocol no. 09/20) and was registered at the German clinical trial register (DRKS00022876). Materials and collected data The online questionnaire included a general part about demographic and clinical characteristics which is described in detail by Leibrock et al. (20).The data collection took place between June and September 2021. To assess psychological symptoms in children and adolescents with SMA, the parental version of the Strengths and Difficulties Questionnaire (SDQ) was completed by parents/caregivers in children aged 3 years or older, and as self-report in children from the age of 12 years onwards. The SDQ is an internationally validated, standardized screening questionnaire for 3-17 year old children and adolescents consisting of 25 items about psychological and behavioral symptoms, each scored on a three-point scale (not true (0) – somewhat true (1) – certainly true(2)) (22). Five subscales can be calculated (each from 5 items): emotional symptoms (5 items), conduct problems (5 items), hyperactivity (5 items), peer problems (5 items) and prosocial behavior (5 items). The total problem behavior score (TPBS) is calculated as a sum of the first four scale scores except ‘prosocial behavior’. According to German norms, subscale scores and the TBPS were divided into clinical (>90 th percentile), borderline (80-90 th percentile), and average (<80 th percentile) cut-offs (23,24). The clinical cut-off at the 90 th percentile was used as identification of clinically relevant mental health symptoms. To assess psychological symptoms in adult individuals with SMA and in parents/caregivers, the German Mini-Symptom-Checklist (Mini-SCL) self-report was completed (25). The Mini-SCL, also known as Brief Symptom Inventory (BSI-18) is a validated and reliable short form of the Symptom Checklist (SCL-90-R). Three scales (somatization, depression and anxiety) assessed by 6 items each, as well as the Global Severity Index (GSI) based on all 18 items can be calculated. The 18 items refer to current psychological symptoms and are rated on a 5-point Likert-scale ranging from 0 (not at all) to 4 (extremely). Psychometric properties of the Mini-SCL are satisfactory or good for all subscales and the GSI. According to German norms, the 93 rd percentile (~T=65) is used as a cut-off for clinically relevant symptoms (25). The parent/caregiver also filled in the Mini-SCL self-version in order to assess their own mental health symptoms. Statistical analysis Statistical calculations were performed with IBM SPSS Statistics Version 25. Descriptive data was reported by relative and absolute frequencies for non-parametric variables and by means and standard deviation (SD) for parametric data. Group differences for nominal data were calculated by Chi 2 -tests and Fisher’s exact tests. Correlations were calculated by Spearman correlations. Results are considered as significant at a p‐value < .05. Results Out of 742 patients enrolled in the SMA patient registry, 513 met the inclusion criteria, and 117 agreed to participate in the study. Completed questionnaires on mental health problems are available for n=21 children, n=82 adults and n=67 caregivers. Descriptive data of the sample is outlined in Table 1 . Participants were classified based on SMA subtype (i.e., SMA1, 2, and 3) as well as according to current best motor function of the lower limb (i.e., non-sitter, sitter, and walker). Table 1: Descriptive data by SMA subtype (sex, age, motor function, medication intake) Total Children (<18 years) Adults N=103 N=21 N=82 Mean age in years (SD) 35.8 (19.0) 9.7 (4.5) 42.5 (15.1) Sex distribution in % (n) Male 47.6 (49) 47.6 (10) 47.6 (39) Female 51.5 (53) 52.4 (11) 51.2 (42) Other 1.0 (1) - 1.2 (1) Subtype in % (n) SMA1 6.8 (7) 19.0 (4) 3.7 (3) SMA2 35.9 (37) 42.9 (9) 34.1 (28) SMA3 57.3 (59) 38.1 (8) 62.2 (51) Best current motor function in % (n) Non-sitter 9.7 (10) 14.3 (3) 8.5 (7) Sitter 64.1 (66) 52.4 (11) 67.1 (55) Walker 26.2 (27) 33.3 (7) 24.4 (20) Medication intake in % (n) None 22.3 (23) 9.5 (2) 25.6 (21) Nursinersen 55.3 (57) 71.4 (15) 51.2 (42) Risdiplam 22.3 (23) 19.0 (4) 23.2 (19) Clinically relevant mental health symptoms in children, adults and caregivers Figure 1 presents rates of psychological symptoms in the clinical and average range in children, adults with SMA and caregivers focusing on the assessed symptom scales and table 2 shows only clinically relevant psychological symptoms in children and adults with SMA in the total sample, differed by SMA subtypes and motor function. In children (n=21), 10% show relevant mental health problems being emotional problems (19%), hyperactivity (10%) and peer problems (10%) the most common one recorded by SDQ parental report. Regarding SMA types, peer problems were mainly reported in SMA1 (50%) and emotional problems were highest in SMA3 (38%). Regarding motor function, emotional problems were seen in non-sitters and walkers (33% and 29% respectively). Self-reports were available for n=7 children and no symptoms in the clinical range were described. Only one child reported borderline (80 th -90 th percentile) symptoms of hyperactivity, and another one reported lower prosocial behavior in the borderline range. Mean scores (SDs) of the SDQ scales (self- and parental report) are summarized in the additional file 1. Table 2: Clinically relevant psychological symptoms in children (proxy report), adults with SMA and caregivers/close relatives (self-report) SMA subtypes Lower limb motor function Total SMA1 SMA2 SMA3 e P c Non-Sitters Sitters Walkers P c Children with SMA – Parent reported SDQ – % in the clinical range (n) a n=21 n=4 n=9 n=8 n=3 n=11 n=7 Emotional problems 19.0 (4) 0 (0) 11.1 (1) 37.5 (3) n.s. 33.3 (1) 9.1 (1) 28.6 (2) n.s. Conduct problems 0 (0) 0 (0) 0 (0) 0 (0) - 0 (0) 0 (0) 0 (0) - Hyperactivity 9.5 (2) 0 (0) 11.1 (1) 12.5 (1) n.s. 0 (0) 9.1 (1) 14.3 (1) n.s. Peer Problems 9.5 (2) 50.0 (2) 0 (0) 0 (0) .029* 0 (0) 18.2 (2) 0 (0) n.s. Prosocial Behavior 0 (0) 0 (0) 0 (0) 0 (0) - 0 (0) 0 (0) 0 (0) - Total 9.5 (2) 0 (0) 11.1 (1) 12.5 (1) n.s. 33.3 (1) 0 (0) 14.3 (1) n.s. Adults with SMA – Self-reported Mini-SCL – % in the clinical range (n) a n=82 n=3 n=28 n=51 n=7 n=55 n=20 Depression 11.0 (9) 0 (0) 3.6 (1) 15.7 (8) n.s. 14.3 (1) 9.1 (5) 15.0 (3) n.s. Anxiety 14.6 (12) 0 (0) 3.6 (1) 21.6 (11) n.s. 28.6 (2) 12.7 (7) 15.0 (3) n.s. Somatization 14.6 (12) 33.3 (1) 10.7 (3) 15.7 (8) n.s. 28.6 (2) 14.5 (8) 10.0 (2) n.s. Total 13.4 (11) 0 (0) 3.6 (1) 19.6 (10) n.s. 28.6 (2) 9.1 (5) 20.0 (4) n.s. Caregivers – Self-reported Mini-SCL – % in the clinical range (n) b in % (n) b n=67 n=6 n=25 n=36 n=10 n=40 n=17 Depression 11.9 (8) 33.3 (2) 0 (0) 16.7 (6) .021* (1>2) 0 (0) 15.0 (6) 11.8 (2) n.s. Anxiety 14.9 (10) 50.0 (3) 4.0 (1) 16.7 (6) .022* (1>2) 10.0 (1) 15.0 (6) 17.6 (3) n.s. Somatization 14.9 (10) 16.7 (1) 4.0 (1) 22.2 (8) n.s. 20.0 (2) 12.5 (5) 17.6 (3) n.s. Total 14.9 (10) 16.7 (1) 4.0 (1) 22.2 (8) n.s. 10.0 (1) 15.0 (6) 17.6 (3) n.s. a based on parental SDQ (Strengths and Difficulties Questionnaire) scores > 90 th percentile b based on self-reported Mini-SCL (Symptom Checklist) scores > T=65 (~93 rd percentile) c Fisher’s Exact test if not otherwise specified. d Depression scale reports available for n=81 (n=27 in type II, n=54 in non-sitters) e SMA3 also included one patient with SMA4 <> Figure 2 presents an item analysis of the three SDQ scales ‘emotional’, ‘peer problems’ and ‘hyperactivity’ in which symptoms were reported most often in the clinical range. The most frequent reported symptoms in the emotional problems scale were ‘often complains of headaches, stomach-aches or sickness’ (in 11/21 children) and ‘nervous or clingy in new situations, easily loses confidence’ (in 9/21 children). Most often reported items in the peer problems scale were ‘gets on better with adults than with other children’ (in 12/21 children) and ‘rather solitary, tends to play alone’ (in 7/21 children). Regarding the hyperactivity scale, most frequent reported symptoms are ‘doesn’t think things out before acting’ and ‘doesn’t see tasks through to the end’ (in 8/21 children each). In adults (n=82) clinically relevant psychological symptoms recorded by Mini-SCL self-report are reported by 13% of adults (figure 1 and table 2) . Adults with SMA3 had the highest rates of anxiety (22%) and depression (16%), whereas somatization was reported in all SMA types. Regarding motor function, symptom rates were highest among non-sitters (29%) mainly because of anxiety and somatization, followed from walkers (20%) mainly because of depression and anxiety. However, no differences between SMA types or motor function reached statistical significance. An item analysis of the ‘depression’, ‘anxiety’ and ‘somatization’ scales of the adult self-report is shown in figure 3. The most frequent depression symptoms were ’feeling lonely’ and ‘feeling hopeless about the future’. The most frequent anxiety symptoms were ‘nervousness or shakiness inside’ and ‘feeling tense or keyed up’. Regarding somatization, the most frequent symptoms were ‘feeling weak in parts of the body’ and ‘numbness or tingling in parts of the body’. Mental health symptoms of caregivers n=67 (mostly parents of 21 children, 46 adults) are outlined in figure 1 and table 2 . Parents reported own clinically relevant psychological symptoms in 15% of cases. Regarding SMA type, 22% of caregivers of individuals with SMA3 complain about psychological symptoms, mainly because of somatization whereas 17% of caregivers of individuals with SMA1 mainly complain about anxiety and depression. Regarding motor function, symptom rates were highest among caregivers of walkers (18%) because of anxiety and somatization, followed from sitters (15%) because of anxiety and depression and non-sitters (10%) because of somatization. Association of patient and caregiver mental health symptoms Parental symptoms of depression are significantly associated with their children’s emotional problems, peer problems and the total score. Parental anxiety was correlated to children’s conduct problems. In adults with SMA, nearly all scales were significantly correlated to those in their parents/caregivers, revealing a strong association between the symptoms of patient and caregiver. Significant correlations between mental health symptoms of SMA patients and of their parents and caregivers are shown in the additional file 2 . Association of mental health symptoms and pharmacological treatment Table 3 reports mental health symptoms of children, adults and caregivers depending on their current pharmacological treatment. Overall, there is no statistical difference in the extent of psychological symptoms between patients with no medication, those treated with nursinersen and those treated with risdiplam. Regarding children with SMA, clinical scores were only reported in individuals treated with medication (n=19) in contrast to those with no medication (n=2). In adults with SMA (medication n=61, no medication n=21) clinical scores for somatization and anxiety where higher in those individuals without medication (24% and 19% vs 11% and 13%). The most frequent reported symptoms were somatization, with the highest rates in persons with no medication (23.8%) and those treated with risdiplam (21.1%), in contrast to lower symptom rates (7.1%) in the group treated with nursinersen. Mental health of caregivers does not differ between the medication groups, as well. The most frequent reported symptoms are somatization in the risdiplam group (21.4%), anxiety and depression in the nursinersen group (17.1% each), as well as anxiety and total symptoms in the ‘no medication’ group (16.7% each). Table 3: Association of mental health symptoms (children, adults and caregivers) and pharmacological treatment c No medication Medication Nursinersen Risdiplam Children with SMA – Parent reported SDQ – % in the clinical range (n) a N=2 N=19 N=15 N=4 Emotional problems 0.0 (0) 21.1 (4) 13.3 (2) 50.0 (2) Conduct problems 0.0 (0) 0.0 (0) 0.0 (0) 0.0 (0) Hyperactivity 0.0 (0) 10.5 (2) 13.3 (2) 0.0 (0) Peer Problems 50.0 (1) 5.3 (1) 6.7 (1) 0.0 (0) Prosocial Behavior 0.0 (0) 0.0 (0) 0.0 (0) 0.0 (0) Total 0.0 (0) 10.5 (2) 6.7 (1) 25.0 (1) Adults with SMA – Self-reported Mini-SCL – % in the clinical range (n) b N=21 N=61 N=42 N=19 Depression 9.5 (2) 11.5 (7) 11.9 (5) 10.5 (2) Anxiety 19.0 (4) 13.1 (8) 11.9 (5) 15.8 (3) Somatization 23.8 (5) 11.5 (7) 7.1 (3) 21.1 (4) Total 9.5 (2) 14.8 (9) 14.3 (6) 15.8 (3) Caregivers – Self-reported Mini-SCL – % in the clinical range (n) b N=12 N=55 N=41 N=14 Depression 8.3 (1) 12.7 (7) 17.1 (7) 0.0 (0) Anxiety 16.7 (2) 14.5 (8) 17.1 (7) 7.1 (1) Somatization 8.3 (1) 16.4 (9) 14.6 (6) 21.4 (3) Total 16.7 (2) 14.5 (8) 17.1 (7) 7.1 (1) a based on parental SDQ (Strengths and Difficulties Questionnaire) scores > 90 th percentile b based on self-reported Mini-SCL (Symptom Checklist) scores > T=65 (~93 rd percentile) c Fisher’s Exact test revealed no significant differences between medication and no medication group <> Discussion To our knowledge, this is the first detailed description of psychological symptoms assessed by standardized questionnaires and self- and proxy-reports in SMA children, adults and their caregivers. Our data include all SMA subtypes, levels of motor function and pharmacological treatment statuses. Children were less affected by psychological symptoms than adults with SMA, with internalizing symptoms being the most common symptoms reported in both groups. Internalizing symptoms were as well present in caregivers, especially in those of persons with SMA1. Caregiver and patient psychological symptoms were strongly associated, whereas pharmacological treatment seem to not affect symptom rates. Psychological symptoms in children Psychological symptoms in children ranged from 0% in self-reports to emotional problems in 19% rated by parents. Children and adolescents rated themselves as less impaired as their parents did. The self-ratings must be interpreted cautiously, because only 7 adolescents (age range 12–16 years) completed the questionnaires. Otherwise, in parental rating, reported symptoms may have been mixed with parents’ own worries about their child and perceived stress which could overestimate symptom rates. Psychological symptoms in children were assessed by self-report only by Yao et al. ( 11 ) before, who found much higher rates of anxiety (40%) and depression (25%), being unusually high compared to other studies on children with SMA ( 9 , 10 ). The low rates of psychological symptoms (especially in children) in our study may result from the access to medical care and social support systems, which is fairly good for children (but not quite for SMA adults) in Germany and allows a sufficient participation in social and public life ( 20 ). In our sample, more children with SMA1 (21 vs. 8%) were included, as many more children received pharmacological treatment (92% vs. 5%) than in the Chinese study population ( 11 ). Also, in our sample, all children received supportive therapy, especially physiotherapy (vs. 54% of Chinese children with ‘rehabilitation exercise’) and all German children visited an appropriate school (vs. traditional schooling in 69% and academic delay in 55% in Chinese children) ( 11 , 20 ). The Chinese colleagues also found a specific association between psychological symptoms and the less available social and medical support ( 11 ), which is in line with research outcomes stating clearly that social participation, e.g. school visits, and an adequate medical care are protective factors for mental health ( 26 ). In line with other publications, internalizing symptoms (as anxiety, depression) were more common than externalizing problems (e.g. aggressive behavior, hyperactivity, ADHD symptoms) in the present sample ( 9 , 10 , 12 ). All in all, the rates of internalizing symptoms are only slightly higher than known in the German normative population (~ 10–15%; ( 27 )) and could be symptoms of so-called ‘pediatric medical traumatic stress’ that occurs in patients and parents after learning about a serious diagnosis or invasive medical treatments ( 28 ). Further, most SMA patients have good cognitive and adaptive abilities ( 9 , 12 ) are further protective factors that promote mental well-being, as e.g. genetic syndromes that are associated with intellectual disability reveal much higher rates of concomitant psychiatric diagnoses than individuals with SMA ( 29 ). There was only one significant difference between SMA types, for peer problems were mainly reported in SMA1 (in 50%), but only by parental rating. Regarding the item analysis of the peer problems scale, it was reported that affected children ‘get on better with adults than with other children’ and ‘rather solitary, tend to play alone’, which could reflect a social exclusion and missing social participation opportunities in children with SMA. Peer problems were not assessed in children with SMA before, but were also higher in a sample of children with rare diseases ( 2 ). Children with SMA1 have the most severe type of disease, with extremely limiting physical impairments, e.g. including the need of ventilatory support, which of course may lead to social problems or difficulties in interacting with other children. Otherwise, with the new pharmacological treatments, these children have a much better outcome and a longer survival prognosis, so that increasing and improving the opportunities to social participation in these patients is a relevant clinical implication for the future. Regarding the level of motor function, our data showed no significant differences in mental health symptoms between the groups. The association of mental health and motor function of the lower limbs was not assessed before, so we may assume that motor function may be independent from psychological symptoms. Hopefully, future studies with larger sample sizes will reveal more information to that topic. Psychological symptoms in adults Adults with SMA report psychological symptoms in 11% (depression) to 15% (somatization). These symptom rates are slightly higher than in children but lower than in the few studies known on adults with SMA ( 13 – 15 ). However, only Mix et al. used a validated instrument for assessing depressive symptoms ( 15 ), others worked e.g. with non-standardized symptom lists and qualitative research, which could have overestimated symptom rates ( 13 , 14 ). Günther et al. found symptoms of e.g. anxiety in 17%, loss of interest in 9%, and insomnia in 31%, but all rates were not higher than in the healthy control group ( 13 ). These symptoms can indicate a psychiatric disorder, but one can assume that not all of these participants would receive a manifest diagnosis e.g. of depression. We found neither differences between SMA types nor between groups of lower limb motor level. Former studies did not find SMA type differences as well ( 13 ), but psychological symptoms were associated with social participation and physical function ( 15 , 30 ). Regarding the item analysis of the depression and anxiety scale in our adult sample, the most common symptoms reported can be connected to physical/somatic complaints (‘nervousness/shakiness’, ‘feeling tense or keyed up’) or to a deficient social participation (‘feeling lonely’, ‘feeling hopeless’). As seen in children with SMA, a functioning social support system and access to medical care are relevant factors for participation in daily life and mental well-being. Qualitative research from Australia on healthcare experiences of SMA patients during transition into adulthood reveals some distressing problems, e.g. that adult healthcare services is perceived as less structured and of lower quality, the reliance on others for assistance with basic needs, or social stigmatization. Further, participants described feelings of sadness in reaction to decreasing functional capability and autonomy ( 31 ). These aspects play a major role in the life of adults with SMA and may explain well the increased rates of psychological symptoms. The small sample sizes may be an explanation for the missing differences between groups of motor function, as the rates are highest among non-sitters (somatization and anxiety symptoms in 28.6%). The results could have missed statistical significance, as only 7 adults were included in that subgroup. These findings from Mix et al. show that depressive symptoms correlated significantly with better physical function and remained unaffected after treatment ( 15 ). As in our sample only anxiety and somatization symptoms were higher in non-sitters, future studies should not only focus depression, but also include other psychiatric disorders, e.g. anxiety disorders with their different aspects. One can speculate that a decreased physical ability may cause social phobia or lead to a generalized anxiety characterized by concerns or fear towards future and progress of the disease. The Mini-SCL subscale ‘somatization’ includes questions about ‘breathing difficulties’ or ‘feelings of weakness in body parts’, which could be confounded with symptoms of severe SMA and therefore could have caused higher ratings in that scale. Psychological symptoms in caregivers Mental health symptoms of caregivers were reported in 15% of cases, notably anxiety and somatization in 15%. The rates of the total sample are slightly lower than in other studies on SMA caregivers, which reported depression symptoms in 21–36%, and anxiety symptoms in 26–76% of caregivers ( 14 , 16 – 19 ). With focus on SMA types, we see significantly more psychological problems in parents of patients with SMA1, showing similarly high rates than former studies (33% depression, 50% anxiety). Caregivers of individuals with this severe type of SMA seem to have the highest risk of developing mental health problems. These may be caused by higher stress and involvement with the care and support of the affected person. A study from Saudi Arabia found the same association in caregivers of SMA1 patients ( 16 ), and also found higher hospitalization and needs for mechanical support (e.g. ventilatory) in these patients. In our sample, all of SMA1 individuals needed ventilatory support, 80% needed food intake support, all needed medical equipment (e.g. orthoses, wheelchair) and all received any kind of supportive therapy ( 20 ). In a study on 96 children with SMA, parental stress was significantly higher in parents of children with SMA1 + 2 than in those with SMA3. Parental stress was significantly correlated to psychological symptoms and could be predicted by social support and number of children in the family ( 32 ). A newer study on a Dutch sample revealed a significant association between emotional well-being of SMA caregivers and participation in social and leisure activities ( 17 ), which explains very well the increased psychological symptoms in caregivers, especially of persons with SMA1. One can imagine that especially caregivers of the SMA1 group invest much more time in the care and organization of support which can easily lead to higher perceived stress, mental overload, less time for other social activities or self-care. The level of achieved motor function seems to not affect psychological symptoms of caregivers. That means that other factors must have a higher impact on mental health on caregivers, e.g. the access to support systems or further assistance. Association of symptoms between caregiver and individual with SMA The significant correlations between caregiver and patient psychological symptoms confirm the strong association regarding emotional well-being of the whole family system, not only in young patients, but in adults, as well. Correlations between parental and child psychological symptoms were assessed only in one Chinese study on children with SMA, so far, reporting a strong connection of depression and anxiety, too ( 11 ). Our results on children reveal associations of psychological symptoms that have not been assessed before, e.g. that parental symptoms of depression are significantly associated with their children’s emotional and peer problems; as well as that parental anxiety was correlated to children’s conduct problems. As symptoms were assessed only in a cross-sectional study design, we can only speculate about causal attributions, but several ways of associations are possible. The diagnosis of a rare and chronic illness of the child, as well as the following responsibilities and care duties can cause traumatic stress in child and parents, which increases the risk of mental health problems in both ( 28 ). Parental stress is associated to behavioral problems of the child in SMA, as well to social support and level of disability ( 32 ). The association between parental anxiety and conduct problems of the child may also be explained bi-directionally. Conduct problems of the child (e.g. aggressive behavior) can cause anxiety of parents, as they worry about their future, fear social problems or exclusion of their child. Or otherwise, anxious parents could tend to overprotect their child, be less strict or show a more inconsequent parenting style, which may cause conduct problems. A systematic analysis of parent-child interaction in families with a chronic ill child supports these hypotheses. Parents of children with a chronic physical illness tended to be less positive and showed higher levels of responsiveness, but also of control and overprotection ( 33 ). Future studies should include longitudinal analysis on psychological symptoms in caregivers and patients to provide more information about the directions of symptom associations. In adults with SMA, nearly all scales were significantly correlated to those in their parents/caregivers, revealing a strong association between the symptoms, as well. To our knowledge, this connection has not been assessed in adults with SMA before. But it means that although ~ 70% of adults in our sample do not live with their parents anymore ( 20 ), there still exists a strong relationship regarding mental health in both. A Dutch study showed that rates of maternal depression (and anxiety) symptoms were not significantly higher in mothers of children than in mothers of adult patients ( 17 ), which supports our findings. One can state that the risk of psychological symptoms in caregivers does not decrease with age of the patient or because the patient moved out, but still impacts the social life and well-being of the caregiver. The findings are in line with the implications of the systematic analysis on family needs in SMA stating that the needs of parents must be included in psychosocial care to prevent health problems due to stress ( 4 ). Our results may add that this applies not only for parents of children with SMA, but equally to parents/caregivers of adult patients. Psychological symptoms and pharmacological treatment The rates of psychological symptoms did not differ significantly between groups based on their current pharmacological treatment. In children, clinical scores were mainly reported in those treated with nursinersen, but one has to consider that the sample sizes of the other two groups (no medication n = 2; risdiplam n = 4) were too low to interpret these data. In adults, reported clinical symptoms were distributed similarly among the groups, with no specific trend observed. Mental health symptoms of caregivers did not differ between medication groups. There are only a few other studies on this topic. Mix et al. evaluated 26 patients (14 adults, 12 children) before and after nursinersen treatment and revealed that depressive symptoms did not change after treatment ( 15 ). An increase in physical function correlated even with more depressive symptoms. Ergenekon et al. showed a positive association between medical treatment and parental depression scores, as well ( 19 ). The authors of these studies discuss that patients with poorer physical abilities have a better mental health, as they receive the SMA diagnosis at a young age and integrate it better into their self-concept which causes lower mental problems. The authors of the study on caregivers pose the question if a delayed treatment initiation may have contributed to higher parental depression rates. The results imply that the pharmacological treatment does improve psychological symptoms neither in individuals with SMA nor in their caregivers, which is comprehensible and should not be expected. Manifest psychiatric disorders, e.g. a depression or anxiety disorder are usually caused by multiple biological, psychological and social factors. Further, treatment recommendations include a multimodal treatment approach ( 26 ). Therefore, we cannot assume that the change in one factor (improvement of SMA symptoms) leads immediately to a better mental health outcome in patients or even their caregivers. In the long-term, the change of SMA prognosis due to medical treatment options may improve quality of life, lower perceived stress and parental burden; and this could decrease psychological symptoms as a secondary outcome after a certain period of time. This should be included into future research on long-term effects of pharmacological treatment in SMA. Strengths and limitations Strengths of our study are the validated and standardized questionnaires allowing assessment of clinically relevant psychological symptoms in different age groups of persons with SMA, as well as their caregivers. Further, the sample size in adults with SMA was large enough to analyze differences between subtypes, levels of motor function and pharmacological treatment status regarding mental health. The combination of self- and proxy-reports, as well as of patient and caregiver reports revealed associations that were not assessed before. Limitations are the recruitment via the nationwide registry that may include information biases and selection biases. The sample size in children was too small to receive solid information on subgroup levels. Further, the cross-sectional design does not allow causal attributions. Conclusions Our study represents a significant advancement in understanding the psychological symptomatology of individuals with SMA and their caregivers. Through the comprehensive assessment of standardized questionnaires and self- and proxy-reports, we have provided the first detailed description of psychological symptoms across SMA subtypes, levels of motor function, and in individuals receiving modern pharmacological treatment. Our findings reveal that while children with SMA exhibit lower rates of psychological symptoms compared to adults, internalizing symptoms are predominant in both age groups, with caregivers of SMA1 individuals experiencing heightened psychological distress. Importantly, we have demonstrated a significant association between caregiver and patient psychological symptoms, underscoring the interdependence of mental health within SMA families. Furthermore, the influence of access to medical care and social support systems on the manifestation of psychological symptoms, particularly in adults with SMA, highlights the critical role of psychosocial interventions in promoting well-being in chronic-ill patients. The correlation between parental and patient psychopathology emphasizes the need for integrated psychosocial care tailored to both individuals with SMA and their caregivers to reduce stress and improve quality of life. Moving forward, our findings provide valuable insights for developing holistic approaches to support the mental health of SMA patients and their families. Abbreviations ADHD Attention-deficit/Hyperactivity Disorder GSI Global Severity Index Mini-SCL Mini-Symptom-Checklist SCL-90-R Symptom Checklist SD Standard deviation SDQ Strengths and Difficulties Questionnaire SMA Spinal Muscular Atrophy SMN1 Survival motor neuron gene TPBS Total problem behavior score TREAT-NMD Translational Research in Europe for the Assessment and Treatment of Neuromuscular Disease Declarations Ethics approval and consent to participate: The study was approved by the local Ethics Committee of the Saarland Medical Association (February 4, 2020, protocol no. 09/20). Consent for publication: Not applicable Availability of data and materials: The data that support the findings of this study are available from Dr. M. Flotats-Bastardas but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Dr. M. Flotats-Bastardas. Competing interests: Dr Marina Flotats-Bastardas has received consultant fees from Roche and Biogen. Dr Landfeldt is an employee of IQVIA, a contract research organization. Dr Maggie C. Walter has served on advisory boards for Avexis, Biogen, Novartis, Pfizer, Roche, Santhera, Sarepta, Pharnext, PTC Therapeutics, Ultragenyx, Wave Sciences, received funding for Travel or Speaker Honoraria from Avexis, Biogen, PTC Therapeutics, Ultragenyx, Santhera, Sarepta, and worked as an ad-hoc consultant for AskBio, Audentes Therapeutics, Avexis, Biogen Pharma GmbH, Fulcrum Therapeutics, GLG Consult, Guidepoint Global, Gruenenthal Pharma, Novartis, Pharnext, PTC Therapeutics, Roche. Simone Thiele has received financial support for advisory services from PTC Therapeutics. The other authors declare that there is no conflict of interest. Funding: The non-profit patient association “Initiative SMA – Gemeinsam für eine Therapie” within the “Deutsche Gesellschaft für Muskelkranke e.V.” provided financial support for the license fees of the proprietary HRQoL instruments, as well as the allowance for the SMA patient registry. Authors' contributions: JH: conception, design, data analysis and interpretation, draft, revision BL: conception, design, data acquisition, analysis, revision TH: design, data acquisition and analysis HM: conception, design, data analysis and interpretation EL: data analysis and interpretation, revision ST: design, data acquisition MCW: design, data acquisition MZ: conception, data interpretation, revision EM: data interpretation, revision UD: data interpretation, revision SA: data analysis and interpretation MFB: conception, design, data analysis and interpretation, revision All authors read and approved the final manuscript. Acknowledgements: The authors sincerely thank all members of the German SMA community for their invaluable contribution to this research. We deeply appreciate their willingness to participate, complete the questionnaires, and openly share insights into their physical and mental health as well as their daily experiences. We are also very grateful for the financial support generously provided by the German non-profit patient organization ‘Initiative SMA e.V.’. References Bogart K, Hemmesch A, Barnes E, Blissenbach T, Beisang A, Engel P, u. a. Healthcare access, satisfaction, and health-related quality of life among children and adults with rare diseases. Orphanet J Rare Dis. 12. Mai 2022;17(1):196. Wiegand-Grefe S, Liedtke A, Morgenstern L, Hoff A, Csengoe-Norris A, Johannsen J, u. a. Health-Related Quality of Life and mental health of families with children and adolescents affected by rare diseases and high disease burden: the perspective of affected children and their siblings. BMC Pediatr. 14. Oktober 2022;22(1):596. Cousino MK, Hazen RA. Parenting stress among caregivers of children with chronic illness: a systematic review. J Pediatr Psychol. September 2013;38(8):809–28. Brandt M, Johannsen L, Inhestern L, Bergelt C. Parents as informal caregivers of children and adolescents with spinal muscular atrophy: a systematic review of quantitative and qualitative data on the psychosocial situation, caregiver burden, and family needs. Orphanet J Rare Dis. 19. Juli 2022;17(1):274. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet Lond Engl. 21. Juni 2008;371(9630):2120–33. Sarv S, Kahre T, Vaidla E, Pajusalu S, Muru K, Põder H, u. a. The Birth Prevalence of Spinal Muscular Atrophy: A Population Specific Approach in Estonia. Front Genet [Internet]. 2021 [zitiert 30. April 2024];12. Verfügbar unter: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729775/ Sansone VA, Walter MC, Attarian S, Delstanche S, Mercuri E, Lochmüller H, u. a. Measuring Outcomes in Adults with Spinal Muscular Atrophy - Challenges and Future Directions - Meeting Report. J Neuromuscul Dis. 2020;7(4):523–34. Finkel RS, Mercuri E, Meyer OH, Simonds AK, Schroth MK, Graham RJ, u. a. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord NMD. März 2018;28(3):197–207. Gosar D, Košmrlj L, Musek PL, Meško T, Stropnik S, Krkoč V, u. a. Adaptive skills and mental health in children and adolescents with neuromuscular diseases. Eur J Paediatr Neurol. 1. Januar 2021;30:134–43. Laufersweiler-Plass C, Rudnik-Schöneborn S, Zerres K, Backes M, Lehmkuhl G, von Gontard A. Behavioural Problems in Children and Adolescents with Spinal Muscular Atrophy and their Siblings. Dev Med Child Neurol. 2003;45(1):44–9. Yao M, Xia Y, Feng Y, Ma Y, Hong Y, Zhang Y, u. a. Anxiety and depression in school-age patients with spinal muscular atrophy: a cross-sectional study. Orphanet J Rare Dis. 9. September 2021;16(1):385. Panda PK, Ramachandran A, Verma PK, Sharawat IK. Behavioral problems in infants and young children with spinal muscular atrophy and their siblings: A cross-sectional study. Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc. Januar 2023;42:47–52. Günther R, Wurster CD, Cordts I, Koch JC, Kamm C, Petzold D, u. a. Patient-Reported Prevalence of Non-motor Symptoms Is Low in Adult Patients Suffering From 5q Spinal Muscular Atrophy. Front Neurol [Internet]. 1. November 2019 [zitiert 30. April 2024];10. Verfügbar unter: https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.01098/full Ch’ng GS, Koh K, Ahmad-Annuar A, Taib F, Koh CL, Lim ESC. A mixed method study on the impact of living with spinal muscular atrophy in Malaysia from patients’ and caregivers’ perspectives. Orphanet J Rare Dis. 16. Mai 2022;17(1):200. Mix L, Winter B, Wurster CD, Platen S, Witzel S, Uzelac Z, u. a. Quality of Life in SMA Patients Under Treatment With Nusinersen. Front Neurol. 2021;12:626787. Alotaibi KM, Alsuhaibani M, Al-Essa KS, Bamaga AK, Mukhtar AS, Alrumaih AM, u. a. The socioeconomic burden of spinal muscular atrophy in Saudi Arabia: a cross-sectional pilot study. Front Public Health [Internet]. 1. Februar 2024 [zitiert 30. April 2024];12. Verfügbar unter: https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2024.1303475/full Cremers CH, Fischer MJ, Kruitwagen-van Reenen ET, Wadman RI, Vervoordeldonk JJ, Verhoef M, u. a. Participation and mental well-being of mothers of home-living patients with spinal muscular atrophy. Neuromuscul Disord. 1. April 2019;29(4):321–9. Du L, Dong H, Miao C, Jia F, Shan L. Analysis of scores of Symptom Checklist 90 (SCL-90) questionnaire of 182 parents of children with spinal muscular atrophy: a cross-sectional study. Transl Pediatr. November 2022;11(11):1776–86. Ergenekon AP, Gümüş Z, Yegit CY, Cenk M, Gulieva A, Kalyoncu M, u. a. Depression, anxiety, and sleep quality of caregivers of children with spinal muscular atrophy. Pediatr Pulmonol. Juni 2023;58(6):1697–702. Leibrock B, Landfeldt E, Hussong J, Huelle T, Mattheus H, Thiele S, u. a. Areas of improvement in the medical care of SMA: evidence from a nationwide patient registry in Germany. Orphanet J Rare Dis. 21. Februar 2023;18(1):32. Landfeldt E, Leibrock B, Hussong J, Thiele S, Abner S, Walter MC, u. a. Self-Reported Health-Related Quality of Life of Children with Spinal Muscular Atrophy: Preliminary Insights from a Nationwide Patient Registry in Germany. J Neuromuscul Dis. 11(1):117–28. Goodman R. The Strengths and Difficulties Questionnaire: a research note. J Child Psychol Psychiatry. Juli 1997;38(5):581–6. Becker A, Wang B, Kunze B, Otto C, Schlack R, Hölling H, u. a. Normative Data of the Self-Report Version of the German Strengths and Difficulties Questionnaire in an Epidemiological Setting. Z Für Kinder- Jugendpsychiatrie Psychother. November 2018;46(6):523–33. Woerner W, Becker A, Friedrich C, Klasen H, Goodman R, Rothenberger A. [Normal values and evaluation of the German parents’ version of Strengths and DIfficulties Questionnaire (SDQ): Results of a representative field study]. Z Kinder Jugendpsychiatr Psychother. Mai 2002;30(2):105–12. Franke GH. Mini-Symptom-Checklist. Göttingen: Hogrefe; 2017. RISKS TO MENTAL HEALTH: AN OVERVIEW OF VULNERABILITIES AND RISK FACTORS BACKGROUND PAPER BY WHO SECRETARIAT FOR THE DEVELOPMENT OF A COMPREHENSIVE MENTAL HEALTH ACTION PLAN. In 2012 [zitiert 30. April 2024]. Verfügbar unter: https://www.semanticscholar.org/paper/RISKS-TO-MENTAL-HEALTH%3A-AN-OVERVIEW-OF-AND-RISK-BY/bfbedefc6db265ca474add283af034e8f55cc4de Hölling H, Schlack R, Petermann F, Ravens-Sieberer U, Mauz E, KiGGS Study Group. Psychische Auffälligkeiten und psychosoziale Beeinträchtigungen bei Kindern und Jugendlichen im Alter von 3 bis 17 Jahren in Deutschland – Prävalenz und zeitliche Trends zu 2 Erhebungszeitpunkten (2003–2006 und 2009–2012). Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. 1. Juli 2014;57(7):807–19. Price J, Kassam-Adams N, Alderfer MA, Christofferson J, Kazak AE. Systematic Review: A Reevaluation and Update of the Integrative (Trajectory) Model of Pediatric Medical Traumatic Stress. J Pediatr Psychol. 2016;41(1):86–97. von Gontard A, Backes M, Laufersweiler-Plass C, Wendland C, Lehmkuhl G, Zerres K, u. a. Psychopathology and familial stress - comparison of boys with Fragile X syndrome and spinal muscular atrophy. J Child Psychol Psychiatry. Oktober 2002;43(7):949–57. Kruitwagen-van Reenen ET, van der Pol L, Schröder C, Wadman RI, van den Berg LH, Visser-Meily JMA, u. a. Social participation of adult patients with spinal muscular atrophy: Frequency, restrictions, satisfaction, and correlates. Muscle Nerve. Dezember 2018;58(6):805–11. Wan HWY, Carey KA, D’Silva A, Kasparian NA, Farrar MA. „Getting ready for the adult world“: how adults with spinal muscular atrophy perceive and experience healthcare, transition and well-being. Orphanet J Rare Dis. 2. April 2019;14(1):74. von Gontard A, Rudnik-Schöneborn S, Zerres K. Stress and coping in parents of children and adolescents with spinal muscular atrophy. Klin Padiatr. Juli 2012;224(4):247–51. Pinquart M. Do the parent-child relationship and parenting behaviors differ between families with a child with and without chronic illness? A meta-analysis. J Pediatr Psychol. August 2013;38(7):708–21. Supplementary Files Additionalfile1.pdf Additionalfile2.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 23 Nov, 2025 Reviewers invited by journal 21 Nov, 2025 Editor assigned by journal 20 Nov, 2025 First submitted to journal 11 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8086836","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":548533473,"identity":"7ee52a45-aea9-4537-9374-cdd748f66c95","order_by":0,"name":"Justine Hussong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIiWNgGAWjYBACxgYgkQDEBlABOQYewloYG5C1GBPUArMIriWxgZAW5hnpzx883GHDYC6R/vjDxx216RvOHH/A8LENjxUzcgwbEs+kMVjOyDGTnHnmeO6Gsz0GjDPxa2FsSGw7zGBwI4eNmbftWO6G8zwMQAY+LekPgVr+A7WkP/4M1JJucJ79AfNfvFoSgA5rOwDUkmAgzdtWk2BwtsGAmRGflp43hjMS25J5DM68Afql7YDhzDNnDA72nMOtxbA9/cHHn212cgbHQSHWVifPdyb94YMfZXi0NEBoWGQcBpMHcGtgYJBH49fhUzwKRsEoGAUjFAAA2+RZbor7mYUAAAAASUVORK5CYII=","orcid":"","institution":"Child and Adolescent Psychiatry, Saarland University Hospital, Homburg","correspondingAuthor":true,"prefix":"","firstName":"Justine","middleName":"","lastName":"Hussong","suffix":""},{"id":548533474,"identity":"bab46f18-0329-4894-83fc-f376566158e9","order_by":1,"name":"Berenike Leibrock","email":"","orcid":"","institution":"University of Saarland, Department of Medicine, Saarbruecken","correspondingAuthor":false,"prefix":"","firstName":"Berenike","middleName":"","lastName":"Leibrock","suffix":""},{"id":548533475,"identity":"794dfa6d-abd0-4b8c-8932-c92af06f7745","order_by":2,"name":"Tabea Huelle","email":"","orcid":"","institution":"University of Saarland, Department of Medicine, Saarbruecken","correspondingAuthor":false,"prefix":"","firstName":"Tabea","middleName":"","lastName":"Huelle","suffix":""},{"id":548533476,"identity":"eb63351d-2cb5-4e17-b697-404f91452a4a","order_by":3,"name":"Hannah Mattheus","email":"","orcid":"","institution":"Clinical Psychology and Psychotherapy, Saarland University, Saarbruecken","correspondingAuthor":false,"prefix":"","firstName":"Hannah","middleName":"","lastName":"Mattheus","suffix":""},{"id":548533477,"identity":"88e1b25f-3390-407e-b758-61488af3042e","order_by":4,"name":"Erik Landfeldt","email":"","orcid":"","institution":"IQVIA Stockholm","correspondingAuthor":false,"prefix":"","firstName":"Erik","middleName":"","lastName":"Landfeldt","suffix":""},{"id":548533478,"identity":"ecfb3e8d-bda9-43d9-b0b5-451b2a5fe024","order_by":5,"name":"Simone Thiele","email":"","orcid":"","institution":"Friedrich Baur Institute at the Department of Neurology, LMU University Hospital, Munich","correspondingAuthor":false,"prefix":"","firstName":"Simone","middleName":"","lastName":"Thiele","suffix":""},{"id":548533479,"identity":"c8dc1549-d805-495d-877a-842e8dd6a84e","order_by":6,"name":"Maggie C. Walter","email":"","orcid":"","institution":"Friedrich Baur Institute at the Department of Neurology, LMU University Hospital, Munich","correspondingAuthor":false,"prefix":"","firstName":"Maggie","middleName":"C.","lastName":"Walter","suffix":""},{"id":548533480,"identity":"9ee4e95c-2bad-4f2b-9272-ad508c33fbf4","order_by":7,"name":"Michael Zemlin","email":"","orcid":"","institution":"Department of General Pediatrics and Neonatology, Saarland University, Homburg","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Zemlin","suffix":""},{"id":548533481,"identity":"f6180dd3-a02e-4449-944c-ffdb25aec093","order_by":8,"name":"Eva Moehler","email":"","orcid":"","institution":"Child and Adolescent Psychiatry, Saarland University Hospital, Homburg","correspondingAuthor":false,"prefix":"","firstName":"Eva","middleName":"","lastName":"Moehler","suffix":""},{"id":548533482,"identity":"7c78adfc-48cf-45f4-b21f-7e5df8976ec0","order_by":9,"name":"Ulrich Dillmann","email":"","orcid":"","institution":"Department of Neurology, Saarland University, Homburg","correspondingAuthor":false,"prefix":"","firstName":"Ulrich","middleName":"","lastName":"Dillmann","suffix":""},{"id":548533483,"identity":"8041bffc-cb12-4884-ab56-430946e9107f","order_by":10,"name":"Marina Flotats-Bastardas","email":"","orcid":"","institution":"Department of General Pediatrics and Neonatology, Division of Neuropediatrics, Saarland University, Homburg","correspondingAuthor":false,"prefix":"","firstName":"Marina","middleName":"","lastName":"Flotats-Bastardas","suffix":""}],"badges":[],"createdAt":"2025-11-11 12:29:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8086836/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8086836/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97115289,"identity":"9e83336b-2990-467a-97f4-1f9624cf6515","added_by":"auto","created_at":"2025-12-01 07:03:30","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":12009,"visible":true,"origin":"","legend":"","description":"","filename":"ojrdOJRDD2501699.xml","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/fc3fc34c8532f12155d1f920.xml"},{"id":97141449,"identity":"47c043cf-fd50-4ad5-ba7c-669de4088c4f","added_by":"auto","created_at":"2025-12-01 10:06:42","extension":"xml","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1111,"visible":true,"origin":"","legend":"","description":"","filename":"OJRDD250169927362.go.xml","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/bfa6753bcf7534645cda1e2b.xml"},{"id":97115288,"identity":"4a7f051b-f056-4b85-a890-f9d152b4a2ef","added_by":"auto","created_at":"2025-12-01 07:03:30","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":865,"visible":true,"origin":"","legend":"","description":"","filename":"OJRDD2501699Import.xml","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/5d90828a97b57b45d368dddb.xml"},{"id":97115293,"identity":"9ec1c705-fd14-49e8-b14f-9c58d0e92274","added_by":"auto","created_at":"2025-12-01 07:03:31","extension":"xml","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":150473,"visible":true,"origin":"","legend":"","description":"","filename":"OJRDD25016990enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/9a0f3f041434db8ae8e7740a.xml"},{"id":97115294,"identity":"0eb33979-3c6c-4906-8da8-972f529963f1","added_by":"auto","created_at":"2025-12-01 07:03:31","extension":"pptx","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":173289,"visible":true,"origin":"","legend":"","description":"","filename":"Figures123.pptx","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/51fd3d956a98ccc0428002b1.pptx"},{"id":97115295,"identity":"79bb3918-a4d8-498c-b774-89166934f260","added_by":"auto","created_at":"2025-12-01 07:03:31","extension":"xml","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":148472,"visible":true,"origin":"","legend":"","description":"","filename":"OJRDD25016990structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/425d3dcd1d1dfd8ca1a00048.xml"},{"id":97115296,"identity":"6287c394-7eaf-424c-ab51-8c220eb8d727","added_by":"auto","created_at":"2025-12-01 07:03:31","extension":"html","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":160071,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/a76be5fed895ee918751becd.html"},{"id":97115286,"identity":"646d741a-b7ab-4332-9338-f30fa521849f","added_by":"auto","created_at":"2025-12-01 07:03:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":34234,"visible":true,"origin":"","legend":"\u003cp\u003eClinically relevant psychological symptoms in children, adults with SMA and caregivers/close relatives (self-report)\u003c/p\u003e","description":"","filename":"Slide1.png","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/593387c780516b329f6abb82.png"},{"id":97115287,"identity":"d6ea4ce6-09a1-4040-ad50-074e9e706982","added_by":"auto","created_at":"2025-12-01 07:03:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":55681,"visible":true,"origin":"","legend":"\u003cp\u003eItem analysis of SDQ scales ‚Emotional problems‘, ‚Peer problems‘ and ‚Hyperactivity‘ (proxy-report)\u003c/p\u003e","description":"","filename":"Slide2.png","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/b8e2ed778451de30c1dfbe77.png"},{"id":97115285,"identity":"313f342e-5d60-4fd0-9b68-e70603dc89bd","added_by":"auto","created_at":"2025-12-01 07:03:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":57330,"visible":true,"origin":"","legend":"\u003cp\u003eItem analysis of Mini-SCL scales ‚Depression‘, ‚Anxiety‘ and ‚Somatization‘ in adults with SMA (self-report)\u003c/p\u003e","description":"","filename":"Slide3.png","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/cc0939f20eda1f52d649dd78.png"},{"id":97145011,"identity":"561f5795-d6c1-4349-a53b-06eb2833c327","added_by":"auto","created_at":"2025-12-01 10:12:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1307675,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/12a6dc75-ed16-4003-9e95-8b53ef29227b.pdf"},{"id":97115291,"identity":"9bdfa42f-21be-4abb-91f3-6d18d0b3fb27","added_by":"auto","created_at":"2025-12-01 07:03:30","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":581890,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/8d364068ad8501513bcd1146.pdf"},{"id":97115292,"identity":"6e626bba-d0eb-470d-8e70-89e98376566f","added_by":"auto","created_at":"2025-12-01 07:03:30","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":543054,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8086836/v1/097106513efaed419b593bc1.pdf"}],"financialInterests":"","formattedTitle":"Psychological symptoms in individuals with Spinal Muscular Atrophy (SMA) and their caregivers – results from a nation-wide study in Germany","fulltext":[{"header":"Background","content":"\u003cp\u003ePersons with rare diseases or chronic illnesses have a higher risk of developing mental health problems, especially anxiety and depression (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Affected children and adolescents often develop symptoms due to maladjustment, school problems, or reduced social participation. Their parents and caregivers usually report higher perceived stress and lower quality of life which increase the risk of own psychological problems (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). A recent systematic analysis of the psychosocial situation of caregivers of children with spinal muscular atrophy (SMA) identified multiple stressors that may cause mental health problems in the long term, e.g. parental distress or insufficient supportive care (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe present paper focuses on psychological symptoms in persons with SMA and their caregivers, as little is known about the associations between symptoms of caregiver and patient, as well as about the impact of motor function and new pharmacological treatments on mental health of both.\u003c/p\u003e\n\u003ch3\u003eSpinal muscular atrophy\u003c/h3\u003e\n\u003cp\u003eSpinal muscular atrophy (SMA) is a rare autosomal recessive disease causing degeneration and loss of motor neurons of the spinal cord leading to a progressive impairment of motor skills, physical disability and in severe cases to a reduced life expectancy (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Prevalence of SMA in Europe is about 13\u0026ndash;14 per 100,000 live births (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) and is caused by mutations in the survival motor neuron (\u003cem\u003eSMN1\u003c/em\u003e) gene (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe severity of SMA is variable and can be classified into different phenotypes according to age of symptom onset and highest achieved motor function (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In severe SMA type 1 (SMA1) symptoms begin in the first half year of life, children never learn to sit and have a reduced life expectancy (\u0026lt;\u0026thinsp;2 years) when untreated. Persons affected by SMA type 2 (SMA2) show motor regression before the age of 18 months. Sitting is the highest achievable motor function but can be lost over the time. Without therapy life expectancy is reduced. In SMA type 3 (SMA3), children learn to walk on his own but muscle weakness appear beyond the age of 18 months, and without therapy some of them are over the time wheel chair bound. Individuals with SMA type 4 (SMA4) show muscle weakness in the adulthood but they don\u0026rsquo;t lose the ability to walk. This existence and frequency of this type is controversial, as in many patients, first mild (less disabling) symptoms may appear in young adulthood (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn the last years, new gene therapy treatments became available (i.e., nusinersen, onasemnogene abeparvovec, and risdiplam) leading to major improvements of the motor function and thus improving dramatically the prognosis of SMA (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Therefore the prevalence of SMA is increasing and new phenotypes are appearing, thus a classification by the current level of current motor function (non-sitters, sitters, walkers) help clinicians to adjust and allow the appropriate medical care (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eMental health problems in individuals with SMA and their caregivers\u003c/h2\u003e\u003cp\u003ePsychological symptoms in children with SMA are reported in 12%-40% (\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Externalizing symptoms (e.g. attention-deficit, hyperactivity, aggressive behavior) are rather uncommon (in 0\u0026ndash;2%) and not higher than in control groups, whereas slightly higher rates (in 7%-19%) of internalizing symptoms (e.g. depression, anxiety) are reported (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), except for one Chinese study that found even higher rates of anxiety (40%) and depression (25%) in children with SMA (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eLess is known about psychological symptoms in adults with SMA. In a symptom list assessed in 70 adult German patients with SMA2\u0026thinsp;+\u0026thinsp;3 compared to 59 healthy controls, frequency of self-reported anxiety (17%), loss of interest (9%), concentration difficulties (20%), and insomnia (31%) was not significantly increased in SMA patients and did not differ between SMA2 and SMA3 (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Further evaluations from Germany and Malaysia reported anxiety and depressive symptoms in 29\u0026ndash;38% of adults with SMA (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eRegarding caregivers, studies report clinical depression symptoms in 21\u0026ndash;36%, and clinical anxiety symptoms in 26\u0026ndash;76% (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Parental depression symptoms were associated with higher children\u0026rsquo;s and parental age, patient living at home and medical treatment (with nursinersen), and absence of rehabilitation management was associated with caregivers\u0026rsquo; anxiety symptoms (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The association of parental emotional symptoms and SMA type were inconsistent (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe effect of modern SMA medical treatment on psychological symptoms in patients is scarcely examined so far. One study evaluated 26 patients (14 adults, 12 children) before and after nursinersen treatment and showed no change of depressive symptoms after 6 months of treatment (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Another study from Turkey found even higher depression scores in caregivers of treated SMA children compared to untreated children (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe aim of our study was to explore psychological symptoms in children and adults with SMA, as well as in their caregivers.\u003c/p\u003e\u003c/div\u003e"},{"header":"Methods","content":"\u003cp\u003eThe present study is part of a cross-sectional, observational assessment of individuals with SMA and their caregivers on health-related quality of life and psychological symptoms (20,21).\u003c/p\u003e\n\u003ch2\u003e\u003cem\u003eSample\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003ePatients were recruited trough the national German SMA registry (www.sma-register.dewww.sma-register.de), which is part of the \u0026lsquo;Translational Research in Europe for the Assessment and Treatment of Neuromuscular Disease\u0026rsquo; (TREAT-NMD) network. TREAT-NMD aims to facilitate recruitment of patients to neuromuscular research, in order to raise awareness and improve treatment methods. The enrollment in the SMA registry is voluntary and free of charge. To be recruited for the present study, participants had to meet all of the following criteria: (1) genetically confirmed diagnosis of SMA, (2) \u0026ge; 4 years of age, and (3) currently residing in Germany. A study invitation and information sheet was sent via email by the SMA registry to all listed individuals meeting the study criteria. In children (participants \u0026lt; 18 years), parents/caregivers were contacted. After given informed consent, patients and one of their caregivers were invited to complete a questionnaire administered online via the study website www.soscisurvey.de. The study was approved by the local Ethics Committee of the Saarland Medical Association (February 4, 2020, protocol no. 09/20) and was registered at the German clinical trial register (DRKS00022876).\u003c/p\u003e\n\u003ch2\u003e\u003cem\u003eMaterials and collected data\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eThe online questionnaire included a \u003cem\u003egeneral part about demographic and clinical characteristics\u003c/em\u003e which is described in detail by\u0026nbsp;Leibrock et al.\u0026nbsp;(20).The data collection took place between June and September 2021.\u003c/p\u003e\n\u003cp\u003eTo assess psychological symptoms in children and adolescents with SMA, the parental version of the \u003cem\u003eStrengths and Difficulties Questionnaire (SDQ)\u003c/em\u003e was completed by parents/caregivers in children aged 3 years or older, and as self-report in children from the age of 12 years onwards. The SDQ is an internationally validated, standardized screening questionnaire for 3-17 year old children and adolescents consisting of 25 items about psychological and behavioral symptoms, each scored on a three-point scale (not true (0) \u0026ndash; somewhat true (1) \u0026ndash; certainly true(2)) (22). Five subscales can be calculated (each from 5 items): emotional symptoms (5 items), conduct problems (5 items), hyperactivity (5 items), peer problems (5 items) and prosocial behavior (5 items).\u0026nbsp;The total problem behavior score (TPBS) is calculated as a sum of the first four scale scores except \u0026lsquo;prosocial behavior\u0026rsquo;. According to German norms, subscale scores and the TBPS were divided into clinical (\u0026gt;90\u003csup\u003eth\u003c/sup\u003e percentile), borderline (80-90\u003csup\u003eth\u003c/sup\u003e percentile), and average (\u0026lt;80\u003csup\u003eth\u003c/sup\u003e percentile) cut-offs\u0026nbsp;(23,24). The clinical cut-off at the 90\u003csup\u003eth\u003c/sup\u003e percentile was used as identification of clinically relevant mental health symptoms.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo assess psychological symptoms in adult individuals with SMA and in parents/caregivers, the\u003cem\u003e\u0026nbsp;\u003c/em\u003eGerman\u003cem\u003e\u0026nbsp;Mini-Symptom-Checklist (Mini-SCL)\u0026nbsp;\u003c/em\u003eself-report was completed (25). The Mini-SCL, also known as Brief Symptom Inventory (BSI-18) is a validated and reliable short form of the\u0026nbsp;Symptom Checklist (SCL-90-R). Three scales (somatization, depression and anxiety) assessed by 6 items each, as well as the Global Severity Index (GSI) based on all 18 items can be calculated. The 18 items refer to current psychological symptoms and are rated on a 5-point Likert-scale ranging from 0 (not at all) to 4 (extremely). Psychometric properties of the Mini-SCL are satisfactory or good for all subscales and the GSI. According to German norms, the 93\u003csup\u003erd\u003c/sup\u003e percentile (~T=65) is used as a cut-off for clinically relevant symptoms\u0026nbsp;(25).\u0026nbsp;The parent/caregiver also filled in the \u003cem\u003eMini-SCL self-version\u0026nbsp;\u003c/em\u003ein order to assess their own mental health symptoms.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eStatistical calculations were performed with\u0026nbsp;IBM SPSS Statistics Version 25. Descriptive data was reported\u0026nbsp;by relative and absolute frequencies for non-parametric variables and by means and standard deviation (SD) for parametric data. Group differences for nominal data were calculated by Chi\u003csup\u003e2\u003c/sup\u003e-tests and Fisher\u0026rsquo;s exact tests. Correlations were calculated by Spearman correlations. Results are considered as significant at a p‐value \u0026lt; .05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOut of 742 patients enrolled in the SMA patient registry, 513 met the inclusion criteria, and 117 agreed to participate in the study. Completed questionnaires on mental health problems are available for n=21 children, n=82 adults and n=67 caregivers. Descriptive data of the sample is outlined in \u003cstrong\u003eTable 1\u003c/strong\u003e. Participants were classified based on SMA subtype (i.e., SMA1, 2, and 3) as well as according to current best motor function of the lower limb (i.e., non-sitter, sitter, and walker). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003eDescriptive data by SMA subtype (sex, age, motor function, medication intake)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"567\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChildren (\u0026lt;18 years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdults\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN=103\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN=21\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN=82\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eMean age in years (SD)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cem\u003e35.8 (19.0)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cem\u003e9.7 (4.5)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003e42.5 (15.1)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eSex distribution in % (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eMale\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e47.6 (49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e47.6 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e47.6 (39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eFemale\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e51.5 (53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e52.4 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e51.2 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eOther\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e1.0 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e1.2 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eSubtype in % (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eSMA1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e6.8 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e19.0 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e3.7 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eSMA2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;35.9 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e42.9 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e34.1 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eSMA3\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e57.3 (59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e38.1 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e62.2 (51)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eBest current motor function in % (n)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eNon-sitter\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e9.7 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e14.3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e8.5 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eSitter\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e64.1 (66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e52.4 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e67.1 (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eWalker\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e26.2 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e33.3 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e24.4 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eMedication intake in % (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eNone\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e22.3 (23)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e9.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e25.6 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eNursinersen\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e55.3 (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e71.4 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e51.2 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cem\u003eRisdiplam\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e22.3 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e19.0 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e23.2 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eClinically relevant mental health symptoms in children, adults and caregivers\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1\u0026nbsp;\u003c/strong\u003epresents rates of psychological symptoms in the clinical and average range in children, adults with SMA and caregivers focusing on the assessed symptom scales and \u003cstrong\u003etable 2\u003c/strong\u003e shows only clinically relevant psychological symptoms in children and adults with SMA in the total sample, differed by SMA subtypes and motor function. In children (n=21), 10% show relevant mental health problems being emotional problems (19%), hyperactivity (10%) and peer problems (10%) the most common one recorded by SDQ parental report. Regarding SMA types, peer problems were mainly reported in SMA1 (50%) and emotional problems were highest in SMA3 (38%). Regarding motor function, emotional problems were seen in non-sitters and walkers (33% and 29% respectively). Self-reports were available for n=7 children and no symptoms in the clinical range were described. Only one child reported borderline (80\u003csup\u003eth\u003c/sup\u003e-90\u003csup\u003eth\u003c/sup\u003e percentile) symptoms of hyperactivity, and another one reported lower prosocial behavior in the borderline range. Mean scores (SDs) of the SDQ scales (self- and parental report) are summarized in the \u003cstrong\u003e\u003cem\u003eadditional file 1.\u003c/em\u003e\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2:\u0026nbsp;\u003c/strong\u003eClinically relevant psychological symptoms in children (proxy report),\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eadults with SMA and caregivers/close relatives (self-report)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"804\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSMA subtypes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 182px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower limb motor function\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSMA1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSMA2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSMA3\u003csup\u003ee\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003csup\u003ec\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-Sitters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSitters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWalkers\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003csup\u003ec\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChildren with SMA \u0026ndash;\u0026nbsp;\u003c/strong\u003e\u003cem\u003eParent reported SDQ \u0026ndash; % in the clinical range (n)\u003csup\u003ea\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=21\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cem\u003en=4\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=9\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=8\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=3\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=11\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cem\u003en=7\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eEmotional problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e19.0 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e11.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e37.5 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e33.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e9.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e28.6 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eConduct problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eHyperactivity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e9.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e11.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e12.5 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e9.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e14.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003ePeer Problems\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e9.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e50.0 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.029*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e18.2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eProsocial Behavior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e9.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e11.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e12.5 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e33.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e14.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdults with SMA \u0026ndash;\u0026nbsp;\u003c/strong\u003e\u003cem\u003eSelf-reported Mini-SCL \u0026ndash; % in the clinical range (n)\u003csup\u003ea\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=82\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cem\u003en=3\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=28\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=51\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=7\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=55\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cem\u003en=20\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e11.0 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e3.6 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e15.7 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e14.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e9.1 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e15.0 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eAnxiety\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e14.6 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e3.6 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e21.6 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e28.6 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e12.7 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e15.0 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eSomatization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e14.6 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e33.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e10.7 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e15.7 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e28.6 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e14.5 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e10.0 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e13.4 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e3.6 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e19.6 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e28.6 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e9.1 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e20.0 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCaregivers \u0026ndash;\u0026nbsp;\u003c/strong\u003e\u003cem\u003eSelf-reported Mini-SCL \u0026ndash; % in the clinical range (n)\u003csup\u003eb\u003c/sup\u003e\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;in % (n)\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=67\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cem\u003en=6\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=25\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=36\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=10\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003en=40\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cem\u003en=17\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e11.9 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e33.3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e16.7 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.021* (1\u0026gt;2)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e15.0 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e11.8 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eAnxiety\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e14.9 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e50.0 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e4.0 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e16.7 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.022* (1\u0026gt;2)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e10.0 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e15.0 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e17.6 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eSomatization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e14.9 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e16.7 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e4.0 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e22.2 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e20.0 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e12.5 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e17.6 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 261px;\"\u003e\n \u003cp\u003eTotal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e14.9 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e16.7 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e4.0 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e22.2 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e10.0 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e15.0 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e17.6 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003en.s.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e based on parental SDQ (Strengths and Difficulties Questionnaire) scores \u0026gt; 90\u003csup\u003eth\u003c/sup\u003e percentile\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u0026nbsp;\u003c/sup\u003ebased on self-reported Mini-SCL (Symptom Checklist) scores \u0026gt; T=65 (~93\u003csup\u003erd\u003c/sup\u003e percentile)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ec\u003c/sup\u003e Fisher\u0026rsquo;s Exact test if not otherwise specified.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ed\u003c/sup\u003e Depression scale reports available for n=81 (n=27 in type II, n=54 in non-sitters)\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ee\u0026nbsp;\u003c/sup\u003eSMA3 also included one patient with SMA4\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026lt; Table 2 \u0026gt;\u0026gt;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 2\u003c/strong\u003e presents an item analysis of the three SDQ scales \u0026lsquo;emotional\u0026rsquo;, \u0026lsquo;peer problems\u0026rsquo; and \u0026lsquo;hyperactivity\u0026rsquo; in which symptoms were reported most often in the clinical range. The most frequent reported symptoms in the emotional problems scale were \u0026lsquo;often complains of headaches, stomach-aches or sickness\u0026rsquo; (in 11/21 children) and \u0026lsquo;nervous or clingy in new situations, easily loses confidence\u0026rsquo; (in 9/21 children). Most often reported items in the peer problems scale were \u0026lsquo;gets on better with adults than with other children\u0026rsquo; (in 12/21 children) and \u0026lsquo;rather solitary, tends to play alone\u0026rsquo; (in 7/21 children). \u0026nbsp;Regarding the hyperactivity scale, most frequent reported symptoms are \u0026lsquo;doesn\u0026rsquo;t think things out before acting\u0026rsquo; and \u0026lsquo;doesn\u0026rsquo;t see tasks through to the end\u0026rsquo; (in 8/21 children each).\u003c/p\u003e\n\u003cp\u003eIn adults (n=82) clinically relevant psychological symptoms recorded by Mini-SCL self-report are reported by 13% of adults \u003cstrong\u003e(figure 1 and table 2)\u003c/strong\u003e. Adults with SMA3 had the highest rates of anxiety (22%) and depression (16%), whereas somatization was reported in all SMA types. Regarding motor function, symptom rates were highest among non-sitters (29%) mainly because of anxiety and somatization, followed from walkers (20%) mainly because of depression and anxiety. However, no differences between SMA types or motor function reached statistical significance.\u003c/p\u003e\n\u003cp\u003eAn item analysis of the \u0026lsquo;depression\u0026rsquo;, \u0026lsquo;anxiety\u0026rsquo; and \u0026lsquo;somatization\u0026rsquo; scales of the adult self-report is shown in \u003cstrong\u003efigure 3.\u0026nbsp;\u003c/strong\u003eThe most frequent depression symptoms were \u0026rsquo;feeling lonely\u0026rsquo; and \u0026lsquo;feeling hopeless about the future\u0026rsquo;. The most frequent anxiety symptoms were \u0026lsquo;nervousness or shakiness inside\u0026rsquo; and \u0026lsquo;feeling tense or keyed up\u0026rsquo;. Regarding somatization, the most frequent symptoms were \u0026lsquo;feeling weak in parts of the body\u0026rsquo; and \u0026lsquo;numbness or tingling in parts of the body\u0026rsquo;.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMental health symptoms of caregivers n=67 (mostly parents of 21 children, 46 adults) are outlined in \u003cstrong\u003efigure 1 and table 2\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eParents reported own clinically relevant psychological symptoms in 15% of cases. Regarding SMA type, 22% of caregivers of individuals with SMA3 complain about psychological symptoms, mainly because of somatization whereas 17% of caregivers of individuals with SMA1 mainly complain about anxiety and depression. Regarding motor function, symptom rates were highest among caregivers of walkers (18%) because of anxiety and somatization, followed from sitters (15%) because of anxiety and depression and non-sitters (10%) because of somatization.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAssociation of patient and caregiver mental health symptoms\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eParental symptoms of depression are significantly associated with their children\u0026rsquo;s emotional problems, peer problems and the total score. Parental anxiety was correlated to children\u0026rsquo;s conduct problems. In adults with SMA, nearly all scales were significantly correlated to those in their parents/caregivers, revealing a strong association between the symptoms of patient and caregiver. Significant correlations between mental health symptoms of SMA patients and of their parents and caregivers are shown in the \u003cstrong\u003e\u003cem\u003eadditional file 2\u003c/em\u003e\u003c/strong\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAssociation of mental health symptoms and pharmacological treatment\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003ereports mental health symptoms of children, adults and caregivers depending on their current pharmacological treatment. Overall, there is no statistical difference in the extent of psychological symptoms between patients with no medication, those treated with nursinersen and those treated with risdiplam. Regarding children with SMA, clinical scores were only reported in individuals treated with medication (n=19) in contrast to those with no medication (n=2). In adults with SMA (medication n=61, no medication n=21) clinical scores for somatization and anxiety where higher in those individuals without medication (24% and 19% vs 11% and 13%). The most frequent reported symptoms were somatization, with the highest rates in persons with no medication (23.8%) and those treated with risdiplam (21.1%), in contrast to lower symptom rates (7.1%) in the group treated with nursinersen. Mental health of caregivers does not differ between the medication groups, as well. The most frequent reported symptoms are somatization in the risdiplam group (21.4%), anxiety and depression in the nursinersen group (17.1% each), as well as anxiety and total symptoms in the \u0026lsquo;no medication\u0026rsquo; group (16.7% each).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3:\u003c/strong\u003e Association of mental health symptoms (children, adults and caregivers) and pharmacological treatment\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"748\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo medication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedication\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNursinersen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRisdiplam\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChildren with SMA \u0026ndash;\u0026nbsp;\u003c/strong\u003e\u003cem\u003eParent reported SDQ \u0026ndash; % in the clinical range (n)\u003csup\u003ea\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=2\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=19\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=15\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=4\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eEmotional problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e21.1 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e13.3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e50.0 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eConduct problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eHyperactivity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e10.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e13.3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003ePeer Problems\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e50.0 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e5.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e6.7 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eProsocial Behavior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e10.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e6.7 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e25.0 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdults with SMA \u0026ndash;\u0026nbsp;\u003c/strong\u003e\u003cem\u003eSelf-reported Mini-SCL \u0026ndash; % in the clinical range (n)\u003csup\u003eb\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=21\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=61\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=42\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=19\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e9.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e11.5 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e11.9 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e10.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eAnxiety\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e19.0 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e13.1 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e11.9 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e15.8 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eSomatization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e23.8 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e11.5 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e7.1 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e21.1 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e9.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e14.8 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e14.3 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e15.8 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCaregivers \u0026ndash;\u0026nbsp;\u003c/strong\u003e\u003cem\u003eSelf-reported Mini-SCL \u0026ndash; % in the clinical range (n)\u003csup\u003eb\u003c/sup\u003e\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=12\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=55\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=41\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eN=14\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e8.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e12.7 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e17.1 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eAnxiety\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e16.7 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e14.5 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e17.1 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e7.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eSomatization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e8.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e16.4 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e14.6 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e21.4 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eTotal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e16.7 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e14.5 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 130px;\"\u003e\n \u003cp\u003e17.1 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e7.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e based on parental SDQ (Strengths and Difficulties Questionnaire) scores \u0026gt; 90\u003csup\u003eth\u003c/sup\u003e percentile\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u0026nbsp;\u003c/sup\u003ebased on self-reported Mini-SCL (Symptom Checklist) scores \u0026gt; T=65 (~93\u003csup\u003erd\u003c/sup\u003e percentile)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ec\u003c/sup\u003e Fisher\u0026rsquo;s Exact test revealed no significant differences between medication and no medication group\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026lt; Table 3 \u0026gt;\u0026gt;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this is the first detailed description of psychological symptoms assessed by standardized questionnaires and self- and proxy-reports in SMA children, adults and their caregivers. Our data include all SMA subtypes, levels of motor function and pharmacological treatment statuses. Children were less affected by psychological symptoms than adults with SMA, with internalizing symptoms being the most common symptoms reported in both groups. Internalizing symptoms were as well present in caregivers, especially in those of persons with SMA1. Caregiver and patient psychological symptoms were strongly associated, whereas pharmacological treatment seem to not affect symptom rates.\u003c/p\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003ePsychological symptoms in children\u003c/h2\u003e\u003cp\u003ePsychological symptoms in children ranged from 0% in self-reports to emotional problems in 19% rated by parents. Children and adolescents rated themselves as less impaired as their parents did. The self-ratings must be interpreted cautiously, because only 7 adolescents (age range 12\u0026ndash;16 years) completed the questionnaires. Otherwise, in parental rating, reported symptoms may have been mixed with parents\u0026rsquo; own worries about their child and perceived stress which could overestimate symptom rates.\u003c/p\u003e\u003cp\u003ePsychological symptoms in children were assessed by self-report only by Yao et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) before, who found much higher rates of anxiety (40%) and depression (25%), being unusually high compared to other studies on children with SMA (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe low rates of psychological symptoms (especially in children) in our study may result from the access to medical care and social support systems, which is fairly good for children (but not quite for SMA adults) in Germany and allows a sufficient participation in social and public life (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In our sample, more children with SMA1 (21 vs. 8%) were included, as many more children received pharmacological treatment (92% vs. 5%) than in the Chinese study population (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Also, in our sample, all children received supportive therapy, especially physiotherapy (vs. 54% of Chinese children with \u0026lsquo;rehabilitation exercise\u0026rsquo;) and all German children visited an appropriate school (vs. traditional schooling in 69% and academic delay in 55% in Chinese children) (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). The Chinese colleagues also found a specific association between psychological symptoms and the less available social and medical support (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), which is in line with research outcomes stating clearly that social participation, e.g. school visits, and an adequate medical care are protective factors for mental health (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn line with other publications, internalizing symptoms (as anxiety, depression) were more common than externalizing problems (e.g. aggressive behavior, hyperactivity, ADHD symptoms) in the present sample (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). All in all, the rates of internalizing symptoms are only slightly higher than known in the German normative population (~\u0026thinsp;10\u0026ndash;15%; (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)) and could be symptoms of so-called \u0026lsquo;pediatric medical traumatic stress\u0026rsquo; that occurs in patients and parents after learning about a serious diagnosis or invasive medical treatments (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFurther, most SMA patients have good cognitive and adaptive abilities (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) are further protective factors that promote mental well-being, as e.g. genetic syndromes that are associated with intellectual disability reveal much higher rates of concomitant psychiatric diagnoses than individuals with SMA (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThere was only one significant difference between SMA types, for peer problems were mainly reported in SMA1 (in 50%), but only by parental rating. Regarding the item analysis of the peer problems scale, it was reported that affected children \u0026lsquo;get on better with adults than with other children\u0026rsquo; and \u0026lsquo;rather solitary, tend to play alone\u0026rsquo;, which could reflect a social exclusion and missing social participation opportunities in children with SMA. Peer problems were not assessed in children with SMA before, but were also higher in a sample of children with rare diseases (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Children with SMA1 have the most severe type of disease, with extremely limiting physical impairments, e.g. including the need of ventilatory support, which of course may lead to social problems or difficulties in interacting with other children. Otherwise, with the new pharmacological treatments, these children have a much better outcome and a longer survival prognosis, so that increasing and improving the opportunities to social participation in these patients is a relevant clinical implication for the future.\u003c/p\u003e\u003cp\u003eRegarding the level of motor function, our data showed no significant differences in mental health symptoms between the groups. The association of mental health and motor function of the lower limbs was not assessed before, so we may assume that motor function may be independent from psychological symptoms. Hopefully, future studies with larger sample sizes will reveal more information to that topic.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003ePsychological symptoms in adults\u003c/h2\u003e\u003cp\u003eAdults with SMA report psychological symptoms in 11% (depression) to 15% (somatization). These symptom rates are slightly higher than in children but lower than in the few studies known on adults with SMA (\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). However, only Mix et al. used a validated instrument for assessing depressive symptoms (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), others worked e.g. with non-standardized symptom lists and qualitative research, which could have overestimated symptom rates (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). G\u0026uuml;nther et al. found symptoms of e.g. anxiety in 17%, loss of interest in 9%, and insomnia in 31%, but all rates were not higher than in the healthy control group (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). These symptoms can indicate a psychiatric disorder, but one can assume that not all of these participants would receive a manifest diagnosis e.g. of depression. We found neither differences between SMA types nor between groups of lower limb motor level. Former studies did not find SMA type differences as well (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), but psychological symptoms were associated with social participation and physical function (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Regarding the item analysis of the depression and anxiety scale in our adult sample, the most common symptoms reported can be connected to physical/somatic complaints (\u0026lsquo;nervousness/shakiness\u0026rsquo;, \u0026lsquo;feeling tense or keyed up\u0026rsquo;) or to a deficient social participation (\u0026lsquo;feeling lonely\u0026rsquo;, \u0026lsquo;feeling hopeless\u0026rsquo;).\u003c/p\u003e\u003cp\u003eAs seen in children with SMA, a functioning social support system and access to medical care are relevant factors for participation in daily life and mental well-being. Qualitative research from Australia on healthcare experiences of SMA patients during transition into adulthood reveals some distressing problems, e.g. that adult healthcare services is perceived as less structured and of lower quality, the reliance on others for assistance with basic needs, or social stigmatization. Further, participants described feelings of sadness in reaction to decreasing functional capability and autonomy (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). These aspects play a major role in the life of adults with SMA and may explain well the increased rates of psychological symptoms.\u003c/p\u003e\u003cp\u003eThe small sample sizes may be an explanation for the missing differences between groups of motor function, as the rates are highest among non-sitters (somatization and anxiety symptoms in 28.6%). The results could have missed statistical significance, as only 7 adults were included in that subgroup.\u003c/p\u003e\u003cp\u003eThese findings from Mix et al. show that depressive symptoms correlated significantly with better physical function and remained unaffected after treatment (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). As in our sample only anxiety and somatization symptoms were higher in non-sitters, future studies should not only focus depression, but also include other psychiatric disorders, e.g. anxiety disorders with their different aspects. One can speculate that a decreased physical ability may cause social phobia or lead to a generalized anxiety characterized by concerns or fear towards future and progress of the disease. The Mini-SCL subscale \u0026lsquo;somatization\u0026rsquo; includes questions about \u0026lsquo;breathing difficulties\u0026rsquo; or \u0026lsquo;feelings of weakness in body parts\u0026rsquo;, which could be confounded with symptoms of severe SMA and therefore could have caused higher ratings in that scale.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003ePsychological symptoms in caregivers\u003c/h2\u003e\u003cp\u003eMental health symptoms of caregivers were reported in 15% of cases, notably anxiety and somatization in 15%. The rates of the total sample are slightly lower than in other studies on SMA caregivers, which reported depression symptoms in 21\u0026ndash;36%, and anxiety symptoms in 26\u0026ndash;76% of caregivers (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). With focus on SMA types, we see significantly more psychological problems in parents of patients with SMA1, showing similarly high rates than former studies (33% depression, 50% anxiety). Caregivers of individuals with this severe type of SMA seem to have the highest risk of developing mental health problems. These may be caused by higher stress and involvement with the care and support of the affected person. A study from Saudi Arabia found the same association in caregivers of SMA1 patients (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), and also found higher hospitalization and needs for mechanical support (e.g. ventilatory) in these patients. In our sample, all of SMA1 individuals needed ventilatory support, 80% needed food intake support, all needed medical equipment (e.g. orthoses, wheelchair) and all received any kind of supportive therapy (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn a study on 96 children with SMA, parental stress was significantly higher in parents of children with SMA1\u0026thinsp;+\u0026thinsp;2 than in those with SMA3. Parental stress was significantly correlated to psychological symptoms and could be predicted by social support and number of children in the family (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). A newer study on a Dutch sample revealed a significant association between emotional well-being of SMA caregivers and participation in social and leisure activities (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), which explains very well the increased psychological symptoms in caregivers, especially of persons with SMA1. One can imagine that especially caregivers of the SMA1 group invest much more time in the care and organization of support which can easily lead to higher perceived stress, mental overload, less time for other social activities or self-care.\u003c/p\u003e\u003cp\u003eThe level of achieved motor function seems to not affect psychological symptoms of caregivers. That means that other factors must have a higher impact on mental health on caregivers, e.g. the access to support systems or further assistance.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eAssociation of symptoms between caregiver and individual with SMA\u003c/h2\u003e\u003cp\u003eThe significant correlations between caregiver and patient psychological symptoms confirm the strong association regarding emotional well-being of the whole family system, not only in young patients, but in adults, as well. Correlations between parental and child psychological symptoms were assessed only in one Chinese study on children with SMA, so far, reporting a strong connection of depression and anxiety, too (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eOur results on children reveal associations of psychological symptoms that have not been assessed before, e.g. that parental symptoms of depression are significantly associated with their children\u0026rsquo;s emotional and peer problems; as well as that parental anxiety was correlated to children\u0026rsquo;s conduct problems.\u003c/p\u003e\u003cp\u003eAs symptoms were assessed only in a cross-sectional study design, we can only speculate about causal attributions, but several ways of associations are possible. The diagnosis of a rare and chronic illness of the child, as well as the following responsibilities and care duties can cause traumatic stress in child and parents, which increases the risk of mental health problems in both (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Parental stress is associated to behavioral problems of the child in SMA, as well to social support and level of disability (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe association between parental anxiety and conduct problems of the child may also be explained bi-directionally. Conduct problems of the child (e.g. aggressive behavior) can cause anxiety of parents, as they worry about their future, fear social problems or exclusion of their child. Or otherwise, anxious parents could tend to overprotect their child, be less strict or show a more inconsequent parenting style, which may cause conduct problems. A systematic analysis of parent-child interaction in families with a chronic ill child supports these hypotheses. Parents of children with a chronic physical illness tended to be less positive and showed higher levels of responsiveness, but also of control and overprotection (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Future studies should include longitudinal analysis on psychological symptoms in caregivers and patients to provide more information about the directions of symptom associations.\u003c/p\u003e\u003cp\u003eIn adults with SMA, nearly all scales were significantly correlated to those in their parents/caregivers, revealing a strong association between the symptoms, as well. To our knowledge, this connection has not been assessed in adults with SMA before. But it means that although ~\u0026thinsp;70% of adults in our sample do not live with their parents anymore (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), there still exists a strong relationship regarding mental health in both. A Dutch study showed that rates of maternal depression (and anxiety) symptoms were not significantly higher in mothers of children than in mothers of adult patients (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), which supports our findings. One can state that the risk of psychological symptoms in caregivers does not decrease with age of the patient or because the patient moved out, but still impacts the social life and well-being of the caregiver.\u003c/p\u003e\u003cp\u003eThe findings are in line with the implications of the systematic analysis on family needs in SMA stating that the needs of parents must be included in psychosocial care to prevent health problems due to stress (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Our results may add that this applies not only for parents of children with SMA, but equally to parents/caregivers of adult patients.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003ePsychological symptoms and pharmacological treatment\u003c/h2\u003e\u003cp\u003eThe rates of psychological symptoms did not differ significantly between groups based on their current pharmacological treatment. In children, clinical scores were mainly reported in those treated with nursinersen, but one has to consider that the sample sizes of the other two groups (no medication n\u0026thinsp;=\u0026thinsp;2; risdiplam n\u0026thinsp;=\u0026thinsp;4) were too low to interpret these data. In adults, reported clinical symptoms were distributed similarly among the groups, with no specific trend observed. Mental health symptoms of caregivers did not differ between medication groups.\u003c/p\u003e\u003cp\u003eThere are only a few other studies on this topic. Mix et al. evaluated 26 patients (14 adults, 12 children) before and after nursinersen treatment and revealed that depressive symptoms did not change after treatment (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). An increase in physical function correlated even with more depressive symptoms. Ergenekon et al. showed a positive association between medical treatment and parental depression scores, as well (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The authors of these studies discuss that patients with poorer physical abilities have a better mental health, as they receive the SMA diagnosis at a young age and integrate it better into their self-concept which causes lower mental problems. The authors of the study on caregivers pose the question if a delayed treatment initiation may have contributed to higher parental depression rates.\u003c/p\u003e\u003cp\u003eThe results imply that the pharmacological treatment does improve psychological symptoms neither in individuals with SMA nor in their caregivers, which is comprehensible and should not be expected. Manifest psychiatric disorders, e.g. a depression or anxiety disorder are usually caused by multiple biological, psychological and social factors. Further, treatment recommendations include a multimodal treatment approach (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Therefore, we cannot assume that the change in one factor (improvement of SMA symptoms) leads immediately to a better mental health outcome in patients or even their caregivers. In the long-term, the change of SMA prognosis due to medical treatment options may improve quality of life, lower perceived stress and parental burden; and this could decrease psychological symptoms as a secondary outcome after a certain period of time. This should be included into future research on long-term effects of pharmacological treatment in SMA.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eStrengths and limitations\u003c/h2\u003e\u003cp\u003eStrengths of our study are the validated and standardized questionnaires allowing assessment of clinically relevant psychological symptoms in different age groups of persons with SMA, as well as their caregivers. Further, the sample size in adults with SMA was large enough to analyze differences between subtypes, levels of motor function and pharmacological treatment status regarding mental health. The combination of self- and proxy-reports, as well as of patient and caregiver reports revealed associations that were not assessed before.\u003c/p\u003e\u003cp\u003eLimitations are the recruitment via the nationwide registry that may include information biases and selection biases. The sample size in children was too small to receive solid information on subgroup levels. Further, the cross-sectional design does not allow causal attributions.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur study represents a significant advancement in understanding the psychological symptomatology of individuals with SMA and their caregivers. Through the comprehensive assessment of standardized questionnaires and self- and proxy-reports, we have provided the first detailed description of psychological symptoms across SMA subtypes, levels of motor function, and in individuals receiving modern pharmacological treatment.\u003c/p\u003e\u003cp\u003eOur findings reveal that while children with SMA exhibit lower rates of psychological symptoms compared to adults, internalizing symptoms are predominant in both age groups, with caregivers of SMA1 individuals experiencing heightened psychological distress. Importantly, we have demonstrated a significant association between caregiver and patient psychological symptoms, underscoring the interdependence of mental health within SMA families. Furthermore, the influence of access to medical care and social support systems on the manifestation of psychological symptoms, particularly in adults with SMA, highlights the critical role of psychosocial interventions in promoting well-being in chronic-ill patients. The correlation between parental and patient psychopathology emphasizes the need for integrated psychosocial care tailored to both individuals with SMA and their caregivers to reduce stress and improve quality of life. Moving forward, our findings provide valuable insights for developing holistic approaches to support the mental health of SMA patients and their families.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eADHD Attention-deficit/Hyperactivity Disorder\u003c/p\u003e\n\u003cp\u003eGSI Global Severity Index\u003c/p\u003e\n\u003cp\u003eMini-SCL Mini-Symptom-Checklist\u003c/p\u003e\n\u003cp\u003eSCL-90-R Symptom Checklist\u003c/p\u003e\n\u003cp\u003eSD Standard deviation\u003c/p\u003e\n\u003cp\u003eSDQ Strengths and Difficulties Questionnaire\u003c/p\u003e\n\u003cp\u003eSMA Spinal Muscular Atrophy\u003c/p\u003e\n\u003cp\u003eSMN1 Survival motor neuron gene\u003c/p\u003e\n\u003cp\u003eTPBS Total problem behavior score\u003c/p\u003e\n\u003cp\u003eTREAT-NMD Translational Research in Europe for the Assessment and Treatment of Neuromuscular Disease\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe study was approved by the local Ethics Committee of the Saarland Medical Association (February 4, 2020, protocol no. 09/20).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe data that support the findings of this study are available from Dr. M. Flotats-Bastardas but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Dr. M. Flotats-Bastardas.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eDr Marina Flotats-Bastardas has received consultant fees from Roche and Biogen. Dr Landfeldt is an employee of IQVIA, a contract research organization. Dr Maggie C. Walter has served on advisory boards for Avexis, Biogen, Novartis, Pfizer, Roche, Santhera, Sarepta, Pharnext, PTC Therapeutics, Ultragenyx, Wave Sciences, received funding for Travel or Speaker Honoraria from Avexis, Biogen, PTC Therapeutics, Ultragenyx, Santhera, Sarepta, and worked as an ad-hoc consultant for AskBio, Audentes Therapeutics, Avexis, Biogen Pharma GmbH, Fulcrum Therapeutics, GLG Consult, Guidepoint Global, Gruenenthal Pharma, Novartis, Pharnext, PTC Therapeutics, Roche. Simone Thiele has received financial support for advisory services from PTC Therapeutics. The other authors declare that there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThe non-profit patient association \u0026ldquo;Initiative SMA \u0026ndash; Gemeinsam f\u0026uuml;r eine Therapie\u0026rdquo; within the \u0026ldquo;Deutsche Gesellschaft f\u0026uuml;r Muskelkranke e.V.\u0026rdquo; provided financial support for the license fees of the proprietary HRQoL instruments, as well as the allowance for the SMA patient registry.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJH:\u0026nbsp;conception, design, data analysis and interpretation, draft, revision\u003c/p\u003e\n\u003cp\u003eBL:\u0026nbsp;conception, design, data acquisition, analysis, revision\u003c/p\u003e\n\u003cp\u003eTH:\u0026nbsp;design, data acquisition and analysis\u003c/p\u003e\n\u003cp\u003eHM:\u0026nbsp;conception, design, data analysis and interpretation\u003c/p\u003e\n\u003cp\u003eEL: data\u0026nbsp;analysis and interpretation, revision\u003c/p\u003e\n\u003cp\u003eST: design, data\u0026nbsp;acquisition\u003c/p\u003e\n\u003cp\u003eMCW: design, data\u0026nbsp;acquisition\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMZ:\u0026nbsp;conception,\u0026nbsp;data interpretation,\u0026nbsp;revision\u003c/p\u003e\n\u003cp\u003eEM: data interpretation, revision\u003c/p\u003e\n\u003cp\u003eUD: data interpretation, revision\u003c/p\u003e\n\u003cp\u003eSA: data\u0026nbsp;analysis and interpretation\u003c/p\u003e\n\u003cp\u003eMFB:\u0026nbsp;conception, design, data analysis and interpretation,\u0026nbsp;revision\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eThe authors sincerely thank all members of the German SMA community for their invaluable contribution to this research. We deeply appreciate their willingness to participate, complete the questionnaires, and openly share insights into their physical and mental health as well as their daily experiences. We are also very grateful for the financial support generously provided by the German non-profit patient organization \u0026lsquo;Initiative SMA e.V.\u0026rsquo;.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBogart K, Hemmesch A, Barnes E, Blissenbach T, Beisang A, Engel P, u. a. Healthcare access, satisfaction, and health-related quality of life among children and adults with rare diseases. Orphanet J Rare Dis. 12. Mai 2022;17(1):196. \u003c/li\u003e\n\u003cli\u003eWiegand-Grefe S, Liedtke A, Morgenstern L, Hoff A, Csengoe-Norris A, Johannsen J, u. a. Health-Related Quality of Life and mental health of families with children and adolescents affected by rare diseases and high disease burden: the perspective of affected children and their siblings. BMC Pediatr. 14. Oktober 2022;22(1):596. \u003c/li\u003e\n\u003cli\u003eCousino MK, Hazen RA. Parenting stress among caregivers of children with chronic illness: a systematic review. J Pediatr Psychol. September 2013;38(8):809\u0026ndash;28. \u003c/li\u003e\n\u003cli\u003eBrandt M, Johannsen L, Inhestern L, Bergelt C. Parents as informal caregivers of children and adolescents with spinal muscular atrophy: a systematic review of quantitative and qualitative data on the psychosocial situation, caregiver burden, and family needs. Orphanet J Rare Dis. 19. Juli 2022;17(1):274. \u003c/li\u003e\n\u003cli\u003eLunn MR, Wang CH. Spinal muscular atrophy. Lancet Lond Engl. 21. Juni 2008;371(9630):2120\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003eSarv S, Kahre T, Vaidla E, Pajusalu S, Muru K, P\u0026otilde;der H, u. a. The Birth Prevalence of Spinal Muscular Atrophy: A Population Specific Approach in Estonia. Front Genet [Internet]. 2021 [zitiert 30. April 2024];12. Verf\u0026uuml;gbar unter: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729775/\u003c/li\u003e\n\u003cli\u003eSansone VA, Walter MC, Attarian S, Delstanche S, Mercuri E, Lochm\u0026uuml;ller H, u. a. Measuring Outcomes in Adults with Spinal Muscular Atrophy - Challenges and Future Directions - Meeting Report. J Neuromuscul Dis. 2020;7(4):523\u0026ndash;34. \u003c/li\u003e\n\u003cli\u003eFinkel RS, Mercuri E, Meyer OH, Simonds AK, Schroth MK, Graham RJ, u. a. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord NMD. M\u0026auml;rz 2018;28(3):197\u0026ndash;207. \u003c/li\u003e\n\u003cli\u003eGosar D, Ko\u0026scaron;mrlj L, Musek PL, Me\u0026scaron;ko T, Stropnik S, Krkoč V, u. a. Adaptive skills and mental health in children and adolescents with neuromuscular diseases. Eur J Paediatr Neurol. 1. Januar 2021;30:134\u0026ndash;43. \u003c/li\u003e\n\u003cli\u003eLaufersweiler-Plass C, Rudnik-Sch\u0026ouml;neborn S, Zerres K, Backes M, Lehmkuhl G, von Gontard A. Behavioural Problems in Children and Adolescents with Spinal Muscular Atrophy and their Siblings. Dev Med Child Neurol. 2003;45(1):44\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eYao M, Xia Y, Feng Y, Ma Y, Hong Y, Zhang Y, u. a. Anxiety and depression in school-age patients with spinal muscular atrophy: a cross-sectional study. Orphanet J Rare Dis. 9. September 2021;16(1):385. \u003c/li\u003e\n\u003cli\u003ePanda PK, Ramachandran A, Verma PK, Sharawat IK. Behavioral problems in infants and young children with spinal muscular atrophy and their siblings: A cross-sectional study. Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc. Januar 2023;42:47\u0026ndash;52. \u003c/li\u003e\n\u003cli\u003eG\u0026uuml;nther R, Wurster CD, Cordts I, Koch JC, Kamm C, Petzold D, u. a. Patient-Reported Prevalence of Non-motor Symptoms Is Low in Adult Patients Suffering From 5q Spinal Muscular Atrophy. Front Neurol [Internet]. 1. November 2019 [zitiert 30. April 2024];10. Verf\u0026uuml;gbar unter: https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.01098/full\u003c/li\u003e\n\u003cli\u003eCh\u0026rsquo;ng GS, Koh K, Ahmad-Annuar A, Taib F, Koh CL, Lim ESC. A mixed method study on the impact of living with spinal muscular atrophy in Malaysia from patients\u0026rsquo; and caregivers\u0026rsquo; perspectives. Orphanet J Rare Dis. 16. Mai 2022;17(1):200. \u003c/li\u003e\n\u003cli\u003eMix L, Winter B, Wurster CD, Platen S, Witzel S, Uzelac Z, u. a. Quality of Life in SMA Patients Under Treatment With Nusinersen. Front Neurol. 2021;12:626787. \u003c/li\u003e\n\u003cli\u003eAlotaibi KM, Alsuhaibani M, Al-Essa KS, Bamaga AK, Mukhtar AS, Alrumaih AM, u. a. The socioeconomic burden of spinal muscular atrophy in Saudi Arabia: a cross-sectional pilot study. Front Public Health [Internet]. 1. Februar 2024 [zitiert 30. April 2024];12. Verf\u0026uuml;gbar unter: https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2024.1303475/full\u003c/li\u003e\n\u003cli\u003eCremers CH, Fischer MJ, Kruitwagen-van Reenen ET, Wadman RI, Vervoordeldonk JJ, Verhoef M, u. a. Participation and mental well-being of mothers of home-living patients with spinal muscular atrophy. Neuromuscul Disord. 1. April 2019;29(4):321\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eDu L, Dong H, Miao C, Jia F, Shan L. Analysis of scores of Symptom Checklist 90 (SCL-90) questionnaire of 182 parents of children with spinal muscular atrophy: a cross-sectional study. Transl Pediatr. November 2022;11(11):1776\u0026ndash;86. \u003c/li\u003e\n\u003cli\u003eErgenekon AP, G\u0026uuml;m\u0026uuml;ş Z, Yegit CY, Cenk M, Gulieva A, Kalyoncu M, u. a. Depression, anxiety, and sleep quality of caregivers of children with spinal muscular atrophy. Pediatr Pulmonol. Juni 2023;58(6):1697\u0026ndash;702. \u003c/li\u003e\n\u003cli\u003eLeibrock B, Landfeldt E, Hussong J, Huelle T, Mattheus H, Thiele S, u. a. Areas of improvement in the medical care of SMA: evidence from a nationwide patient registry in Germany. Orphanet J Rare Dis. 21. Februar 2023;18(1):32. \u003c/li\u003e\n\u003cli\u003eLandfeldt E, Leibrock B, Hussong J, Thiele S, Abner S, Walter MC, u. a. Self-Reported Health-Related Quality of Life of Children with Spinal Muscular Atrophy: Preliminary Insights from a Nationwide Patient Registry in Germany. J Neuromuscul Dis. 11(1):117\u0026ndash;28. \u003c/li\u003e\n\u003cli\u003eGoodman R. The Strengths and Difficulties Questionnaire: a research note. J Child Psychol Psychiatry. Juli 1997;38(5):581\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eBecker A, Wang B, Kunze B, Otto C, Schlack R, H\u0026ouml;lling H, u. a. Normative Data of the Self-Report Version of the German Strengths and Difficulties Questionnaire in an Epidemiological Setting. Z F\u0026uuml;r Kinder- Jugendpsychiatrie Psychother. November 2018;46(6):523\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003eWoerner W, Becker A, Friedrich C, Klasen H, Goodman R, Rothenberger A. [Normal values and evaluation of the German parents\u0026rsquo; version of Strengths and DIfficulties Questionnaire (SDQ): Results of a representative field study]. Z Kinder Jugendpsychiatr Psychother. Mai 2002;30(2):105\u0026ndash;12. \u003c/li\u003e\n\u003cli\u003eFranke GH. Mini-Symptom-Checklist. G\u0026ouml;ttingen: Hogrefe; 2017. \u003c/li\u003e\n\u003cli\u003eRISKS TO MENTAL HEALTH: AN OVERVIEW OF VULNERABILITIES AND RISK FACTORS BACKGROUND PAPER BY WHO SECRETARIAT FOR THE DEVELOPMENT OF A COMPREHENSIVE MENTAL HEALTH ACTION PLAN. In 2012 [zitiert 30. April 2024]. Verf\u0026uuml;gbar unter: https://www.semanticscholar.org/paper/RISKS-TO-MENTAL-HEALTH%3A-AN-OVERVIEW-OF-AND-RISK-BY/bfbedefc6db265ca474add283af034e8f55cc4de\u003c/li\u003e\n\u003cli\u003eH\u0026ouml;lling H, Schlack R, Petermann F, Ravens-Sieberer U, Mauz E, KiGGS Study Group. Psychische Auff\u0026auml;lligkeiten und psychosoziale Beeintr\u0026auml;chtigungen bei Kindern und Jugendlichen im Alter von 3 bis 17 Jahren in Deutschland \u0026ndash; Pr\u0026auml;valenz und zeitliche Trends zu 2 Erhebungszeitpunkten (2003\u0026ndash;2006 und 2009\u0026ndash;2012). Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. 1. Juli 2014;57(7):807\u0026ndash;19. \u003c/li\u003e\n\u003cli\u003ePrice J, Kassam-Adams N, Alderfer MA, Christofferson J, Kazak AE. Systematic Review: A Reevaluation and Update of the Integrative (Trajectory) Model of Pediatric Medical Traumatic Stress. J Pediatr Psychol. 2016;41(1):86\u0026ndash;97. \u003c/li\u003e\n\u003cli\u003evon Gontard A, Backes M, Laufersweiler-Plass C, Wendland C, Lehmkuhl G, Zerres K, u. a. Psychopathology and familial stress - comparison of boys with Fragile X syndrome and spinal muscular atrophy. J Child Psychol Psychiatry. Oktober 2002;43(7):949\u0026ndash;57. \u003c/li\u003e\n\u003cli\u003eKruitwagen-van Reenen ET, van der Pol L, Schr\u0026ouml;der C, Wadman RI, van den Berg LH, Visser-Meily JMA, u. a. Social participation of adult patients with spinal muscular atrophy: Frequency, restrictions, satisfaction, and correlates. Muscle Nerve. Dezember 2018;58(6):805\u0026ndash;11. \u003c/li\u003e\n\u003cli\u003eWan HWY, Carey KA, D\u0026rsquo;Silva A, Kasparian NA, Farrar MA. \u0026bdquo;Getting ready for the adult world\u0026ldquo;: how adults with spinal muscular atrophy perceive and experience healthcare, transition and well-being. Orphanet J Rare Dis. 2. April 2019;14(1):74. \u003c/li\u003e\n\u003cli\u003evon Gontard A, Rudnik-Sch\u0026ouml;neborn S, Zerres K. Stress and coping in parents of children and adolescents with spinal muscular atrophy. Klin Padiatr. Juli 2012;224(4):247\u0026ndash;51. \u003c/li\u003e\n\u003cli\u003ePinquart M. Do the parent-child relationship and parenting behaviors differ between families with a child with and without chronic illness? A meta-analysis. J Pediatr Psychol. August 2013;38(7):708\u0026ndash;21. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Spinal Muscular Atrophy (SMA), Psychological symptoms, Caregivers, Internalizing symptoms, Mental health, Psychosocial care","lastPublishedDoi":"10.21203/rs.3.rs-8086836/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8086836/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThis study investigates the prevalence and associations of psychological symptoms in individuals with Spinal Muscular Atrophy (SMA) and their caregivers, utilizing data from a cross-sectional, observational assessment conducted in Germany. Participants were recruited through the national German SMA registry (June \u0026ndash; September 2021), and psychological symptoms were assessed using validated measures such as the Strengths and Difficulties Questionnaire (SDQ) in children with SMA (n\u0026thinsp;=\u0026thinsp;21) and the German Mini-Symptom-Checklist (Mini-SCL) in adults with SMA (n\u0026thinsp;=\u0026thinsp;82) and caregivers (n\u0026thinsp;=\u0026thinsp;67).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eResults indicate that children with SMA exhibit lower rates of psychological symptoms compared to adults (9.5% vs. 13.4%), with internalizing symptoms (emotional problems, depression, anxiety) being the most prevalent in both age groups. Caregivers also demonstrate psychological symptoms in 14.9%, particularly those of individuals with SMA type 1. Symptom rates did not differ between groups with different motor function level. Significant correlations between caregiver and patient psychological symptoms were observed, while pharmacological treatment showed no significant impact on symptom rates.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eIn conclusion, the well-established access to medical care and social support systems appeared to influence the manifestation of psychological symptoms. Additionally, the correlation of patient and caregiver symptoms highlight the interplay between the mental health of both. These findings underscore the importance of integrating psychosocial care for both individuals with SMA and their caregivers to alleviate stress and promote well-being.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e\u003cp\u003eGerman clinical trial register (DRKS), DRKS00022876. Registered 19 October 2020.\u003c/p\u003e","manuscriptTitle":"Psychological symptoms in individuals with Spinal Muscular Atrophy (SMA) and their caregivers – results from a nation-wide study in Germany","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-01 07:03:26","doi":"10.21203/rs.3.rs-8086836/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-11-23T12:39:22+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-21T07:01:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-20T09:42:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"Orphanet Journal of Rare Diseases","date":"2025-11-11T07:28:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2bdf8ed2-f2dc-475e-8e55-4f09b2cf30eb","owner":[],"postedDate":"December 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-10T08:40:17+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-01 07:03:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8086836","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8086836","identity":"rs-8086836","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}