Acta Neurol Scand DOI: 10.1111/ane.12356
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Psychological characteristics of patients with myotonic dystrophy type 1 Bertrand JA, Jean S, Laberge L, Gagnon C, Mathieu J, Gagnon JF, Richer L. Psychological characteristics of patients with myotonic dystrophy type 1. Acta Neurol Scand: DOI 10.1111/ane.12356. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives – Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy. It is associated with motor symptoms but patients also display non-motor symptoms such as particular personality traits. Studies have reported mixed results about personality characteristics which may be attributable to small sample sizes, different disease severity of groups studied, and use of different questionnaires or method. This study aimed to describe the psychological characteristics of a large cohort of patients with DM1, to characterize those at risk of developing a psychiatric disorder, and to compare characteristics between two DM1 phenotypes, a mild and more severe adult-onset phenotype. Methods – Two hundred patients with DM1 (152 adult-onset; 48 mild) were asked to complete questionnaires assessing personality traits, psychological symptoms, self-esteem, and suicidal risk. Neurological and neuropsychological assessments were performed to compare personality characteristics to clinical and cognitive measures. Results – Patients with DM1 globally showed personality traits and psychological symptoms in the average range compared to normative data, with normal levels of self-esteem and suicidal ideation. However, 27% of patients were found to be at high risk of developing a psychiatric disorder. Moreover, psychological traits differed across phenotypes, with the most severe phenotype tending to show more severe psychological symptoms. The presence of higher phobic anxiety and lower self-esteem was associated with lower education, a higher number of CTG repeats, more severe muscular impairment, and lower cognitive functioning (P < 0.001). Conclusions – Different phenotypes should thus be taken into account in clinical settings for individual management of patients and optimizing therapeutic success.
Introduction
First described by Steinert in 1909, myotonic dystrophy type 1 (DM1) is a multisystemic disease characterized by myotonia, muscle weakness, cataracts, cardiovascular dysfunctions, endocrine abnormalities, cognitive deficits, and particular personality traits (1–4). DM1 is the most common adult-onset muscular dystrophy and is caused by an autosomal-dominant mutation, a CTG sequence expansion within the noncoding 30 untranslated region of myotonic dystrophy protein kinase (DMPK) gene on chromosome
J. A. Bertrand1,2, S. Jean3, L. Laberge4,5, C. Gagnon6,7, J. Mathieu6,7, J. F. Gagnon2, L. Richer4 1 Rotman Research Institute, Baycrest Center, Toronto, ON, Canada; 2Universite du Quebec a Montreal, Montreal, QC, Canada; 3Centre de sante et de services sociaux de Chicoutimi, Chicoutimi, QC, Canada; 4 Universite du Quebec a Chicoutimi, Chicoutimi, QC, Canada; 5ECOBES – Recherche et transfert, Cegep de Jonquiere, Jonquiere, QC, Canada; 6Clinique des maladies neuromusculaires, Centre de sante et de services sociaux de Jonquiere, Jonquiere, QC, Canada; 7 Universite de Sherbrooke, Sherbrooke, QC, Canada
Key words: myotonic dystrophy type 1; personality traits; psychological symptoms; mild myotonic dystrophy type 1; adult-onset myotonic dystrophy type 1 L. Richer, Departement des sciences de la sante, Universite du Quebec a Chicoutimi, 555, boul. de l’Universite, Chicoutimi (Quebec) G7H 2B1, Canada Tel.: (418) 545-5011 x5418 Fax: (418) 545-5012 e-mail: [email protected] Accepted for publication October 31, 2014
19q13.3 (5). CTG repeats in DM1 patients can range from 50 to several thousands. The number of CTG repeats is partly correlated to disease severity and age at onset of symptoms (6). Considering various European populations, worldwide prevalence of DM1 is estimated at 5–20 per 100 000 although it reaches 158 per 100 000 in the Saguenay-Lac-Saint-Jean region located in the eastern part of the province of Quebec (Canada) (7, 8). While behavioral particularities in DM1 were first described by Steinert at the beginning of the 20th century, it is only in the 1980s that 1
Bertrand et al. personality characteristics became a matter of interest. Previous studies reported heterogeneous results; some reported avoidant or schizotypal personality traits, whereas others mainly noted bodily concerns such as somatization and hypochondria bringing patients to seek medical attention (8–12). Moreover, personality disorders have been reported in 20–60% of patients with DM1 (9, 10, 13, 14). Depressive symptoms, such as low self-esteem and motivation, are also encountered (11, 13, 15–18). In clinical settings, disturbed personality and psychosocial adjustment may represent a burden as they can lead to unsuccessful therapeutic compliance, in addition to limiting everyday functioning and quality of life of patients (14). Most previous studies had small sample sizes, potentially limiting the relevance of their findings (9–12, 15, 17). Some exclusively considered individuals with mild muscular involvement or lower repeat sizes (10, 12, 15), while others did not take disease severity into account (13, 16–18). Relationship between personality traits and disease severity based on both phenotypic (age at onset, muscular impairment) and genotypic (number of CTG repeats) measures is thus unclear. Moreover, in clinical settings, some patients with adult-onset DM1 with a very small number of CTG repeats display severe muscular impairment, whereas others with a high number of CTG repeats show only weak muscular impairment. Our group recently established criteria to distinguish between what appears to be two different phenotypes, for instance the mild, late-onset, asymptomatic phenotype and the classic adultonset phenotype of DM1 (19). A patient with DM1 was identified with the mild phenotype if he presented at least two of the following criteria: 1) less than 200 CTG repeats over the DMPK gene; 2) a Muscular Impairment Rating Scale (MIRS) score of 1 or 2 indicating no or very weak muscular impairment; 3) symptoms arising after 40 years old. No study has yet determined whether the reportedly peculiar personality profile of patients with DM1 varies within these phenotypes. Whether personality peculiarities in DM1 are related to nature or nurture is still a matter of debate. Personality traits could be a direct consequence of DM1 pathology affecting the brain. Cerebral abnormalities are well known in DM1 (20, 21) and may be linked to personality differences. Another possibility is that psychological symptoms arise as a consequence of DM1 clinical manifestations. For instance, motor impairment could be debilitating in common social situation 2
and push patients to isolate themselves and become distrustful. Other factors such as pain and fatigue could also bring patients to avoid social situations and eventually develop avoidant, schizotypical personality traits in response to the disease. Linking traits to a genotypic factor such as the number of CTG repeats, and a clinical manifestation such as the level of motor impairment may help understanding the relationship between DM1 and patient’s atypical personalities. This study generally aimed to investigate psychological characteristics of a large sample of DM1 patients and to identify those at risk of psychiatric disorder. Personality traits will also be compared between two different phenotypes, the mild and adult-onset phenotypes, to assess whether more severe psychological symptoms would be linked to a more severe DM1 condition. Finally, this study will try to clarify the relationship between psychological traits and sociodemographic, clinical, and cognitive characteristics. Methods Participants
Two hundred DNA-confirmed patients with DM1 were recruited at the Neuromuscular Clinic of the Centre de sante et de services sociaux de Jonquiere (Quebec, Canada). Sociodemographic and clinical characteristics of patients are presented in Table 1. Age at onset of symptoms was noted only if it was precisely and unequivocally given by the patient (n = 142). Muscular impairment was assessed using MIRS; a score of 1 represents ‘No muscular impairment’ and 5 ‘Severe proximal weakness’ (22). Patients were identified with mild DM1 if they presented at least 2 of the 3 above-mentioned criteria (see the introduction section; 19). Patients with DM1 not fulfilling those criteria were classified with the adult-onset phenotype. Congenital and infantile DM1 phenotypes were excluded. From the 416 DM1 individuals listed at the Neuromuscular Clinic, 82 potential participants were excluded from the study for various reasons: moving out or incorrect contact information (57%), refusing clinical follow-up (20.7%), or health or personal reasons (22%). One hundred and 31 potential participants refused to participate in the study due to lack of interest (59%) or other personal reasons (41%) and finally three dropped out. The 200 participants who completed the study did not differ from the 216 non-participants in terms of gender, CTG repeat number, and proportion of mild vs adult-onset phenotype but slightly differed in
DMI Psychological characteristics Table 1 Sociodemographic, clinical, and psychological characteristics of patients with DM1 (n = 200) All DM1, mean (SD) Age (years) Education (years) Gender (% men)b % in a relationshipb % employedb Age at symptoms onset (years)c,d CTG repeats (n) MIRS, mean score Score of 1 (%) Score of 2 (%) Score of 3 (%) Score of 4 (%) Score of 5 (%) NEO-FFI Neuroticism Extraversion Openness to experience Agreeableness Conscientiousness SCL-90-R Somatization Obsessive-compulsive Interpersonal sensitivity Depression Anxiety Hostility Phobic anxiety Paranoid ideation Psychoticism Global Severity Index Positive Symptom Distress Index Positive Symptom Total Rosenberg Self-Esteem score ASIQ score
Mild DM1 (n = 42), mean (SD)
44.26 9.77 39 29 17 20.37 1021.58 3.70 0 12 19 56 13
(9.20) (2.55)
P-valuea
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Psychological characteristics of patients with myotonic dystrophy type 1 Bertrand JA, Jean S, Laberge L, Gagnon C, Mathieu J, Gagnon JF, Richer L. Psychological characteristics of patients with myotonic dystrophy type 1. Acta Neurol Scand: DOI 10.1111/ane.12356. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives – Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy. It is associated with motor symptoms but patients also display non-motor symptoms such as particular personality traits. Studies have reported mixed results about personality characteristics which may be attributable to small sample sizes, different disease severity of groups studied, and use of different questionnaires or method. This study aimed to describe the psychological characteristics of a large cohort of patients with DM1, to characterize those at risk of developing a psychiatric disorder, and to compare characteristics between two DM1 phenotypes, a mild and more severe adult-onset phenotype. Methods – Two hundred patients with DM1 (152 adult-onset; 48 mild) were asked to complete questionnaires assessing personality traits, psychological symptoms, self-esteem, and suicidal risk. Neurological and neuropsychological assessments were performed to compare personality characteristics to clinical and cognitive measures. Results – Patients with DM1 globally showed personality traits and psychological symptoms in the average range compared to normative data, with normal levels of self-esteem and suicidal ideation. However, 27% of patients were found to be at high risk of developing a psychiatric disorder. Moreover, psychological traits differed across phenotypes, with the most severe phenotype tending to show more severe psychological symptoms. The presence of higher phobic anxiety and lower self-esteem was associated with lower education, a higher number of CTG repeats, more severe muscular impairment, and lower cognitive functioning (P < 0.001). Conclusions – Different phenotypes should thus be taken into account in clinical settings for individual management of patients and optimizing therapeutic success.
Introduction
First described by Steinert in 1909, myotonic dystrophy type 1 (DM1) is a multisystemic disease characterized by myotonia, muscle weakness, cataracts, cardiovascular dysfunctions, endocrine abnormalities, cognitive deficits, and particular personality traits (1–4). DM1 is the most common adult-onset muscular dystrophy and is caused by an autosomal-dominant mutation, a CTG sequence expansion within the noncoding 30 untranslated region of myotonic dystrophy protein kinase (DMPK) gene on chromosome
J. A. Bertrand1,2, S. Jean3, L. Laberge4,5, C. Gagnon6,7, J. Mathieu6,7, J. F. Gagnon2, L. Richer4 1 Rotman Research Institute, Baycrest Center, Toronto, ON, Canada; 2Universite du Quebec a Montreal, Montreal, QC, Canada; 3Centre de sante et de services sociaux de Chicoutimi, Chicoutimi, QC, Canada; 4 Universite du Quebec a Chicoutimi, Chicoutimi, QC, Canada; 5ECOBES – Recherche et transfert, Cegep de Jonquiere, Jonquiere, QC, Canada; 6Clinique des maladies neuromusculaires, Centre de sante et de services sociaux de Jonquiere, Jonquiere, QC, Canada; 7 Universite de Sherbrooke, Sherbrooke, QC, Canada
Key words: myotonic dystrophy type 1; personality traits; psychological symptoms; mild myotonic dystrophy type 1; adult-onset myotonic dystrophy type 1 L. Richer, Departement des sciences de la sante, Universite du Quebec a Chicoutimi, 555, boul. de l’Universite, Chicoutimi (Quebec) G7H 2B1, Canada Tel.: (418) 545-5011 x5418 Fax: (418) 545-5012 e-mail: [email protected] Accepted for publication October 31, 2014
19q13.3 (5). CTG repeats in DM1 patients can range from 50 to several thousands. The number of CTG repeats is partly correlated to disease severity and age at onset of symptoms (6). Considering various European populations, worldwide prevalence of DM1 is estimated at 5–20 per 100 000 although it reaches 158 per 100 000 in the Saguenay-Lac-Saint-Jean region located in the eastern part of the province of Quebec (Canada) (7, 8). While behavioral particularities in DM1 were first described by Steinert at the beginning of the 20th century, it is only in the 1980s that 1
Bertrand et al. personality characteristics became a matter of interest. Previous studies reported heterogeneous results; some reported avoidant or schizotypal personality traits, whereas others mainly noted bodily concerns such as somatization and hypochondria bringing patients to seek medical attention (8–12). Moreover, personality disorders have been reported in 20–60% of patients with DM1 (9, 10, 13, 14). Depressive symptoms, such as low self-esteem and motivation, are also encountered (11, 13, 15–18). In clinical settings, disturbed personality and psychosocial adjustment may represent a burden as they can lead to unsuccessful therapeutic compliance, in addition to limiting everyday functioning and quality of life of patients (14). Most previous studies had small sample sizes, potentially limiting the relevance of their findings (9–12, 15, 17). Some exclusively considered individuals with mild muscular involvement or lower repeat sizes (10, 12, 15), while others did not take disease severity into account (13, 16–18). Relationship between personality traits and disease severity based on both phenotypic (age at onset, muscular impairment) and genotypic (number of CTG repeats) measures is thus unclear. Moreover, in clinical settings, some patients with adult-onset DM1 with a very small number of CTG repeats display severe muscular impairment, whereas others with a high number of CTG repeats show only weak muscular impairment. Our group recently established criteria to distinguish between what appears to be two different phenotypes, for instance the mild, late-onset, asymptomatic phenotype and the classic adultonset phenotype of DM1 (19). A patient with DM1 was identified with the mild phenotype if he presented at least two of the following criteria: 1) less than 200 CTG repeats over the DMPK gene; 2) a Muscular Impairment Rating Scale (MIRS) score of 1 or 2 indicating no or very weak muscular impairment; 3) symptoms arising after 40 years old. No study has yet determined whether the reportedly peculiar personality profile of patients with DM1 varies within these phenotypes. Whether personality peculiarities in DM1 are related to nature or nurture is still a matter of debate. Personality traits could be a direct consequence of DM1 pathology affecting the brain. Cerebral abnormalities are well known in DM1 (20, 21) and may be linked to personality differences. Another possibility is that psychological symptoms arise as a consequence of DM1 clinical manifestations. For instance, motor impairment could be debilitating in common social situation 2
and push patients to isolate themselves and become distrustful. Other factors such as pain and fatigue could also bring patients to avoid social situations and eventually develop avoidant, schizotypical personality traits in response to the disease. Linking traits to a genotypic factor such as the number of CTG repeats, and a clinical manifestation such as the level of motor impairment may help understanding the relationship between DM1 and patient’s atypical personalities. This study generally aimed to investigate psychological characteristics of a large sample of DM1 patients and to identify those at risk of psychiatric disorder. Personality traits will also be compared between two different phenotypes, the mild and adult-onset phenotypes, to assess whether more severe psychological symptoms would be linked to a more severe DM1 condition. Finally, this study will try to clarify the relationship between psychological traits and sociodemographic, clinical, and cognitive characteristics. Methods Participants
Two hundred DNA-confirmed patients with DM1 were recruited at the Neuromuscular Clinic of the Centre de sante et de services sociaux de Jonquiere (Quebec, Canada). Sociodemographic and clinical characteristics of patients are presented in Table 1. Age at onset of symptoms was noted only if it was precisely and unequivocally given by the patient (n = 142). Muscular impairment was assessed using MIRS; a score of 1 represents ‘No muscular impairment’ and 5 ‘Severe proximal weakness’ (22). Patients were identified with mild DM1 if they presented at least 2 of the 3 above-mentioned criteria (see the introduction section; 19). Patients with DM1 not fulfilling those criteria were classified with the adult-onset phenotype. Congenital and infantile DM1 phenotypes were excluded. From the 416 DM1 individuals listed at the Neuromuscular Clinic, 82 potential participants were excluded from the study for various reasons: moving out or incorrect contact information (57%), refusing clinical follow-up (20.7%), or health or personal reasons (22%). One hundred and 31 potential participants refused to participate in the study due to lack of interest (59%) or other personal reasons (41%) and finally three dropped out. The 200 participants who completed the study did not differ from the 216 non-participants in terms of gender, CTG repeat number, and proportion of mild vs adult-onset phenotype but slightly differed in
DMI Psychological characteristics Table 1 Sociodemographic, clinical, and psychological characteristics of patients with DM1 (n = 200) All DM1, mean (SD) Age (years) Education (years) Gender (% men)b % in a relationshipb % employedb Age at symptoms onset (years)c,d CTG repeats (n) MIRS, mean score Score of 1 (%) Score of 2 (%) Score of 3 (%) Score of 4 (%) Score of 5 (%) NEO-FFI Neuroticism Extraversion Openness to experience Agreeableness Conscientiousness SCL-90-R Somatization Obsessive-compulsive Interpersonal sensitivity Depression Anxiety Hostility Phobic anxiety Paranoid ideation Psychoticism Global Severity Index Positive Symptom Distress Index Positive Symptom Total Rosenberg Self-Esteem score ASIQ score
Mild DM1 (n = 42), mean (SD)
44.26 9.77 39 29 17 20.37 1021.58 3.70 0 12 19 56 13
(9.20) (2.55)
P-valuea
