Neurodegenerative and psychiatric diseases among families with amyotrophic lateral sclerosis

Abstract

Objective:To estimate risks of neurodegenerative and psychiatric diseases among patients with amyotrophic lateral sclerosis (ALS) and their families.Methods:We conducted a register-based nested case-control study during 1990–2013 in Sweden to assess whether patients with ALS had higher risks of other neurodegenerative and psychiatric diseases before diagnosis. We included 3,648 patients with ALS and 36,480 age-, sex-, and county of birth–matched population controls. We further conducted a follow-up study of the cases and controls to assess the risks of other neurodegenerative and psychiatric diseases after ALS diagnosis. To assess the potential contribution of familial factors, we conducted similar studies for the relatives of patients with ALS and their controls.Results:Individuals with previous neurodegenerative or psychiatric diseases had a 49% increased risk of ALS (odds ratio 1.49, 95% confidence interval 1.35–1.66) compared to individuals without these diseases. After diagnosis, patients with ALS had increased risks of other neurodegenerative or psychiatric diseases (hazard ratio 2.90, 95% confidence interval 2.46–3.43) compared to individuals without ALS. The strongest associations were noted for frontotemporal dementia, Parkinson disease, other dementia, Alzheimer disease, neurotic disorders, depression, stress-related disorders, and drug abuse/dependence. First-degree relatives of patients with ALS had higher risk of neurodegenerative diseases, whereas only children of patients with ALS had higher risk of psychiatric disorders, compared to relatives of the controls.Conclusions:Familial aggregation of ALS and other neurodegenerative diseases implies a shared etiopathogenesis among all neurodegenerative diseases. The increased risk of psychiatric disorders among patients with ALS and their children might be attributable to nonmotor symptoms of ALS and severe stress response toward the diagnosis.

Relationship between neuropsychiatric disorders and cognitive and behavioural change in MND

“…This resulted in small numbers in some analyses; therefore, these results should be interpreted cautiously. We were unable to examine associations with psychosis, schizophrenia or autism, and neuropsychiatric disorders, which have been shown to occur at higher rates in MND kindreds 11 14 15. The number of patients with neuropsychiatric medication was higher than those with a neuropsychiatric history (127 vs 60).…”

“…An association between neuropsychiatric disorders and ALS has previously been shown 9 10. Neuropsychiatric symptoms including schizophrenia, depression, anxiety, and drug abuse or dependence are common in the years prior to and following diagnosis in both ALS10 11 and behavioural-variant FTD 12. Genome-wide association studies have revealed a modest genetic correlation between schizophrenia and ALS 13.…”

“…Genome-wide association studies have revealed a modest genetic correlation between schizophrenia and ALS 13. Furthermore, higher rates of psychosis, suicidal behaviour14 and autism15 have been shown in the first-degree and second-degree relatives of patients with ALS,14 15 particularly in their children 11. Despite evidence of an overlap of ALS-FTSD and neuropsychiatric disorders, it is unclear if neuropsychiatric disorders also contribute to the spectrum of cognitive and behavioural changes in ALS.…”

ALS in Danish Registries

“…A Swedish national registry study, which identified 3,648 ALS cases and 364,800 matched controls found higher rates of psychiatric disorders in children of those with ALS. 31 The overlap between ALS and schizophrenia is unlikely to be attributed to C9orf72 mutations Abbreviations: ALS = amyotrophic lateral sclerosis; MI = myocardial infarction; RR = risk ratio. Note 0.5 was added to the case count for anorexia to enable estimation of the RR.…”

Facial Onset Sensory and Motor Neuronopathy

“…11 This suggests that these diseases may cluster with pedigrees, like other neurodegenerative diseases. 34,35 The fact that patients develop severe bulbar symptoms with respiratory insufficiency (reminiscent of ALS) and may develop cognitive and behavioral changes within the FTD spectrum supports considering FOSMN as part of the FTD-Multiple lines of evidence seem to support the hypothesis that FOSMN is a neurodegenerative disorder.…”