Is psychological stress a predisposing factor for amyotrophic lateral sclerosis (ALS)? An online international case-control study of premorbid life events, occupational stress, resilience and anxiety

Abstract

Psychological stress has been suggested to be relevant to the pathogenesis of neurodegenerative disorders, possibly via the generation of oxygen free radicals. We therefore sought to determine whether people with amyotrophic lateral sclerosis (ALS) had been subjected to more potentially stressful life events or occupations than controls, and whether they had differences in resilience or trait anxiety that would moderate their responses to these stressors. An online anonymous multilingual questionnaire was used to collect data on significant life events from people with and without ALS, using items from a modified Social Readjustment Rating Scale and from self-described significant events, which were combined to create a Life Events Inventory. Inventory scores were subdivided into 0–20 years and 21–40 years age ranges, and for the preceding 2, 5 and 10 years. Respondents also rated levels of stress experienced during different occupations. Resilience was measured using the Connor-Davidson Resilience Scale, and trait anxiety with a modified Geriatric Anxiety Inventory. Scores were compared using nonparametric statistics. Data from 400 ALS (251 male, 149 female) and 450 control (130 male, 320 female) respondents aged 40 years and over showed that Life Events Inventory scores were similar in male ALS respondents and controls, but lower in female ALS respondents than female controls for the preceding 5-year and 10-year periods. Occupational stress did not differ between ALS respondents and controls. Both male and female ALS respondents had higher resilience scores than controls. Anxiety scores did not differ between ALS and control groups. In conclusion, people with ALS reported no raised levels of potentially stressful premorbid life events or occupational stress, and did not have reduced levels of resilience, or increased levels of anxiety, that would augment the deleterious effects of stressors. On the contrary, ALS respondents had higher resilience than controls, though this conclusion relies on ALS respondents recalling their premorbid status. These results do not support the hypothesis that psychological stress from significant life events or occupational stress plays a role in the pathogenesis of ALS.

Sports and trauma as risk factors for Motor Neurone Disease: New Zealand case–control study

“…In the current study, elevated risks were associated with having experienced more than two different types of traumatic life events, with an almost twofold risk associated with having experienced four or more types of traumatic life events. An Australian ALS case–control study, 30 which used a checklist for potentially stressful life events as part of an anonymous online questionnaire, found no difference in life events inventory scores between cases and controls, but results for specific traumatic life events were not presented. We are not aware of other studies that evaluated the association between traumatic life events and MND.…”

“…A Japanese case–control study 13 showed that self‐reported stress was associated with an increased risk of ALS (OR 1.8, 95% CI 1.3–2.7) while a UK study 29 reported a 1.5‐fold increased MND risk for a former diagnosis of depression. However, a recent Australian study 30 found no difference in exposures to potentially stressful life events between ALS cases and controls.…”

The Link between Oxidative Stress, Redox Status, Bioenergetics and Mitochondria in the Pathophysiology of ALS

“…This suggestion could also lead to hypothesizing a correlation between mitochondrial dysfunction and excessive stress [28]. However, a recent study showed that people with ALS reported no raised levels of potentially stressful premorbid life events or occupational stress and did not have reduced levels of resilience [29]. Therefore, a possible role of exceptional physical or psychological stress (at least by itself) in the pathogenesis of ALS is still an open question.…”

Association of Stress-Related Disorders With Subsequent Neurodegenerative Diseases

“…Epidemiological studies support that stress exposure, including everyday life stress, work stress, life events, and trauma, is associated with dementia risk, whereas results for PD have been inconsistent . The potential association between stressful life events and amyotrophic lateral sclerosis (ALS) was not supported in 2 previous studies, but this association is underexplored to date.…”