Neuropsychiatric Conditions Common in Relatives of Patients With Amyotrophic Lateral Sclerosis

depression old man
depression old man
Repeat expansion of the C9orf72 gene does not account for the elevated prevalence of neuropsychiatric disease in relatives of patients with amyotrophic lateral sclerosis.

Family members of patients with amyotrophic lateral sclerosis (ALS) have greater rates of neuropsychiatric conditions, such as autism, alcoholism, and depression compared with controls, according to a population-based study published in JAMA Neurology.

Investigators of this population-based case-control study evaluated the rates of obsessive-compulsive disorder (OCD), alcoholism, and autism among first-, second-, and third-degree family members (n=924, n=1128, and n=64, respectively) of 127 patients with incident ALS. A total of 132 matched controls, with 829 first-degree and 1310 second-degree relatives, were also included for direct comparison.

At least 1 family member (first- or second-degree) of a patient with ALS (61.4%) and control (38.6%) had a clinical history of psychosis, schizophrenia, autism, depression, suicide, or alcoholism (relative risk [RR] 1.50; 95% CI, 1.08-2.17; P =.02). Family members of patients with ALS had a significantly higher rate of neuropsychiatric symptoms compared with controls (71.8%; mean [SD] number of siblings, 4.29 [1.41];P =.001).

In addition, family members of patients with ALS had significantly greater rates of autism (RR 10.10; 95% CI, 1.30-78.80; P =.03), schizophrenia (RR 3.40; 95% CI, 1.27-9.30; P =.02), alcoholism (RR 1.48; 95% CI, 1.01-2.17; P =.045), and suicide (RR 3.30; 95% CI, 1.07-10.05; P =.04).

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The investigators of this study did not use direct examination to obtain information regarding neuropsychiatric symptoms of family members, with verification of neuropsychiatric signals obtained only by interviews. The investigators suggest this could have resulted in incomplete diagnostic categorization.

The increased risk for neuropsychiatric symptoms in first- and second-degree relatives of patients with ALS may be driven “primarily by kindred[s] at risk for particular neuropsychiatric conditions that recapitulate the cognitive and behavioral sub-phenotypes described in ALS.”


O’Brien M, Burke T, Heverin M, et al. Clustering of neuropsychiatric disease in first-degree and second-degree relatives of patients with amyotrophic lateral sclerosis [published online October 16, 2017]. JAMA Neurol. doi:10.1001/jamaneurol.2017.2699