AANEM News Express

AANEM News Express

Science News: Clustering of Neuropsychiatric Disease in First-degree and Second-degree Relatives of Patients with Amyotrophic Lateral Sclerosis

Submitted by Niranjan N. Singh, MD, News Science Editorial Board

O'Brien M, Burke T, Heverin M, Vajda A, McLaughlin R, Gibbons J, Byrne S, Pinto-Grau M, Elamin M, Pender N, Hardiman O. Clustering of neuropsychiatric disease in first-degree and second-degree relatives of patients with amyotrophic lateral sclerosis. JA​MA Neurol. 2017 Dec 1;74(12):1425-1430. doi:10.1001/jamaneurol.2017.2699. PubMed PMID: 29049464; PubMed Central PMCID:PMC5822189.

In this issue of JAMA Neurology, O’Brien et al present a case-control family aggregation study of genetic pleiotropy within amyotrophic lateral sclerosis (ALS) kindreds. Patients and controls were interviewed and asked about first-degree and second-degree relatives with schizophrenia, bipolar disorder, autism, suicide, obsessive-compulsive disorder, addiction, and alcoholism using definitions from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. They collected survey data on 2,116 relatives of patients with ALS and 2,139 relatives of control participants. Confirming results of the previous study, they identified a relative risk of 3.4 (P = .02) for developing schizophrenia or other psychotic disorders in relatives of patients with ALS compared with controls. There was also an association between ALS and the development of autism (relative risk, 10.1; P = .03), alcoholism (relative risk, 1.48; P = .045), and obsessive-compulsive disorder (relative risk, 5.6; P = .02). Clustering of psychiatric disease with 3 or more affected family members was higher in the ALS kindreds than the control kindreds. The C9orf72 mutation did not fully explain these findings, as only 17% of the 29 kindreds with 3 or more affected relatives had the expansion; 81% did not have the expansion.

Comment: ALS is a progressive neurodegenerative condition primarily involving the motor system. There is increasing epidemiologic evidence of an association between ALS and a wider spectrum of neurodegenerative and neuropsychiatric disorders among family members, including schizophrenia and psychotic illness and suicidal behavior. The data presented is very suggestive of an association between these diseases and may offer insight into new therapeutic options, but further study is needed before we can conclude that there is any definitive association between them.

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