Common Gene Mutations May Link ALS and Schizophrenia, Study Reports

Joana Fernandes, PhD avatar

by Joana Fernandes, PhD |

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ALS-schizophrenia link

Amyotrophic lateral sclerosis (ALS) and schizophrenia may be caused by similar gene mutations that affect the way neurons work, according to new research.

Researchers found that 14.3 percent of the genetic variations linked to ALS were also present in people with schizophrenia, suggesting the diseases may be related.

The study, “Genetic Correlation Between Amyotrophic Lateral Sclerosis And Schizophrenia,” was published in the journal Nature Communications.

Schizophrenia, a psychiatric disorder, is characterized by persistent mental illness that affects a person’s behavior, thinking, and emotions. Symptoms can include hallucinations and delusions, reduced motivation, poor cognitive abilities and social interaction difficulties.

Both ALS and schizophrenia are caused by genetic mutations, meaning they can strike people in different generations of the same family. Previous research has shown that the incidence of schizophrenia can be high in relatives of ALS patients, again suggesting a relationship between the two.

“There is evolving clinical, epidemiological and biological evidence for an association between ALS and psychotic illness, particularly schizophrenia,” the researchers wrote.

The team investigated the possibility of a genetic connection by analyzing the genes of more than 100,000 individuals, and relating the findings with the presence or absence of each disease in these people.

A significant overlap was seen, with researchers estimating the genetic correlation to be 14.3 percent. This indicates that certain genes associated with increased risk are common between ALS and schizophrenia, and that the diseases share common biological mechanisms.

Indeed, although both diseases are clinically different — one is a mental illness and the other mainly a motor disease — both may be triggered by mutations in genes that affect the functioning of neurons. These genes include known ALS genes, such as C9orf72, but also five newly associated genes: CNTN6, TNIP1, PPP2R2D, NCKAP5L and ZNF295-AS1. All of these genes — along with others either known or yet to be identified — may underlie a  shared mechanism between ALS and schizophrenia.

Researchers found no association between ALS and other neuropsychiatric conditions, such as bipolar disorder, autism and major depression, but recommended studies with larger populations to confirm their finding.

“As both ALS and schizophrenia are [different] conditions, further [genetic], biological and clinical studies are likely to yield novel insights into the pathological processes for both diseases and will provide clinical [distinction] parameters that could drive novel drug development for both neurodegenerative and psychiatric conditions,” the researchers concluded.