Individuals who carry high-risk genes for schizophrenia and autism, but who do not have these disorders, show subtle brain changes and impairments in cognitive function. This according to a new study published in Nature.
The research offers a glimpse into brain changes that occur just before the onset of mental illness and may lead to early intervention and prevention.
Copy number variants (CNVs) — in which certain segments of the genome have an abnormal number of copies — play an important role in mental disorders. Individuals who carry certain CNVs have a significantly greater risk of developing schizophrenia or autism.
“In psychiatry we always have the problem that disorders are defined by symptoms that patients experience or tell us about, or that we observe,” said co-author Andreas Meyer-Lindenberg, M.D., Ph.D., a psychiatrist and director of the Central Institute of Mental Health in Mannheim, Germany, affiliated with the University of Heidelberg.
This study, however, looks at the biological underpinnings of people who are at risk for these disorders, he said.
For the study, researchers examined a genealogical database of more than 100,000 Icelanders, focusing on 26 genetic variants that have been shown to increase the risk of schizophrenia or autism. Overall, 1,178 people (1.16 percent) in the sample carried one or more of these CNVs.
The research team then recruited carriers between the ages of 18 and 65 who had never been diagnosed with a neuropsychiatric disorder. These participants and several control groups underwent several neuropsychiatric and cognitive tests, as well as magnetic resonance imaging (MRI) to observe structural brain differences.
Those who carried the variants performed worse than controls on cognitive tests and measures of general day-to-day functioning, and they were more likely to have a history of learning disabilities.
For example, carriers of one particular CNV — a deletion in a specific region of chromosome 15 — tend to have a history of dyslexia and a difficulty with numbers. MRI revealed that the same deletion alters brain structure in a way also seen in people with early stages of psychosis, and in individuals with dyslexia.
“Now we want to see whether we can find mutations in the genome that affect how people perform on exams in school, how people advance through the educational system, and how they do socio-economically,” said co-author Kári Stefánsson, Ph.D., chief executive and co-founder of deCODE Genetics, a biotechnology company based in Reykjavik. “We are going to take this out of the realm of artificial tests into the real world.”