Genetic markers for schizophrenia linked to unrelated cognitive impairments

A team of geneticists has identified a possible link between mutations that cause early cognitive impairments, such as dyslexia, and schizophrenia and autism.

The study was led by members of an Icelandic biopharmaceutical company specialising in the human genome, called deCODE genetics, and was based on work done by those before them into possible links between copy number variant (CNV) mutations and schizophrenia and autism.

CNVs occur when parts of the genome have an abnormal number of copies -- this could be represented as a deletion or duplication of a section of a particular chromosome. A number of these CNVs have in the past been identified in those suffering from psychiatric disorders, and the deCODE genetics team sought to track down how these markers alter the brain over time by comparing the genetics of sufferers of psychiatric disorders against healthy volunteers that carry those same mutations.

"In a small fraction of patients with schizophrenia or autism, alleles of CNVs in their genomes are probably the strongest factors contributing to the pathogenesis of the disease," write the authors in the paper, published in Nature. "These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike."

Working alongside the Central Institute of Mental Health in Mannheim, Germany, the team used a genealogical database of more than 100,000 Icelanders to track down carriers of the mutations. They found 26 CNV alleles, already identified as being markers for an increased predisposition of the disorders, in just 1.16 percent of candidates -- those 1,178 people carried one or more of the mutations each. According to a report by medwireNews, of these 167 carried specific neuropsychiatric-related CNVs but had not been diagnosed with any such condition.

The team then went about administering a series of neuropsychiatric and cognitive tests to those 167 individuals, along with a healthy control group, schizophrenia sufferers and carriers of other unrelated CNVs.

What they found, was a distinct link between mild cognitive impairments and CNVs linked to neuropsychiatric disorders, which makes sense, considering autism and schizophrenia are cognitive impairments. The carriers of neuropsychiatric-linked CNVs performed significantly worse in cognitive tasks than those with unrelated CNVs, and were more likely to have a history of learning disabilities such as dyslexia. They did, however, perform far better than patients with schizophrenia.

Digging further, the team broke down the specific CNVs. They found that those that performed poorly in the cognitive tasks and also had a history of dyslexia and dyscalculia carried the same CNV -- a deletion in chromosome 15, known as 15q11.2. Carrying out MRI scans of these volunteers' brains, they found the structure had altered in the same regions that are altered in patients with early signs of schizophrenia and in those with dyslexia

"This study provides one of the first footholds into biochemical understanding of humans' unique cognitive abilities," lead author on the study and deCODE genetics CEO Kari Stefansson said in a statement. "The findings also provide insight into which cognitive abilities put individuals at risk of developing schizophrenia and demonstrate that control carriers provide an opportunity to study cognitive abnormalities without the confounding effects of psychosis or medication."

This is not the first time a significant genetic link has been made between different cognitive impairments. Earlier this year a paper published in Nature Communications revealed the results of a novel study that involved the descendants of those living in isolated small towns in northern Finland, where cases of neuropsychiatric disorders are unusually common.

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Genetic markers for schizophrenia linked to unrelated cognitive impairments