The number of times a specific DNA sequence is repeated in the genome (called copy number) may influence the development of schizophrenia, scientists report.

Specifically, the team developed and used a new, more accurate method based on fluorescently-labelled DNA sequence and determined that patients showing signs of schizophrenia had variations in the copy number (called copy number variants or CNV) of particular DNA stretches.

Schizophrenia is a chronic mental disorder with debilitating and severe symptoms. Usually manifesting during the teenage years, the symptoms of this mental disorder include delusions, muted emotions, memory failures, hallucinations, and weak motor skills.

Currently, drugs and psychological therapies are used to treat schizophrenia. Drugs are usually in the form of antipsychotics which may have some temporary side effects.

Psychological therapy, on the other hand, usually involves talking with a certified therapist; the goal of therapy is to enable the patient to cope with their disability and improve the quality of life.

Several factors may lead to the development of schizophrenia. For example, most scientists think that being exposed to various environmental and chemical factors during pregnancy may affect the brain chemistry and result in an imbalance that may become schizophrenia in the future.

Genetics is also one factor as schizophrenia has been observed to run in some families. On the other hand, some schizophrenias arise in patients that do not have any family history of mental disorder. Thus, the genetic landscape surrounding schizophrenia has not yet been clearly elucidated.

Recent studies surrounding this have implicated CNVs in the genetic bases of schizophrenia. Specifically, eleven rare CNVs – which represent less than 1 percent of all CNVs – are associated with schizophrenia. These CNVs are either through deletion or duplication of entire DNA stretches.

While having these CNVs do not guarantee schizophrenia, they do increase the risk of schizophrenia and other neurodegenerative disorders.

To get to the bottom of CNVs, the researchers used a technique that allowed them to map CNVs on the patients' genomes accurately. In particular, their sophisticated technique was able to detect even the short CNVs.

The research team had to label a reference and a test genome with different colors to distinguish CNVs. Then, using a control, normal genome, they assessed the nature of the CNVs (duplications or deletions) based on the dominant color they observed.

Upon comparison, the team found at least 7,000 rare CNVs. Of these, more than 70 percent were short (less than 100,000 base pairs long). As a whole, clinically relevant CNVs were more common in schizophrenic patients than in healthy controls.

In particular, those with two clinically significant CNVs exhibited severe schizophrenic and neurodegenerative symptoms.

Interestingly, the researchers found that some of the CNVs were associated with genes involved in repairing genomic damages and coping with oxidative stress.

The findings, although early-stage, can help further the research in the pathogenesis and genetics surrounding schizophrenia. The researchers propose a model wherein CNVs affecting oxidative and genomic damage repair may cause a cascade of damages that ultimately culminates in schizophrenia and other neurodegenerative diseases.

Norio Ozaki, the corresponding author, concludes: "This model helps explain the new CNVs seen in previous studies of schizophrenia, as well as the differences in affected patients' phenotypes." MIMS