Researchers at the Indiana University School of Medicine have developed a test that can predict how likely an individual is to develop schizophrenia. The scientists combined data from several different types of studies in order to identify and prioritize a group of genes most associated with the disease.

Combined, these genes can generate a score, and determine whether an individual is at lower or higher risk of developing schizophrenia. The study, which was conducted along with a group of national and international collaborators, is published online in the journal Molecular Psychiatry.

In addition, the authors applied their top genes to data from other studies of schizophrenia and were able to successfully identify which patients had been diagnosed with the disease and which had not.

When they examined the biological pathways in which the genes were active, they also proposed a model of schizophrenia, given that the disease's underlying causes are a mix of genetic variations that affect the development of the brain and neuronal connections together with environmental factors; in particular stress.

Lead researcher, Alexander B. Niculescu III, M.D., Ph.D., associate professor of psychiatry and medical neuroscience at the IU School of Medicine, and director of the Laboratory of Neurophenomics at the IU Institute of Psychiatric Research, said:

"At its core, schizophrenia is a disease of decreased cellular connectivity in the brain, precipitated by environmental stress during brain development, among those with genetic vulnerability."

Niculescu, who is also staff psychiatrist and investigator at the Richard L. Roudebush Veterans Affairs Medical Center, continued:

"For first time we have a comprehensive list of the genes that have the best evidence for involvement in schizophrenia."

Schizophrenia is a psychiatric disease that makes it difficult for the person to distinguish between real and unreal experiences and to think logically. Approximately 1% of the population is affected by the disease, often with devastating impact.

Once the new test is refined, it could help physicians and caregivers identify which young people in families with a history of the disease are more likely to develop schizophrenia, prompting early intervention and treatment.

Niculescu notes that a score indicating a higher risk of schizophrenia...:

"...doesn't determine your destiny. It just means that your neuronal connectivity is different, which could make you more creative, or more prone to illness.

It's all on a continuum; these genetic variants are present throughout the population. If you have too many of them, in the wrong combination, in an environment where you are exposed to stress, alcohol and drugs, and so on, that can lead to the development of the clinical illness."

In about two-thirds of cases, the prototype test was able to determine whether an individual was at a lower or higher risk of developing the disease.

The team found that when analyses were conducted using gene-level data, the results were stronger compared to when analyses were based on individual variations - called single nucleotide polymorphisms (SNPs) - in those genes.

Several different SNPs can trigger a particular gene's role in the development of schizophrenia. The researchers state that evidence for the genes, as well as the biological mechanisms in which they play a role, were significantly stronger from study to study than evidence for individual SNPs.

According to Dr. Niculescu, prior studies examining individual variations were difficult to replicate from study to study. However, this latest study suggests that the majority of research conducted in recent years has produced consistent results at a gene and biological pathway level.

Dr. Niculescu explained:

"There is a lot more reproducibility and concordance in the field than people realized.

Finally now, by better understanding the genetic and biological basis of the illness, we can develop better tests for it, as well as better treatments. The future of medicine is not just treatment but prevention, so we hope this work will move things in the right direction."

Written by Grace Rattue