Previous studies have linked multiple genetic changes to schizophrenia, but they have not managed to explain the varying symptoms.

The condition can give rise to hallucinations, and people can find it hard to interpret reality. It can also lead to learning difficulties, emotional withdrawal, and a lack of motivation.

Statistics from the National Institute of Mental Health (NIMH) indicate that schizophrenia affects 1.1 percent of adults in the United States within a 12-month period.

People who had modifications in each of the four distinct genes had different symptoms, intelligence levels and other features distinct from those with the other modifications.

The research, published in EBioMedicine, supports a call to see “ schizophrenia ” as an umbrella term for a range of conditions that may need different, more targeted treatment options.

Schizophrenia is not a single disease, say researchers who have uncovered four key genetic changes that explain four previously unknown conditions.

Researchers from New York University (NYU) Langone Medical Center in New York, NY, led by psychiatrist Dr. Dolores Malaspina, examined 48 patients from different ethnic backgrounds with a diagnosis of schizophrenia.

The team focused on symptom sets in patients and genetic changes that led to brain function disruption. The modifications that were studied were either rare or little known.

The results link four important genes with specific conditions. All of these impact the growth or regulation of nerve circuits.

One gene, known as PTPRG, encodes a protein that enables nerve cells to connect as they form nerve networks.

Fast facts about schizophrenia “Positive” symptoms include delusions, agitated movement and unusual thinking

“Negative” symptoms include “flat” expression of emotions and difficulty starting or sustaining activity

Cognitive effects include difficulty understanding information or being able to use it to make decisions. Learn more about schizophrenia

In people with some rare mutations in this gene, symptoms of relatively severe psychosis emerge at a younger age, and learning difficulties may occur. Although some of these patients are highly intelligent, they may be held back by impairments in their working memory. Working memory is described as the “scratchpad” that the brain uses to store and process temporary memories.

A second gene, SLC39SA13, affects a zinc transporter that guides nerve cells to increase or decrease nerve impulses. People with SLC39SA13 modifications may face a range of cognitive issues, linked with low achievement at school and serious problems with emotions and motivation.

A third gene is ARMS/KIDINS220, which is involved in nerve cell growth. Alterations in this gene may not cause problems until later in life, after a person graduates from college. Cognitive decline follows, which is characteristic of a degenerative disease.

The fourth gene is TGM5, which plays a role in the stabilization of protein groups, including some groups linked to degenerative conditions that progress with older age, such as Huntington’s disease. In people with TGM5 modifications, symptoms are less severe, but they can include attention deficit disorder (ADD) during childhood.

First author Thorsten Kranz explains that treatments that do not work for one patient may be highly effective for another. For example, patients with modifications in ARMS/KIDINS220 could benefit from therapies aimed at protecting nerve cells, while those with a mutation in PTPRF may need treatment to enhance their working memory.

“A common fallacy is that schizophrenia can be treated as a single disease. Our biologically driven study begins to answer longstanding questions in the field about why any two people diagnosed with schizophrenia may have drastically different symptoms. For the first time, we have defined four syndromes mechanistically.” Dr. Dolores Malaspina

Dr. Malaspina adds that up to 1 in 3 patients with schizophrenia could now benefit from more targeted therapy, depending on the changes within these four genes, since 31 percent of patients with schizophrenia are likely to have one of these mutations.

She also expects the findings to provide a clearer insight into the condition as scientists “pull these groups out of the mix.”