More than 80 newly identified genes may place people at risk for developing schizophrenia, strengthening the evidence for a biologic basis for a disorder that affects nearly 24 million people or 1 percent globally, according to the results of a new study.
The study, as expected, confirmed that genes involving dopamine regulation are involved in schizophrenia, but also found that genes tied to the immune system and also related to smoking were linked as well.
The exact relationship of the newly identified genes places importance on the need for additional work to uncover the unexpected findings, especially genes associated with smoking. It is unclear whether smoking truly increases risk, but if confirmed, smoking cessation could be included as part of a risk assessment and evaluation.
The findings of the study were published July 22 in the Journal, Nature.
Schizophrenia, now known to have a genetic basis, leads to a delusional state characterized by abnormal perceptions, including agitation, paranoia, as well as hearing voices, which can also lead to violent behavior.
In the past, there had been controversy among experts about the exact causes of the mental illness, with some not recognizing schizophrenia as a disease at all, and others unclear whether it had its origins from traumatic events and experiences in childhood, or, in fact, was biologically based. About 30 genes were thought to be responsible for the development of schizophrenia, with suspicion of environmental factors contributing to its onset.
With this landmark study--lasting 7 years, involving more than 80,000 genetic samples and evaluating people with and without the disease--it now becomes evident that there is stronger and more convincing evidence that the presence and activity of different genes can account for persons with the symptoms of schizophrenia.
The historic study across 35 countries--the largest to date of those living with schizophrenia--examined the genetic make up of more than 35,000 people living with the condition, compared to 110,000 without the disorder.
The study utilized a technique known as genome wide association, a process comparing the sequenced genomes of those affected by the condition to those unaffected. The differences in the genomes of those with the disease might then provide possible clues to the origins of schizophrenia, which could be potential targets for drug therapy.
The study identified more than 100 genes which place people at a higher risk of developing schizophrenia, of which 83 have never identified in the past. The bulk of the newly identified genes affect the relay of messages via chemical signaling as a measure of plasticity, but some were also noted to be integral in the immune system and the potential to fight off disease.
Interestingly, previous research has already uncovered data indicating patients with schizophrenia have signs of inflammation based on specific blood markers called cytokines. Of note, one report has suggested that relatives of persons with schizophrenia have up to a 45 % increased chances of developing schizophrenia. The findings from this study now confirm and support the connection with the immune system.
Of note, there have not been any groundbreaking advances in the pharmacologic treatment of schizophrenia since the drug thorazine was first utilized in the late 1950’s. The target of thorazine, the dopamine pathway, has been the basis for every drug developed for treating the disease.
Dr. Kyle Lapidus, Assistant Professor of Psychiatry and Neuroscience at the Icahn School of Medicine, Mount Sinai Medical Center in New York City, explains that pharmacologic advances have not been a major part of changes in approach to patients with schizophrenia since the 1960s.
“Clozapine is the most distinct of currently approved drugs for schizophrenia,” said Lapidus. “Although other drugs have been approved more recently, these do not target novel mechanisms or demonstrate superior efficacy.”
With the discovery of additional genes now implicated in the development of schizophrenia, many scientists are hopeful that there will be additional opportunities to identify drugs or biologic agents to intervene in the pathways leading to abnormal brain chemistry or signaling as part of the disorder.