Medical News Today: Schizophrenia: Largest genetic study offers new insights

A new, largest-of-its-kind study finds more evidence of the genetic underpinnings of schizophrenia. The findings may ultimately lead to the development of new drugs.

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Researchers have uncovered a new gene that may explain the onset of schizophrenia.

The new study appears in the journal Nature Neuroscience.

Elliott Rees, a research fellow at the Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics at Cardiff University in the United Kingdom, is the first author of the paper.

As Rees and his colleagues explain, both common and rare risk genetic variants contribute to the onset of schizophrenia.

However, scientists have discovered few of these variants, or alleles — common or rare — in the existing genome-wide association studies.

So, the researchers set out to discover rarer genetic variants involved in schizophrenia.

With this goal in mind, the team performed exome sequencing — a cutting-edge technique that allows for the rapid sequencing of large chunks of DNA — on 613 schizophrenia genetic trios. A genetic trio refers to two parents and one child.

The team looked at de novo variants in this sample of trios — in other words, they looked at the offspring's new genetic variations that arose from the genes of the two parents.

Then, the researchers combined this data with existing information from 2,831 genetic trios (including 617 that Rees and colleagues had analyzed in previous research), yielding a total of 3,444 trios.

According to the authors, this provided "the largest analysis of coding [de novo variants] in schizophrenia to date."

Furthermore, the scientists focused on high-risk genes that overlap between schizophrenia, autism spectrum disorder (ASD), and neurodevelopmental disorders.

One step closer to new therapies

The team found that one gene called SLC6A1 had much higher de novo mutation rates than expected.

The mutated genes were rare in the sense that only about 3 in 3,000 people with schizophrenia had them.

However, the findings are significant not because of how common the mutations are, but because they affect GABA, a major chemical neurotransmitter that is key to the central nervous system.

The findings strengthen previous research, which suggested that disruptions in the GABAergic neuronal signaling are involved in the genetic risk for schizophrenia.

"This work increases our understanding of the biological causes of this condition, which we hope will lead to the development of new and more effective treatments — because identifying the key genes involved provides molecular targets for the development of novel drugs," explains Rees.

"It can take many years to develop new therapies, but this potentially brings us a step closer," he adds.

The mutations that the team found seem to raise the genetic risk significantly, which increases the impact of the results and the therapeutic interventions that may ensue from them.

Study co-author professor Sir Michael Owen, who is a former director of the MRC Center, also comments on the findings.

He says, "As well as implicating a specific gene, SLC6A1, for the first time in schizophrenia, our findings suggest that new mutations in genes that are important in brain development can be a major factor in some cases and that these mutations can also increase the risk of other disorders such as autism and developmental delay."

"As well as understanding how the mutations impact on brain function, it will be important to understand what factors modify their effects as these may also be possible targets for new treatments."

Globally, schizophrenia affects about 1% of the population and is among the top 15 leading causes of disability.

In the United States, estimates suggest about 1.5 million people live with the condition.

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Medical News Today: Does the air we breathe influence our schizophrenia risk?

Schizophrenia affects millions of people around the world and is a chief contributor to disability. Researchers are still working to uncover all the risk factors that could facilitate the development of this condition. A new study suggests that air pollution may be one of them.

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Researchers have found some evidence that exposure to polluted air during childhood could increase a person's risk of schizophrenia.

According to the World Health Organization (WHO), around 20 million people all around the globe live with schizophrenia.

Hallucinations, persistent false beliefs, disordered thinking, and emotional disconnect chiefly characterize this mental health condition, and it is one of the main contributors to disability.

People who live with schizophrenia also have a higher risk of premature death compared with the general population.

Still, researchers are unsure of what causes this condition and why. So far, they argue that the top risk factor might be a person's genetic makeup, which interacts with environmental factors, such as social isolation and substance abuse.

The search for risk factors, however, continues, and a new study from Aarhus University in Denmark may have identified another one: exposure to air pollution during childhood.

Increasingly, researchers are showing that poor air quality may contribute not just to the development of pulmonary conditions — such as lung cancer or asthma — but also to the deterioration of brain health.

Recently, Medical News Today reported on a study linking exposure to poor air quality with cognitive functioning problems, including memory loss.

The current study — whose findings appear in JAMA Network Open — adds to the evidence that suggests researchers ought to take seriously ambient air pollution as a risk factor for brain and mental health.

Pollution increases schizophrenia risk

In the present study, the researchers analyzed data regarding 23,355 people — all born in Denmark between May 1, 1981, and December 31, 2002 — whose evolution they followed up from the participants' 10th birthday "until the first occurrence of schizophrenia, emigration, death, or December 31, 2012, whichever came first," as they state in the study paper.

The research team had access to information on the participants' genetic data — via The Lundbeck Foundation Initiative for Integrative Psychiatric Research, or iPSYCH — as well as the evolution of their mental health, and data on air pollution during their childhoods.

Of the total number of study participants, 3,531 developed schizophrenia.

The investigators' analysis indicated that individuals who had experienced exposure to high levels of air pollution growing up also had an increased risk of developing schizophrenia in adulthood.

"The study shows that the higher the level of air pollution, the higher the risk of schizophrenia," says senior researcher Henriette Thisted Horsdal, Ph.D.

"For each 10 micrograms per cubic meter [referring to the concentration of the pollutant nitrogen dioxide in ambient air] increase in the daily average, the risk of schizophrenia increases by approximately 20%," she adds.

"Children who are exposed to an average daily level above 25 micrograms per cubic meter have an approximately 60% greater risk of developing schizophrenia compared to those who are exposed to less than 10 micrograms per cubic meter."

Henriette Thisted Horsdal, Ph.D.

What this means, the researchers explain, is that if the average person's lifetime risk of schizophrenia is about 2%, people who have grown up in areas with the lowest levels of air pollution will have a risk of under 2%.

By contrast, those who have grown up in areas with the highest levels of air pollution have a lifetime risk of schizophrenia of approximately 3%.

While it is unclear why childhood exposure to air pollution appears to affect the schizophrenia risk, the investigators note that, according to their study, this environmental risk factor is independent of other risk factors for this condition, such as genetic risk.

"The risk of developing schizophrenia is also higher if you have a higher genetic liability for the disease," says Thisted Horsdal. But, she adds, "[o]ur data show that these associations are independent of each other."

"The association between air pollution and schizophrenia cannot be explained by a higher genetic liability in people who grow up in areas with high levels of air pollution," she continues.

Nevertheless, many questions about the potential relationship between schizophrenia and air quality remain unanswered, so the investigators emphasize the need for further research on this topic.

Original Article