South Africa part of research unlocking genetic triggers for schizophrenia

Prof. Louw Roos of the Faculty of Health Sciences, University of Pretoria

"Schizophrenia is a serious mental health disorder and has huge implications for sufferers and their families - some patients are unable to work or function in ordinary society. It is an umbrella term that may include different illnesses when we find the cause," says Prof. Louw Roos of the Faculty of Health Sciences, University of Pretoria. "We currently treat the symptoms not the causes, and - depending on treatment compliance - sufferers may end up in care facilities for long periods of time."

Prof. Roos and his team, based at Weskoppies Hospital, have been involved in research on schizophrenia for many years and have cared for many patients with the condition. An estimated 1% of the population (1 in a 100) suffers from schizophrenia but many remain undiagnosed and untreated until their symptoms become too hard to manage. "Some families may try to keep them at home until they can't manage them anymore, then they seek assistance. Unfortunately stigma in mental illness still remains unacceptably high.

"In cases like this, people may end up as involuntary patients in psychiatric hospitals, usually following an extreme incident. Diagnosis then involves complex psychiatric evaluation and treatment, including a combination of medication (anti-psychotic drugs) and psychotherapy, often involving the rest of the family."

However, this may be a long-term process and the newer anti-psychotic drugs are expensive and don't necessarily work for everyone. Compliance with treatment is also vital but often difficult to achieve.

The cause of schizophrenia appears to be a combination of genetic, developmental and environmental factors. Stress may often be the trigger that causes incidents. Known risk factors also include migration and being part of a minority group which is linked to social isolation and withdrawal.

According to Prof. Roos, students on their gap years may have their first episodes because of their first experience of isolation from family, friends and community. There is also a link to high levels of cannabis use. "In cases like this, very specific interventions are needed to treat this co-morbidity." There is also sometimes a link to other neurodevelopmental diseases such as intellectual disability and autism. There is also a genetic overlap with bipolar disorder.

Mapping human genome

Worldwide research has been undertaken for many years to understand the underlying genetic architecture which causes a predisposition to the illness. Mapping of the human genome, which was completed in 2003, opened the door to even more advanced genetics research for illnesses like schizophrenia.

According to the US National Institutes of Health, "Using advanced tools and methods for studying disease genetics, researchers have identified a number of possible susceptibility genes and are closer than ever to understanding how these genes may affect brain development and function in schizophrenia."

What is generally of interest is to identify both common variants as well as more rare genetic variants which may have a big effect. It is clear that multiple genes are involved. However, gene sequencing work is expensive and long-term, and once genetic markers are identified there is a need to replicate the research in different populations to verify it. Prof Roos has worked over a long period with researchers from the University of Columbia in New York to further investigate and verify some of their findings in broader populations.

'Founder population' may provide clues

Prof. Roos and his co-workers have provided evidence of positions where schizophrenia genes are located contributing to knowledge about the genes on chromosome 22q11.2 and of the phenotypes of patients with these gene deletions. The specific gene variants that contribute to the disease may also vary in different populations.

Prof. Roos has specifically looked at the genetic mutations and deletions believed to be linked to schizophrenia in the Afrikaner population. As a so-called 'Founder population', the Afrikaner population offers unique opportunities in genetics research. (A founder effect occurs when a new colony is started by a few members of the original population. The small population size means that the colony may have reduced genetic variation or a non-random sample of specific genes. The Afrikaner population has been found to have genetic markers for porphyria and ischaemic heart disease with unusually large frequency because the original Dutch colonists happened to carry those genes.)

The group's research in the Afrikaner population has highlighted variants on chromosome 13q34 and chromosome 1p36. Genetic findings in the founder population have been replicated in other populations worldwide. Some 60% of patients do not have a family history of schizophrenia.

"This is important because it shows that the work is on track and heading in the right direction. We have good, reliable data and access to excellent archival data on patients under our care. We need better information regarding the cause of the illness to develop better treatments," concludes Prof. Roos.

For more information on schizophrenia, go to www.safmh.org.