A number of studies have demonstrated that genetic predisposition plays a very important role in the development of schizophrenia, bipolar disorder and depression. Research supports the idea that the different psychiatric disorders have overlapping genetic susceptibility factors and a mutation of the gene, DISC-1 (Disrupted-In-Schizophrenia-1) is strongly implicated in all of them.

One mutation within the gene itself leads to schizophrenia-like symptoms whereas another mutation leads to depressive symptoms. Using animal models, he has been able to alter the molecular structure of a single gene in mice and study its behavioural and physiological consequences. Although the association of the mutant DISC-1 gene with psychiatric disorders was first was identified in 2005 in a large Scottish family with a strong history of schizophrenia, depression and bipolar affective disorder, Dr. Roder’s research demonstrated, for the first time, that malfunction of the DISC-1 gene, does, in fact, cause the symptoms of these disorders in an animal model.

The mouse carries virtually the same set of genes (99 per cent) as the human and therefore, it is an important animal model in laboratory research enabling scientists to experimentally test and learn more about the function of human genes. Although mice have a similar genome (genetic blueprint) to humans, there is no question that rodent models of schizophrenia have significant limitations because the brain circuitry in humans is far more complex than the brain circuitry of the mice. There is also a candidate susceptibly gene for schizophrenia that occurs in humans and monkeys but not mice. The negative symptoms such as hallucinations and delusions are impossible to address but the positive symptoms (cognitive loss) can be modeled. DISC-1 mutant mice are significantly more active than the control mice without the mutant gene. They also and have problems navigating the T-maze which models working memory in humans and shows deficits in sensory-motor-gating tasks as well as with a task that measures attention which is also similar to human symptoms. Research by scientists at Johns Hopkins in Baltimore, Maryland has confirmed Dr. Roder’s finding using the same DISC-1 gene in transgenic mice.

Dr. Roder’s research shows other strong similarities between the mutant mouse with the mutated gene and humans with schizophrenia by examining the brains of these mice with MRI scans. The mutation also increases the sensitivity of the mice to amphetamines causing increased dopamine activity and an increase in GSK-3, which also occurs in schizophrenia. Symptoms can be reversed in these DICS-1 mice using lithium and other GSK-3 enzyme inhibitors that are used to treat bipolar disorders in humans.

When Dr. Roder’s son Nathan was diagnosed with schizophrenia in 2001, he switched his research objectives because he wanted to make a difference to the lives of people with mental illnesses. Internationally recognized for his groundbreaking work with “killer cells,” Dr. Roder decided to leave the well-funded world of cancer research because of the realization that tumour cells are able to mutate and change, enabling them to escape the benefits of specific treatments.. According to Dr. Roder, research into mental illnesses is where cancer research was 30 years ago and the money is scarce.

Dr. Roder, and his team at Mount Sinai, has already made a difference by establishing the fact that the mutated DISC-1 gene actually causes the symptoms of schizophrenia and other psychiatric disorders. Their research leads the way for further investigations to better understand the development of these disorders, which many scientists now believe start before birth.

Dr. Roder continues to develop animal models that have the potential of pointing the way to new treatments not only for a common psychiatric disorder such as schizophrenia, and affective disorders such as depression and bipolar disorder.