Schizophrenia is a severe psychiatric illness that accounts for a significant healthcare burden worldwide. Patients experience a very low quality of life and symptoms associated with both high and low levels of the “happy hormone” dopamine. Hallucinations and delusions, associated with high dopamine levels (called positive symptoms), are prevalent, as well as lack of motivation and interest in wanting to socialise, associated with low dopamine (called negative symptoms). Patients can also experience limitations in thinking and memory, affecting their learning and everyday activities.
For the past 70 years, doctors relied heavily anti-psychotics, which are medicines targeted to reduce dopamine activity. This is achieved by blocking the dopamine responding protein called dopamine receptor. However, these medications are limited, because they always come with side effects (such as weight gain), don’t treat the negative symptoms and most become resistant to their effects. The gold standard drug is clozapine, which treats both negative and positive symptoms. However, it has significant side effects, including weakening the immune system and therefore is used as a last resort.
TAAR1 is a novel target that is gaining significant amount of attention in the scientific community due to its dopamine-controlling capacity. In studies using animals showed that targeting TAAR1 using TAAR1 acting drugs improves both positive and negative symptoms of schizophrenia, without any significant side effects. This allows for a different approach that is superior to treat the schizophrenia symptoms. Interestingly, rare TAAR1 mutations have been reported in schizophrenia patients and individuals affected by mental health related issues. Currently, there is no conclusive evidence nor studies have been conducted in humans to study whether TAAR1 mutations cause schizophrenia. However, in animals, absence of TAAR1 activity bring up symptoms of schizophrenia in animals. One of the ways in which TAAR1 can become inactive is through mutations.
In this study, we will use the whole genome sequencing data from UK Biobank to investigate the presence of mutations in schizophrenia patients. Long term benefits of the study includes;
* Understanding the role/contribution of mutations in the development of Schizophrenia.
* Investigate whether presence of mutations cause therapeutic failures, side-effects or toxicity.
* Potentially find genetic markers that can predict schizophrenia using genetic tests (e.g. Blueprint Genetics Parkinson Disease Panel for understanding genetic predisposition to Parkinson’s disease).
* Development of new personalised treatment options for schizophrenia patients.
* Inform better treatment practices in schizophrenia.