Daniel Scott | Health Science Correspondent
A study published in Nature last week exposed some 108 genetic loci associated with Schizophrenia. In simpler terms, research has further proven the inheritability of the mental disease with an increase of 70 genetic hotspots as opposed to the previous 30. The largest genetic study on neuropsychiatric disorder to date is particularly applicable to University Times as TCD’s Department of Psychiatry made a large contribution to the study, with Professor Aiden Corvin listed as a major author.
John Forbes Nash, A Beautiful Mind’s protagonist and Nobel Prize winner is probably the most documented account of schizophrenia to the public, with his son also classified as schizophrenic. In recent times, the former child star Amanda Byne’s bizarre tweets were suspected to be due to the disease with treatment a long and complex process often involving a specific “cocktail” of medications, taking up to a year to get an effective treatment regimen. Symptoms are stereotypically appreciated as those with a “split personality” with hallucinations, social detachment and paranoia being more relative features. This study comes at a particularly interesting time as the generalised drug development process seen for the last 70 years becomes flooded and often unsuccessful, and gene therapy paving the way to the future for the treatment of many debilitating diseases.
An imbalance in the brain’s neurochemistry is known to be a major contributor to mental illnesses such as depression, anxiety, bipolar and indeed schizophrenia. The latter is generally treated by a dopaminergic D2 antagonist which prevents further dopamine to pass through the brain, which is a major contributor to a person’s behaviour as well as movement. Since the development of the first antipsychotics in the 1950s, the phenothiazine class of drugs have shown little long term success in treatment, with antiepileptic drugs such as carbamazepine (Tegretol) being used “off label”. D2 antagonists also act as anti emetics (anti nausea & vomiting), the most commonly used including the over the counter medication domperidone (Motilium) but due to poor absorption in the central nervous system, the most it affects the brain is with a little drowsiness.
Other forms of Schizophrenia still exist, putting it mildly for such a complex and personal disease. Along with many mental illnesses such as bipolar and depression, schizophrenia is hypothesised rather than diagnosed, although all correlated to an imbalance in one’s neurochemistry. Serotonin is a neurotransmitter related to appetite and mood in which an overproduction has been eluded to schizophrenia in the form of hallucinations. A newer class of antipsychotics were in fact developed following the effects of LSD on individuals. The overproduction of serotonin inducing hallucinations also seen in bipolar disorder, with a potential blockade catching the eye of researchers such as those at Eli Lilly in the 1970s which led to the discovery of olanzapine (Zyprexa), which is very widely prescribed even today.
Further genetic understanding is crucial to the treatment of illnesses in the 21st century in order to decipher the mechanism of action for a disease. In a nutshell, the study found that 108 locations along the 3 billion base pairs along your genome contains could contribute to a disease. The difference between a healthy individual and a susceptible one can be as subtle as a change in one atom per base pair. One single base pair can mean that an amino acid within a protein is changed, which could very well be either an enzyme or substrate for example. Due to tedious specificity with relation to enzyme kinetics, this can make the normal process different or not function at all. Rather than taking general drugs into a very unique patient on a long term basis to correct the error, genetics looks at how to optimise treatment. The Department of Genetics at TCD in particular have made great advances on steps to treat blindness caused by retinal degradation with small snippets of RNA containing the correct genetic information that can be transported in viruses (think of it like Space Invaders, level 5 gazillion). However, treatment is notoriously expensive and vast research has accounted for slow advances in recent years. An advance in genetics is also essential for choice of drug treatment guidance, based on the body’s enzyme capacities for metabolism. For example, did you know a particular CP450 enzyme in the liver which breaks down opioid drugs such as codeine found in Solpadeine is lacking in roughly 10% of the population meaning the drug has little to no pain relieving effect?
Genome screening is essential for this style of therapy that is becoming more and more reasonable, from billions to $900 for an entire genome sequence within 15 years. Screening is now also available to test particular sets of genes for sports performance for as little as €250, as well as “labs on chips” which will detect errors in base pair matchings for other diseases such as various cancers in the pipeline for early detection at a very low cost of production. Although it might be a long way away, genetics paves the way to the future in modern medicine from drug selection to novel treatment.
