Cure for Schizophrenia?

A Cure for Schizophrenia?

I decided to write an article on schizophrenia, seeing as it has been prevalent in the news recently. If you’re unsure why, a scientific breakthrough regarding schizophrenia development has been discovered by Steve McCarroll (Associate Professor and Director of Genetics for Harvard) and his research team. After almost two decades of research and billions of pounds spent, these scientists from Harvard Medical School have may have discovered the biological origin of the illness – the role of the gene complement component 4 (C4).

Before we get into the science, I’ll cover a bit about the illness. So what is schizophrenia? If we split the word up, we have ‘schizo’ or the Greek term ‘skhizein’, meaning ‘to split’, and the ending ‘phren’ meaning ‘mind’. But contrary to popular belief, this mental disorder doesn’t really have anything to do with having a split personality, or drastically changing from a calm and collected mood to a raging, manic episode. It’s an illness affecting over 200,000 individuals in the UK alone and over 200 million people across the globe with onset starting from late adolescence to early adulthood. It involves symptoms that have been split into categories of positive and negative. Positive symptoms represent delusions, auditory and visual hallucinations, and negative symptoms refer to feelings of disconnection from yourself, people around you and a lack of interest in general life. This tends to have a pretty big impact on your day to day activities and maintaining responsibilities including going to work, looking after your family etc.

Schizophrenia is probably one of the most misunderstood mental disorders that is heavily stigmatised and feared by many people in the public. It’s usually due to lack of understanding of the illness or the ability to empathise with people affected by schizophrenia. Portrayal of schizophrenia and mental illnesses in general in the media and on screen is usually associated with violence and sinister behaviour, which is probably the stem of the fear behind this illness. It’s easy enough for you to believe that you suddenly know everything you could possibly know about schizophrenia after watching a 90 minute psychological thriller about it on Netflix one night, but there’s more to the disorder that is usually forgotten about – the direct impact on the patient having to deal with the illness itself, in addition to knowing that your peers are perceiving you as strange or out of the ordinary. One of the main ways we can change the public perception on many psychiatric illnesses is to be able to educate people about areas they are unfamiliar about. This really emphasises how important it is for scientists to continue research and why we’re so excited by the recent breakthrough discovered that could possibly lead to the development of new therapies and treatment.

So now I should probably tell you what the breakthrough actually is. After McCarroll et. al analysed 100,000 human DNA samples from 30 different countries, they were able to locate genetic variants in particular regions of the genomes that are related to the increased risk of schizophrenia. The gene that stood out to them the most was C4, which is involved in the complement cascade and is part of the immune system. The variability in structure of most human genes is not usually much, unlike the gene C4. By genetically analysing more than 65,000 people, it was found that individuals with a particular form or structure of the gene showed higher expression of C4, consequently having a higher risk of developing schizophrenia.


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Figure 1 – Image credit: Psychiatric Genomics Consortiu. Studies by McCarroll et al., 2016.

You can see in Figure 1 how the C4 gene on chromosome 6 is pretty much dominating and is much higher than the other genes, all of which have been linked to schizophrenia. This is indicating that C4 may possibly pose the strongest risk for the disorder. But how is the C4 gene related to this disorder? C4 is a critical component of the classic complement cascade and has a key role in pruning synapses whilst the brain matures. Previous studies and this study in particular have found that animals with a high level of C4 activity had more of their synapses eliminated during a key stage of brain development. Elimination of connections between cells has long been associated with schizophrenic patients.



Figure 2 – C4 protein localisation in human brain tissue (McCarroll et al.)

The group of confocal images in Figure 2 show the localisation of the C4 gene in hippocampal tissue. This increased C4 activity is thought to lead to impairment in cognition, which is a symptom seen in schizophrenia. These findings suggest that therapies in the future may involve reducing C4 activity to prevent synaptic pruning in patients showing early symptoms and help prevent further progression of the disorder.

This study has been described as a crucial turning point in the fight against mental illness by the director of the US National Institute of Mental Health. For over a hundred years, the pathology of complex brain diseases that comprise cognition have been studied using carefully constructed behavioural tasks and it is thought that the regulation of biogenic amine neurotransmitters is abnormal in psychiatric disorders such as schizophrenia. Findings by McCarroll et al. have provided additional knowledge that may be important in dealing with many symptoms associated with the disorder, which are fundamental in scientists’ quest to try and find a cure. Although this breakthrough is unlikely to lead towards immediate treatments, researchers are one step closer towards understanding the key molecular and cellular events of the illness.

If you’d like to read about McCarroll’s study in depth, here’s a link to the journal that was published in Nature:


Whiteman, Honor. “Schizophrenia breakthrough: scientists shed light on biological cause.” Medical News Today. Available from:

Purves D. & Augustine G.J. et al. 2001. Neuroscience. 2nd ed. Sunderland MA: Sinauer Associates.

Author: Aisha Islam 

Editor: Molly Campbell


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