Their findings, published today in Science, reveal a vulnerable period in the early stages of the brain’s development which could be targeted for future efforts in treating schizophrenia.
The study focused on the DISC-1 gene, which when mutated, presents a high risk factor for a variety of mental illnesses including schizophrenia, bipolar disorder and clinical depression. The aim of this latest study was to determine whether DISC-1’s interactions with other proteins, early on in the brain’s development, had a bearing on the brain’s ability to adapt its structure and function later on in adulthood.
The team, led by Professor Kevin Fox found that in order for healthy development of the brain’s synapses to take place, the DISC-1 gene first needs to bind with two other molecules known as ‘Lis’ and ‘Nudel’. Their experiments in mice revealed that by preventing DISC-1 from binding with these molecules – using a protein-releasing drug called Tamoxifen at an early stage of the brain’s development – it would lack plasticity once it grows to its adult state, preventing cells (cortical neurons) in the brain’s largest region from being able to form synapses.
The ability to form coherent thoughts and to properly perceive the world is damaged as a consequence of this.
Preventing DISC-1 from binding with ‘Lis’ and ‘Nudel’ molecules, when the brain was fully formed, showed no effect on its plasticity. However, the researchers were able to pinpoint a seven-day window early on in the brain’s development – one week after birth – where failure to bind had an irreversible effect on the brain’s plasticity later on in life.
Professor Jeremy Hall, a principal investigator at NCMH and director of NMHRI said “This paper provides strong experimental evidence that subtle changes early on in life can lead to much bigger effects in adulthood. This helps explain how early life events can increase the risk of adult mental health disorders like schizophrenia.”
Schizophrenia affects around 1 in 100 people and an estimated 635,000 people in the UK. The symptoms of schizophrenia can be extremely severe and frightening for people experiencing them. They can include hallucinations, delusions, confusion and withdrawal from social situations. The condition is estimated to society around £11.8 billion a year.
Read the full paper