The genetic codes of mice, chimpanzees and humans all share remarkable similarities. Ninety-nine percent of mouse genes match a sequence in the human genome. So what makes the three species so different? Clearly the complexity of the genome lies in how the genes interact and are regulated. Understanding longterm changes in gene regulation, and especially how they occur after birth, is critical in determining the impact that nutrition and other environmental factors have on healthy development and adult life. Moreover, since most of the development of the human brain occurs after birth, there is considerable interest in trying to identify how social and environmental changes can affect brain functioning and lead to alterations in gene expression that span across generations.

Epigenetics is the study of how a set of reversible heritable changes in the functioning of a gene can occur without any alterations to the DNA sequence. These changes may be induced spontaneously, in response to environmental factors, or in response to the presence of a particular gene. Studies of animal behaviour have shown that the offspring of a mother with good nurturing skills are more likely to be good parents themselves. Importantly, well-nurtured animals show long-term brain changes, especially in an area called the hippocampus, where genes that respond to stress are silenced in the presence of good mothering. This epigenetic effect is passed on to the next generation and continues until the cycle of good mothering is broken.

The contribution of genetics to the understanding of cognition and psychiatric disorders has tended to focus on gene polymorphisms. However, although there are increasing numbers of genetic polymorphisms under investigation, they are still unable to account for much of the variance seen in many psychiatric illnesses. In contrast, gene-environment interactions can account for much more of the aetiology of psychiatric disorders. For example, schizophrenia is only 50% concordant in genetically identical (monozygotic) twins, while the severity of different ‘life-events’ is known to predispose some people to certain psychiatric disorders. It is now established in animal and human studies that some environmental events can induce long-term developmental changes in chromatin structure through various mechanisms such as histone de-acetylation and DNA methylation of non-coding sequences, which produce long-term silencing of transcription. Since most human brain development occurs postnatally, the brain more than any other organ is under strong social and environmental influences that can have long-lasting effects on brain function and wellbeing.

The study of epigenetic marks on chromosomes was pioneered in Cambridge, with studies of genomic imprinting and gene expression. This type of regulation is unique to mammals, and it may play an important role in brain development and evolution. Cambridge has fostered a strong multi-disciplinary approach to epigenetics, especially in terms of its relevance to neuroscience. Currently, researchers from the Gurdon Institute, Physiology, Development & Neuroscience, and the Department of Zoology, in collaboration with the Babraham Institute, are undertaking complex functional studies on imprinted genes for brain development, brain evolution and behaviour. The aim of this exciting research is to have a greater understanding of foetal programming and postnatal social influences on well-being.