Of mice and men, depression and schizophrenia

Fifty years ago depression, schizophrenia and many other psychiatric disorders were often attributed solely to one's present or past environment: one's upbringing, one's parents, early childhood experiences, alcohol, drugs etc. And while such factors continue to play a critical role, it is now accepted that many of these conditions also have an underlying genetic component. Furthermore, recent advances in genetics suggest that many human genes are replications of those found in fruit flies, worms, mice and our nearest primate relatives. The genes that are involved in brain development in mice are the same genes as those involved in brain development in humans and thus human brains are amazingly similar to mouse brains in components, development, biochemistry, physiology and connectivity.

Animal model systems have been central in human medical research for many years leading to an understanding of how the human body works and to the development of antibiotics, vaccines and treatments for a whole range of viral, bacterial and protozoan diseases. However, animal models up to now have generally been considered very inadequate as representations of human behaviour or specific psychiatric conditions.

Now through the manipulation of genes in animals new types of mutant animals have been produced and these, be they flies or mice, have been found to do all kinds of odd things including mimicking certain syndromes seen in psychiatric patients.

Thirty years research in neurogenetics in fruit flies is reviewed in a recent issue of the science journal Nature.  Flies with insomnia, learning difficulties and homosexual courtship behaviour have all been shown to have mutations in single genes.  Aspects of schizophrenia can be studied in mice whose genes have been manipulated.  These mutant mice have enlarged brain ventricles, particularly on the left side – a feature of human schizophrenia.

No animal model will replicate the human condition is its entirety, so the idea is to find animal models that are representative of single aspects of the disorder and through these search for new drugs. Nature also had a recent report on the discovery of a mutant mouse that showed an obsessive compulsive disorder (OCD) – excessive grooming and "anxiety". The area of the mouse brain affected was the same area found to be affected in humans with OCD and the drugs, used in humans to help people with OCD, worked for the mice as well.

Human fascination with how the mind works, or doesn't work, has driven neuroscience. The rapid progress in this field, and the money available for funding it , is quite remarkable and this research now looks set to open doors to a deeper understanding of how the human mind works, how genes influence behaviour and to more specific and effective treatment of psychiatric disorders.

Rosemary Dolan