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Genes and Mental Disorders
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Michael O' Donovan is Senior Lecturer and Honorary Consultant Psychiatrist at the University of Wales College of Medicine, Cardiff. |
The idea that mental health problems tend to run in families is not new. Genes, however, are only one cause of family resemblance which may also be the result of shared family environment. Thus, support of a football team is familial but is not likely to be genetic. The contribution of genes and environment can be estimated from twin studies. All twins share a family environment with their co-twin regardless of whether they are 'identical' or non-identical. However, identical twin pairs share all of their genes whereas non-identical twins only share about half. Therefore if a certain illness occurs in both members of a pair of identical twins more often than in both members of a pair or non-identical twins, it is likely to be because of shared genes rather than shared environment.
In fact, identical twins are much more similar than non-identical for the presence of major mental illnesses such as schizophrenia and mania, indicating that most of the risk of developing such disorders comes from our genes. However twin study designs are not perfect. One of the most obvious deficiencies is that genetically identical twins may experience a greater degree of environmental sharing than non-identical twins, for example they are more frequently dressed the same. Fortunately, evidence from twin studies can be independently corroborated by adoption study designs. Such studies have shown that the risk for developing a major mental illness in adoptees is dependent upon the mental health of their biological relatives (or genes) and largely independent of the mental health of their adoptive relatives (or family environment).
It should be stressed that even though the causation of major mental illness seems to be subject to a large genetic contribution, most individuals who suffer from these disorders do not have affected parents and the risk to the children of affected individuals is relatively low. The reason is that expression of the disease may require the inheritance of more than one gene, and even then, environmental triggers may be required. Thus we need to think in terms of inheriting susceptibility to mental illnesses rather than simple genetic causation.
Most of the 'milder' mental disorders (e.g. anxiety and minor depression) have been less intensively studied than schizophrenia or the major disorders of mood such as mania. Nevertheless, the data available suggest that these disorders also run in families largely because of genes, although other environmental influences outside the family are more important in determining overall risk of illness.
Most of the 'milder' mental disorders (e.g. anxiety and minor depression) have been less intensively studied than schizophrenia or the major disorders of mood such as mania. Nevertheless, the data available suggest that these disorders also run in families largely because of genes, although other environmental influences outside the family are more important in determining overall risk of illness.
The fact that most mental illness has a significant genetic component is of limited academic interest per se. However, by comparing the DNA (the 888877'building blocks' of genes) of affected and unaffected individuals it is now possible to identify the actual genes involved.
From this the identity, function and dysfunction of the protein molecules which are made by the genes implicated in the disorders can be unravelled and, hopefully, this will provide a secure foundation for better diagnostic and therapeutic approaches.
So far, we have artificially differentiated between genes or environment. However, genes obviously need an environment in which to act, and the risk of developing any mental disorder is therefore a function of genes and environment.
Therefore even where there is a substantial genetic contribution to a disorder, it does not follow that interventions in the 'environmental' realm will be of lesser importance. For example while genes play a clear and major involvement in determining liability for abusing alcohol, it is also obvious that without alcohol in the environment, there could be no such thing as alcohol abuse.
Despite the efforts of numerous dedicated researchers, the key biological, psychological and cultural environmental factors that trigger or prevent the expression of most mental disorders remain unknown. However, when the relevant genes are known, the ability to identify individuals who are unaffected, despite a high genetic risk for a disorder, will facilitate the search for these crucial environmental factors.
Thus, the ultimate goal of genetic research is a complete understanding of the complex genesis of mental disorders through unravelling the interactions of biological, psychological and social factors. At present we are still far from this, but there have been some notable achievements. Thus, some of the genes that are involved in susceptibility to dementia (e.g. Alzheimer's disease and Huntington's disease) have been identified and the function of their encoded proteins partially characterized.
However, for most mental illnesses, research is still at the stage of hunting for the genes, but, as a result of several recent promising findings for both schizophrenia and severe recurrent mood disorder, there is now optimism that at least some of the genes involved in the genesis of these disorders will be known within the next few years.
Of course scientific advances confer risks as well as benefits and it is up to society to ensure that the improved ability to detect disease susceptibility that will come in the future is not used to the detriment of those individuals who may be at greater than average risk.
Although this seems to be overlooked outside the field of genetics, such ethical concerns should not be thought of as unique to this discipline. Any advances in uncovering the non-genetic factors that lead to raised disease susceptibility also carry the same risks of misuse.