Mental health and genetics

1 April 2008

Recent work has highlighted the role genetics plays in shaping our personality and consequently our psychological status. Numerous studies have already shown the influence of genetics on individual personality and behaviour, and also on mental health and the risk of specific psychiatric disorders. According to the mental health charity Mind, one in four people suffer from mental health problems at some point in their lives. An understanding of the prevalence of mental health problems, as well as new diagnostics and therapies, are important in managing health care resources; provision of adult mental health services alone cost the NHS 4.5 billion in 2004/05.

A recent study compared personality traits in identical and non-identical twins in order to determine the extent genes influence personality traits [Weiss A et al. (2008), Psychol. Sci. 19(3), 205-10]. This work suggested that many personality traits including emotional stability, social and physical activity and constraint were influenced by genetics. Another recent paper in the Archives of General Psychiatry showed that variations in a specific gene called RGS2 could be linked with personality traits, specifically those relating to anxiety [Smoller et al. (2008), Arch. Gen. Psychiatry, 65(3), 298-308]. A better understanding of the genetic factors involved in psychiatric disorders and their associated biological pathways, is a valuable step towards a better understanding of these diseases, and could potentially lead to novel diagnostics, or therapeutic interventions.

The identification of individual genetic factors also opens up the possibility of developing susceptibility testing for these diseases. A ‘predictive’ genetic test for bipolar disorder is already being marketed in the US by Psynomics, and more are likely to emerge. One recent study also claims that it is could even be possible to diagnose depression by monitoring the level of a single biomarker, the GS alpha protein [Donati RJ et al. (2008), J. Neurosci. 28(12), 3042-50]; the researchers found that GS alpha protein localization differed between depressive suicides and controls (non-suicide individuals without any overt psychological disorder. Studies by the same group using animal and cell culture models have also shown that anti-depressants were able to restore normal localisation of the protein; leading the authors to propose that GS alpha could serve as a biomarker for depression and for monitoring the effectiveness of anti-depressants.

As highlighted in an article in Science, we are likely to see an increase in the number of genetic tests available on the market [Couzin J (2008), Science 319(5861), 274-7]. However, although many psychiatric disorders seem to have significant genetic contributions, they are nevertheless complex diseases influenced by the interplay of many different genetic and environmental factors. Testing to identify the presence of a particular genetic variant that has been associated with a given psychiatric disease does not necessarily provide reliable or indeed useful information about an individual’s susceptibility towards that disease (see previous news). Moreover, recent findings suggest that the genetics of psychiatric diseases may be much more complex than previously supposed. Another new paper in Science reports a study of gene variants associated with autism spectrum disorder, which concluded not only that there were very many of these variants, but also that some were individually very rare [Sebat J et al. (2008) Science 316 (5823), 445 - 449]. This echoes earlier findings in other mental health disorders, and the authors propose that different variations in the hundreds of genes that play a role in normal development and function of the brain might lead to multiple different outcomes, and that each individual with the same psychiatric disorder might well have different genetic contributions to the development of that disease. So in fact, testing for a limited number of specific genetic variants may be of no utility at all in terms of predicting psychiatric disease risk. Even were it feasible to test for genetic factors that conferred a substantially increased risk of such diseases, such testing would raise multiple ethical and regulatory issues, including the usual concerns over potential discrimination with respect to employment or insurance. The potential harms from these sorts of tests are therefore significant, especially when delivered direct to consumers.

So, if susceptibility testing is unlikely, what is the potential benefit of new findings in the genetics of mental health disorders? New tools to identify psychiatric diseases or monitor the efficacy of treatment would be valuable; it might even one day become feasible to determine different underlying pathological pathways in different patients, and tailor therapeutics accordingly (see ScienceNOW news).

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