Month: July 2009

Over the last couple of days, there’s been a great deal of coverage of three new studies on the genetics of schizophrenia. While the coverage has actually been pretty good, almost all the news stories make the same error when talking about the ‘genetic risk’ for the condition.

Twenty years ago, geneticists were searching for the ‘gene for schizophrenia’ until it became apparent that there was not going to be a single gene, or even a handful, found responsible for the mental illness.

It since became a mantra that the genetic risk for schizophrenia would be conferred by ‘many genes of small effect’. In other words, the cumulative effect of lots of genes that, on their own, would be quite benign.

Nature has just published three studies that use the only-recently-feasible technique of scanning the whole genome and has reported the first convincing positive evidence for the ‘many genes of small effect’ theory by finding that a whole bunch of genes, when considered together, account for about a third of the total difference in schizophrenia risk.

Interestingly, all three studies find that many of the genes lie in a <a href="region called the ‘major histocompatibility complex’ – a series of genes involved in the function of the immune system.

However, lots of the news reports, even from science publications give variations on the theme that ‘genetic factors account for 80 percent of the total risk of getting schizophrenia’.

This 80% figure (which can vary, some give 90%) is not an estimate of risk and shows a misunderstanding of estimated heritability taken from twin studies.

Luckily, I tackled exactly this issue in a column for July’s edition of The Psychologist:

Nature versus nurture is a lie. Music is not melody versus rhythm, wine is not grapes versus alcohol and we are not environment versus genes. We are their sum, their product and their expression. They dance together and we are their performance, but neither is an adversary. The art of understanding this elegant ballet is complex and arcane but you may never realise this from reading the quoted results of genetic studies, because the extent to which a trait is heritable, that is, accounted for by genetics, is usually expressed as a simple percentage.

If you search Google for the phrase “80 percent genetic”, you will discover hundreds of sources that claim that everything from schizophrenia, to height, to intelligence has been found to be four fifths ‘genetic’. Pick any other figure and you can find everyone from psychologists, to politicians, to journalists claiming that this or that is explained by genes to a given percentage. Geneticists know the subtly of this percentage and why these statements, usually lifted from the results of twin studies, are misleading, but clearly many others do not.

Imagine a mental illness is described as being 80% heritable. This is often taken to mean that four fifths of an individual’s risk is down to his or her genes, but this is not the case. What it means is that 80% of the variance in the measured illness was explained by genetic factors in the specific group that was studied. If this seems like a frivolous distinction, bear with me, because it is key in understanding heritability and it becomes crystal clear when tackled as an example.

Imagine that we could study a population where everybody lived in an identical environment. They did the same things everyday; they ate identical foods, had identical relationships and were stressed by identical events. Their lives were carbon copies of each other. A twin study would find that mental illness would be close to 100% heritable, because if the environment is fixed, any difference must be down to genetics. In fact, twin studies would find that everything is close to 100% heritable, for exactly the same reason. To flip our thought experiment on its head, if we only studied genetically identical clones, everything would be 0% heritable, because any difference must be down to the environment.

These figures do not necessarily tell us anything about the potential for a trait to be influenced by nature or nurture, because heritability is rarely an immutable and absolute fact about biology; it is an overall measure of how things are for that group, at that moment. In other words, the process of measuring the influence of genetics is, itself, subject to environmental factors. It captures the dance, not the dancers.

Thanks to Jon Sutton, editor of The Psychologist who has kindly agreed for me to publish my column on Mind Hacks as long as I include the following text:

“The Psychologist is sent free to all members of the British Psychological Society (you can join here), or you can subscribe as a non-member by emailing sarsta[at]bps.org.uk”

Link one two three to Nature genetics of schizophrenia studies.
Link to good write up from Science News, despite 80% genetic risk slip-up.

A 64 year old woman developed a phantom third arm after a stroke, but unusually, the patient was able to see and feel the illusory limb. A study just published online in the journal Annals of Neurology used brain scans to examine the patient. They established that the phantom sensations were accompanied by similar sorts of brain activity as you’d get from a real arm.

Unlike a classic ‘phantom limb‘, where a patient feels sensations as if they’re coming from the previously amputated body part, a ‘supernumerary phantom limb’ is where a phantom seems to appear additional to the already existing arm or leg.

The condition is rare but has been reported before and is known as the ‘supernumerary phantom limb’ in the medical literature. As we discussed last year, it is usually associated with strokes that affect the subcortical areas of the brain.

One of the reasons this new case is so interesting is because not only could the patient feel their additional limb, but they claimed to be able to see it and feel touches from it as well.

Tactile sensations in the SPL [supernumerary phantom limb] happened when she clenched her hand (she could then feel her phantom palm with her phantom fingers) and when she ‘touched’ certain parts of her body (in which case, the sensation was felt both in the phantom and the touched body part).

She could touch parts of her head, as well as her right shoulder. She claimed to be able to use the SPL to scratch an itch on her head (with an actual sense of relief). Moreover, she reported that the phantom could not penetrate solid obstacles (see supplementary materials for more details).

While a handful of cases of ‘visible’ supernumerary phantom limbs have been reported, this combination of seeing and feeling the touch of one is unique.

Importantly, the patient was not delusional – they didn’t believe they had an extra limb – they knew the sensations were unrealistic, but the experience was still there.

The limb was also not permanently felt – the patient could trigger it at will – and it appeared “pale,” “milk-white,” and “transparent.”

The researchers were keen to see if these sensations were reflected in the activity of the brain by using fMRI scans.

They found that ‘moving’ the phantom limb in front of the line of sight caused increased activation in the visual cortex of the brain.

Most strikingly, they found that when asked to ‘touch’ her cheek with the illusory hand, activity in brain areas representing cheek sensation increased.

There is always the chance that someone with very bizarre symptoms could be lying, but it is also the case that brain disturbance can cause all sort of confusions and distortions – so in some cases a patient’s description of what’s happening may not always be a reliable guide to exactly what they’re experiencing.

In this case, the brain imaging suggests that the ‘supernumerary phantom limb’ was genuinely being perceived as a visible additional arm and that its ‘touches’ were being processed by the sensory system in a similar way to touches from existing limbs.

Because the condition is so rare, and so conceptually bizarre, there is no good explanation of why it occurs except that it may be linked to the disturbance of our already established body and action ‘maps’ in the brain.

Apparently, there is more information about the case in supplementary material which can be found ‘in the online version of this article’, but the additional information doesn’t seem to be online. Ironically, the study seems to have a phantom of its own.

Link to study.
Link to PubMed entry for same.