Showing posts from 2012

Genetic entropy and the human intellect (or why we're not getting dumber)

This is a modified version of a letter published in Trends in Genetics: Kevin J. Mitchell (2012). Genetic entropy and the human intellect. Trends in Genetics, 14th December 2012.
Two articles by Gerald Crabtree float the notion that we, as a species, are gradually declining in average intellect, due to the accumulation of mutations that deleteriously affect brain development or function [1, 2]. The observations that prompted this view seem to be: (i) intellectual disability can be caused by mutations in any one of a very large number of genes, and: (ii) de novo mutations arise at a low but steady rate in every new egg or sperm. He further proposes that: (iii) genes involved in brain development or function are especially vulnerable to the effects of such mutations. Considered in isolation, these could reasonably lead to the conclusion that mutations reducing intelligence must be constantly accumulating in the human gene pool. Thankfully, these factors do not act in isolation.
If we, as …

Do you see what I see?

An enduring question in philosophy and neuroscience is whether any individual’s subjective perceptual experiences are the same as those of other people. Do you experience a particular shade of red the same way I do? We can both point to something in the outside world and agree that it’s red, based on our both having learned that things causing that perceptual experience are called “red”. But whether the internal subjective experience of that percept is really the same is almost impossible to tell.
There are some exceptions, of course, where there are clear differences between people’s perceptions. Colour blindness is the most obvious, where individuals clearly do not experience visual stimuli in the same way as non-colourblind people. This can be contrasted with the experience of people who are tetrachromatic – who can distinguish between a greater number of colours, due to expression of a fourth opsin gene variant. Conditions like face blindness and dyslexia may involve difficulties …

It’s not the crime, it’s the cover-up: reactivity in the developing brain and the emergence of schizophrenia

In thinking about the causes of schizophrenia, a central question keeps coming up: why does the brain end up in that particular state? Despite a high degree of variability in presentation and difficulties in defining it precisely, there is a recognisable syndrome that we call schizophrenia. This has a number of characteristic attributes, most striking of which are psychotic symptoms such as hallucinations, delusions and disorganised thoughts. These are truly, deeply strange phenomena that require an explanation: why do brain systems fail in that particular way? More to the point, why does that particular brain state emerge in so many people from so many different initial causes?
Because though we don’t know all the causes of this disorder, we know for sure that there are a lot of them. On the genetic front, a large number of distinct, rare mutations in different genes (or regions of the genome) are associated with a high risk for schizophrenia. Genome-wide association studies have imp…

The grand schema things

Even a quick glance at the adjacent picture should bring to mind for most people not only the name of this famous person, but a whole host of associated information – what he does (he’s an actor), perhaps some movies he’s been in, who he’s married to, maybe even who he’s no longer married to. Most of this information (depending on one’s level of familiarity with the particulars of the gentleman in question) will have sprung to mind automatically and effortlessly– indeed, it would be very difficult to actively stop it springing to mind, once the person is recognised. (Try thinking of an elephant without thinking of what colour it is).
For some people, however, it is anything but effortless – it is impossible. Readers with prosopagnosia, for example, may still be waiting to find out who the hell I’ve been writing about (it’s Brad Pitt). This condition, also known as face blindness, impairs the ability to recognise people by their faces – the visual stimulus of the face is not linked in …

Why have genetic linkage studies of schizophrenia failed?

“If there really were rare, highly penetrant mutations that cause schizophrenia, linkage would have found them”. This argument is often trotted out in discussions of the genetic architecture of schizophrenia, which centre on the question of whether it is caused by rare, single mutations in most cases or whether it is due to unfortunate combinations of thousands of common variants segregating in the population. (Those are the two extreme starting positions).
It is true that many genetic linkage studies have been performed to look for mutations that are segregating with schizophrenia across multiple affected members in families. It is also true that these have been unsuccessful in identifying specific genes, but what does this tell us? Does it really rule out or even argue against the idea that most cases are caused by a single, rare mutation? (In the sense that, if the person did not have that mutation, they would not be expected to have the disorder).
This depends very much on the d…

Are human brains especially fragile?

As many as a quarter of people will experience mental illness at some point in their life (over a third in any given year with more expansive definitions). At least 5% of the population suffer from lifelong brain-based disorders, including intellectual disability, autism spectrum disorders, schizophrenia, epilepsy and many others. Many of these conditions dramatically increase mortality rates and reduce fecundity (number of offspring), impacting heavily on evolutionary fitness.
Faced with these numbers, we have to ask the question: are human brains especially fragile? Are we different from other species in this regard? Is the brain different from other organs? As all of the disorders listed above are highly heritable, these questions can be framed from a genetic perspective: is there something about the genetic program of human brain development that makes it especially sensitive to the effects of mutations?
I have written lately about the robustness of neural development – how, desp…