Dyslexia under pressure

LONDON — Epidemiological studies can be a blessing or a curse. In the best cases, they can highlight new avenues of research to establish causal links behind certain diseases; in the worst, they can turn out to be little more than pointless distractions. Only time will tell which one the latest such study on the origins of dyslexia, published in Archives of Disease in Childhood, turns out to be.The study, by a team at the Laboratory of Physiology, Oxford University, explored the possible links between dyslexia — a condition that is thought to affect one in ten children in the UK — and familial blood pressure (Arch Dis Childhood 2002, 86:30-33). This rather unusual line of investigation is the latest in a series by the same researchers into the possibility that there may be a biological basis to the disorder.Their hypothesis was that phospholipids, the fatty acids that form the basis of cell membranes, are somehow incriminated in the development of dyslexia and other neurodevelopmental disorders — such as schizophrenia and autism — through abnormalities in the way they are metabolised. In a previous study, the same researchers — John Stein, lecturer in neurophysiology, and Kathleen Taylor — showed that concentrations of the phospholipid platelet activating factor (PAF) are raised in dyslexia sufferers. If that was the case, they predicted, then there should also be a correlation between the excess PAF levels and blood pressure, since one of its many roles is as a potent vasodilator — lowering blood pressure. Earlier studies have already shown that in patients with borderline hypertension, antibodies to PAF are significantly raised.To test the combined theories that PAF might be a contributory factor — and that there might be a partial genetic basis to dyslexia — they set out to check if there was any association with blood pressure, not just with dyslexia sufferers themselves but their families as well. They selected 112 dyslexic children aged between six and 18, along with a control group of 12 without the disorder. The parents of 90 families with one or more confirmed dyslexic children were asked to complete questionnaires stating whether they or a close relative had ever been diagnosed with high blood pressure. If they or one relative had a history of hypertension, they were recorded as positive — if not they were negative. In addition, the children were given a standard range of psychometric tests to assess their verbal and non-verbal reasoning, working memory, reading and spelling.The results showed that among the dyslexic children, 49 came from families with a history of hypertension and 63 from families with no such history. In the 16 families where all the children were dyslexic, seven had a history of high blood pressure and nine did not. To add to the evidence that high blood pressure was associated with reduced risk of dyslexia, the psychometric tests showed dyslexic children from hypertensive families performed better on number recall, reading and spelling. The researchers conceded that the study had several limitations — such as the relatively small numbers involved and the fact that it relied on self-reported data.But they concluded: "We believe this study is consistent with the PAF hypothesis of dyslexia. To our knowledge, no other hypothesis of developmental dyslexia has made this particular prediction or proposed mechanisms that could explain this finding. "This is not to say there are not other mechanisms. PAF is part of an extremely complex network of cytokines whose effects on intracellular signalling systems have yet to be disentangled. However, the prediction has been confirmed."The next step, explained Stein, is to plan a bigger epidemiological study to replicate the findings before moving on to animal studies to assess whether genetically altered mice are any more or less likely to develop dyslexia. Dyslexia is characterised by reading problems, difficulty with sequences (such as dates), poor organisation, erratic spelling and difficulty organising thoughts. On the other hand, dyslexics can often be innovative thinkers, solve problems intuitively and be highly creative. One of the most puzzling aspects is that it can affect people of all backgrounds and abilities, from the illiterate to those with university degrees.The Oxford study findings add to the growing bank of evidence for a genetic basis to the disorder. Finnish researchers have claimed previously to have found a dominant gene for developmental dyslexia on chromosome 3 (J Med Genet 2001, 38:658-664) while other teams have identified potential responsible genes elsewhere (J Med Genet 1999, 36:664-669).But Stein is keen to stress that PAF's role is far from proven. "It's interesting and totally unexpected but we need a bigger epidemiological study. But it does provide evidence for the theory that damage to brain cells that occurs in dyslexia is caused by an inflammatory process that involves PAF. What we have shown is that dyslexic families are less likely to have high blood pressure and this is very interesting from a theoretical point of view because nobody has seen the relationship between the two before. It suggests some corroboratory evidence for our theory that cells get damaged during development and that dyslexia might have some good side-effects, in that it means reduced blood pressure."Stein emphasised that as dyslexia and hypertension are both multi-factorial, the precise role of PAF in the relationship between them remains unclear. "This is pure epidemiology — it's a starting point. The evidence so far is circumstantial and nobody would say it's conclusive. 'Now we have got to do animal experiments, using gene knock-out mice, to find out how it might work in practice. At the moment there's no link to any particular gene and there are lots of genes involved in PAF."

Dyslexia under pressure

Immunological responses to elevated levels of platelet activating factor could cause dyslexia.

Interested in reading more?

Become a Member of