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Birth size correlates with relative risk of neuropsychiatric disorders

18 September 2014

Title: Opposite risk patterns for autism and schizophrenia associated with normal birth size variation:support for hypothesized diametric gene-dosage effects

Authors: Sean G. Byars, Stephen C. Stearns and Jacobus J. Boomsma

Journal: Proceedings of the Royal Society B

A study published in Proceedings of the Royal Society B today shows a correlation between birth size and relative risk for autism and schizophrenia. Studying a data set of more than 1.75 million births researchers found that heavier and longer babies had an enhanced risk for autism and reduced risk for schizophrenia, while the opposite was true for lighter and shorter babies.

The patterns in relative risks uncovered in this study represent only small changes to small absolute disease risk but the results represent a significant finding and could be useful in helping scientist uncover the origin of these disorders.

In their study the researchers used birth size as a representation of how babies have grown in the womb and the different gene-dosages they might have been exposed to which could affect the allocation of maternal resources during pregnancy. In particular the team were interested in variations in the expression of ‘imprinted’ genes where only the version inherited from one parent is expressed. Scientists don’t yet understand the mechanism behind this imprinting but think if disturbed it can affect a baby’s growth, including their neuropsychiatric development.

To test the hypothesis the scientists behind the study analysed data from more than 1.75 million Danish births grouped according to birth weight and length. Looking across the whole range of babies of all birth-sizes the team found that the larger a baby was the higher their relative risk of autistic spectrum disorders but the lower their relative risk of schizophrenic spectrum disorders.

At the extreme end of the range of data they analysed, the heaviest babies, who were between 4.5 and 5.4 kg at birth, had a 53% increased risk of autism spectrum disorders compared to babies in the middle of the sample group who were between 3.3 and 3.7 kg. Conversely the heavier babies had a below average risk of schizophrenia spectrum disorders.

The reverse was true for smaller than average babies who had a decreased risk of autism spectrum disorders but an increased risk of schizophrenic spectrum disorders. The only exception was for extremely light babies for whom the separation between relative risk of autistic spectrum or schizophrenic spectrum disorders was less distinct. The team suggests this is consistent with previous findings that abnormal pregnancies resulting in very small babies may be harmful for brain development in general, increasing the risk for many psychiatric disorders.

The team conclude from their study that the results are consistent with the theory that autism and schizophrenia are the opposite extreme of a single spectrum of mental disorders. They add that the results lend credibility to the idea that differences in gene-dosage in the womb may contribute to these complex disorders.