New research from the Copenhagen Centre for Social Evolution and Yale University offers compelling support for the general evolutionary theory that birth-weight and birth-length can partially predict the likelihood of being diagnosed with mental health disorders such as autism and schizophrenia later in life. The study analyzed medical records of 1.75 million Danish births, and subsequent hospital diagnoses for up to 30 years, and adjusted for almost all other known risk factors. The study is published in the Proceedings of the Royal Society, London B.

The number of people diagnosed with mental health disorders is on the rise in most affluent countries, but we do not yet have a comprehensive understanding of the factors that make people vulnerable to these disorders.

A new analysis of the extensive Danish public health database1 suggests that part of the answer may reside in genetic imprints established at conception that influence both size at birth and mental health during childhood and early adolescence.

The study tests predictions of the evolutionary theory of genomic imprinting - the idea that during fetal development some genes inherited from the mother are expressed differently to those inherited from the father. The potential consequence of this asymmetry is that maternal and paternal genes in a fetus will not cooperate fully during this period, even though they subsequently have shared interests due to their lifetime commitment to the same body.

Opposite forces balance each other

The reason for the conflict is that some of the genes known to be expressed in the placenta and the brain carry imprints that affect resource provisioning of the unborn child. When such genes come from the father, they favor investment of more of the mother's resources in the developing fetus, whereas the maternally-imprinted genes will normally compensate for such paternally-influenced manipulative effects to lessen the drain on maternal resources. These opposite forces balance each other in most pregnancies, with the result that most children are born with close to average length and weight and with a high likelihood of balanced mental health development.

Small deviations may well be favorable in human populations, when somewhat heavier babies are more likely to develop abstract talents and somewhat lighter babies above average social talents, for instance. However, this incurs the risk of increasing the frequency of autistic- and schizophrenic-spectrum disorders in the rare cases where imprinting imbalances are larger. The theory may explain why natural selection has not removed this portion of the burden of mental disease from our ancestors.

"We did not expect that the results would match the predictions as consistently as we found," Professor Jacobus Boomsma said.

The new study tests these predictions2, and its results are remarkably consistent. They show that the change to the risk of developing mental disorders when born smaller or larger than average are relatively small, but very consistent, clearly diametrical, and part of the single continuum that the theory predicts.

"When we started this large scale analysis four years ago, we hoped to find evidence that genetic imprinting happens, but we did not expect that the results would match the predictions as consistently as we found", explains Professor Jacobus Boomsma, Director of the Centre for Social Evolution, University of Copenhagen, who coordinated the work.

Boomsma adds: "Our study confirms that larger babies have a higher risk for incurring autism-spectrum diagnoses later in life and lower risk for schizophrenia-spectrum disorders. For example, Danish newborns are on average 52 cm long and being born at 54 cm increases the autism risk by 20%. However, these are relative risks and these disorders remain rare: in this example the absolute risk increases from 0.65% to 0.78%. Risk patterns are opposite in smaller newborns, who have higher risks for schizophrenia and lower risks for autism. Only for the smallest, prematurely-born babies does this diametric pattern disappear, because they have elevated risks for almost all disease categories".

Evolutionary conflicts

Boomsma also underlines that focused genomic studies will be needed to find out which genes are involved and how they affect brain function: "Our Centre's main objective is to develop and test evolutionary theory about the ways in which gene-level conflicts can corrupt even the most sophisticated forms of naturally evolved cooperation. It is no surprise that humans are vulnerable to such deep evolutionary conflicts, as are other mammals, and it is both useful and interesting to be aware of this part of our biological heritage", says Professor Boomsma.

The research program was supported by the Danish National Research Foundation who funds the Centre for Social Evolution and their Evolutionary Medicine program at the University of Copenhagen. The program is also part of a Copenhagen-Yale research connection under the auspices of the International Alliance of Research Universities (IARU).