The theory that schizophrenia and autism are opposing ends of a neurological continuum recently found support in a group of 1.7 million Danish babies.
With this sample, Yale professor of ecology and evolutionary biology Stephen Stearns and two colleagues from the University of Copenhagen sought to understand how the struggle between maternal and paternal genes during development might manifest in neuropsychiatric disorders. Their results show that babies with lower than average birth weights have a higher risk of developing schizophrenia and a lower risk of developing autism, while babies with greater than average birth weights have a higher risk of developing autism and a lower risk of developing schizophrenia. While the finding cannot yet be used clinically for diagnosis, the discovery provides supporting evidence for the importance of the balance between parental genetic interests in utero, Stearns said.
“The risk of autism goes up with birth weight and the risk of schizophrenia goes down,” Stearns said. “That is a very striking observation. The next step is to [find] which explanations [for this observation] are available out there.”
Over the last five decades, several evolutionary biologists hypothesized that maternal genes and paternal genes may be in conflict with each other. Stearns said the theory posits that maternal genes favor smaller offspring for their reduced biological burden during care. He added that a recent finding also suggested that there could be similar conflicting effects on the development of a baby’s brain that could have an impact on behavior.
To ground the theory in evidence, Stearns and his colleagues analyzed medical and demographic data collected from the population of Denmark between 1978 and 2009. The presence of a centralized database on a single population allowed the team to search for associations between different demographic variables and the risk of developing neurological conditions such as autism and schizophrenia. The results of their analysis of birth weights provided insight into the nature of the relationship between these conditions, showing evidence that higher risks of autism and schizophrenia are associated with competing evolutionary genetic interests.
Since the balance between parental genes is thought to influence birth weight, the relationship between birth weight and the disorders suggests a possible connection between maternal and paternal genes and risk of disorders, Stearns said.
“I was astounded,” Stearns said. “I never expected to see such a clear confirmation, at least in the level of pattern, if not in the level of mechanism, of this idea. I think that the only reason we were able to get it is because we had such a big sample size.”
The study suggests that evolutionarily influenced traits can have competing interests that are played out on the level of genetic development. While birth weight cannot yet be used to predict whether a baby will develop one of these neurological disorders, this knowledge can be used by clinicians to better understand the nature of the conditions.
Stearns noted that there are many factors that can contribute to the risk of developing autism or schizophrenia, and that variation in birth weight may be an associative occurrence. For instance, Stearns said that gender of the offspring and parental age are also associated with development of the disorders.
David Haig, a professor of biology at Harvard who was not involved in the paper but has studied the opposing relationship between autism and schizophrenia, said he thought the study was important in that it bolstered the theory about parental genes during development.
He noted that future research could explore the association between brain size and the risk of developing either autism or schizophrenia. The study used body weight as a proxy for variation in neural development, and Haig said that looking directly at brain size might shed light on the biological root of the disorder.
When asked about future work, Stearns said that understanding the reasoning and mechanisms behind the relationship discovered in this study was paramount. Translating this discovery into clinically applicable knowledge is also a future area of inquiry.
Tonia Ferguson, vice president of external affairs of the Autism Society, said that while her organization focuses more on aiding the families of patients who are affected by autism as opposed to commenting on the validity of underlying biological mechanisms, she hopes that studies such as this one will inspire conversation on how to help families cope with these diseases.
The article was published in the Proceedings of the Royal Society B on Sept. 17, 2014.