The authors of a study that claimed to find a link between typical male brain anatomy and autism spectrum disorder (ASD) have retracted it and replaced it with a dramatically changed version after finding an error in their methodology.

Dr Christine Ecker

The article, published in April 2017 in JAMA Psychiatry and reported by Medscape Medical News at that time, contained "serious errors," writes lead author Christine Ecker, PhD, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe University, Frankfurt am Main, Germany, in a letter published in the journal today.

The study authors "found that the vast majority (79.6%) of women with ASD were allocated to the category of phenotypic male individuals."

The original paper concluded that the findings "highlight the need for considering normative sex-related phenotypic diversity when determining an individual's risk for ASD and provide important novel insights into the neurobiological mechanisms mediating sex differences in ASD prevalence."

Fourteen other papers have cited the study, which also earned significant press coverage. In an editorial simultaneously published with the article, Larry Cahill, PhD, Department of Neurobiology and Behavior, University of California, Irvine, wrote that the study "represents an important new step" in recognizing sex influences as fundamental to understanding both normal and abnormal brain function.

The new paper, however, concludes that the findings "imply that the male neuroanatomical phenotype does not carry a higher intrinsic risk for ASD than the female neurophenotype and provide important novel insights into the neurobiological mechanisms mediating sex differences in ASD prevalence."

In the letter, Ecker wrote that she and her coauthors had "identified a problem with the script that was used for the prediction of biological sex in male and female individuals with ASD based on their respective neuroanatomy in our original sample."

That meant that "the probabilities we assumed to be indicative of the default (male) category in the female individuals with ASD, as shown in Figure 1B of our article, were flipped and in fact reflect the probabilities for the category of biological female individuals."

"Still Overstated"

Emily Willingham, PhD, critiqued the article at the time it was published, writing that the findings "do not, however, live up to the breathless headlines or to claims of one of its authors, Simon Baron-Cohen, who excitedly tweeted that '79.6% of women with autism have a male brain, and women with a male brain are 3 times more likely to have autism.' "

Willingham, co-editor of Thinking Person's Guide to Autism , told Medscape Medical News that the new conclusions "are still overstated," noting that even Ecker had acknowledged in Forbes that the distinctions between autistic and nonautistic brains were "subtle."

The new findings, said Willingham, suggest more of a "mosaic brain" model, which was discussed in the original article.

JAMA and its family of journals have increasingly been using the "retract and replace" approach to correcting scientific literature.

Ecker did not respond to a request for comment.

This study was supported by a grant from the Autism Imaging Multicenter Study Consortium, funded by Medical Research Council United Kingdom, and by the European Union–Autism Imaging Multicentre Study Consortium, supported by the Innovative Medicines Initiative Joint Undertaking. Additional support to individual investigators is listed in the article. Ecker, Cahill, and Willingham have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online March 27, 2019. Notice of Retraction and Replacement

Ivan Oransky, MD, is Medscape vice president for editorial and cofounder of Retraction Watch.