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Study finds no association between FMR1 premutation and either ADHD or anxiety

Introduction

A research project analysing data collected from 53,707 women undergoing genetic testing for family planning purposes has found no link between the presence of the FMR1 premutation and either ADHD or anxiety. The study consisting of 464 premutation carriers and 53,243 non-carriers (the largest sample size to date among similar studies) explored the prevalence of neuropsychiatric conditions identified by electronic medical records (EMR) in the participants who received free voluntary screening for autosomal recessive disorders and two X-linked disorders, including Fragile X syndrome (FXS). 

The Debate

Authors Liraz Klausner, Shai Carmi, Shay Ben-Shachar, Noa Lev-El Halabi, Lina Basel-Salmon,

and Dana Brabbing Goldstein in their findings contribute to the ongoing debate on the association between neuropsychiatric conditions and the FMR1 premutation. A common opinion is that the existence of an association between the two results from an ‘ascertainment bias’ because FMR1 premutation carriers are very often only confirmed as such after the diagnosis of a family member who lives with FXS. The authors note that such premutation carriers might have a ‘higher number of repeats, have predisposing genetic modifiers, or suffer from exposure to the challenges of caring for someone with FXS. 

The Results 

Studying the data from this large population-wide screening allowed the authors to reach conclusions that were less prone to ascertainment bias towards families of individuals living with FXS. An in-depth study of  neuropsychiatric conditions, as identified by electronic medical records in the 53,243 women who voluntarily underwent the screening voluntary free-of-charge screening for autosomal recessive disorders and two X-linked disorders revealed that there was no association between the FMR1 premutation and ADHD/anxiety. 

An Important Call for more Research 

The authors acknowledge that their contribution, although groundbreaking, focuses only on ADHD and anxiety as these are the most common among FMR1 premutation carriers.This could mean that the results may not necessarily be used to give a general analysis of all neuropsychiatric conditions. They also note that neuropsychiatric symptoms previously associated with the FMR1 premutation are often mild and could have gone undetected in the EMR. Mild difficulties in learning and attention may go unnoticed in the EMR unless research comprises targeted testing/ specific awareness. 

This study makes an important contribution to the debate and suggestions for future research on the connection between the FMR1 premutation and ADHD/anxiety. In particular, the findings of this paper are helpful to understand and improve genetic counselling for parents who have newly discovered that they are FMR1 premutation carriers.