Title: Autistic Traits and Mental Health in Females with the Fragile X Premutation: A Multi-Level Study of Behavioural, Cognitive and Genetic Profiles
Funder: The Academy of Medical Sciences

Abstract: This proposal concerns the social and emotional wellbeing of females with the Fragile X-premutation (FX-p). Using a novel approach, integrating behaviour observation with measures of social-cognition and genetic correlates, I will evaluate the prevalence, profile and cognitive and genetic mechanisms underlying the development of autistic traits and mental health challenges in this population. The FX-p is highly prevalent in the general population occurring in 0.4% of females and 0.12% of males and is associated with risk for having a child with a neurodevelopmental condition (Fragile X syndrome). Emergent literature strongly indicates that the FX-p is also a risk marker for autistic traits and negative mental health outcome. This risk is evident prior to having a child with Fragile X syndrome, but critically, individuals with the FX-p are not aware of their genetic status until after their child or a close relative is diagnosed with Fragile X syndrome. Although the FX-p is particularly prevalent in females, affected females have historically been considered largely unimpaired by their genetic mutation, leading to two inequalities: 1. there is no clear pathway for diagnosing female relatives of individuals with Fragile X syndrome, diagnosis is typically only pursued after clinical concerns arise, 2. females with the FX-p have been significantly underrepresented in research. The findings will inform clinical guidance, providing evidence to support: 1. earlier and broader genetic screening for the FX-p in the general population and 2. improved mental health screening and targeted intervention for females found to carry the FX-p.

Lay abstract: My research focuses on a genetic mutation which can deeply affect whole families. This mutation (the Fragile X premutation; FX-p) is very common in the general population, particularly in females. Those who have the FX-p are likely to have a child with a neurodevelopmental condition (Fragile X syndrome). Typically, FX-p carriers are unaware of their genetic status until their child or a close relative is diagnosed with Fragile X syndrome. So, for newly diagnosed FX-p carriers, the discovery of the gene mutation within their family is devastating: on top of the stress of caring for a disabled child are fears about their own and their relatives’ physical and cognitive degeneration, fears about the mutation replicating in their own future children or broader family; and, as my study aims to understand better, the increased likelihood that they will experience social difficulties and poor mental health. Although the FX-p is very common in females, this population have been neglected both in terms of access to clinical services and within research. To support females with the FX-p and their families we need to better understand the nature and causes of the challenges they face. I will explore the impact of the FX-p on females using assessments of social behaviour and wellbeing to evaluate the prevalence of autistic traits and mental health challenges. I will consider both biological (genetic) and cognitive aspects of the condition, to analyse the relationship between these factors and behavioural and mental health outcomes.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH