Autistic traits and mental health in women with the fragile-X premutation: maternal status versus genetic risk

White, Sarah; Gerber, Denise; Hernandez, Romina D Sanchez; Efiannayi, Anthonia; Chowdhury, Ishita; Partington, Hannah; Moss, Joanna

doi:10.1192/bjp.2020.231

Cited by 9 publications

(9 citation statements)

References 29 publications

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“…Contrary to our hypothesis, there were no significant differences in levels of autistic traits between any of the three groups. This is inconsistent with previous findings that have found that both relatives of autistic individuals (Bishop et al, 2008;Rubenstein & Chawla, 2018) and individuals with the FXP (Clifford et al, 2007;Schneider et al, 2016;White et al, 2021) tend to show higher rates of autistic traits than the general population.…”

Section: Autistic Symptomologycontrasting

confidence: 99%

“…A proportion of women remain largely unaffected by their premutation status and do not experience any mental health or autismrelated challenges at all. However, recent studies have found that women with the FXP are more likely to experience mental health challenges and elevated autistic traits compared to women without the FXP even when accounting for maternal experience (White et al, 2021;Gossett et al, 2016;Schneider et al, 2016). Thus, the challenges are not solely caused by the extra stress of caring for a child with a disability, as was previously proposed.…”

Section: Introductionmentioning

confidence: 74%

“…Thus, the challenges are not solely caused by the extra stress of caring for a child with a disability, as was previously proposed. White et al (2021) found that women with the FXP, regardless of maternal status, still showed higher rates of autistic traits and mental health difficulties compared to women without the FXP. Little is currently known about how or why some FXP women exhibit these elevated levels of mental health difficulties and autistic features.…”

Section: Introductionmentioning

confidence: 90%

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Exploring the relationship between mentalizing and autistic traits in women with and without the fragile x premutation

Hughes,

Lim,

Skinner

et al. 2024

Preprint

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Individuals with the fragile X premutation (FXP) are more likely to display elevated levels of autistic traits; however, these traits are not fully understood, and an underlying cause has not yet been studied. A reduction in spontaneous mentalizing has been found among other populations with high autistic traits, and it is widely accepted that this cognitive difference results in the social difficulties that these individuals experience. To explore this hypothesis in women with the FXP, we examined implicit mentalizing performance using an eye-tracking paradigm and evaluated its relationship with self-reported autistic traits. We included three groups: mothers of autistic children (M-ASD; N=27), mothers of children with FXS, who themselves have the FXP (M-FXP, N=20), and mothers of neurotypically developing children (M-NT, N=24). Group membership had a main effect on implicit mentalizing ability, with the M-FXP group showing poorer performance than the M-NT group. These findings suggest that a reduction in implicit mentalizing may be a feature of at least a subset of women with the FXP, but additional studies are required to further examine the mechanistic relationship between implicit mentalizing ability and autistic traits in this population.

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Section: Autistic Symptomologycontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 90%

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Exploring the relationship between mentalizing and autistic traits in women with and without the fragile x premutation

Hughes,

Lim,

Skinner

et al. 2024

Preprint

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“…The BAP occurs more frequently in first-degree relatives of autistic individuals and is believed to reflect genetic liability to ASD. Evidence suggests that PM carriers also demonstrate significantly elevated rates of BAP features [ 69 , 213 , 267 , 290 , 306 , 307 ]. For instance, using direct assessment tools to study BAP features in a group of over 150 women PM carriers, Maltman et al (2021) reported that approximately half of the PM-carrier group displayed personality traits of the BAP.…”

Section: Fxpac and Relationships With Genetic Markersmentioning

confidence: 99%

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation

Tassone,

Protic,

Allen

et al. 2023

Cells

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The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5’ untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.

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“…Indeed, the incidence of ASD was much higher in this cohort (32.8%) as compared to the 1.0–2.3% prevalence rates in the general population [ 34 , 35 ]. Previous studies have also highlighted higher rates of ASD and ASD traits in PM carriers as compared to the general population [ 17 , 18 , 36 ]. For example, Farzin and colleagues (2006) suggested that PM carriers, even those who do not present clinically, may be at increased risk for ASD and/or ADHD, based on a small sample size (14 male probands who presented to clinic, 13 male non-probands, and control group of 16 male siblings) [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers

Aishworiya

Protić

Tang

et al. 2022

Genes

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Background: The fragile X premutation carrier state (PM) (55–200 CGG repeats in the fragile X messenger ribonucleoprotein 1, FMR1 gene) is associated with several conditions, including fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor ataxia (FXTAS), with current literature largely primarily investigating older PM individuals. The aim of this study was to identify the prevalence of fragile X-associated neurodevelopmental disorders (FXAND) in a sample of young PM individuals. Methods: This was a retrospective study conducted through a medical record review of PM individuals who were seen either for clinical concerns (probands, 45.9%) or identified through the cascade testing (non-probands, 54.1%) of an affected sibling with fragile X syndrome. Information on the presence of autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, depression, long-term psychiatric medication intake, and cognitive function, based on standardized assessments, was obtained. Molecular data, including CGG repeat number and FMR1 mRNA levels, were also available for a subset of participants. Analysis included descriptive statistics and a test of comparison to describe the clinical profile of PM individuals pertinent to FXAND. Results: Participants included 61 individuals (52 males and 9 females) aged 7.8 to 20.0 years (mean 12.6 ± 3.4) with a mean full-scale IQ of 90.9 ± 22.7. The majority (N = 52; 85.2%) had at least one mental health disorder, with anxiety being the most common (82.0% of subjects), followed by ADHD (66.5%), and ASD (32.8%). Twenty-seven (87.1%) of non-probands also had at least one mental health condition, with probands having lower cognitive and adaptive skills than non-probands. ASD was present in 20 participants (17/52 males and 3/9 females; 15 probands) with significantly lower FSIQ in those with ASD (mean 73.5 vs. 98.0, p < 0.001). Participants with ASD had a higher number of long-term medications compared to those without (2.32 vs. 1.3, p = 0.002). Conclusions: Our findings indicate a high rate of FXAND diagnoses within a cohort of young PM individuals, including those identified via cascade testing, although this was not a population sample. An awareness of the entity of FXAND and the early recognition of the symptoms of associated conditions may facilitate timely and appropriate care for PM individuals.

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Autistic traits and mental health in women with the fragile-X premutation: maternal status versus genetic risk

Cited by 9 publications

References 29 publications

Exploring the relationship between mentalizing and autistic traits in women with and without the fragile x premutation

Exploring the relationship between mentalizing and autistic traits in women with and without the fragile x premutation

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation

Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers

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