TY - JOUR
T1 - The Phenotypic Profile Associated With the FMR1 Premutation in Women
T2 - An Investigation of Clinical-Behavioral, Social-Cognitive, and Executive Abilities
AU - Maltman, Nell
AU - Guilfoyle, Janna
AU - Nayar, Kritika
AU - Martin, Gary E.
AU - Winston, Molly
AU - Lau, Joseph C.Y.
AU - Bush, Lauren
AU - Patel, Shivani
AU - Lee, Michelle
AU - Sideris, John
AU - Hall, Deborah A.
AU - Zhou, Lili
AU - Sharp, Kevin
AU - Berry-Kravis, Elizabeth
AU - Losh, Molly
N1 - Funding Information:
The research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under award numbers R01 HD038819, P30 HD03110, and T32 HD007489, the National Institute of Mental Health under award numbers R01 MH091131 and R03 MH079998, the National Institute on Deafness and Other Communication Disorders under award number R01 DC010191 and P30 DC012035, and the National Science Foundation under award number DGE-1324585. Additional funding was received from the Developmental Science Institute Doctoral Student Research Grant at Northwestern University.
Publisher Copyright:
© Copyright © 2021 Maltman, Guilfoyle, Nayar, Martin, Winston, Lau, Bush, Patel, Lee, Sideris, Hall, Zhou, Sharp, Berry-Kravis and Losh.
PY - 2021/8/6
Y1 - 2021/8/6
N2 - The FMR1 gene in its premutation (PM) state has been linked to a range of clinical and subclinical phenotypes among FMR1 PM carriers, including some subclinical traits associated with autism spectrum disorder (ASD). This study attempted to further characterize the phenotypic profile associated with the FMR1 PM by studying a battery of assessments examining clinical-behavioral traits, social-cognitive, and executive abilities in women carrying the FMR1 PM, and associations with FMR1-related variability. Participants included 152 female FMR1 PM carriers and 75 female controls who were similar in age and IQ, and screened for neuromotor impairments or signs of fragile X-associated tremor/ataxia syndrome. The phenotypic battery included assessments of ASD-related personality and language (i.e., pragmatic) traits, symptoms of anxiety and depression, four different social-cognitive tasks that tapped the ability to read internal states and emotions based on different cues (e.g., facial expressions, biological motion, and complex social scenes), and a measure of executive function. Results revealed a complex phenotypic profile among the PM carrier group, where subtle differences were observed in pragmatic language, executive function, and social-cognitive tasks that involved evaluating basic emotions and trustworthiness. The PM carrier group also showed elevated rates of ASD-related personality traits. In contrast, PM carriers performed similarly to controls on social-cognitive tasks that involved reliance on faces and biological motion. The PM group did not differ from controls on self-reported depression or anxiety symptoms. Using latent profile analysis, we observed three distinct subgroups of PM carriers who varied considerably in their performance across tasks. Among PM carriers, CGG repeat length was a significant predictor of pragmatic language violations. Results suggest a nuanced phenotypic profile characterized by subtle differences in select clinical-behavioral, social-cognitive, and executive abilities associated with the FMR1 PM in women.
AB - The FMR1 gene in its premutation (PM) state has been linked to a range of clinical and subclinical phenotypes among FMR1 PM carriers, including some subclinical traits associated with autism spectrum disorder (ASD). This study attempted to further characterize the phenotypic profile associated with the FMR1 PM by studying a battery of assessments examining clinical-behavioral traits, social-cognitive, and executive abilities in women carrying the FMR1 PM, and associations with FMR1-related variability. Participants included 152 female FMR1 PM carriers and 75 female controls who were similar in age and IQ, and screened for neuromotor impairments or signs of fragile X-associated tremor/ataxia syndrome. The phenotypic battery included assessments of ASD-related personality and language (i.e., pragmatic) traits, symptoms of anxiety and depression, four different social-cognitive tasks that tapped the ability to read internal states and emotions based on different cues (e.g., facial expressions, biological motion, and complex social scenes), and a measure of executive function. Results revealed a complex phenotypic profile among the PM carrier group, where subtle differences were observed in pragmatic language, executive function, and social-cognitive tasks that involved evaluating basic emotions and trustworthiness. The PM carrier group also showed elevated rates of ASD-related personality traits. In contrast, PM carriers performed similarly to controls on social-cognitive tasks that involved reliance on faces and biological motion. The PM group did not differ from controls on self-reported depression or anxiety symptoms. Using latent profile analysis, we observed three distinct subgroups of PM carriers who varied considerably in their performance across tasks. Among PM carriers, CGG repeat length was a significant predictor of pragmatic language violations. Results suggest a nuanced phenotypic profile characterized by subtle differences in select clinical-behavioral, social-cognitive, and executive abilities associated with the FMR1 PM in women.
KW - FMR1 premutation
KW - broad autism phenotype
KW - executive function
KW - latent profile analysis
KW - social cognition
UR - http://www.scopus.com/inward/record.url?scp=85113268175&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85113268175&partnerID=8YFLogxK
U2 - 10.3389/fpsyt.2021.718485
DO - 10.3389/fpsyt.2021.718485
M3 - Article
C2 - 34421690
AN - SCOPUS:85113268175
SN - 1664-0640
VL - 12
JO - Frontiers in Psychiatry
JF - Frontiers in Psychiatry
M1 - 718485
ER -
