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Brief Report: Aggression and Stereotypic Behavior in Males with Fragile X Syndrome—Moderating Secondary Genes in a “Single Gene” Disorder

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Abstract

Although fragile X syndrome (FXS) is a single gene disorder with a well-described phenotype, it is not known why some individuals develop more significant maladaptive behaviors such as aggression or autistic symptoms. Here, we studied two candidate genes known to affect mood and aggression, the serotonin transporter (5-HTTLPR) and monoamine oxidase A (MAOA-VNTR) polymorphisms, in 50 males with FXS ages 8–24 years. Mothers and fathers of participants reported the frequency and severity of aggressive/destructive, self-injurious, and stereotypic behaviors. Polymorphism genotypes were unrelated to age and IQ. Results showed a significant effect of 5-HTTLPR genotype on aggressive/destructive and stereotypic behavior; males with FXS who were homozygous for the high-transcribing long (L/L) genotype had the most aggressive and destructive behavior, and individuals homozygous for the short (S/S) genotype had the least aggression. Those with the L/L genotype also had the highest levels of stereotypic behavior. There was no effect of MAOA-VNTR on behavior; however those with the high-activity, 4-repeat genotype were more likely to be taking SSRI or SNRI medication. This preliminary study prompts consideration of secondary genes that may modify behavioral phenotype expression in neurodevelopmental disorders, even those with a single gene etiology such as FXS.

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Acknowledgments

We thank the boys and young men with fragile X syndrome and their families for their participation and generous time and effort. We also thank Patrick Adams and Aaron Campbell for their time and dedication to this research. A portion of this work was presented at the 10th International Fragile X Conference, Atlanta, GA, in July 2006. This research was supported by a grant from the National Fragile X Foundation (D. Hessl) and NIH grants MH77554 (D. Hessl) and HD36071 (R. Hagerman).

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Hessl, D., Tassone, F., Cordeiro, L. et al. Brief Report: Aggression and Stereotypic Behavior in Males with Fragile X Syndrome—Moderating Secondary Genes in a “Single Gene” Disorder. J Autism Dev Disord 38, 184–189 (2008). https://doi.org/10.1007/s10803-007-0365-5

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