Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-22T18:35:32.879Z Has data issue: false hasContentIssue false
  • English
  • Français

The cognitive developmental profile associated with fragile X syndrome: A longitudinal investigation of cognitive strengths and weaknesses through childhood and adolescence

Published online by Cambridge University Press:  09 December 2015

Eve-Marie Quintin ,
Booil Jo ,
Scott S. Hall ,
Jennifer L. Bruno ,
Lindsay C. Chromik ,
Mira M. Raman ,
Amy A. Lightbody ,
Arianna Martin  and
Allan L. Reiss
Eve-Marie Quintin*
Affiliation:
McGill University
Booil Jo
Affiliation:
Stanford University
Scott S. Hall
Affiliation:
Stanford University
Jennifer L. Bruno
Affiliation:
Stanford University
Lindsay C. Chromik
Affiliation:
Stanford University
Mira M. Raman
Affiliation:
Stanford University
Amy A. Lightbody
Affiliation:
Stanford University
Arianna Martin
Affiliation:
Stanford University
Allan L. Reiss
Affiliation:
Stanford University
*
Address correspondence and reprint requests to: Eve-Marie Quintin, Educational and Counseling Psychology Department, McGill University, 3700 McTavish Street, Montreal, QCH3A 1Y2, Canada; E-mail: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

Few studies have investigated developmental strengths and weaknesses within the cognitive profile of children and adolescents with fragile X syndrome (FXS), a single-gene cause of inherited intellectual impairment. With a prospective longitudinal design and using normalized raw scores (Z scores) to circumvent floor effects, we measured cognitive functioning of 184 children and adolescents with FXS (ages 6 to 16) using the Wechsler Scale of Intelligence for Children on one to three occasions for each participant. Participants with FXS received lower raw scores relative to the Wechsler Scale of Intelligence for Children normative sample across the developmental period. Verbal comprehension, perceptual organization, and processing speed Z scores were marked by a widening gap from the normative sample, while freedom from distractibility Z scores showed a narrowing gap. Key findings include a relative strength for verbal skills in comparison with visuospatial–constructive skills arising in adolescence and a discrepancy between working memory (weakness) and processing speed (strength) in childhood that diminishes in adolescence. Results suggest that the cognitive profile associated with FXS develops dynamically from childhood to adolescence. Findings are discussed within the context of aberrant brain morphology in childhood and maturation in adolescence. We argue that assessing disorder-specific cognitive developmental profiles will benefit future disorder-specific treatment research.

Type
Regular Articles
Information
Development and Psychopathology , Volume 28 , Special Issue 4pt2: Epigenetics: Development, Psychopathology, Resilience, and Preventive Intervention , November 2016 , pp. 1457 - 1469
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author.Google Scholar
Bailey, D. B. Jr., Hatton, D. D., & Skinner, M. (1998). Early developmental trajectories of males with fragile X syndrome. American Journal on Mental Retardation, 103, 29–39.2.0.CO;2>CrossRefGoogle ScholarPubMed
Bailey, D. B. Jr., Hatton, D. D., Skinner, M., & Mesibov, G. (2001). Autistic behavior, FMR1 protein, and developmental trajectories in young males with fragile X syndrome. Journal of Autism and Developmental Disorders, 31, 165–174. doi:10.1023/A:1010747131386 CrossRefGoogle ScholarPubMed
Barnea-Goraly, N., Eliez, S., Hedeus, M., Menon, V., White, C. D., Moseley, M., et al. (2003). White matter tract alterations in fragile X syndrome: Preliminary evidence from diffusion tensor imaging. American Journal of Medical Genetics, 118, 81–88. doi:10.1002/ajmg.b.10035 Google Scholar
Bray, S., Hirt, M., Jo, B., Hall, S. S., Lightbody, A. A., Walter, E., et al. (2011). Aberrant frontal lobe maturation in adolescents with fragile X syndrome is related to delayed cognitive maturation. Biological Psychiatry, 70, 852–858. doi:10.1016/j.biopsych.2011.05.038 CrossRefGoogle ScholarPubMed
Bruno, J., Walter Shelly, E., Quintin, E. M., Rostami, M., Patnaik, S., Spielman, D., et al. (2013). Aberrant basal ganglia metabolism in fragile X syndrome a magnetic resonance spectroscopy study. Journal of Neurodevelopmental Disorders, 5, 1–9. doi:10.1186/1866-1955-5-20 CrossRefGoogle ScholarPubMed
Cornish, K., Cole, V., Longhi, E., Karmiloff-Smith, A., & Scerif, G. (2013). Mapping developmental trajectories of attention and working memory in fragile X syndrome: Developmental freeze or developmental change? Development and Psychopathology, 25, 365–376. doi:10.1017/S0954579412001113 Google Scholar
Cornish, K. M., Munir, F., & Cross, G. (1998). The nature of the spatial deficit in young females with fragile-X syndrome: A neuropsychological and molecular perspective. Neuropsychologia, 36, 1239–1246. doi:10.1016/S0028-3932(97)00162-0 Google Scholar
Cornish, K. M., Munir, F., & Cross, G. (1999). The spatial cognition in males with fragile X syndrome: Evidence for a neuropsychological phenotype. Cortex, 35, 263–271.Google Scholar
Cornish, K., Scerif, G., & Karmiloff-Smith, A., (2007). Tracing syndrome-specific trajectories of attention across the lifespan. Cortex, 43, 672–685.Google Scholar
Curfs, L. M., Schreppers-Tijdin, G., Wiegers, A., Borghgraef, M., & Fryns, J. P. (1989). Intelligence and cognitive profile in the fra(X) syndrome: A longitudinal study in 18 fra(X) boys. Journal of Medical Genetics, 26, 443–446.CrossRefGoogle ScholarPubMed
Dykens, E. M., Hodapp, R. M., Ort, S., Finucane, B., Shapiro, L. R., & Leckman, J. F. (1989). The trajectory of cognitive development in males with fragile X syndrome. Journal of the American Academy of Child & Adolescent Psychiatry, 28, 422–426.CrossRefGoogle ScholarPubMed
Fisch, G. S. (2006). Cognitive–behavioral profiles of females with the fragile X mutation. American Journal of Medical Genetics, 140A, 673–677. doi: 10.1002/ajmg.a.31113 Google Scholar
Fisch, G. S., Carpenter, N., Holden, J. J., Howard-Peebles, P. N., Maddalena, A., Borghgraef, M., et al. (1999). Longitudinal changes in cognitive and adaptive behavior in fragile X females: A prospective multicenter analysis. American Journal of Medical Genetics, 83, 308–312.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
Fisch, G. S., Carpenter, N., Howard-Peebles, P. N., Holden, J. J., Tarleton, J., & Simensen, R. (2010). The course of cognitive-behavioral development in children with the FMR1 mutation, Williams-Beuren syndrome, and neurofibromatosis type 1: The effect of gender. American Journal of Medical Genetics, 152A, 1498–1509. doi:10.1002/ajmg.a.33412 Google Scholar
Fisch, G. S., Simensen, R. J., & Schroer, R. J. (2002). Longitudinal changes in cognitive and adaptive behavior scores in children and adolescents with the fragile X mutation or autism. Journal of Autism and Developmental Disorders, 32, 107–114.Google Scholar
Fisch, G. S., Simensen, R., Tarleton, J., Chalifoux, M., Holden, J. J., Carpenter, N., et al. (1996). Longitudinal study of cognitive abilities and adaptive behavior levels in fragile X males: A prospective multicenter analysis. American Journal of Medical Genetics, 64A, 356–361.Google Scholar
Golder, D. E, Inaba, Y., Shi, E. Z., Skinner, C., Bui, Q. M., Francis, D., et al. (2013). Relationships between age and epi-genotype of the FMR1 exon 1/intron 1 boundary are consistent with non-random X-chromosome inactivation in FM individuals, with the selection for the unmethylated state being most significant between birth and puberty. Human Molecular Genetics, 22, 1516–1524. doi:10.1093/hmg/ddt002 Google Scholar
Gothelf, D., Furfaro, J. A., Hoeft, F., Eckert, M. A., Hall, S. S., O'Hara, R., et al. (2008). Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP). Annals of Neurology, 63, 40–51. doi:10.1002/ana.21243 Google Scholar
Green, T., Barnea-Goraly, N., Raman, M., Hall, S. S., Lightbody, A. A., Bruno, J., L., et al. (2015). Specific effect of the fragile-X mental retardation-1 gene (FMR1) on white matter microstructure. British Journal of Psychiatry. Advance online publication. doi:10.1192/bjp.bp.114.151654 CrossRefGoogle ScholarPubMed
Haas, B. W., Barnea-Goraly, N., Lightbody, A. A., Patnaik, S. S., Hoeft, F., Hazlett, H., et al. (2009). Early white-matter abnormalities of the ventral frontostriatal pathway in fragile X syndrome. Developmental Medicine & Child Neurology, 51, 593–599. doi:10.1111/j.1469-8749.2009.03295.x CrossRefGoogle ScholarPubMed
Hall, S. S., Burns, D. D., Lightbody, A. A., & Reiss, A. L. (2008). Longitudinal changes in intellectual development in children with fragile X syndrome. Journal of Abnormal Child Psychology, 36, 927–939. doi:10.1007/s10802-008-9223-y Google Scholar
Hall, S. S., Jiang, H., Reiss, A. L., & Greicius, M. D. (2013). Identifying large-scale brain networks in fragile X syndrome. JAMA Psychiatry, 70, 1215–1223. doi:10.1001/jamapsychiatry.2013.247 Google Scholar
Hallahan, B. P., Craig, M. C., Toal, F., Daly, E. M., Moore, C. J., Ambikapathy, A., et al. (2011). In vivo brain anatomy of adult and males with fragile X syndrome: An MRI study. NeuroImage, 54, 16–24. doi:10.1016/j.neuroimage.2010.08.015 CrossRefGoogle ScholarPubMed
Hessl, D., Nguyen, D. V., Green, C., Chavez, A., Tassone, F., Hagerman, R. J., et al. (2009). A solution to limitations of cognitive testing in children with intellectual disabilities: The case of fragile X syndrome. Journal of Neurodevelopmental Disorders, 1, 33–45. doi:10.1007/s11689-008-9001-8 Google Scholar
Hoeft, F., Carter, J. C., Lightbody, A. A., Cody Hazlett, H., Piven, J., & Reiss, A. L. (2010). Region-specific alterations in brain development in one- to three-year- old boys with fragile X syndrome. Proceedings of the National Academy of Science, 107, 9335–9339. doi:10.1073/pnas1002762107 CrossRefGoogle ScholarPubMed
Kogan, C. S., Bertone, A., Cornish, K., Boutet, I., Der Kaloustian, V. M., Andermann, E., et al. (2004). Integrative cortical dysfunction and pervasive motion perception deficit in fragile X syndrome. Neurology, 63, 1634–1639. doi:10.1212/01.WNL.0000142987.44035.3B CrossRefGoogle ScholarPubMed
Kogan, C. S., Boutet, I., Cornish, K., Graham, G. E., Berry-Kravis, E., Drouin, A., et al. (2009). A comparative neuropsychological test battery differentiates cognitive signatures of fragile X and Down syndrome. Journal of Intellectual Disability Research, 53, 125–142. doi:10.1111/j.1365-2788.2008.01135.x Google Scholar
Kogan, C. S., Boutet, I., Cornish, K., Zangenehpour, S., Mullen, K. T., Holden, J. J., et al. (2004). Differential impact of the FMR1 gene on visual processing in fragile X syndrome. Brain, 127, 591–601. doi:10.1093/brain/awh069 Google Scholar
Kover, S. T., Pierpont, E. I., Kim, J. S., Brown, W. T., & Abbeduto, L. (2013). A neurodevelopmental perspective on the acquisition of nonverbal cognitive skills in adolescents with fragile X syndrome. Developmental Neuropsychology, 38, 445–460. doi:10.1080/87565641.2013.820305 CrossRefGoogle ScholarPubMed
Kwon, H., Menon, V., Eliez, S., Warsofsky, I., S., White, C., D., Dyer-Friedman, J., et al. (2001). Functional neuroanatomy of visuospatial working memory in fragile X syndrome: Relation to behavioral and molecular measures. American Journal of Psychiatry, 158, 1040–1051.Google Scholar
Lachewicz, A. M., Dawson, D. V., Spiridigliozzi, G., A., & McConkie-Rosell, A. (2006). Arithmetic difficulties in females with the fragile X premutation. Journal of Medical Genetics, 140A, 665–672. doi:10.1002/ajmg.a.31082 Google Scholar
Little, R. J. A., & Rubin, D. B. (2002). Statistical analysis with missing data (2nd ed.). New York: Wiley.CrossRefGoogle Scholar
Loesch, D. Z., Huggins, R. M., Bui, Q. M., Epstein, J. L., Taylor, A. K., & Hagerman, R. J. (2002). Effect of the deficits of fragile X mental retardation protein on cognitive status of fragile X males and females assessed by robust pedigree analysis. Journal of Developmental and Behavioral Pediatrics, 23, 416–423.Google Scholar
Mazzocco, M. M. (2001). Math learning disability and math LD subtypes: Evidence from studies of Turner syndrome, fragile X syndrome, and neurofibromatosis type 1. Journal of Learning Disabilities, 34, 520–533.Google Scholar
Munir, F., Cornish, K. M., & Wilding, J. (2000). Nature of the working memory deficit in fragile X syndrome. Brain and Cognition, 44, 387–401.Google Scholar
Muthén, L. K., & Muthén, B. O. (1998–2014). Mplus user's guide (7th ed.). Los Angeles: Author.Google Scholar
Ornstein, P. A., Schaaf, J. M., Hooper, S. R., Hatton, D. D., Mirrett, P., & Bailey, D. B. (2008). Memory skills of boys with fragile X syndrome. American Journal of Mental Retardation, 113, 453–465. doi:10.1352/2008.113:453-465 Google Scholar
Peng, D., Kelley, R., Quintin, E. M., Raman, M., Thompson, P., & Reiss, A. L. (2013) Cognitive and behavioral correlates of caudate subregion shape variation in fragile X syndrome. Human Brain Mapping, 35, 2861–2868. doi:10.1002/hbm.22376 Google Scholar
Population Studies Center. (2015). Zip code characteristics: Mean and median household income (2006–2010 US Census data). Ann Arbor, MI: University of Michigan, Institute for Social Research, Population Studies Center. Retrieved on June 1, 2015, from http://www.psc.isr.umich.edu/dis/census/Features/tract2zip/index.html Google Scholar
Rivera, S. M., Menon, V., White, C. D., Glasser, B., & Reiss, A. L. (2002). Functional brain activation during arithmetic processing in females with fragile X syndrome is related to FMR1 protein expression. Human Brain Mapping, 16, 206–218.Google Scholar
Romano, D., Nicolau, M., Quintin, E. M., Mazaika, P., Lightbody, A. A., Hazlett, H., et al. (2014). Topological methods reveal high and low functioning neuro-phenotypes within fragile X syndrome. Human Brain Mapping, 35, 4904–4915. doi:0.1002/hbm.22521 CrossRefGoogle ScholarPubMed
Rousseau, F., Heitz, D., Tarleton, J., MacPherson, J., Malmgren, H., Dahl, N., et al. (1994). A multicenter study on genotype-phenotype correlations in the fragile X syndrome, using direct diagnosis with probe StB12.3: The first 2,253 cases. American Journal of Human Genetics, 55, 225–237.Google Scholar
Sansone, S. M., Schnieder, A., Bickel, E., Berry-Kravis, E., Prescott, C., & Hessl, D. (2014). Improving IQ measurement in intellectual disabilities using true deviation from population norms. Journal of Neurodevelopmental Disorders. Advance online publication. doi:10.1186/1866-1955-6-16 Google Scholar
Simon, E. W., Rappaport, D. A., Papka, M., & Wodruff-Pak, D. S. (1995). Fragile-X and Down's syndrome: Are there syndrome-specific cognitive profiles at low IQ levels? Journal of Intellectual Disability Research, 30, 326–330.Google Scholar
Skinner, M., Hooper, S., Hatton, D. D., Roberts, J., Mirrett, P., Schaaf, J., et al. (2005). Mapping nonverbal IQ in young boys with fragile X syndrome. American Journal of Medical Genetics, 132A, 25–32.Google Scholar
Strauss, E., Spreen, E. M. S., & Spreen, O. (2006). A compendium of neuropsychological tests. New York: Oxford University Press.Google Scholar
van der Molen, M. J. W., Huizinga, M., Huizenga, H. M., Ridderinkhof, K. R., Van der Molen, M. W., Hamel, B. J. C., et al. (2010). Profiling fragile X syndrome in males: Strengths and weaknesses in cognitive abilities. Research in Developmental Disabilities, 31, 426–439. doi:10.1016/j.ridd.2009.10.013 CrossRefGoogle ScholarPubMed
Verkerk, A. J., Pieretti, M., Sutcliffe, J. S., Fu, Y. H., Kuhl, D. P., Pizzuti, A., et al. (1991). Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell, 65, 905–914. doi:10.1016/0092-8674(91)90397-H CrossRefGoogle ScholarPubMed
Wechsler, D. (1991). Wechsler Intelligence Scale for Children (3rd ed.). San Antonio, TX: Psychological Corporation.Google Scholar
Wechsler, D. (2003). Wechsler Intelligence Scale for Children (4th ed.). San Antonio, TX: Psychological Corporation.Google Scholar