Differential Impact of the FMR-1 Full Mutation on Memory and Attention Functioning: A Neuropsychological Perspective

Abstract

Memory and attention processing were examined in a group of 15 adult Fragile-X syndrome (FXS) males with Fragile-X mental retardation 1 (FMR-1) full mutation and compared to two control groups: a learning disabled (LD) control and a normal functioning control. Performance was assessed across a wide range of tasks including working memory, recognition memory, selective attention, sustained attention, and attentional switching. All three groups performed at a comparable level on recognition memory tasks, and the Fragile-X males and LD control group performed worse than the control group on tasks of working memory and sustained attention. On a task of executive function, the Fragile-X males demonstrated a significant deficit in comparison to the LD control group and the normal control group, but performed better than the LD control group and at a comparable level to the control group on tasks of selective attention. Molecular analyses of the lymphocyte DNA provided little evidence for a correlation between expansion size and performance on tasks of memory and attention. The findings from the present study are discussed in the context of functional neuroimaging and brain-behavior-molecular correlates.

The cyclic AMP phenotype of fragile X and autism

“…Memory deficits and anxiety-related social behavior are central to the FX full mutation phenotype (Cornish, Munir et al 2001;. For example, the FMRP defect impacts the anatomy (Reiss, Lee et al 1994) and function of memory related areas like the hippocampus.…”

“…Autism is a behaviorally defined neurodevelopmental disorder with a characteristic triad of deficient diagnostic domains: social, behavioral, and communicative (Rapin 1997). Anxiety-related social behavior and memory deficits are reported in both the autism (Williams, Goldstein et al 2006;Gillott and Standen 2007) and FX behavioral phenotypes (Cornish, Munir et al 2001;. Signaling deficiencies in mGluR and cyclic AMP (cAMP) mediated mechanisms are central to FX pathophysiology (Berry-Kravis 1990;Berry-Kravis, Hicar et al 1995;Miyashiro and Eberwine 2004).…”

Is Theory of Mind Understanding Impaired in Males with Fragile X Syndrome?

“…Although the standard false belief tasks used by Garner et al (1999) and Cornish et al (2005) included check questions to ensure that the participant could remember crucial facts about the story, remembering these facts is not the only demand that the false belief task makes on working memory. Since children with FXS have well-attested impairments in working memory that are disproportionate to their general level of intellectual impairment (Cornish, Munir & Cross, 2001), it could be that any difficulty they have on false belief tasks arises from working memory impairment, rather than a more specific "theory of mind" impairment.…”

Fragile X Syndrome as a Multilevel Model for Understanding Behaviorally Defined Disorders

“…Finally, executive function is clearly deficient in FXS in childhood, with concomitant memory impairments (Lanfranchi, Cornoldi, & Drigo, 2009). All of these characteristic problems continue into adulthood; nonetheless, the most serious cognitive impairments have been shown to reside in executive function and visual-spatial attention in this syndrome (Cornish, Munir, & Cross, 2001). …”