Amygdala dysfunction in men with the fragile X premutation

Hessl, David; Rivera, Susan M.; Koldewyn, Kami; Cordeiro, Lisa; Adams, John S.; Tassone, Flora; Hagerman, Paul J.; Hagerman, Randi J.

doi:10.1093/brain/awl338

Cited by 127 publications

(136 citation statements)

References 54 publications

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“…Structural and functional imaging studies in premutation carriers support this thesis. Notable amygdala abnormalities in male carriers include an impaired response to fearful faces, a significant negative correlation of amygdala volume with CGG size for the 55-85 repeat range, and grey matter volume loss in men with FXTAS [53][54][55]. Additionally, female carriers displayed a significant negative correlation between the hippocampal volume and severity of anxiety symptoms [56].…”

Section: Neuropsychiatric Symptomsmentioning

confidence: 97%

Cognitive Dysfunction in FMR1 Premutation Carriers

Seritan¹,

Cogswell²,

Grigsby³

2013

CPSR

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Premutation carriers of the fragile X mental retardation gene (especially men) older than 50 may develop a neurodegenerative disease, the fragile X-associated tremor/ataxia syndrome (FXTAS). Carriers may present with varied cognitive impairments. Attention, working memory, declarative and procedural learning, information processing speed, and recall are among the cognitive domains affected. Executive dysfunction is a prominent deficit, which has been demonstrated mostly in men with FXTAS. In more advanced stages of FXTAS, both men and women may develop a mixed cortical-subcortical dementia, manifested by psychomotor slowing and deficits in attention, retrieval, recall, visuospatial skills, occasional apraxia, as well as overt personality changes. Studies have shown dementia rates as high as 37-42% in older men with FXTAS, although more research is needed to understand the prevalence and risk factors of dementia in women with FXTAS. Neuropsychiatric symptoms are common and reflect the dysfunction of underlying frontal-subcortical neural circuits, along with components of the cerebellar cognitive affective syndrome. These include labile or depressed mood, anxiety, disinhibition, impulsivity, and (rarely) psychotic symptoms. In this paper we review the information available to date regarding the prevalence and clinical picture of FXTAS dementia. Differential diagnosis may be difficult, given overlapping motor and non-motor signs with several other neurodegenerative diseases. Anecdotal response to cholinesterase inhibitors and memantine has been reported, while symptomatic treatments can address the neuropsychiatric manifestations of FXTAS dementia.

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Section: Neuropsychiatric Symptomsmentioning

confidence: 97%

Cognitive Dysfunction in FMR1 Premutation Carriers

Seritan¹,

Cogswell²,

Grigsby³

2013

CPSR

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“…All subjects whose data is reported here also participated in a study of amygdala function whose results are reported in the Hessl et al (2007) paper referenced above. The two groups did not differ in age, Full Scale IQ (117.9, 113.4; t=0.54, p=0.60), level of education and overall psychiatric symptomology as measured by the SCL-90-R Global Severity Index (see Table 1).…”

Section: Participantsmentioning

confidence: 99%

“…Recently, data from our laboratory has suggested that brain function is also affected by premutation status in relatively young premutation carriers without FXTAS who demonstrate no overt neurological symptoms. Compared with controls on an fMRI task, men with the premutation showed diminished brain activation in the amygdala and several brain areas that mediate social cognition while viewing fearful faces (Hessl et al 2007). The reduced amygdala activation in this group was also significantly associated with self-report of psychiatric symptoms on the Symptom Checklist-90-Revised (SCL-90-R).…”

Section: Introductionmentioning

confidence: 97%

Reduced Hippocampal Activation During Recall is Associated with Elevated FMR1 mRNA and Psychiatric Symptoms in Men with the Fragile X Premutation

Koldewyn

Hessl

Adams

et al. 2008

Brain Imaging and Behavior

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Recent studies reveal that young carriers of the fragile X premutation are at increased risk for psychiatric conditions, memory problems and executive deficits. Post mortem and structural MRI studies suggest the hippocampus is preferentially affected by the premutation. The current study utilized magnetic resonance imaging (MRI) to explore the relationship between hippocampal structure and function as well as molecular/genetic and psychiatric measures in men with the fragile X premutation. Although the groups did not differ in hippocampal volume, the premutation group showed reduced left hippocampal activation and increased right parietal activation during a recall task relative to controls. These results suggest that brain function underlying memory recall is affected by premutation status. Left hippocampal activation was negatively correlated with both FMR1 mRNA level and psychiatric symptomology in the premutation group. These associations support the theory that increased levels of FMR1 mRNA affect brain function and contribute to psychiatric symptoms.

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“…For example, psychological symptoms, such as anxiety and obsessive-compulsive features are associated with abnormal elevation of FMR1 mRNA in adult male premutation carriers with and without FXTAS (15). Also, both reduced FMRP and elevated mRNA contribute to alterations in limbic function and symptom expression in young adult carriers (30,31), providing a gene-brain-behavior basis for an understanding of emergence of these difficulties.…”

Section: Introductionmentioning

confidence: 99%