C9orf72-Associated Frontotemporal Dementia And Psychosis

Volume 3 Issue 1
Article Information

Abstract

Frontotemporal dementia (FTD) is a progressive neurodegenerative disease. About 30-40% of the cases have a positive family history, and genetic mutations are identifiable in an increasing proportion of cases. Although psychosis in FTD has been recognized for many years, it has not been taken as a key feature, and has not been included in the clinical diagnostic criteria.

This paper assesses the prevalence and characteristics of psychotic symptoms in FTD, comparing cases with (FTD-C9+) and without (FTD-C9-) the C9orf 72 pathologic expansion, analyzing also the impact of psychosis in the misdiagnosis of FTD. For this purpose a literature review was carried out.
Psychotic symptoms may occur in FTD and should not exclude the diagnosis. In addition these are more frequent in FTD-C9+ as compared to FTD-C9-, and may be the first clinical manifestation of the disease, often leading to a psychiatric diagnosis years before the diagnosis of FTD is defined. There is no conclusive evidence on the neuroanatomical basis of psychotic symptoms in FTD, although an association with pathological changes of the right hemisphere seems apparent. Given that psychotic features may be the first manifestation of FTD, a differentiation from other psychiatric disorders is essential. Further studies are needed to better characterize psychotic symptoms in FTD-C9+ and understand its pathophysiology, in order to devise better therapeutic strategies.

Key words: Frontotemporal dementia; Frontotemporal lobar degeneration; C9orf 72; TDP-43; psychosis; neuropathology.

Abbreviations:
bvFTD- behavioral variant Frontotemporal dementia
C9orf 72- Chromosome 9 open reading frame 72
CBD- Corticobasal degeneration
CBS- Corticobasal syndrome
CHMP2b- Charged Multivesicular Body Protein 2B
FTD- Frontotemporal dementia
FUS- Fused in sarcoma
GNR- Progranulin
MAPT- Microtubule associated protein tau
MND- Motor neuron disease PNFA- Progressive Non-Fluent Aphasia
PSP- Progressive supranuclear palsy
SD- Semantic dementia
TARDBP- Transactive response DNA binding protein
TDP-43- Transactive response DNA binding protein 43 kDa
VCP- Valosin-containing protein