Late onset bipolar disorder and frontotemporal dementia with mutation in progranulin gene: a case report

Abstract

Bipolar disorder is a chronic psychiatric illness characterised by fluctuation in mood state, with a relapsing and remitting course. Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous syndrome, with the most frequent phenotype being behavioural variant frontotemporal dementia (bvFTD). Here, we report the case of an Italian male presenting with late-onset bipolar disorder that developed into bvFTD over time, carrying a mutation in the GRN gene. Interestingly, the patient carried the c.1639 C > T variant in the GRN gene, resulting in a R547C substitution. Our case report further corroborates the notion that, in addition to FTD, progranulin may be involved in the neurobiology of bipolar disorder type 1, and suggests to screen patients with late-onset bipolar disorder for GRN mutations.

Behavioral variant frontotemporal dementia in patients with previous severe mental illness: a systematic and critical review

“…On LILACS, none of the nine retrieved met the requirements. Therefore, 42 articles were selected, of which 10 were cohort studies 15,16,17,18,19,20,21,22,23,24 , three were case-control studies 25,26,27 , 12 were case repo rts 28,29,30,31,32,33,34,35,36,37,38,39 and 17 other studies were cross-sectional surveys 6,7,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54 .…”

“…Cross-sectional studies comparing the neurocognitive profile between bvFTD and psychiatric disorders mostly found no remarkable differences 44,45,47,53 , or pointed to less severe deficits in bvFTD 49,55 . Lastly, there were several case reports that established a definite FTLD diagnosis, through genetic or histopathological examination, in patients with previous diagnoses or clinical histories compatible with BD/SCZ/SZA or atypical psychiatric symptoms 28,29,30,31,32,33,34,35,36,37,38,39 .…”

“…There are frequent reports of lifelong psychiatric disorders, especially BD, describing patients in whom a definite bvFTD diagnosis was made through the identification of fully penetrant genetic abnormalities (C9orf72 and GRN), suggesting the possibility of a diagnostic superimposition of these two conditions, and the need for a debate on the relationship between them 28,32,35 . In the pursuit of the association between FTLD and primary psychiatric disorders, Schoder and colleagues investigated the risk of SCZ and SZA in first-degree relatives of patients with FTLD, and found a higher risk in this group of individuals in comparison with relatives of AD patients 50 .…”

A review on shared clinical and biological aspects of bipolar disorder and frontotemporal dementia

“…Thus, increasing research in the field has highlighted clinical characteristics common to BD and dementia, and to FTD and psychiatric disorders (Dols et al, 2016;Kerstein et al, 2013;Lopes and Fernandes, 2012;Masouy et al, 2011;Rubino et al, 2017;Woolley et al, 2007). Review studies have investigated the clinical similarities between FTD and BD (Lopes and Fernandes, 2012;Masouy et al, 2011), as have case reports (Kerstein et al, 2013;Rubino et al, 2017;Woolley et al, 2007) and case series , all published by independent groups. Generally, case report studies present the clinical history of FTD patients initially misdiagnosed with lateonset BD based on predominant behavioral changes consistent with manic episodes.…”

“…Clinical similarities between BD and bv-FTD have been a focus of research in the past decade (Dols et al, 2016;Kerstein et al, 2013;Lopes and Fernandes, 2012;Masouy et al, 2011;Rubino et al, 2017;Woolley et al, 2011;Woolley et al, 2007), raising the question whether the same molecular pathways might explain shared clinical symptoms. The presence of different misfolded proteins in the brain, as well as genetic mutations (associated with these misfolded proteins or otherwise), are hallmarks in the pathology of FTD (Lowe, 2011;Mackenzie and Neumann, 2016;Takada, 2015Takada, , 2017.…”