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Investigating Epigenetic and Neuroimaging Profiles in Bipolar Disorder and Behavioral Variant Frontotemporal Dementia: An integrated epigenetic-neuroimaging approach

Published online by Cambridge University Press:  27 August 2024

G. Delvecchio*
Affiliation:
1Department of Neurosciences and Mental Health
M. Serpente
Affiliation:
1Department of Neurosciences and Mental Health
L. Di Consoli
Affiliation:
1Department of Neurosciences and Mental Health
E. Rotondo
Affiliation:
1Department of Neurosciences and Mental Health
V. Borraci
Affiliation:
1Department of Neurosciences and Mental Health
E. Scola
Affiliation:
2Department of Neuroradiology
F. M. Triuzi
Affiliation:
2Department of Neuroradiology
M. Castellani
Affiliation:
3Nuclear Medicine Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
A. Arighi
Affiliation:
1Department of Neurosciences and Mental Health
E. Scarpini
Affiliation:
1Department of Neurosciences and Mental Health
D. Galimberti
Affiliation:
1Department of Neurosciences and Mental Health 4Department of Biomedical, Surgical and Dental Sciences
P. Brambilla
Affiliation:
1Department of Neurosciences and Mental Health 5Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
*
*Corresponding author.

Abstract

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Introduction

Discriminating between bipolar disorder (BD) and behavioral variant Frontotemporal Dementia (bvFTD) is a clinical challenge as it is still based on clinical judgement, which often leads to misdiagnosis. This challenge is particularly pronounced in cases involving the C9orf72 hexanucleotide expansion, a genetic factor responsible for a substantial portion of familial FTD cases, as in these patients the development of late psychoses is particularly frequent. Moreover, individuals with C9orf72 bvFTD are also characterized by behavioral changes that resemble those seen in late-life BD, especially during the early stages of the disease. This raises questions about whether the clinical similarities between BD and bvFTD are rooted in specific alterations within the brain networks involved in cognitive processing or in selective genetic and epigenetic mutations. In light of this, our recently published neuroimaging study has shed light on the presence of distinctive structural and metabolic characteristics in elderly individuals with BD and bvFTD. These findings offer valuable neurobiological insights that may lead to differentiate between bvFTD and elderly BD patients.

Objectives

Building on our previous research, this study further explores the existence of similar epigenetic expression patterns in plasma neural derived extra cellular vesicles (NDEs), such as miRNA and lncRNA, and seeks to correlate these epigenetic data with shared or distinct biological markers obtained through structural Magnetic Resonance Imaging and [18F]-fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET).

Methods

We will plan to conduct statistical analyses on epigenetic and neuroimaging data on C9orf72 and sporadic bvFTD as well as on late-and early-onset BD patients and on healthy controls. Additionally, A PET study will be also performed on a subpopulation of these patients.

Results

Our hypothesis posits that selective epigenetic modifications may impact the brain’s structure and function, in a way that can change the glutamatergic neurotransmission in prefrontal regions, with subsequent indirect effects on subcortical areas.

Conclusions

Our findings will not only help identifying the specific biological signatures of BD and bvFTD, which might have important implications not only in prevention but also in differential diagnosis and treatment, but also offer insights into potential targets for slowing the onset and progression of the structural alterations characterizing these disorders.

Disclosure of Interest

None Declared

Type
Abstract
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of European Psychiatric Association
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