Titre
Irritability in pre-clinical Huntington's disease.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Klöppel, S.
Auteure/Auteur
Stonnington, C.M.
Auteure/Auteur
Petrovic, P.
Auteure/Auteur
Mobbs, D.
Auteure/Auteur
Tüscher, O.
Auteure/Auteur
Craufurd, D.
Auteure/Auteur
Tabrizi, S.J.
Auteure/Auteur
Frackowiak, R.S.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1873-3514
Statut éditorial
Publié
Date de publication
2010-01
Volume
48
Numéro
2
Première page
549
Dernière page/numéro d’article
557
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Irritability, together with depression and anxiety, form three salient clinical features of pre-symptomatic Huntington's disease (HD). To date, the understanding of irritability in HD suffers from a paucity of experimental data and is largely based on questionnaires or clinical anecdotes. Factor analysis suggests that irritability is related to impulsivity and aggression and is likely to engage the same neuronal circuits as these behaviours, including areas such as medial orbitofrontal cortex (OFC) and amygdala. 16 pre-symptomatic gene carriers (PSCs) and 15 of their companions were asked to indicate the larger of two squares consecutively shown on a screen while undergoing functional magnetic resonance imaging (fMRI). Despite correct identification of the larger square, participants were often told that they or their partner had given the wrong answer. Size differences were subtle to make negative feedback credible but detectable. Although task performance, baseline irritability, and reported task-induced irritation were the same for both groups, fMRI revealed distinct neuronal processing in those who will later develop HD. In controls but not PSCs, task-induced irritation correlated positively with amygdala activation and negatively with OFC activation. Repetitive negative feedback induced greater amygdala activations in controls than PSCs. In addition, the inverse functional coupling between amygdala and OFC was significantly weaker in PSCs compared to controls. Our results argue that normal emotion processing circuits are disrupted in PSCs via attenuated modulation of emotional status by external or internal indicators. At later stages, this dysfunction may increase the risk for developing recognised, HD-associated, psychiatric symptoms such as irritability.
Sujets
PID Serval
serval:BIB_B25626477214
PMID
Open Access
Oui
Date de création
2010-03-02T13:17:27.273Z
Date de création dans IRIS
2025-05-21T03:20:43Z
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Nom
19878688_BIB_B25626477214.pdf
Version du manuscrit
published
Taille
664.27 KB
Format
Adobe PDF
PID Serval
serval:BIB_B25626477214.P001
URN
urn:nbn:ch:serval-BIB_B256264772146
Somme de contrôle
(MD5):ee4bc97b3208942aecdab700befdf18d