Irritability in pre-clinical Huntington's disease.
Details
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State: Public
Version: Final published version
State: Public
Version: Final published version
Serval ID
serval:BIB_B25626477214
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Irritability in pre-clinical Huntington's disease.
Journal
Neuropsychologia
ISSN
1873-3514 (Electronic)
ISSN-L
0028-3932
Publication state
Published
Issued date
01/2010
Peer-reviewed
Oui
Volume
48
Number
2
Pages
549-557
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
Keywords
Adult, Brain Mapping, Chi-Square Distribution, Feedback, Physiological/physiology, Female, Humans, Huntington Disease/diagnosis, Huntington Disease/genetics, Huntington Disease/physiopathology, Image Processing, Computer-Assisted/methods, Irritable Mood/physiology, Magnetic Resonance Imaging/methods, Male, Middle Aged, Oxygen/blood, Sex Factors, Statistics as Topic, Surveys and Questionnaires, Time Factors
Pubmed
Web of science
Open Access
Yes
Create date
02/03/2010 15:17
Last modification date
20/08/2019 16:21