title: Functional brain changes underlying irritability in premanifest Huntington's disease.
abstract: The clinical phenotype of Huntington's disease (HD) consists of motor, cognitive and psychiatric symptoms, of which irritability is an important manifestation. Our aim was to identify the functional and structural brain changes that underlie irritability in premanifest HD (preHD). Twenty preHD carriers and 20 gene-negative controls from HD families took part in the study. Although the 5-year probability of disease onset was only 11%, the preHD group showed striatal atrophy and increased clinical irritability ratings. Functional MRI was performed during a mood induction experiment by means of recollection of emotional (angry, sad, and happy) and neutral autobiographical episodes. While there were no significant group differences in the subjective intensity of the emotional experience, the preHD group showed increased anger-selective activation in a distributed network, including the pulvinar, cingulate cortex, and somatosensory association cortex, compared to gene-negative controls. Pulvinar activation during anger experience correlated negatively with putaminal grey matter volume and positively with irritability ratings in the preHD group. In addition, the preHD group showed a decrease in anger-selective activation in the amygdala, which correlated with putaminal and caudate grey matter volume. In conclusion, compared to gene-negative controls, anger experience in preHD is associated with activity changes in a distributed set of regions known to be involved in emotion regulation. Increased activity is related to behavioral and volumetric measures, providing insight in the pathophysiology of early neuropsychiatric symptoms in preHD.
authors: Department of Neurosciences, KU Leuven, Psychiatry Research Group, Leuven, Belgium.|Old Age Psychiatry Department, University Hospitals Leuven, Leuven, Belgium.
authors: Jan
authors: J
authors: Van den Stock
authors: Department of Neurosciences, KU Leuven, Psychiatry Research Group, Leuven, Belgium.|Old Age Psychiatry Department, University Hospitals Leuven, Leuven, Belgium.
authors: François-Laurent
authors: FL
authors: De Winter
authors: Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.|Division of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium.
authors: Rawaha
authors: R
authors: Ahmad
authors: Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.|Department of Radiology, University Hospitals Leuven, Leuven, Belgium.
authors: Stefan
authors: S
authors: Sunaert
authors: Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.|Division of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium.
authors: Koen
authors: K
authors: Van Laere
authors: Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
authors: Wim
authors: W
authors: Vandenberghe
authors: Department of Neurosciences, KU Leuven, Psychiatry Research Group, Leuven, Belgium.|Old Age Psychiatry Department, University Hospitals Leuven, Leuven, Belgium.
authors: Mathieu
authors: M
authors: Vandenbulcke
mesh_terms: D000328:Adult; D000786:Anger / Q000502:physiology*; D001284:Atrophy / Q000473:pathology; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006579:Heterozygote; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D007508:Irritable Mood / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000473:pathology*; D062706:Prodromal Symptoms; D020649:Pulvinar / Q000503:physiopathology*; D013003:Somatosensory Cortex / Q000503:physiopathology*
keywords: affective symptoms; aggression; amygdala; emotions; gyrus cingulus; pulvinar