Neural bases of dysphoria in early Huntington's disease

Psychiatric disorders, including disorders of emotion control, are common in Huntington's disease. The neurobiological mechanism of the increased rate of disorders of emotion control are not known. Emotion perception deficits have been reported in Huntington's disease, but studies of emotional experience have been limited. In the present study we aim to expand the research in emotion in Huntington's disease by examining the neural bases of induced dysphoria at an early stage of Huntington's disease. Ten Huntington's disease patients and 12 demographically matched healthy volunteers underwent [(15)O] water positron emission tomography while in a transient state of dysphoria induced by viewing negatively charged affect-laden stimuli. Both groups experienced dysphoric mood, but Huntington's disease patients responded to the stimuli with greater arousal, anger and fear than healthy controls. Induced dysphoric mood was associated with a widespread reduction of activity within the frontal and parietal lobes, thalamus, and cerebellum. These differences could not be explained based on the smaller gray matter volumes of the corresponding regions, although in Huntington's disease patients smaller caudate nucleus volumes predicted lower dorsal-lateral prefrontal activity. Areas of increased activity included the striate and extrastriate cortex, the left thalamus, the transverse temporal gyrus, and the posterior hippocampus. This study elucidates possible mechanisms contributing to psychiatric disturbances of emotion often found in patients with Huntington's disease.