Objectives: Apathy is a debilitating symptom of Huntington’s disease (HD) and manifests before motor diagnosis, making it an excellent therapeutic target in the preclinical phase of Huntington’s disease (prHD). HD is a neurological genetic disorder characterized by cognitive and motor impairment, and psychiatric abnormalities. Apathy is not well characterized within the prHD. In previous literature, damage to the caudate and putamen has been correlated with increased apathy in other neurodegenerative and movement disorders. The objective of this study was to determine whether apathy severity in individuals with prHD is related to striatum volumes and cognitive control. We hypothesized that, within prHD individuals, striatum volumes and cognitive control scores would be related to apathy. Methods: We constructed linear mixed models to analyze striatum volumes and cognitive control, a composite measure that includes tasks assessing with apathy scores from 797 prHD participants. The outcome variable for each model was apathy, and the independent variables for the four separate models were caudate volume, putamen volume, cognitive control score, and motor symptom score. We also included depression as a covariate to ensure that our results were not solely related to mood. Results: Caudate and putamen volumes, as well as measures of cognitive control, were significantly related to apathy scores even after controlling for depression. Conclusions: The behavioral apathy expressed by these individuals was related to regions of the brain commonly associated with isolated apathy, and not a direct result of mood symptoms. (JINS, 2019, 25, 462–469)

The current study examined temporal order memory in preclinical Huntington’s disease (pre-HD). Participants were separated into less than 5 years (pre-HD near) and more than 5 years (pre-HD far) from estimated age of clinical diagnosis. Participants completed a temporal order memory task on a computerized radial eight-arm maze. On the study phase of each trial, participants viewed a random sequence of circles appearing one at a time at the end of each arm. On the choice phase, participants viewed two circles at the end of the study phase arms and chose the circle occurring earliest in the sequence. The task involved manipulations of the temporal lag, defined as the number of arms occurring in the sample phase sequence between the two choice phase arms. Research suggests that there is more interference for temporally proximal stimuli relative to temporally distal stimuli. There were no significant differences between the pre-HD far group and controls on the temporal order memory task. The pre-HD near group demonstrated significant impairments relative to the other groups on closer temporal lags, but were normal on the furthest temporal lag. Therefore, temporal order memory declines with increased temporal interference in pre-HD close to estimated diagnosis of HD. (JINS, 2009, 15, 662–670.)

Huntington's disease (HD) is a neurodegenerative disorder diagnosed clinically with the development of choreiform movements. However, neuropsychological studies have demonstrated cognitive and psychiatric changes during the preclinical phase (pre-HD) prior to formal diagnosis. Previous studies have demonstrated the sensitivity of time reproduction tasks to basal ganglia pathology, as seen in clinical HD and Parkinson's disease. In this study, 29 pre-HD participants, ranging from 3 to 39 years from estimated onset (YEO) of HD based on genetic testing and chronological age, were administered the paced finger-tapping task using target intervals of 600 and 1200 ms. Mean inter-response interval, a measure of timing accuracy, did not systematically deviate from the target interval as a function of YEO. In contrast, timing variability increased curvilinearly as a function of YEO, but not with chronological age alone. Motor timing variability, but not accuracy, may serve as a marker to define the earliest behavioral changes in HD. The present study is among the first to examine the relationship between behavioral measures and YEO in pre-HD. (JINS, 2007, 13, 539–543.)

Patients with Parkinson's disease are frequently treated by psychiatrists. We report on the exacerbation of parkinsonian symptoms in tw o patients prescribed paroxetine, an SSRI antidepressant. We discuss the possible mechanism for such an interaction.