Altered third-party punishment in Huntington's disease: A study using neuroeconomic games.

BACKGROUND: Huntington's disease (HD) is a heritable degenerative brain disease caused by a mutation in the huntingtin gene with excessive repeats of the base triplet cytosine-adenine-guanine (CAG), which codes for the aminoacid glutamine. HD is associated with a broad spectrum of neurocognitive dysfunction, including deficits in social cognition. The appreciation of fairness rules and reciprocity has not been studied in HD. Based on theoretical considerations suggesting that brain regions known to be affected from HD are involved in economic decision-making, the present study sought to examine HD patients' performance in two neuroeconomic games. METHODS: Twenty-nine manifest HD mutation carriers (20 males, nine females) performed an Ultimatum Game (UG) and a Dictator Game (DG) where third-party punishment of observed unfairness was required. In addition, patients were tested for neurocognition and the ability to understand other people's mental states ("theory of mind"). For comparison, a clinical control group of 30 patients with chronic schizophrenia, and 30 unaffected healthy controls matched for age and verbal intelligence took part in the study. RESULTS: Patients with HD had some appreciation of fairness rules, as they tended to reject unfair offers in the UG similar to controls. However, unlike the other two groups, individuals with HD did not punish observed unfairness from a third-party perspective. This lack of "altruistic punishment" was associated with deficits in executive functioning including working memory, inhibitory control and cognitive flexibility, and to a lesser degree with poor "theory of mind." CONCLUSIONS: HD seems to be associated with impairments in understanding of more complex rules of social exchange. Aside from deficits in executive functioning, this behavior could, in part, be linked to an inability to experience third-party punishment as rewarding.

Time will tell: Decision making in premanifest and manifest Huntington's disease.

OBJECTIVE: To investigate cognitive flexibility in premanifest and manifest Huntington's disease (HD). BACKGROUND: HD is an autosomal dominant neurodegenerative disease characterized by motor, cognitive, and behavioral abnormalities with typical motor symptoms. In this study, we wanted to assess decision making in premanifest (pre-HD) and manifest HD patients. METHODS: A total of 77 non-demented subjects including 29 pre-HD, 22 manifest HD patients, and 26 healthy controls (HC) were included. We stratified the pre-HD group based on their estimated years to disease onset into a far (FAR, n = 13) and a near (NEAR, n = 16) group. Furthermore, participants performed the Montreal cognitive assessment battery (MoCA), the trail making task part A and B (TMT A, TMT B), the Symbol digit modalities test (SDMT), and the beads task. RESULTS: In the beads task, HD patients gathered less information than all other groups (all p-values < .001). Furthermore, the NEAR group gathered less information than the FAR group (p < .001) and HC (p = .001). There was no difference between the HC and the FAR group (p = 1.0). In the TMT and the SDMT, HD patients were slower than all other groups (all p-values < .01) but there were no other significant differences. CONCLUSIONS: Decision making with a higher degree of uncertainty may be an early neuropsychological sign to indicate the disease process prior to reaching criteria for motor diagnosis of HD.

Functional and cognitive capacity differ in dystonic motor subtypes when compared to choreatic and hypokinetic-rigid motor subtypes in Huntington's disease.

BACKGROUND: Motor phenotypes in Huntington's disease vary manifold. Phenotype classification is essential to adapt treatment. The aim of this study was to classify a dystonic subtype closer. METHODS: A total of 7,512 manifest ENROLL-HD participants were subdivided into mainly choreatic (N = 606), dystonic (N = 402), and hypokinetic-rigid (N = 369) subjects. Cognitive (verbal fluency, symbol digit, stroop color, trail making, Mini-Mental State Examination), functional (total functional capacity, Independence Scale), and psychiatric (problem behaviors assessment, Hospital Anxiety and Depression Scale) performance was evaluated at baseline visit. RESULTS: Symptoms onset for dystonic were similar to hypokinetic-rigid, but earlier compared to choreatic subjects (p < .001). Cognition was better in both groups compared to hypokinetic rigid (all p < .001). Functionality differed between all groups (all p < .001). Differences remained (all p < .001) after controlling for CAP score, CAG, age, disease duration, and education. CONCLUSIONS: Motor subtypes differ in functional and cognitive capacities but less in psychiatric. We identified better cognitive and functional capacities and similar onsets in predominant dystonic compared to hypokinetic-rigid patients.

Cannabinoids for Treatment of Dystonia in Huntington's Disease.

BACKGROUND: Motor symptoms in Huntington's disease (HD) are heterogeneous with dystonia being described as a symptom with a very high prevalence not only in juvenile cases. OBJECTIVE: Treatment options for dystonia are limited. Cannabinoids have been described as a potential treatment for patients with dystonia of a different origin. Here, we present early onset HD patients with a marked improvement of motor symptoms mainly due to alleviation of dystonia due to treatment with cannabinoids. In addition we review the current literature concerning the use of cannabinoids in HD. METHOD: The Unified Huntington's Disease Rating Scale (UHDRS) motor score, including a chorea and dystonia subscore, was conducted before and after the start of cannabinoids in seven patients without any other changes in medication. RESULTS: The UHDRS motor score and the dystonia subscore (±SD) improved from 70.9 (25.5) to 60.6 (26.9) with a mean change of 10.3 [95% CI 6.0-14.6] and from 12.3 (4.0) to 8.0 (3.6) with a mean change of 4.3 [95% CI 2.3-6.3], respectively (both p = 0.018). CONCLUSION: Improvement of motor symptoms, mainly dystonia, led to several relevant improvements from a global clinical perspective such as improvement of care, gait and fine motor skills and weight gain. Moreover, we observed changes in behavior with less irritability and apathy, as well as less hypersalivation in some cases.