Theory of Mind Can Be Impaired Prior to Motor Onset in Huntington's Disease

Objective: Patients with the inherited movement disorder Huntington's disease (HD) exhibit deficits in executive functions and theory of mind (ToM). We investigated these abilities in individuals with the HD gene who were yet to exhibit motor onset. Method: Participants were HD gene carriers (n = 20) and healthy controls (n = 26). Gene carriers were prescreened for motor symptoms. Participants completed tasks assessing the understanding of socially inappropriate behaviors, recognition of complex mental states from photographs of peoples' eyes, everyday perspective taking, and executive functions. Gene carriers' task performance was compared to controls', and relationships were explored between ToM, executive functions, and clinical factors including disease burden and mood disorder. Results: Performance was intact on nine of the ten executive measures in premanifest HD, with only a mild deficit in semantic fluency. However, gene carriers exhibited impairments in recognizing faux pas and complex mental states. The Interpersonal Reactivity Index yielded evidence of reduced everyday perspective taking in HD, and differences for empathy and personal distress. Everyday perspective taking was predicted by disease burden and recognition of complex mental states. Conclusions: We provide evidence that premanifest HD can be associated with changes in ToM. Furthermore, these deficits appear unlikely to result from executive dysfunction. HD gene carriers' impairments highlight the possibility of a relatively selective impact of early neurodegenerative changes in the striatum on ToM. Neuroimaging studies should investigate whether ToM deficits may arise in premanifest HD because of early neuropathology rather than the psychological effects of diagnostic status.