Editors' Note: Timing and Impact of Psychiatric, Cognitive, and Motor Abnormalities in Huntington Disease

Abstract

Dr. McAllister and colleagues retrospectively analyzed the prevalence, timing, and functional impact of psychiatric, cognitive, and motor abnormalities in Huntington disease (HD) gene carriers in 6,316 individuals in the European HD Network (REGISTRY). They found that psychiatric and cognitive symptoms were common and functionally debilitating in HD gene carriers, with 42.4% of patients with HD reporting at least 1 psychiatric or cognitive symptom before motor symptoms, most commonly depression. However, the initial manifestation of HD was increasingly likely to be motor and less likely to be psychiatric as the age at presentation increased. The authors concluded that nonmotor symptoms should not be used to make a clinical diagnosis of HD because it was impossible to distinguish confidently between nonmotor symptoms arising from HD vs primary psychiatric disorders, particularly in younger premanifest patients. In response, Dr. Bird et al. argue that such a conclusion is too broad and negative, while agreeing that caution is needed and depression should not be used as a diagnostic factor. They argue that psychiatric, behavioral, and cognitive symptoms can be diagnostically meaningful in the setting of a positive genetic test, noting examples like the onset of auditory hallucinations, paranoid delusions, a sustained personality change, or decreased work performance with impaired cognition. They note that such symptoms are part of the diagnostic process for genetic forms of behavioral frontotemporal dementia, which is phenotypically similar to HD, and that earlier diagnosis can help connect patients and families to critical services. Responding to these comments, the authors note that clinical onset of HD is typically diagnosed using the emergence of specific extrapyramidal motor features. They agree that certain neuropsychiatric symptoms like apathy and increased aggression are more strongly suggestive of HD pathology. However, they caution that other commonly reported symptoms may reflect environmental sequelae or those related to the knowledge of their genetic status and should not be used on their own to make an HD diagnosis. This exchange highlights the clinical challenges of defining the onset of a complex neuropsychiatric disease like HD when one already knows the patient's genetic status. Nonetheless, the early diagnosis of HD in the appropriate clinical and genetic setting may allow for deployment of important patient resources. Dr. McAllister and colleagues retrospectively analyzed the prevalence, timing, and functional impact of psychiatric, cognitive, and motor abnormalities in Huntington disease (HD) gene carriers in 6,316 individuals in the European HD Network (REGISTRY). They found that psychiatric and cognitive symptoms were common and functionally debilitating in HD gene carriers, with 42.4% of patients with HD reporting at least 1 psychiatric or cognitive symptom before motor symptoms, most commonly depression. However, the initial manifestation of HD was increasingly likely to be motor and less likely to be psychiatric as the age at presentation increased. The authors concluded that nonmotor symptoms should not be used to make a clinical diagnosis of HD because it was impossible to distinguish confidently between nonmotor symptoms arising from HD vs primary psychiatric disorders, particularly in younger premanifest patients. In response, Dr. Bird et al. argue that such a conclusion is too broad and negative, while agreeing that caution is needed and depression should not be used as a diagnostic factor. They argue that psychiatric, behavioral, and cognitive symptoms can be diagnostically meaningful in the setting of a positive genetic test, noting examples like the onset of auditory hallucinations, paranoid delusions, a sustained personality change, or decreased work performance with impaired cognition. They note that such symptoms are part of the diagnostic process for genetic forms of behavioral frontotemporal dementia, which is phenotypically similar to HD, and that earlier diagnosis can help connect patients and families to critical services. Responding to these comments, the authors note that clinical onset of HD is typically diagnosed using the emergence of specific extrapyramidal motor features. They agree that certain neuropsychiatric symptoms like apathy and increased aggression are more strongly suggestive of HD pathology. However, they caution that other commonly reported symptoms may reflect environmental sequelae or those related to the knowledge of their genetic status and should not be used on their own to make an HD diagnosis. This exchange highlights the clinical challenges of defining the onset of a complex neuropsychiatric disease like HD when one already knows the patient's genetic status. Nonetheless, the early diagnosis of HD in the appropriate clinical and genetic setting may allow for deployment of important patient resources.