Neuropsychiatric symptoms are very common in premanifest and early stage Huntington's Disease

Martínez‐Horta, Saül; Pérez‐Pérez, Jesús; Duijn, Erik van; Fernández-Bobadilla, Ramón; Carceller, Mar; Pagonabarraga, Javier; Pascual-Sedano, Berta; Campolongo, Antònia; Ruiz-Idiago, Jesús; Sampedro, Frederic; Landwehrmeyer, G. Bernhard; Kulisevsky, Jaime

doi:10.1016/j.parkreldis.2016.02.008

Cited by 134 publications

(128 citation statements)

References 27 publications

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“…For each neuropsychiatric symptom covered in the PBA‐s, we considered a severity score >2 points as clinically relevant . The severity score was obtained by multiplying the raw severity × frequency in each symptom.…”

Section: Methodsmentioning

confidence: 99%

“…When compared with other features, apathy in HD has the particularity of being observable in a significant proportion of premanifest gene mutation carriers, and it worsens in a linear manner as the disease progresses . This makes apathy the most prevalent and representative neuropsychiatric feature of HD, observable in nearly all affected individuals at some point …”

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confidence: 99%

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Structural and metabolic brain correlates of apathy in Huntington's disease

et al. 2018

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Our findings indicate that apathy in Huntington's disease is not exclusively a consequence of basal ganglia and related frontal-executive alterations. It is subserved by a complex cortico-subcortical network where critical reward and emotional-related prefrontal, temporal, and limbic nodes contribute strongly to its severity. This highlights the contribution of damage in regions other than the basal ganglia to the clinical expression of Huntington's disease. © 2018 International Parkinson and Movement Disorder Society.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Structural and metabolic brain correlates of apathy in Huntington's disease

et al. 2018

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“…Previous research has suggested that there is no relation between them [1]. More recently, some longitudinal studies showed progression of the majority of the psychiatric symptoms closer to the date of onset [9,13], although this relation with progression was only found for apathy in some other large studies [12,14,15]. While the first couple of articles used the SCL-90R as an assessment tool, the latest studies all used a Problem Behaviour Assessment (which includes depressed mood, suicidal ideation, anxiety, irritability, angry or aggressive behavior, lack of initiative, perseverative thinking or behavior, obsessive compulsive behaviors, delusion and paranoid thinking, hallucinations, and disoriented behavior during the last month).…”

Section: Neuropsychiatric Symptomsmentioning

confidence: 99%

“…One possible explanation is that caring for an HD patient may have an emotional impact on the caregiver. This evidence suggests that depression may be related only to the neuropathology of HD but also to having a family member with a fatal genetic disease and growing up in this environment [15]. …”

Section: Neuropsychiatric Symptomsmentioning

confidence: 99%

Huntington's Disease: Premotor Phase

Ramos

Garrett

2017

Neurodegener Dis

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Huntington's disease (HD) is an incurable, neurodegenerative disease, which manifests via a triad of progressive symptoms: motor impairment, psychiatric disorders, and cognitive decline. Conventionally, the HD diagnosis is based on the presence of involuntary choreiform movements and a positive genetic test for the CAG-expanded allele gene. Although the diagnosis focuses on the motor part of the triad, there is increasing evidence that both cognitive and neuropsychiatric symptoms can, and often do, present decades before the onset of motor symptoms. In this paper, we review the evidence regarding the symptoms in the HD premotor phase and summarize the most relevant and robust studies in the last few years. Regarding neuropsychiatric symptoms, higher levels of depression, anxiety, apathy, irritability, psychosis, disinhibition, hostility, and sleeping problems were found. In terms of cognition, there was impairment in attention, working memory, episodic memory, language, recognition of facial emotions, empathy, and theory of mind. These early symptoms of HD can be very debilitating and are often disregarded by doctors. It is necessary to acknowledge them so that they can be treated or alleviated. Moreover, an earlier diagnosis can lead to the implementation of neurodegenerative prevention therapies, which may slow the progression of the disease and prolong overall functioning. This will improve the patient's independence and their quality of life.

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“…In fact, among the wide range of psychiatric symptoms identified in HD, depression is the only one associated with a decrease in DA transmission [306]. Interestingly, however, depression is not commonly associated with the progression of HD neuropathology, most likely because this symptom is sensitive to social and family environmental factors, which can vary widely among HD patients [297, 313]. …”

Section: Dopamine Modulationmentioning

confidence: 99%

Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation

Rangel‐Barajas

Rebec

2016

JHD

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Aberrant communication between striatum, the main information processing unit of the basal ganglia, and cerebral cortex plays a critical role in the emergence of Huntington’s disease (HD), a fatal monogenetic condition that typically strikes in the prime of life. Although both striatum and cortex undergo substantial cell loss over the course of HD, corticostriatal circuits become dysfunctional long before neurons die. Understanding the dysfunction is key to developing effective strategies for treating a progressively worsening triad of motor, cognitive, and psychiatric symptoms. Cortical output neurons drive striatal activity through the release of glutamate, an excitatory amino acid. Striatal outputs, in turn, release γ-amino butyric acid (GABA) and exert inhibitory control over downstream basal ganglia targets. Ample evidence from transgenic rodent models points to dysregulation of corticostriatal glutamate transmission along with corresponding changes in striatal GABA release as underlying factors in the HD behavioral phenotype. Another contributor is dysregulation of dopamine (DA), a modulator of both glutamate and GABA transmission. In fact, pharmacological manipulation of DA is the only currently available treatment for HD symptoms. Here, we review data from animal models and human patients to evaluate the role of DA in HD, including DA interactions with glutamate and GABA within the context of dysfunctional corticostriatal circuitry.

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Neuropsychiatric symptoms are very common in premanifest and early stage Huntington's Disease

Cited by 134 publications

References 27 publications

Structural and metabolic brain correlates of apathy in Huntington's disease

Structural and metabolic brain correlates of apathy in Huntington's disease

Huntington's Disease: Premotor Phase

Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation

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