Scientists Discover Two Distinct Symptom Profiles in HD Patients

Scientists Discover Two Distinct Symptom Profiles in HD Patients
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Profiles

People with Huntington’s disease may have two different symptom profiles, a cognitive-motor and a psychiatric profile, associated with different clinical and neurobiological features.

The findings of the study, “Specific patterns of brain alterations underlie distinct clinical profiles in Huntington’s disease,” were published in NeuroImage: Clinical.

Huntington’s disease is a genetic neurodegenerative disorder characterized by motor, psychiatric, and cognitive disturbances. Despite being caused by alterations in a single gene, the disease can manifest itself in very different ways among individuals.

“One possible source of such inter-individual differences among [Huntington’s disease] patients could be the variability in the degree of neurodegeneration of different neural circuits. However, the vast majority of neuroimaging studies in the [Huntington’s disease] literature has focused on differences from healthy controls, overlooking the inter-individual differences among patients,” the investigators noted.

“Multivariate approaches including measures of the three symptom domains simultaneously are needed to establish the specificity between brain alterations and each symptom domain. Shedding light on the specificity of this relationship is vital in order to understand disease,” they stated.

In this study, researchers used for the first time a multimodal approach that combines different brain imaging analysis techniques to investigate the relationship between brain alterations and symptom variability in a group of Huntington’s patients.

The study, carried out by a group of researchers at Spain’s Bellvitge Biomedical Research Institute (IDIBELL) in collaboration with investigators at the Institute of Neurosciences of the University of Barcelona (UBNeuro) and the Radboud University in the Netherlands, involved 43 Huntington’s patients, including 20 who showed no symptoms of the disorder (asymptomatic).

All patients performed magnetic resonance imaging (MRI) brain scans and were asked to complete a series of tests to evaluate their motor, cognitive, and psychiatric abilities.

Using this approach, researchers found that cognitive and motor symptoms shared a common neural signature, while psychiatric symptoms were associated with a completely different neurobiological pattern.

“Cognitive and motor symptoms were associated together with a pattern of reduction in gray matter, [cortex] thickness and the integrity of the white substance in brain regions responsible for the execution of movements and the processing of different cognitive functions, such as memory, planning, or visual-spatial processing,” Clara García Gorro, predoctoral researcher and first author of the study, said in a news release.

“Depressive symptoms, on the other hand, were associated with a very different pattern, characterized by a lower thickness in the cerebral cortex in regions responsible for the emotional processing typically associated with psychiatric alterations,” Gorro added.

Of note, gray and white matter refer to areas of the central nervous system (composed of the brain, brainstem, and cerebellum) made up of neuron cell bodies and myelinated nerve segments (axons) responsible for the transmission of nerve signals. The cortex is the outer layer of the brain.

“These results are relevant in the context of clinical trials, since they could be used to define specific biomarkers for each symptom profile, even before clinical signs appear. Having more homogenous groups would potentially increase the likelihood of detecting successful interventions and help to find individualized treatments that target specific cognitive, motor, and psychiatric disturbances,” the researchers concluded.

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