Decreased CSF oxytocin relates to measures of social cognitive impairment in Huntington's disease patients

Hellem, Marie N N; Cheong, Rachel Y.; Tonetto, Simone; Vinther-Jensen, Tua; Hendel, Rebecca K; Larsen, Ida Unmack; Nielsen, Troels Tolstrup; Hjermind, Lena E.; Vogel, Asmus; Budtz‐Jørgensen, Esben; Petersén, Åsa; Nielsen, Jørgen E.

doi:10.1016/j.parkreldis.2022.05.003

Cited by 9 publications

(10 citation statements)

References 42 publications

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“…Similarly, other authors have found an association between lower oxytocin plasmatic and cerebrospinal fluid levels with impaired social cognition in HD. 23,24 The association between IGF-1 and social cognition might be explained by its hypothetical neuroprotective role. According to previous literaure, IGF-1 activates the enzyme serine/threonine kinase Akt, which phosphorylates the mutant huntingtin protein at serine 421, 22 promoting neuronal survival and reducing tau phosphorylation in animal models.…”

Section: Discussionmentioning

confidence: 99%

Association Between Insulin‐Like Growth Factor‐1 and Social Cognition in Huntington's Disease

Gil‐Polo

Martínez‐Horta

Sampedro

et al. 2022

Movement Disord Clin Pract

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Background Insulin‐like growth factor 1 (IGF‐1) seems to be involved in the neural circuits associated with social cognition and brain structure. Objectives To investigate the association of IGF‐1 levels with social cognition and brain structure in Huntington's disease (HD). Methods We evaluated social cognition using the Ekman test in 22 HD patients and 19 matched controls. Brain structure was assessed using standard volume‐based voxel‐based morphometry and surface‐based cortical thickness pipeline. We analyzed the association of IGF‐1 levels with social cognition and brain structure using adjusted regression analysis. Results Social cognition was worse in HD patients (P < 0.001), on antidopaminergic drugs (P = 0.02), and with lower IGF‐1 levels (P = 0.04). In neuroimaging analyses, lower IGF‐1 levels were associated with social cognition impairment and atrophy mainly in frontotemporal regions (P < 0.05 corrected). Conclusions In HD, abnormal IGF‐1 function seems to be associated with brain atrophy leading to clinical deficits in social cognition.

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Section: Discussionmentioning

confidence: 99%

Association Between Insulin‐Like Growth Factor‐1 and Social Cognition in Huntington's Disease

Gil‐Polo

Martínez‐Horta

Sampedro

et al. 2022

Movement Disord Clin Pract

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“…Impairments in social cognition as well as a reduced ability to recognize facial expression of emotions in all three conditions have been established (Craufurd et al, 2001;Christidi et al, 2018;Keech et al, 2018;Palumbo et al, 2022). This could be associated with OXT, in particular in HD and FTD in which direct correlations of OXT levels has been found (Jesso et al, 2011;Labuschagne et al, 2018;Unti et al, 2018;Hellem et al, 2022). Moreover, hypothalamic pathology has been identified in all three conditions with a selective OXT loss in HD and ALS.…”

Section: Similarities Across Huntington's Disease and The Spectrum Of...mentioning

confidence: 96%

“…Moreover, intranasal OXT treatment normalized the ability of premanifest patients to process disgust stimuli ( Labuschagne et al, 2018 ). More recently, Hellem et al (2022) reported that HD patients with social cognitive impairment had significantly lower OXT CSF levels, suggesting a correlation between OXT CSF levels and social cognitive function. OXT may also be associated with executive dysfunction in HD.…”

Section: Introductionmentioning

confidence: 99%

“…In several studies, OXT has been measured in both blood and cerebrospinal fluid (CSF) samples from individuals with HD. A recent study showed a significant 38% reduction in OXT CSF levels in individuals carrying the mutant HTT gene ( Hellem et al, 2022 ). No changes in OXT plasma levels in HD patients have been found, highlighting that changes in OXT levels occur centrally and not in the periphery ( Unti et al, 2018 ; Fisher et al, 2021 ; Hellem et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Oxytocin in Huntington’s disease and the spectrum of amyotrophic lateral sclerosis-frontotemporal dementia

Bergh

Cheong

Petersén

et al. 2022

Front. Mol. Neurosci.

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Neurodegenerative disorders (NDDs) such as Huntington’s disease (HD) and the spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by progressive loss of selectively vulnerable populations of neurons. Although often associated with motor impairments, these NDDs share several commonalities in early symptoms and signs that extend beyond motor dysfunction. These include impairments in social cognition and psychiatric symptoms. Oxytocin (OXT) is a neuropeptide known to play a pivotal role in the regulation of social cognition as well as in emotional behaviors such as anxiety and depression. Here, we present an overview of key results implicating OXT in the pathology of HD, ALS and FTD and seek to identify commonalities across these NDDs. OXT is produced in the hypothalamus, a region in the brain that during the past decade has been shown to be affected in HD, ALS, and FTD. Several studies using human post-mortem neuropathological analyses, measurements of cerebrospinal fluid, experimental treatments with OXT as well as genetic animal models have collectively implicated an important role of central OXT in the development of altered social cognition and psychiatric features across these diseases. Understanding central OXT signaling may unveil the underlying mechanisms of early signs of the social cognitive impairment and the psychiatric features in NDDs. It is therefore possible that OXT might have potential therapeutic value for early disease intervention and better symptomatic treatment in NDDs.

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“…While the striatum does not have a primary social function, it has been suggested to integrate social information into main striatal functions, like reward [265] . Future analyses could consider assessing the expression of markers relevant to social behavior, such as oxytocin and vasopressin [265,266] , and focus on other brain areas affected in HD, like the hypothalamus, which shows changes in neuronal populations expressing these markers [267] . In HD patients, cerebrospinal fluid oxytocin levels were also found to be decreased and to correlate with social cognitive scores [268] .…”

Section: Behavioral Phenotypes In Genetic Rat Models Of Parkinson's D...mentioning

confidence: 99%

Rat models of major neurodegenerative disorders

Novati¹,

Singer-Mikosch²,

Yu-Taeger³

et al. 2022

Ageing Neur Dis

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No single animal model can recapitulate all the features of a particular human disease on its own. Historically, rats have been used to study neurobiology and underlying functional networks. Likewise, rat models have been created to study neurodegenerative mechanisms and therapeutic interventions. In the last decades, a shift towards the use of mice has been observed in many research fields, not least because of the comparatively easier genetic manipulation of mice. However, with the full sequence of the rat genome being available, advances in genetic manipulation of the rat, and advanced test regimens and biomarkers at hand, the rat presents itself once more as a valuable model organism for studying neurodegenerative disorders. This review provides an overview of currently available, well-characterized rat models of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, as well as their advantages for studying neurodegenerative disorders and evaluating therapeutic interventions.

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Decreased CSF oxytocin relates to measures of social cognitive impairment in Huntington's disease patients

Cited by 9 publications

References 42 publications

Association Between Insulin‐Like Growth Factor‐1 and Social Cognition in Huntington's Disease

Association Between Insulin‐Like Growth Factor‐1 and Social Cognition in Huntington's Disease

Oxytocin in Huntington’s disease and the spectrum of amyotrophic lateral sclerosis-frontotemporal dementia

Rat models of major neurodegenerative disorders

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