Acute-phase proteins in relation to neuropsychiatric symptoms and use of psychotropic medication in Huntington׳s disease

Bouwens, J.A.; Hubers, Anna A.M.; Duijn, Erik van; Cobbaert, Christa; Roos, Raymund A.C.; Mast, Roos C. van der; Giltay, Erik J.

doi:10.1016/j.euroneuro.2014.05.004

Cited by 14 publications

(5 citation statements)

References 42 publications

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“…In rodent studies, tetrabenazine biases behavior toward "low-effort" options, 142,143 mirroring the phenotype of apathy, while in HD, antipsychotic use has been associated with worsening apathy. 144 Interestingly, however, an analysis of the Enroll-HD data found antidopaminergic medication usage was not associated with worsening apathy. 145 Thus, on the backdrop of HD pathology, the influence of dopaminergic drugs on behavior remains unclear.…”

Section: Treatment Of Apathy and Impulsivitymentioning

confidence: 98%

“…To complicate matters, current treatments used in HD also alter these neuromodulatory systems. In rodent studies, tetrabenazine biases behavior toward “low‐effort” options, 142,143 mirroring the phenotype of apathy, while in HD, antipsychotic use has been associated with worsening apathy 144 . Interestingly, however, an analysis of the Enroll‐HD data found antidopaminergic medication usage was not associated with worsening apathy 145 .…”

Section: Treatment Of Apathy and Impulsivity Informed By A Cbdm Frame...mentioning

confidence: 99%

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Disordered Decision Making: A Cognitive Framework for Apathy and Impulsivity in Huntington's Disease

2022

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A caregiver's all‐too‐familiar narrative ‐ “He doesn't think through what he does, but mostly he does nothing.” Apathy and impulsivity, debilitating and poorly understood, commonly co‐occur in Huntington's disease (HD). HD is a neurodegenerative disease with manifestations bridging clinical neurology and psychiatry. In addition to movement and cognitive symptoms, neurobehavioral disturbances, particularly apathy and impulsivity, are prevalent features of HD, occurring early in the disease course, often worsening with disease progression, and substantially reducing quality of life. Treatments remain limited, in part because of limited mechanistic understanding of these behavioral disturbances. However, emerging work within the field of decision‐making neuroscience and beyond points to common neurobiological mechanisms underpinning these seemingly disparate problems. These insights bridge the gap between underlying disease pathology and clinical phenotype, offering new treatment strategies, novel behavioral and physiological biomarkers of HD, and deeper understanding of human behavior. In this review, we apply the neurobiological framework of cost‐benefit decision making to the problems of apathy and impulsivity in HD. Through this decision‐making lens, we develop a mechanistic model that elucidates the occurrence of these behavioral disturbances and points to potential treatment strategies and crucial research priorities. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

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Section: Treatment Of Apathy and Impulsivitymentioning

confidence: 98%

Section: Treatment Of Apathy and Impulsivity Informed By A Cbdm Frame...mentioning

confidence: 99%

Disordered Decision Making: A Cognitive Framework for Apathy and Impulsivity in Huntington's Disease

2022

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“…The present study has some limitations. We were unable to control for participants’ prior use of psychotropic medication which has been studied to influence acute phase protein levels due to the naturalistic setting of this study ( Bouwens et al, 2014 ). Nevertheless, there is no significant difference in Hp gene expression levels between groups taking and not taking anti-depressants (2.1 vs 2.4; U = 711.0, p = 0.499).…”

Section: Discussionmentioning

confidence: 99%

Haptoglobin in ultra-high risk of psychosis – Findings from the longitudinal youth at risk study (LYRIKS)

Yee

Chow

Lim

et al. 2022

Brain, Behavior, & Immunity - Health

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“…Cytokines are released from activated microglia to mediate inflammatory responses, and their levels are elevated in the brains and/or plasma of HD patients and mouse models [79][80][81][82][83][84][85]. We previously showed that LM11A-31 decreased microglial activation in multiple HD mouse models and altered the functional phenotypes of microglia by reducing the concentrations of several cytokines that were elevated in the R6/2 striatum, including interleukin (IL)-6 and tumor necrosis factor (TNF)-α [8,16].…”

Section: Lm11a-31 Reduces Plasma Levels Of Certain Pro-inflammatory Cmentioning

confidence: 99%

Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington's Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31

et al. 2021

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Huntington’s disease (HD) is caused by an expansion of the CAG repeat in the huntingtin gene leading to preferential neurodegeneration of the striatum. Disease-modifying treatments are not yet available to HD patients and their development would be facilitated by translatable pharmacodynamic biomarkers. Multi-modal magnetic resonance imaging (MRI) and plasma cytokines have been suggested as disease onset/progression biomarkers, but their ability to detect treatment efficacy is understudied. This study used the R6/2 mouse model of HD to assess if structural neuroimaging and biofluid assays can detect treatment response using as a prototype the small molecule p75NTR ligand LM11A-31, shown previously to reduce HD phenotypes in these mice. LM11A-31 alleviated volume reductions in multiple brain regions, including striatum, of vehicle-treated R6/2 mice relative to wild-types (WTs), as assessed with in vivo MRI. LM11A-31 also normalized changes in diffusion tensor imaging (DTI) metrics and diminished increases in certain plasma cytokine levels, including tumor necrosis factor-alpha and interleukin-6, in R6/2 mice. Finally, R6/2-vehicle mice had increased urinary levels of the p75NTR extracellular domain (ecd), a cleavage product released with pro-apoptotic ligand binding that detects the progression of other neurodegenerative diseases; LM11A-31 reduced this increase. These results are the first to show that urinary p75NTR-ecd levels are elevated in an HD mouse model and can be used to detect therapeutic effects. These data also indicate that multi-modal MRI and plasma cytokine levels may be effective pharmacodynamic biomarkers and that using combinations of these markers would be a viable and powerful option for clinical trials.

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Acute-phase proteins in relation to neuropsychiatric symptoms and use of psychotropic medication in Huntington׳s disease

Cited by 14 publications

References 42 publications

Disordered Decision Making: A Cognitive Framework for Apathy and Impulsivity in Huntington's Disease

Disordered Decision Making: A Cognitive Framework for Apathy and Impulsivity in Huntington's Disease

Haptoglobin in ultra-high risk of psychosis – Findings from the longitudinal youth at risk study (LYRIKS)

Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington's Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31

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