Category: Huntington's Disease
Objective: To determine whether presence and severity of suicidal ideation (SI) are associated with hippocampal volume and histamine H3 receptor (H3R) PET uptake in people with Huntington’s disease (PwHD).
Background: Suicidal ideation occurs in approximately 8–27% of PwHD, yet its causes remain unclear(1–3). The role of histamine in suicide is being increasingly recognized (4) but has not been studied in PwHD.
Method: Baseline data from 55 pwHD (premanifest (n=21), perimanifest (n=17), manifest (n=17)) of the iMarkHD study (5) were analysed. SI was assessed using the Problem Behaviours Assessment Short Version (PBA-s), including a binary definition of past-year SI and an ordinal severity score. Hippocampal H3R availability was quantified using PET imaging. Uptake and volume were assessed using independent t-tests and one-way ANOVA with Tukey post hoc testing. Uptake and SI associations were analysed using logistic regression and Spearman correlation. Linear regression examined predictors of uptake including SI severity, age, gender, depression, and disease stage. ANCOVA assessed uptake differences adjusting for CAP score.
Results: Of 55 pwHD, 15 had clinically meaningful SI. Hippocampal H3R uptake was not associated with SI. Uptake did not differ between SI groups (p=0.601; d=0.17). Logistic regression showed no association between uptake and SI status (OR=0.861, p=0.542), and Spearman correlation showed no relationship between uptake and SI severity (ρ=−0.001, p=0.993). ANCOVA adjusting for CAP score and ANOVA confirmed no uptake differences (p=0.584) or differences across disease stages (p=0.205). Linear regression adjusted for age, gender, and depression demonstrated lower uptake in manifest HD compared with premanifest HD (β=−1.02, p=0.015). Age was independently associated with uptake (β=0.045, p=0.004). Those with SI had smaller hippocampal volumes (p=0.024, d=0.71).
Conclusion: Hippocampal H3R uptake was not associated with SI presence/severity in this HD cohort. Reduced uptake in manifest HD after age adjustment suggests stage-related histaminergic changes independent of suicidality. Smaller hippocampal volumes in individuals with SI suggest structural changes may contribute to suicidality in HD. Larger studies and investigation of other regions, particularly prefrontal networks involved in affect regulation, may further clarify mechanisms underlying SI in HD (6).
References: 1. Hubers AAM, van Duijn E, Roos RAC, Craufurd D, Rickards H, Landwehrmeyer B, et al. Suicidal ideation in a European Huntington’s disease population. J Affect Disord. 2013 Oct;151:248–58. doi:10.1016/j.jad.2013.06.001 PubMed PMID: 23876196.
2. van Duijn E, Vrijmoeth EM, Giltay EJ, Bernhard Landwehrmeyer G. Suicidal ideation and suicidal behavior according to the C-SSRS in a European cohort of Huntington’s disease gene expansion carriers. J Affect Disord. 2018 Mar;228:194–204. doi:10.1016/j.jad.2017.11.074 PubMed PMID: 29253686.
3. Rocha NP, Tuazon MR, Patino J, Furr Stimming E, Teixeira AL. Clinical Correlates of Depression and Suicidality in Huntington Disease: An Analysis of the Enroll-HD Observational Study. Cognitive and Behavioral Neurology. 2022 Jun;35:85–94. doi:10.1097/WNN.0000000000000301 PubMed PMID: 35486527.
4. Martins D, Wamelen D van, Fernandes L, Howes O, Williams S, Shan L. Altered expression of histamine signalling genes in postmortem brain samples of individuals who died by suicide: A candidate gene meta-analysis of bulk transcriptomic data. 2026. doi:10.21203/rs.3.rs-8894094/v1
5. van Wamelen DJ, Martin NH, Makos O, Badenoch J, Valera-Bermejo JM, Hartmann M, et al. Study protocol for the iMarkHD study in individuals with Huntington’s disease. J Huntingtons Dis. 2024 Nov;13:479–89. doi:10.1177/18796397241288165 PubMed PMID: 39973385.
6. Gosnell SN, Velasquez KM, Molfese DL, Molfese PJ, Madan A, Fowler JC, et al. Prefrontal cortex, temporal cortex, and hippocampus volume are affected in suicidal psychiatric patients. Psychiatry Res Neuroimaging. 2016 Oct;256:50–6. doi:10.1016/j.pscychresns.2016.09.005 PubMed PMID: 27685801.
To cite this abstract in AMA style:
P. Eze, C. Madrigal-Esquivel, O. Makos, A. Rangel-Cristales, J. Valera-Bermejo, M. Moretto, N. Martin, P. Tall, J. Staunton, M. Hartmann, F. Turkheimer, J. Badenoch, M. Veronese, N. Palasits, A. Wood, S. Williams, D. van Wamelen. Suicidal Ideation and the Hippocampal Histaminergic System in Huntington’s Disease: A PET Study [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/suicidal-ideation-and-the-hippocampal-histaminergic-system-in-huntingtons-disease-a-pet-study/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/suicidal-ideation-and-the-hippocampal-histaminergic-system-in-huntingtons-disease-a-pet-study/