Hippocampal morphology in Huntington's disease, implications for plasticity and pathogenesis: The IMAGE-HD study.

While striatal changes in Huntington's Disease (HD) are well established, few studies have investigated changes in the hippocampus, a key neuronal hub. Using MRI scans obtained from the IMAGE-HD study, hippocampi were manually traced and then analysed with the Spherical Harmonic Point Distribution Method (SPHARM-PDM) in 36 individuals with presymptomatic-HD, 37 with early symptomatic-HD, and 36 healthy matched controls. There were no significant differences in overall hippocampal volume between groups. Interestingly we found decreased bilateral hippocampal volume in people with symptomatic-HD who took selective serotonin reuptake inhibitors compared to those who did not, despite no significant differences in anxiety, depressive symptoms, or motor incapacity between the two groups. In symptomatic-HD, there was also significant shape deflation in the right hippocampal head, showing the utility of using manual tracing and SPHARM-PDM to characterise subtle shape changes which may be missed by other methods. This study confirms previous findings of the lack of hippocampal volumetric differentiation in presymptomatic-HD and symptomatic-HD compared to controls. We also find novel shape and volume findings in those with symptomatic-HD, especially in relation to decreased hippocampal volume in those treated with SSRIs.

Competing Interests: Declaration of Competing Interest In the past three years, Dr Stout has received funding from CHDI Foundation unrelated to this research. She is also director of Zindametrix Pty Ltd., which has research contracts with several pharma companies to assist in implementing cognitive assessments in HD clinical trials, none of which are relevant to this research. In addition, she has received an honorarium from Teva Australia for participation in a scientific advisory board, none related to this research. Dr Looi self-funded travel and computer infrastructure costs to coordinate this research through the Australian United States Scandinavian-Spanish Imaging Exchange (AUSSIE), based at the Australian National University Medical School. Dr Walterfang has received funding for research from and has received honoraria from Actelion, Vtesse and Biomarin pharmaceuticals, unrelated to this research.

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