The Neurogenetics Clinic and Research Lab, Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej, Section 8008, 2100, Copenhagen, Denmark.
Translational Neuroendocrine Research Unit, Department of Experimental Medical Science, Lund University, 22184, Lund, Sweden.
Parkinsonism Relat Disord. 2022 Jun;99:23-29. doi: 10.1016/j.parkreldis.2022.05.003. Epub 2022 May 13.
Huntington's disease (HD) is an inherited neurodegenerative disease with motor, cognitive and psychiatric symptoms. Non-motor symptoms like depression and altered social cognition are proposed to be caused by dysfunction of the hypothalamus. We measured the hypothalamic neuropeptide oxytocin in plasma and cerebrospinal fluid (CSF) in a cohort of HD gene expansion carriers (HDGECs), compared the levels to healthy HD family controls and correlated oxytocin levels to disease progression and social cognition.
We recruited 113 HDGECs and 33 controls. Psychiatric and cognitive symptoms were evaluated, and social cognition was assessed with the Emotion Hexagon test, Reading the Mind in the Eyes and The Awareness of Social Inference Test. The levels of oxytocin in CSF and blood were analyzed by radioimmunoassay.
We found the level of oxytocin in CSF to be significantly lower by 33.5% in HDGECs compared to controls (p = 0.016). When dividing the HDGECs into groups with or without cognitive impairment, we found the oxytocin level to be significantly lower by 30.3% in the HDGECs with cognitive symptoms (p = 0.046). We found a statistically significant correlation between the level of oxytocin and scores on social cognition (Reading the Mind in the Eyes p = 0.0019; Emotion Hexagon test: p = 0.0062; The Awareness of Social Inference Test: p = 0.002).
This is the first study to measure oxytocin in the CSF of HDGECs. We find that HDGECs have a significantly lower level of oxytocin compared to controls, and that the level of oxytocin may represent an objective and comparable measure that could be used as a state biomarker for impairment of social cognition. We suggest treatment trials to evaluate a potential effect of oxytocin on social cognition in HD.
亨廷顿病(HD)是一种遗传性神经退行性疾病,伴有运动、认知和精神症状。非运动症状,如抑郁和社交认知改变,被认为是由下丘脑功能障碍引起的。我们测量了一组亨廷顿病基因扩展携带者(HDGEC)的血浆和脑脊液(CSF)中的下丘脑神经肽催产素,将其水平与健康的 HD 家族对照进行比较,并将催产素水平与疾病进展和社交认知相关联。
我们招募了 113 名 HDGEC 和 33 名对照者。评估了精神和认知症状,并使用情绪六边形测试、读心术和社会推理意识测试评估社交认知。通过放射免疫分析法分析 CSF 和血液中的催产素水平。
我们发现 HDGEC 组的 CSF 中催产素水平明显低于对照组,下降了 33.5%(p=0.016)。当将 HDGEC 分为有或无认知障碍的组时,我们发现有认知症状的 HDGEC 组的催产素水平下降了 30.3%(p=0.046)。我们发现催产素水平与社交认知评分之间存在统计学显著相关性(读心术:p=0.0019;情绪六边形测试:p=0.0062;社会推理意识测试:p=0.002)。
这是首次在 HDGEC 的 CSF 中测量催产素的研究。我们发现 HDGEC 的催产素水平明显低于对照组,而且催产素水平可能代表一种客观的、可比的测量指标,可用作社交认知受损的状态生物标志物。我们建议进行治疗试验,以评估催产素对 HD 患者社交认知的潜在影响。