{"title":"The pathobiology of depression in Huntington's disease: an unresolved puzzle.","authors":"Kurt A Jellinger","doi":"10.1007/s00702-024-02750-w","DOIUrl":null,"url":null,"abstract":"<p><p>Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative disease that manifests with a triad of symptoms including motor dysfunctions, cognitive deficits, and prominent neuropsychiatric symptoms, the most common of which is depression, with a prevalence between 30 and 70%. Depressive symptoms occur in all stages of HD, beginning in presymptomatic HD gene carriers, and are strongly associated with suicidal ideation and suicidality, but their relationship with other clinical dimensions in HD is controversial and the underlying pathophysiology is poorly understood. Analysis of the available literature until November 2023 concerned the prevalence, clinical manifestations, neuroimaging, transgenic models, and treatment options of HD depression. While it was believed that depression in HD is due to psychosomatic factors in view of the fatal disease, studies in transgenic models of HD demonstrated molecular changes including neurotrophic and serotonergic dysregulation and disorders of the hypothalamic-pituitary-adrenal axis inducing depression-like changes. While relevant neuropathological data are missing, recent neuroimaging studies revealed correlations between depressive symptoms and dysfunctional connectivities in the default mode network, basal ganglia and prefrontal cortex, and changes in limbic and paralimbic structures related to the basic neurodegenerative process. The impact of response to antidepressants in HD patients is controversial; selective serotonin reuptake inhibitors are superior to serotonin-norepinephrine reuptake inhibitors, while electroconvulsive therapy may be effective for pharmacotherapy resistant cases. Since compared to major depressive disorder and depression in other neurodegenerative diseases, our knowledge of the molecular basis in HD depression is limited, further studies to elucidate the heterogeneous pathogenesis in this fatal disorder are warranted.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"1511-1522"},"PeriodicalIF":3.2000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neural Transmission","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00702-024-02750-w","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/13 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative disease that manifests with a triad of symptoms including motor dysfunctions, cognitive deficits, and prominent neuropsychiatric symptoms, the most common of which is depression, with a prevalence between 30 and 70%. Depressive symptoms occur in all stages of HD, beginning in presymptomatic HD gene carriers, and are strongly associated with suicidal ideation and suicidality, but their relationship with other clinical dimensions in HD is controversial and the underlying pathophysiology is poorly understood. Analysis of the available literature until November 2023 concerned the prevalence, clinical manifestations, neuroimaging, transgenic models, and treatment options of HD depression. While it was believed that depression in HD is due to psychosomatic factors in view of the fatal disease, studies in transgenic models of HD demonstrated molecular changes including neurotrophic and serotonergic dysregulation and disorders of the hypothalamic-pituitary-adrenal axis inducing depression-like changes. While relevant neuropathological data are missing, recent neuroimaging studies revealed correlations between depressive symptoms and dysfunctional connectivities in the default mode network, basal ganglia and prefrontal cortex, and changes in limbic and paralimbic structures related to the basic neurodegenerative process. The impact of response to antidepressants in HD patients is controversial; selective serotonin reuptake inhibitors are superior to serotonin-norepinephrine reuptake inhibitors, while electroconvulsive therapy may be effective for pharmacotherapy resistant cases. Since compared to major depressive disorder and depression in other neurodegenerative diseases, our knowledge of the molecular basis in HD depression is limited, further studies to elucidate the heterogeneous pathogenesis in this fatal disorder are warranted.
亨廷顿氏病(Huntington's disease,HD)是一种常染色体显性进行性神经退行性疾病,表现为三联症状,包括运动功能障碍、认知障碍和突出的神经精神症状,其中最常见的是抑郁症,发病率在 30% 到 70% 之间。抑郁症状出现在 HD 的各个阶段,从无症状的 HD 基因携带者开始,抑郁症状与自杀意念和自杀倾向密切相关,但抑郁症状与 HD 其他临床症状之间的关系尚存争议,对其潜在的病理生理学也知之甚少。截至 2023 年 11 月的现有文献分析涉及 HD 抑郁症的患病率、临床表现、神经影像学、转基因模型和治疗方案。鉴于HD是一种致命疾病,人们认为HD抑郁症是由心身因素引起的,但对HD转基因模型的研究表明,分子变化包括神经营养和血清素能失调,以及下丘脑-垂体-肾上腺轴紊乱诱发抑郁症样变化。虽然相关的神经病理学数据缺失,但最近的神经影像学研究揭示了抑郁症状与默认模式网络、基底节和前额叶皮层功能失调之间的相关性,以及与基本神经退行性过程相关的边缘和边缘旁结构的变化。选择性血清素再摄取抑制剂优于血清素-去甲肾上腺素再摄取抑制剂,而电休克疗法对药物治疗耐药的病例可能有效。与重度抑郁症和其他神经退行性疾病中的抑郁症相比,我们对 HD 抑郁症的分子基础了解有限,因此有必要开展进一步研究,以阐明这种致命疾病的异质性发病机制。
期刊介绍:
The investigation of basic mechanisms involved in the pathogenesis of neurological and psychiatric disorders has undoubtedly deepened our knowledge of these types of disorders. The impact of basic neurosciences on the understanding of the pathophysiology of the brain will further increase due to important developments such as the emergence of more specific psychoactive compounds and new technologies.
The Journal of Neural Transmission aims to establish an interface between basic sciences and clinical neurology and psychiatry. It intends to put a special emphasis on translational publications of the newest developments in the field from all disciplines of the neural sciences that relate to a better understanding and treatment of neurological and psychiatric disorders.