Nakamura Shoji
Yamaguchi University Graduate School of Medicine, Ube, 755-8505 Yamaguchi, Japan.
Front Biosci (Schol Ed). 2022 Jan 24;14(1):4. doi: 10.31083/j.fbs1401004.
Recent studies provide evidence that similar to early-stage Parkinson's disease, depression is a neurodegenerative disease characterized by the degeneration of monoamine axons. The major difference between the two disorders is that the symptoms of depression become evident without loss of monoamine neurons, while the motor symptoms of Parkinson's disease appear after loss of the cell body. Given that the axonal degeneration of monoamine neurons underlies the pathophysiology of neurological (Parkinson's disease) and neuropsychiatric (depression) diseases, axonal impairment of monoamine neurons is thought to also occur in schizophrenia and bipolar disorder and play a significant role in the pathophysiology of these mental illnesses. The positive symptoms of schizophrenia and manic symptoms of bipolar disorder are known to occur in hyper-monoaminergic states, opposite to depressive symptoms, negative/cognitive symptoms of schizophrenia, and motor disorders of Parkinson's disease, all occurring in hypo-monoaminergic states. Since monoamine axons have the capacity to spontaneously regenerate or sprout in response to damage in the adult brain and sometimes show hyperinnervation due to excessive regeneration/sprouting beyond normal levels, it is possible that schizophrenia and bipolar disorder are disorders that include excessive regeneration/sprouting of monoamine axons leading to hyper-monoaminergic states. Together, based on accumulating data from animal and human studies, the pathophysiology of schizophrenia, major depression, and bipolar disorder is summarized as follows: The degeneration of monoamine axons is associated with the negative and cognitive symptoms of schizophrenia, major and bipolar depression, while hyper-regeneration/sprouting of monoamine axons underlies the positive symptoms of schizophrenia and bipolar mania. The integrated understanding of schizophrenia, major depression, and bipolar disorder as monoamine axon disorder will open the door to the development of new diagnosis and treatment methods for major mental illnesses as well as early-stage Parkinson's disease.
近期研究表明，与早期帕金森病相似，抑郁症是一种以单胺轴突变性为特征的神经退行性疾病。这两种疾病的主要区别在于，抑郁症的症状在单胺神经元未丧失的情况下就已显现，而帕金森病的运动症状则在细胞体丧失后才出现。鉴于单胺神经元的轴突变性是神经疾病（帕金森病）和神经精神疾病（抑郁症）病理生理学的基础，单胺神经元的轴突损伤被认为也会在精神分裂症和双相情感障碍中发生，并在这些精神疾病的病理生理学中发挥重要作用。已知精神分裂症的阳性症状和双相情感障碍的躁狂症状出现在高单胺能状态，这与抑郁症的症状相反，精神分裂症的阴性/认知症状以及帕金森病的运动障碍均出现在低单胺能状态。由于单胺轴突在成人大脑中具有响应损伤而自发再生或出芽的能力，并且有时会因过度再生/出芽超出正常水平而表现为神经纤维过度支配，因此精神分裂症和双相情感障碍有可能是包括单胺轴突过度再生/出芽导致高单胺能状态的疾病。综合来看，基于动物和人体研究积累的数据，精神分裂症、重度抑郁症和双相情感障碍的病理生理学总结如下：单胺轴突的变性与精神分裂症、重度抑郁症和双相抑郁症的阴性和认知症状相关，而单胺轴突的过度再生/出芽是精神分裂症和双相躁狂症阳性症状的基础。将精神分裂症、重度抑郁症和双相情感障碍理解为单胺轴突疾病，将为开发针对主要精神疾病以及早期帕金森病的新诊断和治疗方法打开大门。
