Depression with an average prevalence of 25–40% is a serious condition in amyotrophic lateral sclerosis (ALS) that can impact quality of life and survival of patients and caregiver burden, yet the underlying neurobiology is poorly understood. Preexisting depression has been associated with a higher risk of developing ALS, while people with ALS have a significantly higher risk of developing depression that can cause multiple complications. Depression may be a prodromal or subclinical symptom prior to motor involvement, although its relations with disease progression and impairment of quality of life are under discussion. Unfortunately, there are no studies existing that explore the pathogenic mechanisms of depression associated with the basic neurodegenerative process, and no specific neuroimaging data or postmortem findings for the combination of ALS and depression are currently available. Experience from other neurodegenerative processes suggests that depressive symptoms in ALS may be the consequence of cortical thinning in prefrontal regions and other cortex areas, disruption of mood-related brain networks, dysfunction of neurotransmitter systems, changing cortisol levels and other, hitherto unknown mechanisms. Treatment of both ALS and depression is a multidisciplinary task, depression generally being treated with a combination of antidepressant medication, physiotherapy, psychological and other interventions, while electroconvulsive therapy and deep brain stimulation might not be indicated in the majority of patients in view of their poor prognosis. Since compared to depression in other neurodegenerative diseases, our knowledge of its molecular basis in ALS is missing, multidisciplinary clinicopathological studies to elucidate the pathomechanism of depression in motor system disorders including ALS are urgently warranted.

平均患病率为 25-40% 的抑郁症是肌萎缩侧索硬化症 (ALS) 的一种严重疾病，会影响患者的生活质量和生存以及护理人员的负担，但其背后的神经生物学却知之甚少。先前存在的抑郁症与患 ALS 的较高风险有关，而 ALS 患者患抑郁症的风险明显较高，抑郁症可能导致多种并发症。抑郁症可能是运动受累之前的前驱症状或亚临床症状，尽管其与疾病进展和生活质量损害的关系仍在讨论中。不幸的是，目前还没有研究探索与基本神经退行性过程相关的抑郁症发病机制，目前也没有关于 ALS 和抑郁症组合的具体神经影像学数据或尸检结果。其他神经退行性过程的经验表明，ALS 的抑郁症状可能是前额叶区域和其他皮质区域皮质变薄、情绪相关大脑网络破坏、神经递质系统功能障碍、皮质醇水平变化和其他迄今未知机制的结果。ALS 和抑郁症的治疗是一项多学科的工作，抑郁症通常采用抗抑郁药物、物理治疗、心理和其他干预措施相结合的治疗方法，而电休克治疗和深部脑刺激可能不适用于大多数患者，因为他们的病情较差预后。由于与其他神经退行性疾病中的抑郁症相比，我们缺乏对其在 ALS 中的分子基础的了解，因此迫切需要开展多学科临床病理学研究来阐明包括 ALS 在内的运动系统疾病中抑郁症的病理机制。