Effects of electroconvulsive therapy on neuronal and immunological parameters in patients with affective disorders

大约30%的患有严重抑郁障碍(MDD)的患者对现有的药物、心理治疗或躯体治疗没有足够的反应。耐药MDD与疾病慢性化、生活质量降低和自杀风险较高有关。对于这些患者，电休克治疗(ECT)是一种公认的治疗策略，有效率为60%至80%，使其成为治疗MDD最有效、见效最快的治疗方法。尽管ECT被频繁而广泛地使用了70多年，但其疗效背后的确切神经生物学机制仍不清楚。从更广泛的意义上讲，了解ECT的治疗效果也可能有助于更多地了解严重抑郁症的病理生理原因和有效治疗的作用机制。最终，阐明ECT的作用可以使它们以一种侵入性更小的方式繁殖，并具有更良性的副作用，从而显著加强MDD的治疗。然而，要做到这一点，我们首先需要更好地了解ECT如何影响大脑功能。因此，拟议的项目旨在调查ECT后治疗反应和缓解背后的神经活性和连接性、神经化学和炎症的标志物。这些措施将在抑郁症患者的ECT前、中、后以及6个月后进行评估。此外，我们还将调查一组接受抗抑郁药物治疗的抑郁症患者。这种针对治疗的方法将使我们能够理清哪些行为、神经元和免疫学改变对抗抑郁反应至关重要，并可能用于反应预测。更广泛地说，该项目将极大地拓宽我们对ECT深刻抗抑郁作用背后的机制的理解，从而为MDD的病理生理原因和有效治疗的作用机制提供更多的信息。

About 30% of patients suffering from major depressive disorder (MDD) do not respond sufficiently to established pharmacological, psychotherapeutic, or somatic treatment. Treatment-resistant MDD is associated with illness chronicity, a reduced quality of life, and a higher risk for suicide. For these patients, electroconvulsive therapy (ECT) is a well-established treatment strategy with response rates of 60% to 80%, making it the most potent and rapidly acting treatment for MDD. Despite the frequent and widespread use of ECT for more than 70 years, the exact neurobiological mechanisms underlying its efficacy remain unclear. In a broader sense, understanding the therapeutic effects of ECT may also shed some more light on the pathophysiological causes of severe depression and the mechanisms of action of an effective treatment. Eventually, the elucidation of the effects of ECT could allow for their reproduction in a less invasive way and with a more benign side-effect profile, thereby resulting in an significantly enhanced treatment of MDD. To achieve this, though, we need first to understand better how ECT influences brain function. The proposed project therefore aims to investigate markers of neural activity and connectivity, neurochemistry and inflammation underlying treatment response and remission after ECT. These measures will be assessed in depressive patients prior, during and after ECT and also after 6 months. Furthermore, we will investigate a control group of depressive patients treated with antidepressants. This treatment- specific approach will enable us to disentangle which behavioral, neuronal and immunological alterations are crucial for an antidepressant response and might be used for response prediction. More generally, the project will greatly broaden our understanding of the mechanisms underlying the profound antidepressant effect of ECT and thereby shed some more light on the pathophysiological causes of MDD and the mechanisms of action of an effective treatment.