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

约30%的重度抑郁症（MDD）患者对现有的药理学、心理治疗或躯体治疗反应不足。难治性重度抑郁症与慢性疾病、生活质量下降和更高的自杀风险有关。对于这些患者，电痉挛疗法（ECT）是一种行之有效的治疗策略，其有效率为60%至80%，使其成为治疗重度抑郁症最有效和最迅速的治疗方法。尽管电痉挛疗法的频繁和广泛应用已有70多年，但其疗效背后的确切神经生物学机制仍不清楚。从更广泛的意义上说，了解电痉挛疗法的治疗效果也可能有助于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，阐明电痉挛疗法的效果可以使它们以一种侵入性更小的方式繁殖，副作用更温和，从而显著提高对重度抑郁症的治疗效果。不过，要做到这一点，我们首先需要更好地了解电痉挛疗法是如何影响大脑功能的。因此，拟议的项目旨在研究ECT后治疗反应和缓解的神经活动和连通性，神经化学和炎症的标志物。这些措施将在抑郁症患者ECT治疗之前、期间和之后以及6个月后进行评估。此外，我们将调查一组接受抗抑郁药物治疗的抑郁症患者。这种治疗特异性的方法将使我们能够弄清楚哪些行为、神经元和免疫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深层抗抑郁作用机制的理解，从而更清楚地了解重度抑郁症的病理生理原因和有效治疗的作用机制。

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.