Veränderung der Exekutivfunktionen als Marker für das Ansprechen auf eine medikamentöse antidepressive Therapie bei Patienten mit einer Majoren Depression

重度抑郁症（MDD）是一种严重的精神疾病。几乎所有MDD患者在生活的几个领域（如身体和社会活动或职业责任）都有轻度至非常严重的损害。MDD被证明与大脑功能受损有关，特别是额叶受损。最近的研究表明，在单相和双相抑郁症的边缘系统和皮层区域的参与一致。特别是，额叶代谢减退与抑郁症严重程度的增加、精神发育迟缓和执行功能障碍有关。使用抗抑郁药（AD）治疗MDD已得到充分证实。然而，目前可用的抗抑郁药的效果大小是相当小的中等和治疗结果仍然令人失望的缓解率最高为37%。因此，开发新的策略来提高急性抑郁症患者的缓解率是明智的。提高缓解率的一种可能性是鉴定可用于预测最终治疗结果的生物标志物。MDD中最常用的预测因子是早期改善，例如在治疗的前两周内症状减轻至少20%。缺乏早期改善预测最终未缓解，具有高灵敏度和特异性，但另一方面，从基线至第2周早期改善的患者中，只有25%在治疗结束时变为缓解者。这些数据清楚地表明，专门需要进一步的生物标志物来改善对阳性治疗结果的预测。在最近完成的DFG项目中，我们发现在治疗开始时有执行缺陷的MDD患者亚组中，治疗前两周语义语言流畅性表现的早期增加高度预测治疗结束时抑郁症状的缓解。本研究的目的是调查已确定的生物标志物语义言语流畅性的神经功能基础，并确定伴有执行缺陷的MDD患者亚组的相关神经生物学变化。为了达到这一目标，30例执行功能缺陷的MDD患者应与30例没有执行功能缺陷的MDD患者和30例健康对照组进行比较。治疗2周后的第二次f-MRI检查应用于确定抗抑郁药治疗对三组脑激活的影响。基于坐标的ALE荟萃分析的结果，在健康对照组的言语流畅性任务的处理过程中的大脑激活，在当前的f-MRI研究的主要区域是左额下回和额中回以及前扣带回。

Major depressive disorder (MDD) is a severe psychiatric. Nearly all patients with MDD suffer from mild to very severe impairment in several domains of life like physical and social activities, or occupational responsibilities. MDD was shown to be associated with impairment of brain functions with particular involvement of the frontal lobes. Recent studies demonstrated the involvement of a consistent set of limbic and cortical regions in both unipolar and bipolar depression. Particularly, a frontal hypometabolism was associated with an increase in depression severity, psychomotor slowdown and executive dysfunctions. The use of antidepressant drugs (ADs) for the treatment of MDD is well established. However, effect sizes of currently available antidepressants are rather small than medium and the treatment outcome remains disappointing with remission rates of maximal 37%. Hence, it is sensible to develop new strategies to increase remission rates in acutely depressed patients. One possibility to increase the remission rates is the identification of biomarkers which can be used to predict the final treatment outcome. The most frequently used predictor in MDD is an early improvement, e.g. a symptom reduction of at least 20% in the first two weeks of treatment. The absence of an early improvement predicts a final non-remission with high sensitivity and specificity, but on the other hand only 25% of patients with an early improvement from baseline to week 2 became remitter at the end of treatment. These data clearly indicate that further biomarkers are needed specifically to improve the prediction of a positive treatment outcome. In a recently completed DFG project, we found that in a subgroup of MDD patients with executive deficits at treatment initiation, an early increase of the semantic verbal fluency performance in the first two weeks of treatment was highly predictive for a remission of the depressive symptoms at the end of treatment. The aim of the current study is the investigation of the neurofunctional basis of the identified biomarker semantic verbal fluency and the identification of the associated neurobiological changes in the subgroup of MDD patients with executive deficits. To reach this aim, 30 MDD patients with executive deficits should be compared to 30 MDD patients without deficits in executive functions and 30 healthy control subjects. The second f-MRI investigation after two weeks of treatment should be used to identify the effect of the antidepressant treatment on the brain activation o the three groups. Based on the results of a coordinate-based ALE meta-analysis on the brain activation during the processing of verbal fluency tasks in healthy controls, the main regions of interest in the current f-MRI study are the left inferior and middle frontal gyrus as well as the anterior cingulate gyrus.