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。几乎所有重度抑郁症患者都在生活的几个领域遭受轻微到非常严重的损害，比如身体和社会活动，或职业责任。研究表明，重度抑郁症与大脑功能受损有关，尤其是与额叶有关。最近的研究表明，在单极抑郁症和双相抑郁症中都涉及一组一致的边缘和皮质区域。特别是，额叶代谢低下与抑郁症严重程度的增加、精神运动减缓和执行功能障碍有关。使用抗抑郁药物（ADs）治疗重度抑郁症是公认的。然而，目前可用的抗抑郁药的效应量相当小而不是中等，治疗结果仍然令人失望，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识别可用于预测最终治疗结果的生物标志物。重度抑郁症最常用的预测指标是早期改善，例如在治疗的前两周症状减轻至少20%。缺乏早期改善具有高敏感性和特异性，预测最终非缓解，但另一方面，从基线到第2周早期改善的患者中只有25%在治疗结束时成为缓解者。这些数据清楚地表明，需要进一步的生物标志物来改善对积极治疗结果的预测。在最近完成的一项DFG项目中，我们发现在治疗开始时具有执行缺陷的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了治疗结束时抑郁症状的缓解。本研究的目的是研究已识别的生物标志物语义语言流畅性的神经功能基础，并确定伴有执行缺陷的重度抑郁症患者亚组中相关的神经生物学变化。为了达到这一目的，应该将30名有执行功能缺陷的MDD患者与30名没有执行功能缺陷的MDD患者和30名健康对照进行比较。治疗两周后的第二次f-MRI检查应用于确定抗抑郁药物治疗对三组患者大脑活动的影响。基于基于坐标的ALE荟萃分析结果，对健康对照在处理语言流畅任务时的大脑激活进行了研究，认为当前的f-MRI研究主要关注左额叶下回和中回以及前扣带回。

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.