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

• Applicant: Privatdozentin Dr. Stefanie Wagner
• Subject Area: Biological Psychiatry
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 186400190

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.

• DFG Programme: Research Grants
• Participating Persons: Professor Dr. Dieter F. Braus; Professor Dr. Klaus Lieb; Dr. André Tadic