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Difficult to Treat Depression / Non-Invasive Brain Stimulation

Leader: Prof. Dr. med Helge Frieling, PD Dr. med. Alexandra Neyazi, Dr. med. Hannah Maier

Deutsche Version


Research Group DTD / Non-Invasive BS, MHH
Research Group DTD / Non-Invasive BS, MHH

Treatment resistant depression (TRD) and difficult to treat depression (DTD) refer to deficient responses to antidepressant therapy (i.e., pharmaceuticals, psychotherapy, electroconvulsive therapy (ECT) or other approaches) after several weeks of treatment. The response rates decrease with the duration of the disease and about 20% of the patients develop a chronic course. Various influencing factors in the multicausal pathogenesis of depression have already been identified, but the complete understanding of its pathophysiology still remains elusive. Probable causes include ineffective drug metabolism or undetected somatic or psychiatric comorbidities. In addition, the different subtypes of depression assumingly have distinct pathomechanisms, of those some cannot be treated by classical antidepressants. Our working group focuses on identifying clinical and molecular biological markers of DTD to improve and personalize its therapy regiments. Highly promising alternatives to pharmacological treatments are techniques that stimulate the brain electrically (e.g., ECT) or magnetically (e.g., transcranial magnetic stimulation (TMS)).  

We specialize in ECT given it is still one of the most effective therapeutic methods for the treatment of severe psychiatric conditions, such as DTD or pharmacotherapy-resistant psychoses. ECT has been proposed to improve neuronal processes such as synaptogenesis (the creation of new nerve cells) by releasing neurotransmitters and nerve growth factors.  Another theory lies in the possible interruption of pathological neurotransmitter patterns that are associated with psychiatric illnesses and that are possibly rearranged by ECT, similar as rebooting a PC. Nevertheless, its mechanism of action has not yet been fully clarified. In the past years we have assuringly performed ECT on a high number of patients suffering from major depressive disorder (MDD) or DTD. The clinical and physiological data is maintained in NEKTOR (=Lower Saxony ECT Outcome Registry) and is available for collaborations and further research questions.   

Other non-invasive brain stimulation methods we are interested in are transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). The transcranial application of small currents can be used to specifically influence neuronal excitability (tDCS) or the oscillatory dynamics of nerve cell assemblies (tACS). These brain stimulation methods allow the non-invasive testing of hypotheses regarding the relevance of cortical brain regions and specific oscillatory patterns for cognitive processing. In addition, research is currently being conducted into the extent to which dysfunctional neural networks in psychiatric diseases such as schizophrenia can be positively influenced by transcranial current stimulation. 

Overall objectives

The overall goal of our research group is to develop biomarkers for the subtyping of patients with severe affective disorders in order to enable personalized therapy. A main focus of the working group is the investigation of non-invasive brain stimulation methods such as electroconvulsive therapy. 

  • Deep phenotyping of DTD 
  • Identification of epigenetic markers to predict the course of therapy in depressed patients  
  • Epigenetic Imaging for prediction of response  
  • Analysis of predictive biomarkers in ECT 

Scientific Collaborations

Awards and Promotions

  • Award of the German Society for Biological Psychiatry (DGBP; 2019). For the scientific contribution to the DGBP-AGNP Congress 2019 (Poster & Presentation), Nicole Moschny 
  • Prize of the Annika-Liese Foundation for Depression Research (2018/19). For the work "P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy", Alexandra Neyazi, endowed with: 10.000 €. 
  • Internal Funding Initiative (HiLF 1, 'Hochschulinterne Leistungsförderung 1'). For the project "Epigenetic regulation and expression of glia cell-derived neurotrophic factor (GDNF) in depressive patients under pharmacological and electroconvulsive treatment", Alexandra Neyazi, grant: 22.397 € 
  • Poster Prize of the German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology (DGPPN; 2016). "Markers for response of electroconvulsive therapy? Homocysteine, vitamin B12, vitamin B11 and S100 plasma levels in the course of treatment", Hannah Maier 

Research group members

Research group leaders

Prof. Dr. med. Helge Frieling 

Deputy director  


Publications: Pubmed


PD Dr. med. Alexandra Neyazi 

Managing senior physician 

Phone: +49 511 532 2397 

Excellence at a glance: 

  • Specialist in psychiatry and psychotherapy 
  • Medical representative for medical devices and stimulation procedures 

Publications: Pubmed


Dr. med. Hannah Maier 

Assistent physician and PostDoc 

Phone: +49 511 532 3167 


Research focus:

  • Difficult to treat depression (DTD) and pharmacotherapy-resistant Depression 
  • Non-invasive brain stimulation, e.g., electroconvulsive therapy (ECT), vagal nerve stimulation (VNS)  
  • Neuroimaging, especially epigenetic imaging 

Publications: Pubmed



Phone: +49 511 532 2397

Fax: +49 511 532 8573