Affective disorders and stress related disease

In a variety of research projects, we investigate the scientific basis of affective disorders and stress-related disorders as well as ways to optimize their treatment.
In particular, our research focuses on the basic principles and treatment options for depressive disorders.

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News

06/2019 - Michael Kaczmarczyk is supported for 3 years by the BIH "Charité Clinician Scientist Program". During this time he will do research on "sex hormones and fear memory".

03/2019 - Woo Ri Chae wins travel award at the 1st Joint Congress of the Working Group for Neuropsychopharmacology and Pharmacopsychiatry and the German Society for Biological Psychiatry

12/2018 - Approval of the DFG-funding of the project: "The influence of different stress neuromodulators on risk behaviour and loss aversion" by Katja Wingenfeld and Hauke Heekeren (Freie Universität Berlin)

06/2018 - Woo Ri Chae has been selected to participate in the European College of Neuropsychopharmacology (ECNP) - School of Neuropsychopharmacology 2018

11/2017 - DFG-funding of the project: "Are early stress effects on cognitive processes mediated by the mineralocorticoidor glucocorticoid receptor?" by Christian Deuter, Katja Wingenfeld and Christian Otte

09/2017 - Helge Hasselmann wins poster prize at the European College of Neuropsychopharmacology (ECNP) - Congress 2017

03/2017 - Michael Kaczmarczyk wins poster prize at the European College of Neuropsychopharmacology (ECNP) - Congress 2017

02/2017 - Completion of the German doctorate (Dr. med. med.) from Dr. med. univ. Dominique Piber with the note "magna cum laude".

02/2017 - Dr. med. univ. Dominique Piber receives Max Kade Foundation funding for a research fellowship at the Cousins Center for Psychoneuroimmunology at the University of California, Los Angeles

12/2016 - Graduation of the doctorate (Dr. phil. von Fr. Dipl. Psych. Katharina Schultebraucks with the grade "summa cum laude".

11/2016 - DFG-funded by Rami Zain within the framework of the "Scientists as Refugees - Integration in Science and Society" programme as an additional application for the "MISO"study

11/2016 - Start of the DFG-funded study "MISO: Effects of Mineralocorticoid Receptor Stimulation on Cognitive Distortion and Social Cognition in Depressive Patients and Healthy Control Samples: What is the Role of NMDA Receptors?

09/2016 - Moritz Düsenberg wins the poster prize at the "International Congress on Borderline Personality and Allied Disorders", Vienna

Study participation:

As a university hospital, we carry out clinical studies on an ongoing basis, and we are always looking for study participants.

Research in the module 'Affective Disorders'

One focus of our research is investigation of the relationship between mental illness and stress. We are especially interested in changes within biological stress regulation systems, such as the immune system, the hypothalamic pituitary adrenal axis and the autonomic nervous system and how alterations in these systems are related to cognition, psychopathology and medical illness.


In addition, we are conducting clinical trials intervening in these systems to improve the outcome of patients with affective and stress-related disorders.


Our research is supported by various organizations and foundations.

A more detailed description of our projects can be found here:

Effects of stress and trauma on neuroendocrine and cognitive-emotional processes

Stress hormones and cognition

Enhanced emotional empathy for Fludrocortison, compared to placebo - measured with the Multifaceted Empathy Test (MET) (Wingenfeld et al., 2014)
Selective attention towards sad faces after fludrocortisone and away from sad faces after placebo administration.

Senior scientists: Prof. Dr. Katja Wingenfeld and Prof. Dr. Christian Otte

A large number of studies investigated the effects of stress and cortisol on different memory processes. In summary, the administration of glucocorticoids improves memory consolidation while worsening memory retrieval. Other cognitive processes are far less well studied in the context of stress, and current research is also focusing on the type of receptor - glucocorticoid receptor (GR) and/or mineralocorticoid receptor (MR). Furthermore, it is of interest how different stress regulation systems, e. g. the endocrine system, interact with the stress hormone cortisol and the autonomic nervous system, which coordinates the release of norepinephrine and adrenaline, for example. In a series of studies with healthy volunteers, we continue to explore these relationships.

One focus of our studies is to investigate the extent to which stress (hormone) affects social cognition. We were able to show that the administration of fludrocortisone, a selective mineralocorticoid receptor (MR) agonist, leads to an improvement in empathy. This effect was found in healthy volunteers as well as in patients with borderline personality disorder. The results are shown in the following figure (left). Furthermore, it was shown that the stimulation of MR leads to a change in attention processes: whereas in the placebo condition the observation of sad faces was rather avoided, the test persons showed an increased tendency - a so-called "attentional bias" - for these faces after administration of fludrocortisone (figure on the right).

The stimulation of MR seems to have effects not only on social cognition, but also on different memory processes, e. g. spatial memory, as we have been able to show in various experiments (Piber et al., 2017; Hinkelmann et al., 2015). In addition, the test persons tended to make riskier decisions (Deuter et al., 2017). We will continue to investigate both phenomena in future studies. One focus is to understand whether and to what extent women and men differ in their reaction to stress (hormones) (e. g., Düsenberg et al., 2016).

Social cognition is an important component of human emotional competence and is necessary for appropriate social interaction. Stress affects social cognition through the release of cortisol, which acts through the glucocorticoid (GR) and mineralocorticoid receptor (MR) in the brain. Up to now, studies have examined the influence of GR on social cognitions, with little attention paid to the role of MR. In this double-blind, placebo-controlled and randomized study, we investigated the influence of MR on selective attention and emotion recognition (Schultebraucks et al. 2017).

We are currently comparing the effects of various stressors, e. g. physical stress versus psychosocial stress on different cognitive processes and are investigating the interaction of the stress hormones cortisol and norepinephrine in an experimental pharmacological study.

  • Piber, D., Nowacki, J., Mueller, S.C., Wingenfeld, K. & Otte, C. (in press). Sex Effects on Spatial Learning but not on Spatial Memory Retrieval in Healthy Young Adults. Behavioural Brain Research.
  • Schultebraucks, K., Deuter, C. E., Duesenberg, M., Schulze, L., Hellmann-Regen, J., Domke, A., ... & Wingenfeld, K. (2016). Selective attention to emotional cues and emotion recognition in healthy subjects: the role of mineralocorticoid receptor stimulation. Psychopharmacology, 233(18), 3405-3415.
  • Deuter, C. E., Wingenfeld, K., Schultebraucks, K., Hellmann-Regen, J., Piber, D., & Otte, C. (2017). Effects of mineralocorticoid-receptor stimulation on risk taking behavior in young healthy men and women. Psychoneuroendocrinology, 75, 132-140.
  • Wingenfeld, K., Kuehl, L. K., Janke, K., Hinkelmann, K., Dziobek, I., Fleischer, J., ... & Roepke, S. (2014). Enhanced emotional empathy after mineralocorticoid receptor stimulation in women with borderline personality disorder and healthy women. Neuropsychopharmacology, 39(8), 1799.

The role of stress neuromodulators in decision making under risk

Funding by the DFG

Applicants: Prof. Dr. Katja Wingenfeld und Prof. Dr. Hauke Heekeren (Freie Universität, FU)
Participating individuals: Sophie Metz, Catarina Rosada, Prof. Dr. Christian Otte & Dr. Adrian Fischer (FU)

Incidental affective states, i.e., affective states that are unrelated to the decision at hand, can influence decision making. Acute stress is such an affective state and is a powerful contextual modulator of decision-making processes. It appeared that after stress exposure, individuals make riskier decisions.
In terms of physiological and neurohormonal changes, the stress response has been well characterized: Exposure to stress elicits an array of autonomic, endocrine, and behavioral responses. The physiological stress response is mediated by the hypothalamic-pituitary adrenal (HPA) axis and the locus coeruleus noradrenergic (LC-NA) system with cortisol and norepinephrine (NE) as their end products.
There is compelling evidence that the stress hormones cortisol and NE influence cognitive processes. However, only very few studies so far used pharmacological approaches to specify the role of stress neuromodulators on decision making and these studies are hardly comparable due to differences in the experimental design, e.g., the decision making task used. Furthermore, the neural underpinnings of stress effects on decision making are uninvestigated so far.
The aim of the project is to clarify the role of the major stress neuromodulators, NE and cortisol, in their contribution to different processes related to decision making under risk. To this end, we will combine precise pharmacological stimulation, behavioral modeling, and fMRI methods to systematically disentangle the effects of stress hormones on risk attitudes and loss aversion as well as their relation to neural correlates of processing subjective value and risk.

Stress and cognition in Borderline Personality Disorder and Post-traumatic stress disorder

The effects of 10mg hydrocortisone on A) percentage of words retrieved in the word list paradigm in relation to the learning list on the previous day (mean [SE]) and B) on autobiographic memory retrieval (number of specific events retrieved; mean [SE]) in patients with PTSD in comparison to sex and age-matched healthy controls

Funding by the DFG
Applicant: Prof. Dr. K. Wingenfeld
Co-applicant: Prof. Dr. Christian Otte, Prof. Dr. Oliver T. Wolf (Ruhr University Bochum)

We were able to show that a single dose of hydrocortisone improves memory recall in patients with post-traumatic stress disorder (PTSD) and borderline personality disorder (BPD). Healthy control subjects, on the other hand, showed a cortisol-induced deterioration of the memory retrieval in accordance with previous findings (e. g., Wingenfeld & Wolf, 2015). The results of PTSD patients are summarized in the following figure. In a go/no-go task, on the other hand, we were unable to detect any changes in BPD patients (Carvallo Fernando, et al., 2013). We are currently investigating which neuronal correlates are underlying the improved memory performance after cortisol delivery in PTSD and BPD and whether the positive effects of cortisol on memory retrieval are also visible after psychosocial stress.

Cortisol acts via two receptor types, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). The synthetic glucocorticoid hydrocortisone binds to both receptor types. We wanted to investigate the extent to which selective stimulation of MR in patients with BPD has similar (positive) effects to those we have shown for healthy volunteers and patients with depression. Interestingly, the results were again dependent on the nature of the task: With regard to emotional empathy and working memory, BPD patients as well as healthy women showed a better performance after stimulation of the MR, while the performance in the declarative and spatial memory deteriorated with BPD patients (Wingenfeld et al., 2016).

Future studies should further investigate the complex interplay between receptor type, task type and different disturbance patterns.

  • Wingenfeld, K., Duesenberg, M., Fleischer, J., Roepke, S., Dziobek, I., Otte, C., & Wolf, O. T. (2018). Psychosocial stress differentially affects emotional empathy in women with borderline personality disorder and healthy controls. Acta Psychiatrica Scandinavica, 137(3), 206-215.
  • Roepke, S., Danker-Hopfe, H., Repantis, D., Behnia, B., Bernard, F., Hansen, M. L., & Otte, C. (2017). Doxazosin, an α-1-adrenergic-receptor Antagonist, for Nightmares in Patients with Posttraumatic Stress Disorder and/or Borderline Personality Disorder: a Chart Review. Pharmacopsychiatry, 50(01), 26-31.
  • Wingenfeld, K., & Wolf, O. T. (2015). Effects of cortisol on cognition in major depressive disorder, posttraumatic stress disorder and borderline personality disorder-2014 Curt Richter Award Winner. Psychoneuroendocrinology, 51, 282-295.
  • Wingenfeld, K., Kuehl, L. K., Janke, K., Hinkelmann, K., Eckert, F. C., Roepke, S., & Otte, C. (2015). Effects of mineralocorticoid receptor stimulation via fludrocortisone on memory in women with borderline personality disorder. Neurobiology of learning and memory, 120, 94-100.
  • Wingenfeld, K., Kuehl, L. K., Janke, K., Hinkelmann, K., Dziobek, I., Fleischer, J., ... & Roepke, S. (2014). Enhanced emotional empathy after mineralocorticoid receptor stimulation in women with borderline personality disorder and healthy women. Neuropsychopharmacology, 39(8), 1799.
  • Fernando, S. C., Beblo, T., Schlosser, N., Terfehr, K., Wolf, O. T., Otte, C., ... & Wingenfeld, K. (2013). Acute glucocorticoid effects on response inhibition in borderline personality disorder. Psychoneuroendocrinology, 38(11), 2780-2788.

Influence of early traumatisation on hormonal, neuronal and cognitive function in life history

Funded by NeuroCure

Scientists in charge: Dipl. -Psych. Sabrina Golde, Prof. Dr. Christian Otte, Prof. Dr. Katja Wingenfeld

An early trauma to life seems to be associated with a change in the function of hormonal stress systems. Reduced basal concentrations of cortisol with simultaneously increased cortisol release in reaction to stress were described. Neuronal imaging studies also indicate a modified fronto-limbic network characterized by increased reactivity of the amygdala, reduced activity of different prefrontal areas and altered reactivity of the hippocampus. Clinically, people with early traumatization and post-traumatic stress disorder often suffer from problems in the regulation of emotions and cognitive control.

We are currently investigating the interaction between hormonal and neuronal stress systems and cognitive function in 1) healthy people with early trauma and 2) patients with post-traumatic stress disorder (PTSD) and borderline personality disorder (BPD) in two studies using functional magnetic resonance imaging (fMRI). Both methods of psychosocial stress induction ("Montreal Stress Imaging Task") and experimental pharmacological methods (hydrocortisone versus placebo) are used.

These studies are intended to help us understand the effects of early trauma in life history. We also hope to gain hypotheses about why some people develop a mental illness as a result of traumatic stress, while others do not.

  • Fernando, S. C., Beblo, T., Schlosser, N., Terfehr, K., Otte, C., Löwe, B., ... & Wingenfeld, K. (2012). Associations of childhood trauma with hypothalamic-pituitary-adrenal function in borderline personality disorder and major depression. Psychoneuroendocrinology, 37(10), 1659-1668.
  • Carvalho Fernando, S., Beblo, T., Schlosser, N., Terfehr, K., Otte, C., Löwe, B., ... & Wingenfeld, K. (2014). The impact of self-reported childhood trauma on emotion regulation in borderline personality disorder and major depression. Journal of Trauma & Dissociation, 15(4), 384-401.
  • Fernando, S. C., Beblo, T., Schlosser, N., Terfehr, K., Otte, C., Löwe, B., ... & Wingenfeld, K. (2012). Associations of childhood trauma with hypothalamic-pituitary-adrenal function in borderline personality disorder and major depression. Psychoneuroendocrinology, 37(10), 1659-1668.
  • Carvalho Fernando, S., Beblo, T., Schlosser, N., Terfehr, K., Otte, C., Löwe, B., ... & Wingenfeld, K. (2014). The impact of self-reported childhood trauma on emotion regulation in borderline personality disorder and major depression. Journal of Trauma & Dissociation, 15(4), 384-401.

Pharmacological modulation of mood and cognition

Cognitive function in depressive patients: The role of the Mineralocorticoid receptor

Executive function as measured by Trail Making Test B minus Trail making test A in seconds; treatment effect: p=0.04, group × treatment: p=NS, group effect p=NS.
Verbal learning memory test; % correct answers in delayed recall; treatment effect: p=0.03, group × treatment: p=NS, group effect p=NS

Compared to healthy volunteers, depressive patients often have elevated levels of the stress hormone cortisol and cognitive impairment. Cortisol modulates cognitive functions via central mineralocorticoid receptors (MRs), especially verbal and non-verbal memory. Preliminary studies have shown that cortisol secretion in depressive patients is increased and is negatively correlated with verbal and non-verbal memory. In healthy young men, an MR blockade led to an identical impairment of these memory functions, so that the cognitive deficits in depressive patients may be mediated by MR. There are no studies on the relationship between MR and memory in depressive patients.

In this experimental study, our primary objective was to determine whether a single stimulation of MR by fludrocortisone in depressive patients compared to healthy control subjects leads to an acute improvement in verbal and non-verbal memory and executive function. Our secondary goal was to determine whether memory and executive function were also affected in healthy fludrocortisone.

To this end, a total of 24 younger depressive patients (< 35 years) and 24 age- and gender-parallelised participants in a double-blind, placebo-controlled design were investigated once-only with an MR agonist (fludrocortisone). In addition to a detailed neuropsychological characterization of the participants, free cortisol in saliva was also determined. In fact, we have shown that fludrocortisone leads to better executive function (Figure 1) and improved verbal memory across all groups (Figure 2). Fludrocortisone led to a decreased cortisol secretion, which correlated with improved performance in verbal memory. Our study has confirmed a central role of the Mineralocorticoid receptor in memory and executive function and demonstrated that it is possible to improve it by MR stimulation.

  • Hinkelmann, K., Hellmann-Regen, J., Wingenfeld, K., Kuehl, L. K., Mews, M., Fleischer, J., ... & Otte, C. (2016). Mineralocorticoid receptor function in depressed patients and healthy individuals. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 71, 183-188.
  • Wingenfeld, K., Kuehl, L. K., Dziobek, I., Roepke, S., Otte, C., & Hinkelmann, K. (2016). Effects of mineralocorticoid receptor blockade on empathy in patients with major depressive disorder. Cognitive, Affective, & Behavioral Neuroscience, 16(5), 902-910.
  • Kloet, E. R., Otte, C., Kumsta, R., Kok, L., Hillegers, M. H. J., Hasselmann, H., ... & Joëls, M. (2016). STRESS and DEPRESSION a crucial role of the mineralocorticoid receptor. Journal of neuroendocrinology.
  • Otte, C., Wingenfeld, K., Kuehl, L. K., Richter, S., Regen, F., Piber, D., & Hinkelmann, K. (2015). Cognitive function in older adults with major depression: effects of mineralocorticoid receptor stimulation. Journal of psychiatric research, 69, 120-125.
  • Fleischer, J., Wingenfeld, K., Kuehl, L. K., Hinkelmann, K., Roepke, S., & Otte, C. (2015). Does fludrocortisone influence autobiographical memory retrieval? A study in patients with major depression, patients with borderline personality disorder and healthy controls. Stress, 18(6), 718-722.
  • Otte, C., Wingenfeld, K., Kuehl, L. K., Richter, S., Regen, F., Piber, D., & Hinkelmann, K. (2015). Cognitive function in older adults with major depression: effects of mineralocorticoid receptor stimulation. Journal of psychiatric research, 69, 120-125.

Noradrenergic activity and attention processes in depression

Funding by the DFG
Applicant: Dr. Linn Kühl
Co-applicant: Prof. Dr. Christian Otte, Prof. Dr. Katja Wingenfeld

Stress plays a central role in the development and maintenance of major depression. Many studies have shown alterations in physiological stress regulation systems for depressive patients. Both the hypothalamus-hypophysis-adrenergic axis (HHNA) and the locus-coeruleus-noradrenergic system (LC-NA-system) were investigated. At a central level, changes in the LC-NA system were observed, which particularly affect a change in the response of adrenergic receptors (regulation of alpha2-adrenergic receptors) in depressive patients. These changes seem to be particularly relevant in patients with early traumatizations. The LC-NA system not only influences the physiological stress response, it also has key effects on cognitive functions. For example, norepinephrine has effects on functions such as attention, learning and memory in healthy volunteers. Although major depression is characterized by various cognitive deficits, such as memory and attention, the relationship between the LC-NA system and cognition in these patients has hardly been investigated. In an initial study, our research group has therefore investigated the effect of stimulation of noradrenergic activity on various memory functions.

In this project, the relationship between the LC-NA system and different attention processes in patients with major depression is to be investigated for the first time, taking into account possible early traumatic experiences. In a placebo-controlled design, the effects of noradrenergic stimulation by administration of the alpha2 receptor blocker yohimbine on different attention processes in patients with major depression compared to healthy control subjects are investigated.

The results of this study could lead to a better understanding of cognitive deficits and the role of the alpha2-adrenergic system in depressive patients and thus contribute to new therapeutic options.

  • Kuffel, A., Eikelmann, S., Terfehr, K., Mau, G., Kuehl, L. K., Otte, C., ... & Wingenfeld, K. (2014). Noradrenergic blockade and memory in patients with major depression and healthy participants. Psychoneuroendocrinology, 40, 86-90.
  • Wingenfeld, K., Kuffel, A., Uhlmann, C., Terfehr, K., Schreiner, J., Kuehl, L. K., ... & Spitzer, C. (2013). Effects of noradrenergic stimulation on memory in patients with major depressive disorder. Stress, 16(2), 191-201.

Steroid receptors and glutamate in depression

Funding by the DFG
Applicant: Prof. Dr. Christian Otte

In our current MISO study, we are investigating the effects of mineralocorticoid receptor stimulation on cognitive biases and social cognition in depressive patients and healthy control subjects and we want to find out what role the NMDA receptors play in this.
In various study projects, we have already observed an improvement in the general cognitive functions after MR stimulation (using fludrocortisone) in depressive patients as well as in healthy subjects (Wingenfeld et al 2014; Hinkelmann et al., 2015; Otte et al., 2015). Now we would like to follow up with a study of attention distortion, emotion recognition in faces, empathy, and spatial memory in depressive patients and healthy volunteers. For all these independent cognitive domains an influence of MR was found. The primary objective of the study is therefore to confirm or expand the effects of fludrocortisone vs. placebo found in the preliminary studies with respect to the four cognitive domains mentioned above.
In addition, it is still unclear by which downstream mechanism of action fludrocortisone has an effect on cognition. Interestingly, it has been observed that, on the one hand, the partial NMDA receptor agonist D-cycloserine (DCS) leads to improvements in learning and memory in humans and, on the other hand, MR stimulation causes glutamate secretion and enhanced NMDA-receptor-mediated signal transmission. It is therefore possible that co-administration of an MR agonist with an NMDA receptor agonist leads to synergistic effects and thus to even more significant improvements in cognition. The secondary exploratory objective of the study is therefore to investigate whether the effect of MR stimulation can be further enhanced by co-administration of the NMDA receptor agonist D-cycloserine.
To this end, we use a randomized double-blind placebo-controlled trial design by administering fludrocortisone, D-cycloserine and/or a placebo, both to patients with depression and healthy control subjects, and then examining various cognitive functions using computer tasks.

  • Hinkelmann K, Kühl L, Wingenfeld, K, Fleischer J, Roepke S, Wiedemann K, Heuser I, Otte C. (2015) Stimulation of the mineralocorticoid receptor improves visuospatial memory and working memory in young and elderly healthy individuals. Neurobiology of Aging: 1-6.
  • Otte C, Wingenfeld K, Kühl L, RS, Quante A, Regen F, Bajbouj M, Zimmermann-Viehoff F, Wiedemann K, Hinkelmann K (2015). Mineralocorticoid receptor stimulation improves cognitive function and decreases cortison secretion in depressed patients and healthy individuals. Neuropsychopharmacology: 1-8.
  • Wingenfeld, K., et al. (2014). Enhanced emotional empathy after mineralocorticoid receptor stimulation in women with borderline personality disorder and healthy women. Neuropsychopharmacology 39(8): 1799-1804.

Receptor-specific effects of cortisol on emotional and cognitive processes

Funding by the DFG
Applicant: Dr. Christian Deuter
Co-applicants: Prof. Dr. Christian Otte, Prof. Dr. Katja Wingenfeld

Stress affects several physiological and psychological domains and triggers a shift in information processing that is mediated by two separate neuroendocrine systems: the fast-responding catecholaminergic system and the slower glucocorticoid system. The glucocorticoid system is based on the hypothalamic-pituitary-adrenal axis, with cortisol as the main downstream glucocorticoid in humans. According to the network model of Hermans et al. (2014), two separate brain networks are implicated in the acute stress response. The salience network is responsible for exogenous attention, especially to potential threats, and the fast mobilization of energy. Resources are primarily allocated to this network immediately after the onset of the stressor until about one hour after stress exposure. In this early part of the stress response, the executive control network that mediates deliberate thinking and planned action is down-regulated. This process is initially driven by catecholaminergic activation, which sets in immediately within seconds with stress exposure. In addition and within minutes rapid non-genomic effects of cortisol appear on the scene and start to modulate the catecholaminergic effects. Cortisol can easily cross the blood-brain barrier and feeds back on the brain via two different receptor types: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). While GRs are widely distributed in the brain, MRs are primarily located in limbic structures and the prefrontal cortex, which are areas critical for cognition and emotion. Several human and animal studies indicated a role for membrane-bound MRs in the early phase of the stress response and in rapid cortisol effects on emotional and cognitive processes. However, while rapid stress effects are often attributed to the MR, recent research in animals indicates a role of the - supposedly membrane bound and non-genomic - GR in rapid stress effects as well.These rapid effects are regionally and functionally specific and may differ between MRs and GRs. Overall, effects of GRs rather suppress, and those of MRs rather enhance neural excitability.In the proposed project, we plan to systematically disentangle MR vs. GR effects in the early stress response on emotional and cognitive processes that represent the salience network (attentional vigilance to emotional stimuli as determined by emotional dot-probe), the executive control network (working memory as assessed by n-back task) or both networks (risk taking as assessed by balloon analogue risk task). To our best knowledge, this would be the first project to investigate the differential contribution of both receptor systems on these cognitive domains in such a systematic manner.

Stress and physical health in mental illnesses

Cardiovascular risk in affective disorders and stress diseases

Psychological traumatisation in childhood increases both the risk of developing depression and becoming chronically depressed as well as the risk of developing other physical co-morbidities in the context of depression (e. g. metabolic syndrome). Patients obviously differ neurobiologically depending on whether or not they have had traumatic experiences in childhood. This could be important for both psychotherapeutic and pharmacological treatment. In a study, we investigate the effects of childhood psychological trauma on cognition, cardiovascular risk and stress hormone release in depressive patients.

  • Kuehl, L. K., Muhtz, C., Hinkelmann, K., Dettenborn, L., Wingenfeld, K., Spitzer, C., & Otte, C. (2016). Association between major depression and cardiovascular risk: the role of antidepressant medication. Psychopharmacology, 233(18), 3289-3295.
  • Agorastos, A., Lederbogen, F., & Otte, C. (2015). Treatment of depression in coronary heart disease. Der Nervenarzt, 86(3), 375-85.
  • Wingenfeld, K., Whooley, M. A., Neylan, T. C., Otte, C., & Cohen, B. E. (2015). Effect of current and lifetime posttraumatic stress disorder on 24-h urinary catecholamines and cortisol: results from the Mind Your Heart Study. Psychoneuroendocrinology, 52, 83-91.
  • Kuehl, L. K., Hinkelmann, K., Muhtz, C., Dettenborn, L., Wingenfeld, K., Spitzer, C., ... & Otte, C. (2015). Hair cortisol and cortisol awakening response are associated with criteria of the metabolic syndrome in opposite directions. Psychoneuroendocrinology, 51, 365-370.
  • Zimmermann-Viehoff, F., Kuehl, L. K., Danker-Hopfe, H., Whooley, M. A., & Otte, C. (2014). Antidepressants, autonomic function and mortality in patients with coronary heart disease: data from the Heart and Soul Study. Psychological medicine, 44(14), 2975-2984.
  • Dettenborn, L., Hinkelmann, K., Muhtz, C., Gao, W., Wingenfeld, K., Spitzer, C., ... & Otte, C. (2013). Hair testosterone and visuospatial memory in middle-aged men and women with and without depressive symptoms. Psychoneuroendocrinology, 38(10), 2373-2377.

Stress hormones, early traumatizations and metabolic disorders

Funding by the German Research Foundation (DFG)
Applicant: Prof. Dr. K. Wingenfeld
Co-applicant: Prof. Dr. C. Spitzer, Prof. Dr. C. Otte
Cooperation partner: Asklepios Fachklinikum Tiefenbrunn


Previous traumatic stress is associated with abnormalities of the hypothalamic hypohyses adrenal cortex axis (HHNA). This is reflected in an increased reactivity to stress, reduced feedback sensitivity and changes in glucocorticoid receptors (GR). Early traumatised people have an increased risk of developing metabolic disorders such as diabetes mellitus type II or metabolic syndrome.

In a DFG-funded study, we investigated participants with and without early traumatization, taking into account the factor of depression, measurements of HHNA activity and assessment of GR. In addition, we also recorded various markers of metabolic syndrome and carried out an oral glucose tolerance test. We also looked into the question of whether eating habits have changed after a stressful situation in people with early traumatisation and thus represent a risk factor for the development of later metabolic abnormalities.

This study is intended to investigate a previously neglected aspect of the consequences of early traumatisation. These results can lead to a better understanding of stress-related eating habits and their consequences.

  • Spitzer, C., Otte, C., Kuehl, L. K., May, A., Schultebraucks, K., Hellmann-Regen, J., & Wingenfeld, K. (2018). The dexamethasone corticotropin releasing hormone test in healthy and depressed women with and without childhood adversity. Psychoneuroendocrinology, 87, 147-151.
  • Wingenfeld, K., Kuehl, L. K., Boeker, A., Schultebraucks, K., Schulz, A., Stenzel, J., ... & Otte, C. (2017). Are adverse childhood experiences and depression associated with impaired glucose tolerance in females? An experimental study. Journal of Psychiatric Research.
  • Wingenfeld, K., Kuehl, L. K., Boeker, A., Schultebraucks, K., Ritter, K., Hellmann-Regen, J., ... & Spitzer, C. (2017). Stress reactivity and its effects on subsequent food intake in depressed and healthy women with and without adverse childhood experiences. Psychoneuroendocrinology, 80, 122-130.
  • Culverhouse, R. C., Saccone, N. L., Horton, A. C., Ma, Y., Anstey, K. J., Banaschewski, T., ... & Goldman, N. (2017). Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. Molecular psychiatry.

Immunological and endocrine changes in depression

Funding by the DFG

Applicant: Prof. Dr. Stefan Gold

Co-applicant: Prof. Dr. Christian Otte  

Main Scientists in charge: MScRes. Helge Hasselmann

The role of the immune system in the development of depressive diseases has been shown to be of great importance in the past. It has been shown that certain immune markers in patients with depression are elevated compared to non-destructive controls. However, little is known about the influence of cell specific processes in depression.

In a DFG/NeuroCure-funded project we (Helge Hasselmann, Prof. Stefan Gold and Prof. Christian Otte) are investigating the extent to which differences in cell-specific immunity exist between depressive and non-depressive patients. We are particularly interested in the role of the body's own stress hormone cortisol: for example, we are interested in the extent to which group differences in the reaction of certain immune cells to the stress hormone cortisol exist and whether this can be correlated with levels of mood. We are investigating this question at the level of RNA and proteins using a variety of different laboratory techniques.

A total of 50 unmedicated patients with clinically diagnosed major depression and 50 healthy controls are to be enrolled. In order to exclude the influence of non-specific factors, only medically healthy people are included and attempts are made to maximise the comparability of both groups.

  • Hasselmann, H., Bellmann-Strobl, J., Ricken, R., Oberwahrenbrock, T., Rose, M., Otte, C., ... & Gold, S. M. (2016). Characterizing the phenotype of multiple sclerosis–associated depression in comparison with idiopathic major depression. Multiple Sclerosis Journal, 22(11), 1476-1484.

Simvastatin add-on to Escitalopram in patients with comorbid obesity and major depression: A multicenter, randomized, double-blind, placebo-controlled trial (SIMCODE)

Study centers for SIMCODE

Funding by the Bundesministerium für Forschung und Bildung (BMBF)

Applicant: Prof. Dr. Christian. Otte

Co-applicant: Prof. Dr. Stefan Gold

Main Scientists in charge: Dr. med. Woo Ri Chae


Major depressive disorder (MDD) and obesity are major contributors to impaired health worldwide. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomized controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and treatment resistance.

Thus, in this randomized controlled trial we will determine whether add-on simvastatin to standard antidepressant medication is more efficacious than add-on placebo. If successful, our trial would have immediate impact on clinical practice and improve the knowledge about treatment of depressive patients with comorbid obesity, especially as simvastatin is available as inexpensive generic drug with established safety.

Project lead

Prof. Dr. med. Christian Otte

Vice Director Department of Psychiatry and Phychotherapy

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