Groundbreaking insights from behavioral science, neuroscience, and immunology have clearly demonstrated that mental and physical processes are deeply interconnected and mutually influential. At the Institute of Medical Psychology and Behavioral Immunobiology, the research groups explore this bidirectional communication between psychological processes, the brain, and bodily systems. The working groups of the Institute use a range of experimental approaches in animal models, as well as studies with healthy individuals and patients.
Manfred Schedlowski is a Professor of Medical Psychology and Behavioral Immunobiology at the University Hospital Essen. After studying psychology, he earned his doctorate at the Hannover Medical School and, following research stays at the University of Newcastle and La Trobe University in Melbourne, Australia. He worked scientifically in the Departments of Clinical Immunology and Clinical Psychiatry at the Hannover Medical School, where he completed his habilitation in 1993.
Since October 1997, Professor Schedlowski has been the Director of the Institute of Medical Psychology and Behavioral Immunobiology at the University Hospital Essen, interrupted by a three-year research stay from 2004 to 2007 at the Swiss Federal Institute of Technology (ETH) Zurich.
Julia Bihorac is a PhD student at the institute of Medical Psychology and Behavioral Immunobiology at the University Hospital Essen.
She studied Medical Biology at the University Duisburg-Essen and completed her master’s degree in biology with a major in cell biology and biomedicine at the Heinrich-Heine University in Düsseldorf in 2023.
In her dissertation at the Institute of Medical Psychology and Behavioral Immunobiology, she focuses on the neural mechanisms and putative networks mediating behavioral conditioning of immune functions.
Martin Hadamitzky is a Professor and Group Leader at the Institute of Medical Psychology and Behavioral Immunobiology at the University Hospital Essen. After studying neurobiology, he earned his doctorate in 2008 at the Institute for Brain Research, Department of Neuropharmacology, at the University of Bremen.
Before joining the University Hospital Essen in 2011, he worked as a postdoctoral researcher in behavioral neuroscience at the University of California, San Diego (UCSD) in the Department of Experimental Psychiatry, at the Max-Planck-Institute for Neurological Research, University of Cologne, and at the Institute of Pharmacology, Toxicology, and Pharmacy at the Ludwig Maximilian University of Munich.
In 2017, he completed his habilitation and received the venia legendi (authorization to teach) in the field of Behavioral Immunobiology at the Medical Faculty of the University of Duisburg-Essen, where he was awarded an adjunct professorship in August 2023.
Classical Conditioning of Immune Functions as Part of the Learned Placebo Response in the Immune System
Remarkably, as early as the time of Nobel laureate Ivan Pavlov, researchers observed that immune system functions could be influenced by classical conditioning. Building on this foundation, the working groups in the Institute of Medical Psychology and Behavioral Immunobiology focus on uncovering the neuropsychological and neurobiological mechanisms behind conditioned immune responses. They also investigate the clinical relevance of these learned placebo effects within the immune system in both healthy participants and patient populations.
The overarching goal of their work is to translate basic scientific findings into innovative treatment strategies, enhancing existing pharmacological and non-pharmacological therapies through the targeted use of behavioral interventions. The groups are committed to bridging science and practice by integrating the latest research findings into medical education and clinical training. The Institute‘s teaching comprises seminars and courses for medical students, as well as continuing education programs for physicians and other healthcare professionals working with patients.
Overview
The behavioral conditioning group of the Institute investigates how classical conditioning can influence immune system functions—forming part of what is known as the learned placebo response. Just like heart rate or hormonal responses, immune activity can be shaped by learning mechanisms. This opens new perspectives for integrating behavioral conditioning into medical treatment strategies.
Using the efferent and afferent communication pathways between the brain and peripheral immune system, together with end-organ functions as hardware (to borrow IT terminology), and sophisticated associative learning protocols as software, the behavioral conditioning of immunopharmacological responses might serve as an activator of the body-own pharmacy and a very valuable supportive treatment tool for the patient’s benefit.
The Model
At the core of the research work is an established experimental model that pairs immunopharmacological agents—such as calcineurin inhibitors (Cyclosporine A, Tacrolimus), mTOR antagonists (Rapamycin, Everolimus), with a neutral, unfamiliar taste stimulus (Fig.1). The drug acts as the unconditioned stimulus; the taste becomes the conditioned stimulus. Over time, the organism learns to produce an immunopharmacological response in reaction to the taste alone.
Figure 1. During conditioning, animals are presented with a novel sweet taste stimulus.
Animal Studies
The preclinical studies have shown that conditioned immunosuppression affects T-cell proliferation and cytokine production at both genetic (mRNA) and protein levels. These effects are centrally mediated mainly by the insular cortex and amygdala and peripherally regulated via the splenic nerve, noradrenaline, and β-adrenoceptor-dependent pathways.
The clinical relevance is compelling: learned immunosuppression has delayed organ rejection in transplant models, diminished tumor growth, and reduced symptoms in allergic and chronic inflammatory disease models (Fig. 2 below).
Figure 2. The potential clinical relevance of conditioned immunosuppression has been tested in preclinical experimental disease models such as organ transplantation, allergy, inflammatory autoimmune diseases, and tumor growth.
Current projects focus on the communication between the immune system and the brain, how the brain detects immune changes, the neurotransmitter systems and cytokines involved in learning processes, and the mechanisms of extinction, renewal, and reconsolidation (memory updating) using chemogenetic tools (DREADDs).
Human Studies
Experimental trials confirm that conditioned immunosuppression is also possible in humans (Fig.3). The ongoing research investigates (i) the influence of cognitive factors on immune conditioning, (II) the duration and stability of learned immune responses, (III) the ability to recall learned responses over time, as well as (IV) the potential to combine behavioral conditioning with reduced drug doses—to maintain therapeutic effects while minimizing detrimental side effects. Studies are conducted in both healthy individuals and kidney transplant patients, with the goal of integrating these findings into clinical practice.
Figure 3. Green colored strawberry milk with a drop of lavender oil is used as taste stimulus in humans. Immunhistological assays are performed with human blood cells (PBMC).
Selected Publications
Flasbeck V, Dersch N, Engler H, Schedlowski M, Brüne (2024). Acute experimental inflammation in healthy women attenuates empathy for psychological pain. Brain Behav Immun. 119:1-5.
Bihorac SJ, Salem Y, Lückemann L, Schedlowski M, Doenlen R, Engler H, Mark MD, Spoida K, Hadamitzky M (2024). Investigations on the ability of the insular cortex to process peripheral immunosuppression. J Neuroimmune Pharm. 19:40.
Basedow LA, Fischer A, Benson S, Bingel U, Brassen S, Büchel C, Engler H, Mueller EM, Schedlowski M, Rief W (2023). The influence of psychological traits and prior experience on treatment expectations. Compr Psychiatry. 127:152431.
Hetze S, Barthel L, Lückemann L, Günther HS, Wülfing C, Salem Y, Jakobs M, Hörbelt-Grünheidt T, Petschulat J, Bendix I, Weber-Stadlbauer U, Sure U, Schedlowski M, Hadamitzky M (2022). Taste-immune associative learning amplifies immunopharmacological effects and attenuates disease progression in a rat glioblastoma model. Brain Behav Immun. 106:270-279.
Hadamitzky M, Schedlowski M (2022). Harnessing associative learning paradigms to optimize drug treatment. Trends Pharmacol Sci. 464-472.
Lückemann L, Hetze S, Hörbelt T, Jakobs M, Schedlowski M, Hadamitzky M (2021). Incomplete reminder cues trigger memory reconsolidation and sustain learned immune responses. Brain Behav Immun. 95: 115-121.
Lasselin J, Lekander M, Benson S, Schedlowski M, Engler H (2020). Sick for science: experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression. Mol Psychiatry. 26: 3672-3683.
Lückemann L, Stangl H, Straub RH, Schedlowski M, Hadamitzky M (2020). Learned immunosuppressive placebo response attenuates disease progression in a rodent model of rheumatoid arthritis. Arthritis Rheumatol. 72: 588-597.
Hadamitzky M, Lückemann L, Pacheco-López G, Schedlowski M (2020). Behaviorally Conditioned Responses in Immunological and Neuroendocrine Functions. Physiol Rev. 100: 357-405.
Kirchhof J, Petrakova L, Brinkhoff A, Benson S, Schmidt J, Unteroberdörster M, Wilde B, Kaptchuk TJ, Witzke O, Schedlowski M (2018). Learned immunosuppressive placebo responses in renal transplant patients. Proc Natl Acad Sci. 115: 4223-4227.
Engler H, Brendt P, Wischermann J, Wegner A, Röhling R, Schoemberg T, Meyer U, Gold R, Peters J, Benson S, Schedlowski M (2017). Selective increase of cerebrospinal fluid IL-6 during experimental systemic inflammation in humans: association with depressive symptoms. Mol Psychiatry. 2017;22: 1448-1454.
Hadamitzky M, Bösche K, Wirth T, Buck B, Beetz O, Christians U, Schniedewind B, Lückemann L, Güntürkün O, Engler H, Schedlowski M (2016). Memory-updating abrogates extinction of learned immunosuppression. Brain Behav Immun. 52: 40-8.
Schedlowski M, Enck P, Rief W, Bingel U (2015). Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice. Pharmacol Rev. 697-730.
Albring A, Wendt L, Benson S, Nissen S, Yavuz Z, Engler H, Witzke O, Schedlowski M (2014). Preserving learned immunosuppressive placebo response: Perspectives for clinical application. Clin Pharmacol Ther. 96: 247-55.
Schedlowski M, Engler H, Grigoleit JS (2014). Endotoxin-induced experimental systemic inflammation in humans: a model to disentangle immune-to-brain communication. Brain Behav Immun. 35: 1-8.
Giovanoli S, Engler H, Engler A, Richetto J, Voget M, Willi R, Winter C, Riva MA, MortensenPB, Schedlowski M, Meyer U (2013). Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice. Science. 339: 1095-9.
Enck P, Bingel U, Schedlowski M, Rief W (2013). The placebo reponse in medicine: minimize, maximize or personalize. Nat Rev Drug Discov. 12: 191-204.
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