Expression of Toll-Like Receptors in peripheral blood mononuclear cells and response to cognitive-behavioral therapy in major depressive disorder |
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| Affiliation: | 1. Department of Cognitive Science, Budapest University of Technology and Economics, Budapest, Hungary;2. Nyírő Gyula Hospital – National Institute of Psychiatry and Addictions, Budapest, Hungary;3. Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary;4. Bács-Kiskun County Hospital, Psychiatry Center, Kecskemét, Hungary;1. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada;2. Department of Psychiatry, University of Toronto, Ontario, Canada;3. Department of Psychiatry, Samsung Seoul Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea;4. Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea;5. Departments of Preventive Medicine, School of Medicine, Kyung Hee University, Seoul, South Korea;6. Cancer Registration and Statistic Branch, National Cancer Control Institute, National Cancer Center, Goyang, South Korea;7. Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), Brazil;8. Department of Medicine, Schulich School of Medicine and Dentistry, University of Western London, Ontario, Canada;9. Institute of Medical Science, University of Tornoto, Toronto, Ontario, Canada;10. Department of Pharmacology, University of Toronto, Ontario, Canada;1. Department of Health Sciences and Centre for Health Economics, University of York, York, UK;2. Leeds Community Healthcare NHS Trust, Leeds, UK;3. Centre for Clinical Practice, National Institute for Health and Care Excellence, Manchester, UK;4. Hull York Medical School and Department of Health Sciences, University of York, York, United Kingdom;5. South West Yorkshire Partnership NHS Foundation Trust and University of Huddersfield, Huddersfield, UK;6. Department of Psychology, University of Trier, Trier, Germany;7. Clinical Psychology Unit, Department of Psychology, University of Sheffield, Sheffield, UK;1. Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;2. Graduate Institute of Clinical Medical Sciences, Chang Gung University, College of Medicine, Kaohsiung, Taiwan;3. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan;1. The Royal’s Institute of Mental Health Research, affiliated with the University of Ottawa, Ottawa, Ontario, Canada;2. Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada;3. Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada;4. Department of Biology, Carleton University, Ottawa, Ontario, Canada;1. Department of Clinical Psychological Science, Faculty of Psychology and Neuroscience, Maastricht University, the Netherlands;2. Department of Clinical Psychology, Faculty of Social and Behavioural Sciences, University of Amsterdam, the Netherlands;3. Owner Therapy, Training, Coaching and Mediation Practice Amsterdam, the Netherlands;4. Department of Psychiatry and Psychology, Maastricht University Medical Center, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, the Netherlands |
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| Abstract: | In recent years, increased attention has been paid to the inflammatory mechanisms of major depressive disorder (MDD). The aim of the present study was to investigate pro-inflammatory pathways related to the “leaky gut” hypothesis of MDD, which is based on the putative intestinal translocation of Gram-negative bacteria and a subsequent abnormal immune response mediated by the Toll-Like Receptor-4 (TLR-4) pathway. 50 patients with first-episode MDD and 30 healthy control subjects participated in the study. Real-time quantitative PCR was used to measure TLR-4 and TLR-2 RNA from peripheral mononuclear blood cells, as well as the expression of NF-κβ, a key transcription factor of the pro-inflammatory response. TLR-4 protein expression was determined by using flow cytometry. TLR-2 served as a control molecule. Low-grade inflammation was characterized by the measurement of interleukin-6 (IL-6) and C-reactive protein (CRP). Bacterial translocation was investigated by the measurement of the 16S rRNA subunit (16S rDNA) of intestinal microbiota in the blood plasma of the participants. We performed these analyses before (t1) and after (t2) cognitive-behavioral therapy (CBT) in MDD. The healthy control subjects were also assessed two times. We found significantly elevated expressions of all three markers (TLR-4 RNA and protein, NF-κβ RNA) and 16S rDNA in MDD at t1 relative to healthy control subjects. These markers showed a significant decrease during CBT (t1 > t2 in MDD). We observed no between-group differences and changes in the case of TLR-2. Greater reduction of pro-inflammatory markers during CBT was associated with more pronounced clinical improvement. IL-6 and CRP displayed a moderately elevated level in MDD and did not change during CBT. In conclusion, TLR-4 signaling is up-regulated in newly diagnosed patients with MDD, which may be related to bacterial translocation or to the presence of various damage-associated molecular patterns. Clinical improvement during psychotherapy is associated with decreased expression of pro-inflammatory markers. |
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| Keywords: | Major depressive disorder Inflammation Toll-Like Receptors Cognitive-behavioral therapy |
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