Adjunctive minocycline for major depressive disorder: A sub-study exploring peripheral immune-inflammatory markers and associated treatment response

Adam J. Walker; Mohammadreza Mohebbi; Michael Maes; Michael Berk; Ken Walder; Chiara C. Bortolasci; Zoe SJ. Liu; Chee H. Ng; Melanie M. Ashton; Lesley Berk; Ajeet B. Singh; Gin S. Malhi; Olivia M. Dean

Brain, Behavior, & Immunity - Health (Feb 2023)

Adjunctive minocycline for major depressive disorder: A sub-study exploring peripheral immune-inflammatory markers and associated treatment response

Adam J. Walker,
Mohammadreza Mohebbi,
Michael Maes,
Michael Berk,
Ken Walder,
Chiara C. Bortolasci,
Zoe SJ. Liu,
Chee H. Ng,
Melanie M. Ashton,
Lesley Berk,
Ajeet B. Singh,
Gin S. Malhi,
Olivia M. Dean

Affiliations

Adam J. Walker: Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia; Corresponding author. Deakin University, IMPACT, School of Medicine, Barwon Health, HERB B Level 3, P.O. Box 281, Geelong, 3220, Australia.
Mohammadreza Mohebbi: Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia; Biostatistics Unit, Faculty of Health, Deakin University, Geelong, Australia
Michael Maes: Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia; Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Psychiatry, Medical University of Plodiv, Plodiv, Bulgaria
Michael Berk: Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia; Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia; Department of Psychiatry, University of Melbourne, Parkville, Australia; Orygen, National Centre of Excellence in Youth Mental Health, Parkville, Australia
Ken Walder: Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia
Chiara C. Bortolasci: Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia
Zoe SJ. Liu: Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia
Chee H. Ng: The Melbourne Clinic, Department of Psychiatry, University of Melbourne, Richmond, Australia
Melanie M. Ashton: Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia
Lesley Berk: Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia
Ajeet B. Singh: Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia
Gin S. Malhi: CADE Clinic and Department of Psychiatry, Royal North Shore Hospital, The University of Sydney, Sydney, Australia
Olivia M. Dean: Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia; Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia

Journal volume & issue: Vol. 27
p. 100581

Abstract

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Background: Adjunctive minocycline shows promise in treating affective and psychotic disorders; however, the therapeutic mechanism remains unclear. Identifying relevant biomarkers may enhance the efficacy of novel adjunctive treatment candidates. We thus investigated the peripheral immune-inflammatory profile in a randomized controlled trial (RCT) of minocycline in major depressive disorder (MDD). Methods: This sub-study investigated serum samples from a RCT evaluating minocycline (200 mg/day, 12 weeks) in addition to treatment as usual for MDD (ACTRN12612000283875). Of the original sample (N = 71), serum assays were conducted in 47 participants (placebo n = 24; minocycline n = 23) targeting an array of 46 immune-inflammatory analytes including cytokines, chemokines, and acute-phase reactants. General estimating equations (GEE) were used to assess whether analyte concentration at baseline (effect modification) and change in analytes (change association) influenced change in Montgomery-Åsberg Depression Rating Scale (MADRS) score over time. The Benjamini–Hochberg approach was applied when adjusting for false discovery rates (FDR). Results: GEE models revealed several interaction effects. After adjusting for FDR several change association-models survived correction. However, no such models remained significant for effect modification. Three-way group × time × marker interactions were significant for complement C3 (B = −10.46, 95%CI [-16.832, −4.095], q = 0.019) and IL-1Ra (B = −9.008, 95%CI [-15.26, −2.751], q = 0.036). Two-way group × biomarker interactions were significant for ICAM-1/CD54 (B = −0.387, 95%CI [-0.513, −0.26], q < 0.001) and IL-8/CXCL8 (B = −4.586, 95%CI [-7.698, −1.475], q = 0.036) indicating that increases in the serum concentration of these analytes were associated with an improvement in MADRS scores in the minocycline group (compared with placebo). Conclusions: Change in complement C3, IL-1Ra, IL-8/CXCL8, and ICAM-1 may be associated with greater change in depressive scores following adjunctive minocycline treatment in MDD. Further investigations are needed to assess the utility of these biomarkers.

Published in Brain, Behavior, & Immunity - Health

ISSN: 2666-3546 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/brain-behavior-and-immunity-health

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