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Exploring interleukin-6, lipopolysaccharide-binding protein and brain-derived neurotrophic factor following 12 weeks of adjunctive minocycline treatment for depression

Published online by Cambridge University Press:  23 December 2021

Kyoko Hasebe Open the ORCID record for Kyoko Hasebe [Opens in a new window] ,
Mohammadreza Mohebbi ,
Laura Gray ,
Adam J. Walker ,
Chiara C. Bortolasci ,
Alyna Turner ,
Michael Berk Open the ORCID record for Michael Berk [Opens in a new window] ,
Ken Walder ,
Michael Maes Open the ORCID record for Michael Maes [Opens in a new window]  and
Buranee Kanchanatawan
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Kyoko Hasebe
Affiliation:
IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Vic, Australia School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia
Mohammadreza Mohebbi
Affiliation:
Biostatistics Unit, Faculty of Health, Deakin University, Geelong, Vic, Australia
Laura Gray
Affiliation:
IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Vic, Australia Centre for Medical and Molecular Research, School of Medicine, Deakin University, Geelong, Vic, Australia Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Vic, Australia
Adam J. Walker
Affiliation:
IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Vic, Australia
Chiara C. Bortolasci
Affiliation:
IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Vic, Australia Centre for Medical and Molecular Research, School of Medicine, Deakin University, Geelong, Vic, Australia
Alyna Turner
Affiliation:
IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Vic, Australia School of Medicine and Public Health, Faculty of Health, The University of Newcastle, Callaghan, NSW, Australia
Michael Berk
Affiliation:
IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Vic, Australia Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Vic, Australia Department of Psychiatry, Royal Melbourne Hospital, University of Melbourne, Parkville, Vic, Australia Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Vic, Australia Centre of Youth Mental Health, The University of Melbourne, Parkville, Vic, Australia
Ken Walder
Affiliation:
IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Vic, Australia Centre for Medical and Molecular Research, School of Medicine, Deakin University, Geelong, Vic, Australia
Michael Maes
Affiliation:
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Buranee Kanchanatawan
Affiliation:
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Melanie M. Ashton
Affiliation:
IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Vic, Australia
Lesley Berk
Affiliation:
IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Vic, Australia Melbourne School of Population and Global Health, University of Melbourne, Carlton, Vic, Australia
Chee H. Ng
Affiliation:
Department of Psychiatry, University of Melbourne, The Melbourne Clinic, Richmond, Vic, Australia
Gin S. Malhi
Affiliation:
Faculty of Medicine and Health, Northern Clinical School, Department of Psychiatry, The University of Sydney, Sydney, NSW, Australia Academic Department of Psychiatry, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, St Leonards, NSW, Australia
Ajeet B. Singh
Affiliation:
IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Vic, Australia
Olivia M. Dean*
Affiliation:
IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Vic, Australia Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Vic, Australia
*
Author for correspondence: Olivia M. Dean, Email: [email protected]
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Abstract

This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.

Keywords

brain-derived neurotrophic factorinterleukin-6lipopolysaccharide-binding proteinmajor depressive disorderminocycline
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 34 , Issue 4 , August 2022 , pp. 220 - 227
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Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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