The effect of exercise interventions on inflammatory markers in major depressive disorder: protocol for a systematic review and meta-analysis

Diana Grunberg; Jason A Martin; John F Cryan; Ken D O'Halloran; Eric Kelleher; Timothy G Dinan; Gerard Clarke

doi:10.12688/hrbopenres.13240.3

The effect of exercise interventions on inflammatory markers in major depressive disorder: protocol for a systematic review and meta-analysis

HRB Open Res. 2022 Jun 15:4:42. doi: 10.12688/hrbopenres.13240.3. eCollection 2021.

Authors

Diana Grunberg^#¹, Jason A Martin^#^{2

3

4

5}, John F Cryan^{3

6}, Ken D O'Halloran⁷, Eric Kelleher⁸, Timothy G Dinan^{2

3}, Gerard Clarke^{2

3

9}

Affiliations

¹ School of Medicine Brookfield Health Sciences Complex, University College Cork, Cork, Cork, T12 YT20, Ireland.
² Department of Psychiatry and Neurobehavioural Science, University College Cork,, Cork, Cork, T12 YT20, Ireland.
³ APC Microbiome Ireland, University College Cork, Cork, Cork, T12 YT20, Ireland.
⁴ German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
⁵ Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of Tübingen, Tübingen, Germany.
⁶ Department of Anatomy and Neuroscience, University College Cork, Cork, Cork, T12 YT20, Ireland.
⁷ Department of Physiology, University College Cork, Cork, Cork, T12 YT20, Ireland.
⁸ Department of Psychiatry and Neurobehavioural Science, Cork University Hospital and Mercy University Hospital, Cork, Cork, T12 YT20, Ireland.
⁹ INFANT Research Centre, University College Cork, Cork, Cork, T12 YT20, Ireland.

^# Contributed equally.

Abstract

Background: Depression currently affects 4.4% of the global population, and 93.7% of this population suffer from major depressive disorder (MDD) according to 2017 statistics. MDD patients are more likely to suffer from co-morbidities such as cardiovascular disease and high body mass index (BMI), thus contributing to its large cost to society. Throughout the literature, there are known links between inflammation and MDD. Interestingly, while exercise is considered a promising intervention for MDD, the mechanism(s) of action remain unclear, thereby preventing the creation of optimal, cost-saving, exercise "prescriptions" for those with MDD. Thus, the aim of this review and meta-analysis is to summarize and analyse the current literature exploring how quantified exercise interventions modulate inflammatory molecules in MDD patients. Methods: Electronic databases (APA PsycINFO, and PubMed/MEDLINE (EBSCO interface), EMBASE) will be searched using a detailed search strategy comprised of three search term themes: exercise, depression/MDD, and inflammation/inflammatory molecules. Only quantified exercise interventions performed in adult humans with MDD validated via a recognized diagnostic criterion will be included. Studies should also include a MDD control group and explore changes in inflammatory molecules. Examples of these molecules include: C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 beta (IL-1b), tumour necrosis factor-alpha (TNF-a), homocysteine, d-dimer and myeloperoxidase (MPO). After eligible studies are identified, standardized data extraction will be employed and the risk of bias in each study will be appraised using the Cochrane handbook checklists. In the event of two or more homogenous studies exploring exercise effects over a similar time period, raw mean differences or standardized mean differences will be pooled using random effects analysis. This systematic review and meta-analysis will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Dissemination: This systematic review and meta-analysis will be disseminated in peer-reviewed journals. PROSPERO registration: CRD42020186006 (31/08/2020).

Keywords: major depressive disorder; MDD; depression; inflammatory biomarkers; inflammatory cytokines; exercise;.

Grants and funding

APC Microbiome Ireland is funded by Science Foundation Ireland (SFI), through the Irish Government’s National Development Plan (Grant no. 12/RC/2273 P2). The authors (GC, TGD, JFC, KOH and JM) are also funded by Health Research Board (HRB) (Grant no. ILP-POR-2017-013). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.