Protocol for systematic review and meta-analysis of the evidence linking hippocampal neurogenesis to the effects of antidepressants on mood and behaviour.

Objective: Studies in rodents associated the deficits of adult hippocampal neurogenesis with behavioural anomalies which may be reversed by antidepressant treatments. A previous systematic review (SR) and meta-analysis (MA) indicated a hierarchy within the proneurogenic effects of different antidepressants in naive rodents. The present review aims to evaluate a more comprehensive sample of studies investigating the links between the effects of different antidepressants and adult hippocampal neurogenesis.

Search strategy screening annotation data management: Protocols were planned following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Searches in Embase, Medline, Scopus and Web of Science followed by screening with inclusion/exclusion criteria will provide relevant publications. First SR will summarise the effects of antidepressants on adult hippocampal neurogenesis on different laboratory rodents. Second SR will summarise the correlations between neurogenic and behavioural effects of antidepressants while the third will focus on cause-effect relationships between them. If feasible, data will be analysed by pairwise or network random-effect or multivariate MA to determine the direction, magnitude, significance and heterogeneity (I²) of the estimated effect sizes on global or subgroup levels. Funnel plotting, Egger regression, 'trim and fill' will be used to estimate the risk of publication bias. Quality assessment of the included publications will be performed by applying adapted CAMARADES, Syrcles' risk of bias or CINeMA tools.

Reporting: Find a preliminary version of this protocol at the Open Science Framework (https://osf.io/gmsvd/). Data extraction has already started. Results shall be published in a peer-reviewed journal. Due to the continuous production in the field, the implementation of a 'living SR' is intended.