Olfaction Under the Shadow of Depression: Objective Evidence from a Comprehensive Meta-Analysis

Abstract

By 2021, twenty-one million people in the US suffered at least one major depressive episode in their lives, while, in 2019, the WHO estimated that 280 million people were living with depression. Recent research may indicate that olfactory dysfunction plays a role in the pathophysiology of depression due to shared neural pathways involving the limbic system. This meta-analysis aims to systematically review the relationship between olfactory dysfunction and depression by analyzing data obtained by objective tests from studies up to January 6, 2024. The overall analysis, including 13 studies relatively homogenous studies without publication bias, showed a slight, nonsignificant decline of olfactory perception in patients with depression vs. controls standardized mean difference (SMD) = −0.137, 95% CI: −0.319 to 0.044; p = 0.137). However, sensitivity analyses using moderators such as gender, age, and type of olfactory test revealed variability in results, with the Sniffin’ Sticks test showing a significant association (SMD = −0.233, 95% CI: −0.454 to −0.012; p = 0.039). These findings suggest that olfactory dysfunction may be associated with depression, particularly when measured with the Sniffin Sticks test. Further research into standardized methodologies is needed to clarify this relationship.