Patients with self-reported impaired smell had a higher likelihood of depression across population-based studies, whereas objectively measured smell impairment showed a weaker association that was largely limited to specific subgroups.
In a systematic review and meta-analysis, investigators included 23 population-based cross-sectional and longitudinal studies representing 17 independent cohorts with 187,056 patients. They searched PubMed, Embase, EBSCOhost, and Web of Science from database inception through July 11, 2024. Following the exclusion of overlapping cohorts, seven independent studies were included in the primary analysis of subjective olfactory impairment and 11 in the analysis of objective olfactory impairment. The investigators performed separate random-effects meta-analyses and prespecified subgroup analyses by age, study design, depression assessment, olfactory impairment severity, and risk of bias.
The patients with self-reported olfactory impairment had about 1.6 times the odds of depression compared with those without self-reported impairment. The association remained consistent in studies with a low risk of bias and across younger and older patient populations. It also was stronger when depression was assessed by patient report compared with by objective measures.
Although objectively measured olfactory impairment was linked to depression in the primary analysis, the association was weaker than that observed for self-reported impairment and was attenuated following adjustment for publication bias. In subgroup analyses, objectively measured olfactory impairment remained associated with depression among patients aged 65 years or older and those with anosmia. The investigators found no association in the longitudinal studies evaluating objectively measured olfactory impairment.
The investigators noted that self-reported olfactory impairment showed a consistent association across the studies, whereas objectively measured impairment demonstrated a more restricted pattern that varied by age and severity.
The study had several limitations. Most included studies were cross-sectional, limiting conclusions about temporal relationships. Few longitudinal studies were available, and none prospectively evaluated subjective olfactory impairment. Most studies assessed odor identification rather than other domains of olfactory function, and depression was usually measured using psychometric instruments rather than clinical diagnoses. The investigators also noted that underlying neurodegenerative disease and other age-related conditions may have contributed to the observed associations.
The findings suggested that self-reported olfactory impairment may be more consistently associated with depression than objectively measured impairment, although the available evidence does not establish causality or support changes in clinical practice.
“Overall, our findings suggest that smell loss, particularly when subjectively reported, may co-occur with depression symptoms and reflect overlapping perceptual and affective processes; however, current evidence is not sufficient to support clinical recommendations,” wrote lead study author Henry Bode, MD, of the Aging Research Center in the Department of Neurobiology at the Care Sciences and Society at the Karolinska Institute in Sweden, and colleagues.
Full disclosures of the study authors can be found in the study.