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Olfactory Dysfunction And Screening For Depression: A QOL Study

Olfactory Dysfunction And Screening For Depression: A QOL Study

Smell loss is a disease that severely impacts a person’s quality of life (QoL). Recently, the number of smell loss cases has surged making it one of the most critical public health concerns during the last few years. There are many different causes of olfactory dysfunction (OD). The most common are head traumas, upper respiratory tract infections, or exposure to toxins. Smell loss can be present in people with neurodegenerative and sinonasal diseases, such as chronic rhinosinusitis (CRS).

Despite smell loss being associated with depressive disorders (such as major depressive disorder or MDD), the links between olfactory-related QoL and risk for depressive symptoms are only evaluated in CRS and OD patients. Experts believe that knowing the link between MDD and smell loss is the key to understanding and improving the clinical interpretability of commonly used patient-reported outcome measures (PROMs).

The Study

Since more and more patients with smell loss or olfactory dysfunction (OD) report symptoms of depression, this study aims to determine how clinical characteristics and olfactory-related quality of life (QoL) measures are associated with the likelihood of major depressive disorders (MDDs).


This was a retrospective study carried out at the out-patient clinic for Smell and Taste Disorders of the Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna. The study protocol was approved by the Ethical Scientific Committee of the Medical University of Vienna (1984/2021). All subjects visited the outpatient clinic between April 2019 and October 2021 with the main complaint of subjective olfactory dysfunction. A total of 192 OD patients were included. 

All patients underwent thorough history taking, standardized ear, nose, and throat examination (including nasal endoscopy) completed validated patient-reported outcome measures (PROMs), and received comprehensive olfactory testing. Patients were asked to report a history of diabetes or hypertension. Smoking history was stratified as a nonsmoker, former smoker, and current smoker. The suspected underlying etiology of smell loss was diagnosed based on the current European Position paper on olfactory dysfunction.  

The likelihood of MDD was assessed using the Patients Health Questionnaire-2 (PHQ-2). Demographics and disease-specific variables (etiology and duration of OD) were collected. Univariate and multivariable analyses were used to associate disease-specific variables and the QOD with the outcome of the PHQ-2. Additionally, the predictive ability of the QOD-NS to predict depressive symptoms was calculated.

Olfactory testing

Quantitative olfactory performance was assessed based on the Sniffin’ Sticks test which measures olfactory function based on three subdimensions: odor threshold (T), discrimination (D), and identification (I). The researchers classified patients using published normative datasets and defined olfactory performance as follows: (i) normosmia (TDI≥30.75), (ii) hyposmia(TDI < 30.75 and >16), and (iii) anosmia (TDI≤16).

Statistical analysis

The researchers performed statistical analysis and data visualization using GraphPad Prism 9.1.0. Continuous data are presented as mean standard deviation, whereas categorical data are presented as absolute numbers (%). 

They used univariate and multivariable linear regression analysis to evaluate the associations between clinical characteristics: age (in years), gender (reference: female), smoking status (nonsmoker compared with a former and current smoker, reference: nonsmoker), duration of smell loss (in months), olfactory function (TDI score), the reason for smell loss (post-infectious, post-traumatic, idiopathic, sinonasal, and viral illness-related smell loss, reference: post-infectious OD), and health-related PROMs (QOD-NS and QOD-PS) with the outcome of the PHQ-2 score. 

To evaluate the diagnostic accuracy of the QOD-NS score in identifying patients who are at a higher risk for MDD (as represented by a PHQ-2 scor-e≥219), we computed receiver operating characteristics(ROC) curves and the area under the ROC curves (AUC). The level of significance was set at 0.05.


Patient demographics included 192 patients with subjective smell loss (62.5% female, mean ageSD=47.818.8 years). The biggest group of patients was classified as viral illness-related OD (n=53), followed by idiopathic (n=52), post-infectious (n=40), posttraumatic (n=18), sinonasal(n=13), iatrogenic (n=6), and toxic (n=4) smell loss.

The researchers also included three cases of neurodegenerative and three cases of congenital OD. The mean duration of smell loss was 32.442.5 months, excluding our congenital cases(Table I). Quantitative testing of olfactory function using the the Sniffin’ Sticks TDI test revealed that most patients were hyposmic (n=106), followed by anosmic (n=66), and normosmic patients (n=20). 

In univariate analysis, viral illness-related smell loss, the QOD-NS, and the QOD-PS were significantly associated with the PHQ-2. In multivariable analyses adjusting for QoL measures, the QOD-NS (ß = 0.532, p < 0.001) and sinonasal OD (compared with post-infectious OD) were significantly associated with the PHQ-2 (ß = 0.146, p = 0.047). When omitting QoL measures from multivariable analyses, only viral illness-related OD (compared with post-infectious OD) was significantly associated with the PHQ-2 (ß = 0.287, p = 0.009). A QOD-NS score > 20.5 had 70.13% sensitivity and 76.32% specificity for detecting symptoms of depression.


The findings suggest that viral illnesses related OD might be associated with a higher likelihood of MDD. Furthermore, the study showed that the QOD-NS score might be helpful in predicting symptoms of depression in OD patients. This study adds to the current literature on clinical olfactory research in two important ways. First, the researchers found associations of QoL measures with the likelihood of MDD, suggesting that a lower olfactory-related QoL might also impact the likelihood of depressive symptoms in OD patients. Second, it provides the first evidence that the QOD-NS can also be used to screen for smell loss patients at a higher risk for MDD.

The results may also have potentially important implications for evaluating patients with smell loss. The relationship between QoL and depression is increasingly found to be co-dependent, our results provide a means for assessing depression symptoms in OD patients querying for MDD in those with lower olfactory-related QoL. 

This might also require the routine use of validated QoL measures during the clinical assessment of patients with smell loss. Previous studies in patients with CRS have shown that those with comorbid depression might not achieve equivalent long-term results after treatment as those without MDD. It is possible that patients with smell loss and comorbid depression might also recover less than those without MDD. Therefore, future studies should investigate the impact of comorbid depression on treatment outcomes in OD patients undergoing factory training.

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