Contents
Research into the relationship between sensory sensitivity and mental illness, particularly depression, often focuses on changes in vision or hearing rather than on smell. Depression is one of the most common psychiatric diagnoses, with approximately one in five women and one in eight men experiencing a major depressive episode during their lifetime. Depression has been well studied, and the genetic, epigenetic, neuroanatomical, neurochemical, neuroendocrinological and neuroimmunological changes that occur against its background have been described, but the exact etiology of depression has not been fully investigated. The proposed models are based on two main factors, namely pharmacological dysfunctions and stress effects. Thus, through connections between the olfactory receptor and areas of the brain involved in regulating mood and emotion (namely, the limbic system and the prefrontal area), it is possible to trace the interaction between the sense of smell and depression. You can find a large number of publications devoted to the interaction between the sense of smell and depression. They put forward several hypotheses that require further research. First, olfactory dysfunction observed in depression may be useful for diagnosing and better understanding the mechanisms of depression. Published data demonstrate decreased sense of smell in major depression, but not in bipolar or seasonal depression. Secondly, it has been experimentally proven that olfactory deficits themselves can cause depressive symptoms. Third, evidence has accumulated that scents can have a positive effect on depressed mood, and scent-based treatments may be a promising way to treat emotional disorders.
Decreased sense of smell is very common in older people, and the problem can be identified in >50% of people aged 65 to 80 years and in 62-80% of people over 80 years of age. Olfactory impairment significantly impacts physical well-being, quality of life, nutritional status, and daily safety and is statistically associated with increased mortality. Multiple factors contribute to age-related decline in olfactory sensitivity, including nasal engorgement, environmental damage to the olfactory epithelium, decreased mucosal enzyme metabolism, loss of odorant receptor cell sensitivity, and changes in neurotransmitter and neuromodulator systems. In addition, structural and functional abnormalities of the olfactory epithelium, olfactory bulb, central olfactory cortex and the main olfactory pathways, in which the expression of aberrant proteins in the neurons of these areas is detected, during aging, as well as against the background of neurodegenerative diseases, can lead to impairment of olfactory sensitivity of varying degrees expressiveness. Impaired odor recognition occurs in parallel with a decrease in cognitive abilities and memory impairment. Hyposmia is thought to be an early and important warning of the onset of neurodegenerative disorders such as Parkinson’s disease or Alzheimer’s disease, and in mild cognitive impairment, olfactory changes may herald progression to dementia. Further research is needed on the potential role of olfactory dysfunction for early diagnosis and prognostic assessment of neurodegenerative diseases.
Drug-induced disorders of smell
Many medications can affect taste and smell, and this occurs much more frequently than was previously thought. A pharmaceutical substance typically affects sensory function at the molecular level, causing two major changes—loss of sensory acuity (i.e., hypogeusia and hyposmia) and/or disturbance (distortion) of sensation (i.e., dysgeusia and dysosmia). Such changes may worsen your appetite, cause changes in lifestyle, and require you to stop taking the drug. The mechanism of drug-induced hyposmia is the inactivation of the olfactory receptor molecule, as a result of which a whole cascade of molecular reactions inside the cell is distorted. The first stage of interaction of a drug with the olfactory receptor consists of binding to the Gs receptor protein on the cell membrane, which leads to inhibition of the energetic inositol triphosphate pathway, through which olfactory epithelial cells transmit the signal. Blocking of signal transmission along the membrane of olfactory neurons occurs due to inactivation of the transmembrane transport of Ca ++ and Na ++ ions. Olfactory distortions can also occur when exposed to drugs that cause persistence or stimulation of abnormal receptor activity (i.e., there is a lack of normal inactivation of the receptor after the transmission of the olfactory signal). The mechanism for the implementation of dysosmia is the interaction with various kinase receptors that affect signal limitation, interaction with the Gi protein, leading to disruption of its function; influence on the activity of cytochrome P450, which is involved in the deactivation of molecules, as well as other effects that have not yet been sufficiently studied. Once drug therapy is stopped, the impaired sense of taste and smell usually recovers completely, but sometimes the effects persist and require special therapy to relieve symptoms. Treatment primarily requires restoring normal sensory receptor function. Treatments that restore sensation include zinc, theophylline, magnesium, and fluoride. Treatments that suppress sensory distortion require either reactivation of the inhibited receptor, inactivation of the stimulus acting on the receptor, or correction of other events leading to olfactory pathology.
Conclusions
The cause of loss of smell can be difficult to determine in many cases, but predicting the prognosis and correct selection of therapy is important. Diagnosis requires a thorough history, appropriate chemosensory tests, and examination, which should include endoscopic examination of the nasal cavity. A diagnostic test with the prescription of systemic steroid drugs can serve to distinguish the level of damage that caused olfactory impairment.
Diagnosis of olfactory disorders
- Chemosensory testing
Chemosensory psychophysical testing is indicated not only for those patients who complain of a decrease or distortion of the sense of smell, but also as part of a complex diagnosis at an appointment with a neurologist or otolaryngologist. The fact is that the patient may not be aware of olfactory distortions, especially if they affect the receptors of only one half of the nose. Chemosensory testing can provide the doctor with very valuable information about the state of the olfactory analyzer, and therefore the nervous system as a whole.
Testing includes several stages and is carried out using a set of odorous substances in different dilutions. The tests begin with the lowest odor concentration, the procedure usually includes diagnostics of threshold odor identification and odor recognition. Tests are carried out separately for the right and left nostrils and are scored. The results of all subtests are summed up and an overall indicator is displayed – the TDI score. Different tests contain different rating scales, but they all differentiate normal sense of smell from hyposmia and functional anosmia. Testing takes about 30 minutes.
- Questionnaire
A special questionnaire designed to assess the subjective degree of loss of smell and associated difficulties (cooking, eating, body hygiene, appetite, problems in daily life), as well as ways to manage this deficiency and the degree of reduction in quality of life, was proposed by the Austrian specialists in collaboration with Arbeitsgemeinschaft Olfaktologie/ Gustologie der Deutschen Gesellschaft für Hals-Nasen-Ohren Heilkunde, Kopf und Halschirurgie, from the German city of Dresden. The questionnaire they proposed contains mainly questions regarding olfactory sensitivity and quality of life (QoL). Both affirmative and symptom-based questions are used. This form must be completed before the olfactory tests begin. In the course of research conducted by this group of scientists, it was shown that chemosensory testing reveals the characteristics of the disturbance of smell, but does not tell the neurologist anything about the cause of the disturbance. That is, the test results did not differ significantly in patients from the group suffering from uremia, neurodegenerative diseases, patients with post-infectious, post-traumatic and other hypo- and anosmia. Significantly more often, a decrease and loss of smell was recorded in women, but this did not apply to the loss of smell associated with injury – men predominated in this group.
Difficulties in everyday life
In surveys conducted by researchers in Austria and Germany, almost all patients reported difficulties in daily life caused by an impaired sense of smell. The majority primarily complained of difficulty preparing food (73%), altered mood (68%), decreased appetite (56%), eating spoiled food (50%), poor perception of one’s own body odor (41%), and late reactions to burning food (30%) and unspecified problems at work (8%). There was a correlation between complaints of difficulties in daily life and age and gender: the youngest patients had the highest degree of difficulties; women experienced more problems than men. The duration of the disease, just like the cause of the disturbance of smell, did not have a significant effect on the severity of complaints. Surprisingly, patients with anosmia had fewer complaints than patients with hyposmia, but there was no significant difference between anosmia and hyposmia in quality of life scores. Patients reporting a depressed mood due to loss of smell had significantly more complaints, as well as a greater decrease in quality of life, than patients with a preserved emotional background.
Conclusions: It appears that the various components of a comprehensive olfactory test do not contribute to identifying the causes of loss or decline in the sense of smell. The nature of anosmia or hyposmia does not have a significant impact on the results of determining the threshold values of odors, their recognition and identification.
However, scientists believe that for a final judgment on these issues, further studies are needed on larger populations of patients of different ages with hypo- and anosmia of various origins and duration.
Since patients with hypo- and anosmia may not report impaired olfactory abilities during a simple survey, chemosensory tests are necessary. Published data reported that 42% of 203 patients were unable to correctly assess smell loss on a 4-point scale (normal, impaired but not absent, completely absent, hypersensitivity to odors) (8). These data confirm that a simple questionnaire cannot serve as a reliable way to diagnose olfactory disorders, even at a preliminary stage.
It is known that the likelihood of complete anosmia increases as the duration of loss of smell increases. These findings are consistent with the view that late recovery from long-standing anosmia is relatively rare (12,13). Older patients are more likely to lose their sense of smell after simple acute respiratory infections; in this age group, the likelihood of recovery also decreases with increasing duration of loss of smell. So, patients over 65 years of age are most susceptible to developing odor perception disorders after respiratory infections, flu or inflammation of the sinuses, while all other causes of hypo- and anosmia are almost equally distributed across different age groups.
Instrumental diagnostic methods
- Magnetic resonance imaging
The study of all parts of the olfactory analyzer using medical imaging methods is rarely used, despite the fact that it can provide valuable information. We were able to find only one study containing a systematic analysis of brain MRI results in patients with anosmia.
The patient group consisted of 36 people with long-term olfactory impairment. Study results differed depending on the cause of hypo- and anosmia. Thus, in 32 of 36 (89%) patients with post-traumatic anosmia, tomography revealed encephalomalacia in the area of the olfactory bulb and olfactory tract, in 22 patients (61%) – changes in the subfrontal lobe, in 11 of 36 examined (31%) – encephalomalacia affected temporal lobe. In many patients, encephalomalacia affected the olfactory bulb, tract, and frontal lobe simultaneously.
Conclusion: MRI examinations of patients with hypo- and anosmia often reveal damage to the olfactory bulb and area of the olfactory tract, which correlates with a lack of odor recognition. In many patients, encephalomalacia of the olfactory bulb, olfactory tract, and frontal lobe coexists. To judge the relationship between the degree of hyposmia and the severity of encephalomalacia, additional research is necessary.
Non-drug treatment of smell disorders
The first report on the effect of olfactory training on the severity and duration of olfactory disorders was published by the group of the Austrian doctor Hummel in 2009. The duration of this training lasted 3 months. Repeated experiments by other research groups have confirmed that short-term, regular exposure to odors can lead to an increase in the density of neural connections and an increase in the expression of olfactory receptors. However, the results of improvement in olfactory function were not as high as reported by Hummel’s group. Therefore, modifications to the anosmia treatment protocol are currently being studied to improve outcomes. It is well known that olfactory receptors and granule cells of the olfactory bulb can regenerate. Thus, the olfactory system is likely to be able to improve or restore its efficiency through daily exposure to odors.
It is noteworthy that the central neurons of the olfactory system are also capable of regenerating, which affects the ability to rehabilitate olfactory function after a viral infection or injury. Increasing the duration of exposure to a wide range of odors improves the survival of young olfactory neurons and transiently improves odor memory, which explains the role of adult neurogenesis in the formation and maintenance of olfactory memory. Mouret et al found that olfactory training based on repetitive odor stimulation promoted the survival of young neurons, providing evidence that olfactory training is capable of altering olfactory bulb neurogenesis. The training has proven to be particularly beneficial for those patients whose olfactory dysfunction is due to upper respiratory infections.