Boriana Atanasova

Olfaction: A potential cognitive marker of psychiatric disorders

Cognitive deficits are well documented in psychiatric disorders, particularly in schizophrenia and depression. Cognitive activity roots in perceptions. However, research on sensorial alterations in psychiatric conditions has mainly focused on visual or auditory processes and less on olfaction. Here, we examine data on olfactory deficits in psychiatric patients using a systematic review of recent publications. Schizophrenic patients are mainly characterized by no reliable change in odour sensitivity and by a deficit in odour identification, recognition and discrimination. Depressed patients principally exhibit a deficit in the hedonic aspects of this perception, even if, in some case, alterations in sensitivity or identification are also found. Changes in odour perception are also found in dementia and in some neurodegenerative disease, but in this case alterations concern all aspects of the sensorial experience (detection threshold, identification and recognition). Taken together, these data indicate that olfactory abnormalities might be a marker of psychiatric conditions, with a specific pattern for each disease.

The perception of odor objects in everyday life: a review on the processing of odor mixtures.

Smelling monomolecular odors hardly ever occurs in everyday life, and the daily functioning of the sense of smell relies primarily on the processing of complex mixtures of volatiles that are present in the environment (e.g., emanating from food or conspecifics). Such processing allows for the instantaneous recognition and categorization of smells and also for the discrimination of odors among others to extract relevant information and to adapt efficiently in different contexts. The neurophysiological mechanisms underpinning this highly efficient analysis of complex mixtures of odorants is beginning to be unraveled and support the idea that olfaction, as vision and audition, relies on odor-objects encoding. This configural processing of odor mixtures, which is empirically subject to important applications in our societies (e.g., the art of perfumers, flavorists, and wine makers), has been scientifically studied only during the last decades. This processing depends on many individual factors, among which are the developmental stage, lifestyle, physiological and mood state, and cognitive skills; this processing also presents striking similarities between species. The present review gathers the recent findings, as observed in animals, healthy subjects, and/or individuals with affective disorders, supporting the perception of complex odor stimuli as odor objects. It also discusses peripheral to central processing, and cognitive and behavioral significance. Finally, this review highlights that the study of odor mixtures is an original window allowing for the investigation of daily olfaction and emphasizes the need for knowledge about the underlying biological processes, which appear to be crucial for our representation and adaptation to the chemical environment.

State and trait olfactory markers of major depression.

Nowadays, depression is a major issue in public health. Because of the partial overlap between the brain structures involved in depression, olfaction and emotion, the study of olfactory function could be a relevant way to find specific cognitive markers of depression. This study aims at determining whether the olfactory impairments are state or trait markers of major depressive episode (MDE) through the study of the olfactory parameters involving the central olfactory pathway. In a pilot study, we evaluated prospectively 18 depressed patients during acute episodes of depression and 6 weeks after antidepressant treatment (escitalopram) against 54 healthy volunteers, matched by age, gender and smoking status. We investigated the participants’ abilities to identify odors (single odors and in binary mixture), to evaluate and discriminate the odors’ intensity, and determine the hedonic valence of odors. The results revealed an “olfactory anhedonia” expressed by decrease of hedonic score for high emotional odorant as potential state marker of MDE. Moreover, these patients experienced an “olfactory negative alliesthesia”, during the odor intensity evaluation, and failed to identify correctly two odorants with opposite valences in a binary iso-mixture, which constitute potential trait markers of the disease. This study provides preliminary evidence for olfactory impairments associated with MDE (state marker) that are persistent after the clinical improvement of depressive symptoms (trait marker). These results could be explained by the chronicity of depression and/or by the impact of therapeutic means used (antidepressant treatment). They need to be confirmed particularly the ones obtained in complex olfactory environment which corresponds a more objective daily life situation.

Olfactory anhedonia and negative olfactory alliesthesia in depressed patients

The present study aimed to investigate olfactory anhedonia and olfactory negative alliesthesia in depressed patients. Two odorants, one with pleasant (vanillin), and one with unpleasant (butyric acid) hedonic valence were evaluated by 30 depressed inpatients and 30 controls (healthy subjects, matched by age and gender). Participants explored the hedonic valence, intensity (discrimination) and perceived quality (identification) of 16 different stimuli (3 concentrations of odorants, their 9 combinations, and 1 control containing distilled water). The hedonic perception showed that patients perceived the unpleasant odorant as significantly more unpleasant than controls (olfactory negative alliesthesia). Concerning the intensity ratings, controls were able to discriminate between all concentrations of odorants, while patients discriminated between the different concentrations only for the unpleasant component and not for the vanillin (olfactory anhedonia). Regarding the identification task in an iso-intense unmixed odorants mixture, patients perceived significantly less the pleasant odorant than the unpleasant one (olfactory anhedonia), whereas controls perceived both odorants equally well. These results support the notion of an olfactory perception impairment in depression. Further studies are needed to replicate these findings and to confirm that such olfactory anhedonia or/and olfactory negative alliesthesia could be a state or a trait of depression.

Interactions of odorants with olfactory receptors and receptor neurons match the perceptual dynamics observed for woody and fruity odorant mixtures

The present study aimed to create a direct bridge between observations on peripheral and central responses to odorant mixtures and their components. Three experiments were performed using mixtures of fruity (isoamyl acetate; ISO) and woody (whiskey lactone; WL) odorants known to contribute to some of the major notes in Burgundy red wine. These experiments consisted of (i) calcium imaging of human embryonic kidney cells (HEK293T) transfected with olfactory receptors (ORs); (ii) single‐unit electrophysiological recordings from olfactory receptor neurons (ORNs) and analyses of electro‐olfactogram (EOG) responses in the rat nose in vivo; and (iii) psychophysical measurements of the perceived intensity of the mixtures as rated by human subjects. The calcium imaging and electrophysiological results revealed that ISO and WL can act simultaneously on single ORs or ORNs and confirm that receptor responses to mixtures are not the result of a simple sum of the effects of the individual mixture compounds. The addition of WL to ISO principally suppressed the ORN activation induced by ISO alone and was found to enhance this activation in a subset of cases. In the human studies, the addition of high concentrations of WL to ISO decreased the perceived intensity of the ISO. In contrast, the addition of low concentrations of WL enhanced the perceived intensity of the fruity note (ISO) in this mixture, as it enhanced EOG responses in ORNs. Thus, both OR and ORN responses to ISO + WL mixtures faithfully reflected perceptual response changes, so the odour mixture information is set up after the peripheral stage of the olfactory system.

Olfactory markers of depression and Alzheimer's disease.

Depression and Alzheimers disease are two common and closely intertwined diseases in the elderly. Bio-markers for their early diagnosis would be helpful for clinicians. The brain areas involved in depression, Alzheimers disease and in olfactory processing overlap, leading to suggestions that olfaction could constitute a potential marker of these diseases. Here, we review the literature in the relevant clinical and olfactory fields, and consider which olfactory measures and factors could serve as markers of these diseases. It has been reported repeatedly that there is an alteration of odor identification in Alzheimers disease but not in depression. These observations provide strong arguments that this olfactory marker may serve as a complementary tool for the early screening of patients. Odor threshold detection and odor hedonic aspect may constitute complementary markers of the efficacy of depression therapy. However, there are numerous contradictory data and innovative methods are required to investigate whether investigations of olfaction can usefully contribute to routine clinical practice.

Perceptive biases in major depressive episode.

Introduction Alterations in emotional processing occur during a major depressive episode (MDE), and olfaction and facial expressions have implications in emotional and social interactions. To gain a better understanding of these processes, we characterized the perceptive sensorial biases, potential links, and potential remission after antidepressant treatment of MDE. Methods We recruited 22 patients with acute MDE, both before and after three months of antidepressant treatment, and 41 healthy volunteers matched by age and smoking status. The participants underwent a clinical assessment (Mini International Neuropsychiatry Interview, Montgomery-Åsberg Depression Rating Scale, State-Trait Anxiety Inventory, Physical and Social Anhedonia scales, Pleasure-Displeasure Scale), an olfactory evaluation (hedonic aspect, familiarity and emotional impact of odors), and a computerized Facial Affect Recognition task. Results MDE was associated with an olfactory bias concerning hedonic and emotional aspects, including negative olfactory alliesthesia (unpleasant odorants perceived as more unpleasant), facial emotion expression recognition (happy facial expressions), and in part olfactory anhedonia (pleasant odorants perceived as less pleasant). In addition, the results revealed that these impairments represent state markers of MDE, suggesting that the patients recovered the same sensory processing as healthy subjects after antidepressant treatment. Discussion This study demonstrated that MDE is associated with negative biases toward olfactory perception and the recognition of facial emotional expressions. The link between these two sensory parameters suggests common underlying processes.

Long-term odor recognition memory in unipolar major depression and Alzheimer׳s disease

Major depression and Alzheimer׳s disease (AD) are often observed in the elderly. The identification of specific markers for these diseases could improve their screening. The aim of this study was to investigate long-term odor recognition memory in depressed and AD patients, with a view to identifying olfactory markers of these diseases. We included 20 patients with unipolar major depressive episodes (MDE), 20 patients with mild to moderate AD and 24 healthy subjects. We investigated the cognitive profile and olfactory memory capacities (ability to recognize familiar and unfamiliar odors) of these subjects. Olfactory memory test results showed that AD and depressed patients were characterized by significantly less correct responses and more wrong responses than healthy controls. Detection index did not differ significantly between patients with major depression and those with AD when the results were analyzed for all odors. However, MDE patients displayed an impairment of olfactory memory for both familiar and unfamiliar odors, whereas AD subjects were impaired only in the recognition of unfamiliar odors, with respect to healthy subjects. If preservation of olfactory memory for familiar stimuli in patients with mild to moderate AD is confirmed, this test could be used in clinical practice as a complementary tool for diagnosis.

Taste identification used as a potential discriminative test among depression and Alzheimer's disease in elderly: A pilot study

Major Depression and Alzheimer׳s disease (AD) are two diseases in the elderly characterized by an overlap of early symptoms including memory and emotional disorders. The identification of specific markers would facilitate their diagnosis. The aim of this study was to identify such markers by investigating gustatory function in depressed and AD patients. We included 20 patients with unipolar major depressive episodes (MDE), 20 patients with mild to moderate AD and 24 healthy individuals. We investigated the cognitive profile (depression, global cognitive efficiency and social/physical anhedonia) and gustatory function (ability to identify four basic tastes and to judge their intensity and hedonic value) in all participants. We found that AD patients performed worse than healthy participants in the taste identification test (for the analysis of all tastants together); however, this was not the case for depressed patients. We found no significant differences among the three groups in their ability to evaluate the intensity and hedonic value of the four tastes. Overall, our findings suggest that a taste identification test may be useful to distinguish AD and healthy controls but further investigation is required to conclude whether such a test can differentiate AD and depressed patients.

Olfactory and gustatory functions in bipolar disorders: A systematic review

HIGHLIGHTSPatients with bipolar disorder present with several olfactory and gustatory dysfunctions.Dysfunction in olfactory identification may be potential marker for bipolar disorder.Olfactory acuity is associated with psychosocial and cognitive performances in bipolar disorder.Bipolar patients have more gustatory dysfunction than non‐bipolar depressed patients and controls. ABSTRACT Olfactory and gustatory dysfunctions have been described in different psychiatric disorders. Several studies have found gustatory and olfactory function change in bipolar disorders with various results. The aim of this study is to have a systematic review of studies evaluating gustatory and olfactory function in bipolar disorders. After a systematic search, 15 studies on olfaction and 5 studies on taste were included in this review. The UPSIT (University of Pennsylvania Smell Identification Test) and Sniffin’ Sticks were the most widely used tests to evaluate smell. Some studies on olfaction described dysfunctions in smell identification as potential markers for bipolar disorders. Moreover, olfactory acuity was associated with psychosocial and cognitive performances. For taste, only few studies used standardized tests to evaluate gustation. These studies showed that patients with Bipolar disorders had more gustatory dysfunction compared to controls, and to non‐bipolar depressed patients.