Olfactory Dysfunction in Mental Illness

Abstract

Purpose of review: Olfactory dysfunction contributes to the psychopathology of mental illness. In this review, we describe the neurobiology of olfaction, and the most common olfactory alterations in several mental illnesses. We also highlight the role, hitherto underestimated, that the olfactory pathways play in the regulation of higher brain functions and its involvement in the pathophysiology of psychiatric disorders, as well as the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in psychiatric conditions.

Recent findings: The olfactory deficits present in anxiety, depression, schizophrenia or bipolar disorder consist of specific alterations of different components of the sense of smell, mainly the identification of odours, as well as the qualifications of their hedonic valence (pleasant or unpleasant). Epidemiological findings have shown that both environmental factors, such as air pollutants, and inflammatory disease of the upper respiratory tract, can contribute to an increased risk of mental illness, at least in part, due to peripheral inflammatory mechanisms of the olfactory system. In this review, we describe the neurobiology of olfaction, and the most common olfactory function alterations in several psychiatric conditions and its role as a useful symptom for the differential diagnosis. We also highlight the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in these psychiatric conditions.

Keywords: Anxiety; Bipolar disorder; Depression; Mental illness; Neurogenesis; Olfaction; Olfactory bulbs; Olfactory neuroepithelium; Schizophrenia.

Fig. 1

Peripheral and central olfactory system. Odour information is initially perceived through the olfactory neurons in the olfactory epithelium and transmitted to the central olfactory system, which is composed of the olfactory bulbs which in turn projects to a variety of secondary olfactory structures including the anterior olfactory nucleus, piriform cortex olfactory tubercle, the lateral entorhinal cortex and para-amygdaloid complex. Neurons within these secondary olfactory structures project to tertiary olfactory structures, which include the orbitofrontal cortex, the insular cortex and the dorsal hippocampus. An overlap has been described between the neural connections of the olfactory system, temporo-limbic and frontal functions that are associated with higher brain functions such as cognition, memory and emotion, which are the ones that are altered in psychiatric disorders. AMYG, amygdala complex; AON, anterior olfactory nucleus; BG, Bowman’s gland; CP, cribriform plate; EC, enthorrinal cortex; GBC, globose basal cells; GC, glomerular cells; Glom, glomerulus; HBC, horizontal basal cells; HC, hippocampus; IN, insular cortex; MC, mitral cells; OB, olfactory bulb; OE, olfactory epithelium; OFC, orbitofrontal cortex; ONs, olfactory neurons; PC, piriform cortex; SC, sustentacular cells; THAL, thalamus; TC, tufted cells