Olfactory impairment in psychiatric disorders: Does nasal inflammation impact disease psychophysiology?

Abstract

Olfactory impairments contribute to the psychopathology of mental illnesses such as schizophrenia and depression. Recent neuroscience research has shed light on the previously underappreciated olfactory neural circuits involved in regulation of higher brain functions. Although environmental factors such as air pollutants and respiratory viral infections are known to contribute to the risk for psychiatric disorders, the role of nasal inflammation in neurobehavioral outcomes and disease pathophysiology remains poorly understood. Here, we will first provide an overview of published findings on the impact of nasal inflammation in the olfactory system. We will then summarize clinical studies on olfactory impairments in schizophrenia and depression, followed by preclinical evidence on the neurobehavioral outcomes produced by olfactory dysfunction. Lastly, we will discuss the potential impact of nasal inflammation on brain development and function, as well as how we can address the role of nasal inflammation in the pathophysiological mechanisms underlying psychiatric disorders. Considering the current outbreak of Coronavirus Disease 2019 (COVID-19), which often causes nasal inflammation and serious adverse effects for olfactory function that might result in long-lasting neuropsychiatric sequelae, this line of research is particularly critical to understanding of the potential significance of nasal inflammation in the pathophysiology of psychiatric disorders.

Fig. 1. Anatomy of olfactory epithelium and neural connection with the olfactory system and higher cerebral cortex in the rodent.

Schematic representation shows tissue and cellular structure of the olfactory epithelium (OE) and the projection of olfactory sensory neurons (OSNs) into the olfactory bulb (OB). In the OE, OSNs are produced from basal cells and project to the glomerular layer of the OB where OSNs make synaptic connections with OB neurons, including mitral and tufted cells. The mitral/tufted cells subsequently relay olfactory sensory information to primary olfactory cortical regions, including the anterior olfactory nucleus (AON) and the piriform cortex (Pir). Recent research has uncovered neural circuit connections between the olfactory system and prefrontal regions such as the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC), which regulate higher brain functions (i.e., the OB-AON-mPFC and OB-Pir-OFC pathways).

Fig. 2. Adverse effects of nasal inflammation on brain development and function.

Schematic representation shows the olfactory epithelium (OE) as an entry point for developmental exposure to environmental inflammatory factors (such as air pollutants and viral infection) and their adverse effects on the central nervous system, initially through the olfactory bulb (OB). OE inflammation may alter maturation of the olfactory system and its functional connectivity to the distal brain regions involved in regulation of higher brain function relevant to psychiatric disorders, and it may have these effects via multiple routes from the OE. mPFC, medial prefrontal cortex; OFC Orbitofrontal cortex, AON Anterior olfactory nucleus, Pir Piriform cortex.