In the first study to examine living nerve cells from patients with psychiatric disease, researchers from the Monell Chemical Senses Center, the University of Pennsylvania, and collaborating institutions reported altered nerve cell function in olfactory receptor neurons from patients with bipolar disorder.

According to lead investigator Nancy E. Rawson, PhD, a cellular biologist at Monell, “Previous studies have used non-nerve cells, such as fibroblasts or red blood cells, to examine how cells function in patients with bipolar disorder. But since this is a psychiatric disorder, we need to understand what’s going on in nerve cells.”

THE NOSE PROVIDES A WINDOW INTO THE BRAIN

Olfactory receptor neurons, located in a small patch of epithelium inside the nose, contain receptors for the thousands of odorant molecules detected by humans. Easily obtained using a simple, five-minute biopsy procedure, olfactory receptor neurons share many characteristics with nerve cells in the brain. These common features make olfactory receptor neurons a useful model to study the neural effects of psychiatric disease.

Calcium responses were predominantly decreased in nerves from patients with bipolar disease. Dr. Rawson commented, “The decreased calcium responses point to a specific set of pathways that will allow us to narrow the target for identifying the defect of calcium regulation associated with bipolar disorder. Once identified, these pathways will provide new targets for drug development.”

In the study, researchers used a fluorescence imaging technique to measure basal and stimulated calcium levels in olfactory receptor neurons from 17 patients with bipolar disorder and age- and sex-matched healthy controls. Seven patients were medication-free and 10 were being treated with mood-stabilizing drugs.

“MEDICATION RESPONSIVENESS TEST”

The researchers regard the olfactory receptor neurons as a valuable model that may provide needed insight into the neurobiologic factors underlying psychiatric disease. Dr. Rawson noted, “The calcium dysregulation that we see in olfactory receptor neurons of bipolar patients is different from what has previously been reported in studies using non-neuronal cells. This suggests that nerve cells might behave differently from other cell types.”

First author Chang-Gyu Hahn, MD, PhD, Assistant Professor of Psychiatry at the Hospital of the University of Pennsylvania School of Medicine, observed, “A major issue in treating bipolar disorder—or psychiatric disorders in general—is that it is hard to predict which medication a patient will respond to. So, clinicians go through a series of trials and errors and the patient suffers until the right medication is found. It is possible that olfactory receptor neurons might be developed as a ‘medication responsiveness test’ to indicate which medication a patient should be on.”

Dr. Hahn continued, “Another strength of this approach is that we can sample neurons from patients during specific stages of the illness and therefore we will be able to distinguish trait- from state-dependent characteristics of the disorder, which is particularly important in understanding mood disorders.”

Suggested Reading
Hahn CG, Han LY, Rawson NE, et al. In vivo and in vitro neurogenesis in human olfactory epithelium. J Comp Neurol. 2005;483:154-163.
Hahn CG, Friedman E. Abnormalities in protein kinase C signaling and the pathophysiology of bipolar disorder. Bipolar Disord. 1999;1:81-86.
Hahn CG, Gomez G, Restrepo D,et al. Aberrant intracellular calcium signaling in olfactory neurons from patients with bipolar disorder. Am J Psychiatry. 2005;162:616-618.

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