Abstract
Regions of the brain that process olfaction have been associated with structural and functional abnormalities in schizophrenia [1–3]. In addition, reviews of the literature report olfactory deficits in people with schizophrenia [2,4], although there is contention whether these deficits are specific to olfactory identification, or occur across the range of olfactory tasks (acuity, identification, discrimination, recognition and memory). Olfactory identification deficits have been reported primarily in males, affecting between 30–50% of individuals with schizophrenia [5,6]. Olfactory identification deficits have also been reported in patients with schizophrenia-like disorders and other psychoses, including affective psychoses [7], and in relatives of patients with schizophrenia [1]. While there is robust evidence showing that smoking is associated with impaired olfactory identification [8], curiously two studies have reported that patients with schizophrenia who were smokers scored higher on the University of Pennsylvania Smell Identification Test (UPSIT) [9] than patients who were non-smokers [5,10]. The aim of this study was to explore the association between smoking and olfactory identification in psychosis.
Method
Subjects
Fifty-nine subjects were recruited for two studies that involved the biopsy and culture of olfactory epithelium; full details are provided elsewhere [3,11]. Twenty-two subjects had nonaffective psychoses (eight female, 14 male; mean age 37.3, standard deviation [SD] 9.0). The nonaffective psychoses included: schizophrenia (n = 18); delusional disorder (n = 2); and atypical psychosis (n = 2). Sixteen subjects had affective psychoses (eight female, eight male; mean age 38.6, SD 10.2). The affective psychoses included bipolar affective disorder (n = 12) and depression with psychosis (n = 4). Twenty-one unaffected controls were also included (seven female, 14 male; mean age 34.8, SD 11.1). The average duration of illness for each patient group was: affective psychoses, mean 16.1 years, SD 9.5; nonaffective psychoses, mean 14.6 years, SD 8.6. The average chlorpromazine equivalent dose of antipsychotic medication for each patient group was: affective psychoses, mean 270.8 mg, SD 124.0; nonaffective psychoses, mean 519.1 mg, SD 307.2. The studies were approved by the relevant ethics committees. After complete description of the studies to the subjects, written informed consent was obtained.
Measures
All subjects were assessed using a modified version of the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) [12]. Well control status or patient's diagnosis was confirmed with the Operational Criteria for Psychosis (OPCRIT), a 90-item checklist linked to a computer diagnostic algorithm [13]. Olfactory identification was assessed using the UPSIT, a 40-item multiple-choice ‘scratch and sniff’ olfactory test [9]. The UPSIT is widely used, and its reliability and validity have been described in detail [2,4,9]. Smoking was assessed on reported average daily cigarette intake.
Analysis
An analysis of variance of the UPSIT scores was performed using Proc GLM within SAS 9.0, adjusting all p-values for multiple comparisons.
Results
Table 1 shows UPSIT scores by diagnostic classification and smoking status. While there was no significant difference between the three groups on UPSIT scores (F = 1.64, df = 2, 53, p = 0.16), there was an interaction involving classification and smoking status (F = 4.71, df = 2, 53, p = 0.01). For affective psychoses, there was a significantly greater mean UPSIT score for smokers compared to non-smokers (t = 2.64, df = 53, p = 0.01), whereas for nonaffective psychoses the increase was not significant (t = 1.65, df = 53, p = 0.11). Among controls there was a corresponding but non-significant decrease in the smokers’ UPSIT scores (t = 1.55, df = 53, p = 0.13). The mean UPSIT scores of the smokers for the three groups were not significantly different (F = 1.85, df = 2, 53, p = 0.16), whereas there were significant differences when the mean scores of the non-smokers were compared (F = 6.24, df = 2, 53, p = 0.004), with patients having lower scores.
Discussion
Analysing smokers and non-smokers separately may assist in understanding the relationship between psychosis and olfactory identification. While our finding that patients with psychoses who smoke performed better on a test of olfactory identification than non-smokers appears paradoxical, this trend has been previously observed [5,10]. Importantly, our study examined patients with both affective and nonaffective psychoses, whereas the cited studies examined only patients with schizophrenia. A ‘normalising’ effect of nicotine on auditory gating for patients with schizophrenia who smoked has been reported. A similar ‘normalising’ effect was reported for relatives of patients with schizophrenia who did not smoke, but were given nicotine orally (in chewing gum) [14]. It is feasible that nicotine may also have a ‘normalising’ effect on olfactory identification ability for patients with psychotic disorders, given that nicotine enhances the release and synaptic transmission of acetylcholine, gamma-aminobutyric acid (GABA) and glutamate [14,15], and given that nicotinic receptors are present in the olfactory system [16]. It is possible that the centrally mediated ‘normalising’ effect of nicotine in patients with psychosis has a greater impact on olfactory identification compared to the locally mediated impact of smoking. An interaction between psychosis, smoking status and olfactory identification may not be specific to schizophrenia, as we found similar results in those with affective psychoses. Curiously, this interaction was only significant in the affective psychoses group versus controls.
University of Pennsylvania Smell Identification Test scores by diagnostic classification and smoking status
The study is limited by the small sample size and the relative imbalance in smoking status between the groups. Therefore, it is not possible to state with confidence whether the failure to detect significantly impaired olfactory identification overall in patients versus controls is attributable to small sample size, smoking status, or other confounding factors. The magnitude of difference in UPSIT scores between well controls who are smokers versus non-smokers is greater than expected. Previous studies report a relatively small effect of smoking on olfactory identification in controls [8,9]. Furthermore, data on dose-related smoking effects on olfactory identification may not be captured by a simple categorization of subjects as smokers or non-smokers [8]. Smoking history is commonly measured in ‘pack years’ [2,4], however, these data were unavailable for this sample. In addition, the participants recruited for our biopsy studies may not be representative of all individuals with psychosis. Finally, the effects of nicotine on brain processes such as auditory gating are transient (lasting approximately 30 min after smoking [14]). Future studies will need to examine the specific time course of the effect of nicotine (via smoking or chewing gum containing nicotine), and potential changes in olfactory identification.
Given the above limitations, our results should be interpreted cautiously. In a review of recent publications examining dysfunctions in olfactory processing in schizophrenia [17], Rupp stated that progress in this field is hampered by various potential confounding factors such as sex, illness duration and medication. We propose that smoking status also requires closer scrutiny in future studies.
Footnotes
Acknowledgements
The Stanley Medical Research Institute supported this project.