Olfactory deficits in schizophrenia

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Olfactory Deficits in Schizophrenia T. Hurwitz, L. Kopala, C. Clark, and B. Jones

OIfactory discrim~~t~on was measured in patients with schizophrenia who were on neuroleptic medication and was compared with other psychiatric patients receiving neuroleptics and normal controls. The perjormance of the patients with schizophrenia was si~nl~cantl~ lower than the psychiatric and normal controls. The latter two groups per$ormed at e~uiv~ent levels. The~~ings are discussed with respect to olfactory deficits found in patients with cerebral lesions and with abnormalities of specific neurotransmitter systems.

Introduction Of all the sensory systems, olfaction is the least understood in terms of the physiological basis for discrimination. It is also unique neuroanatomically, as it is the only sensory system that does not use the thalamus as the primary relay center to the cortex (Pansky and Allen 1980). As humans are more dependent on the visual and auditory systems for orientation and integration of environmental stimuli, the olfactory system has not been studied as extensively. Typically, clinical studies of olfaction have used idiosyncratic test materials, as there has been no accepted or standardized method for assessing this sensory modality. Recently, Doty et al. (1984a) have developed, standardized, and clinically validated a test of olfactory function. The availability of a simple and reliable test greatly facilitates the assessment of olfaction and allows for the results of different studies to be compared directly. Thus far, results based on this instrument have been reported for patients with Kallman’s syndrome, Korsakoff’s syndrome, multiple sclerosis, and Alzheimer’s disease (Doty et al. 1984a; Warner et al. 1986). The purpose of the current study was to administer this test to patients with schizophrenia to determine if an olfactory deficit could be identified. Patients with schizophrenia often report olfactory hallucinations, and yet, we could only find one study by Bradley (1984) that examined otfactory function in these patients. In her study, olfactory acuity for pheromonal substances in men with chronic psychosis was better than in nonpsychotic patients. Therefore, we initiated a study of olfaction in patients with schizophrenia using the University of Pennsyivania Smell Identification Test developed by Doty et al. (1984a).

Prom the Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada. Address reprint requests to Dr. ‘f. A. Horwitz, Department of Psychiatry, UBC. 2255 Wesbrook Mall, vancouver, B.C., v6~ 2A 1, Canada. Received March 10, 1987; revised May 28, 1987.

0 1988 Society of Biological Psychiatry

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Me:t,hods Subjects The Pennsylvania Smell ldenti~cation Test (SIT) (Doty et al. 1984a) was administered to three groups: patients with schizophrenia, psychiatric patients who had never been diagnosed as having schizophrenia, and normal controls. The schizophrenic group comprised 15 men and 3 women with a mean age of 23.9 years (range 17-41). The diagnosis of schizophrenia was made by two independent psychiatrists, and all patients met DSM-III and ICD-9 criteria. At the time of testing, all patients were receiving neuroleptic therapy, and no subject was in remission. The 11 subjects in the psychiatric control group had to meet two entry criteria. First, they could not have been diagnosed as having schizophrenia, and second, neuroleptics were part of their current medication regimens. Of the 11 subjects who met these criteria, 10 were diagnosed as bipolar affective disorders and 1 as a personality disorder. The mean age of this group was 33.2 years (range l&-50), and the group consisted of 2 men and 9 women. The normal group consisted of volunteers from the hospital staff who had no complicating medical conditions. This group comprised 7 men and 3 women, with a mean age of 33.6 years (range 21-43). No subject was excluded from the normal group on the basis of score. All subjects gave informed consent, and the study was approved by the University of British Columbia Human Research Committee. Within 3 months of testing, all patients were physically examined, and the following laboratory investigations were conducted: complete blood count with differentials, urinalysis, electrocardiogram (ECG), chest x-ray, and Tq levels. In addition, any patients whose olfaction score was not in the normal range of the standardization sample was examined by a neurologist (T.A.H.). The purpose of this examination was to identify and exclude any patient whose poor score could be accounted for by other factors. Specific examples of such factors are upper respiratory tract infection, nasal congestion, head injury with loss of consciousness, facial trauma, or any serious medical condition, such as multiple sclerosis or hypothyroidism. Procedures The SIT consists of 4 test booklets, each with 10 items. Each item consists of a scentimpregnated area, which is activated by scratching. Above this area are four potential responses (e.g., lilac, chili, coconut, or whisky). Usually, the subject scratches the area, sniffs it, and then chooses the correct alternative from the four responses. However, given the nature of the clinical samples, each subject was tested individually, rather than the standard self-administration technique, to ensure comprehension of the task and compliance. Each subject was asked to sniff a scratched impregnated area and then to tell the examiner the correct response from the four alternatives on the card. If the subject could not initially identify the scent on a given item, the procedure was repeated until one of the four alternatives was chosen. Examiners were blind to the correct responses. All subjects performed the task within IO-25 min. In addition to the SIT, all patients were assessed on the Global Assessment Rating Scale (GAS). Similarly, the following data were obtained for all subjects (where applicable): smoking history, the presence of olfactory hallucinations, medication regimen, and duration of neuroleptic usage.

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Olfactory Deficits in Schizophrenia

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Table 1. SIT Scores for the Three Groups Contmls

Mean

Nonals

Psychiatric

Patients with schizophrenia

37.7”

37.4” 2.0 34-40 11

33.4 5.7 14-38 18

1.4

SD

Range n

35-39 10

F-value 4.w

“Means are not significantly different. “p 6 0.02.

A one-way Analysis of Variance with Tukey’s pair-wise comparison technique was done between three groups on the SIT scores. These scores were also correlated with age and, for the clinical groups, duration of neuroleptic usage and GAS ratings. Similarly, r-tests were done to determine if gender or smoking were related to test scores. To determine if them was an effect that was a result of a specific medication, ~ipien~/nom~ipien~ of the three most commonly prescribed m~ication~~o~~dol(34.5%), pr~yclidine (44.8%), and lithium (24.16)-were compared using t-tests. Finally, each of the 40 items was considered individually to determine if fatigue was a factor.

Results The means, standard deviations, and ranges for the three groups on the SIT are summ~zed in Table 1. There was a significant between-group F-value, with the schizophrenic group’s performance being significantly lower than the performance of the psychiatric and normal controls. With respect to Doty ‘s standardization data, both the psychiatric and normal control groups scored in thenormosmicrange, whereas the schizophrenic group was inthemicrosmic range. Performance on the SIT was not found to be related to age, whether one smoked, or, for the clinical groups, duration of neuroleptic usage or GS scores. Similarly, no mediationspecific effect was found for haloperidol or procydidine. However, patients receiving lithTable 2. Drug Effects of SIT Prescribed

Dwt

No

Yes

t-Value

Haloperidol Mean

35.1

0.25

19

34.6 4.1 10

34.5 3.3 16

35.4 6.6 13

0.44

34.1 5.5 22

37.3 1.5 7

2.42”

SD

n Procyclidine Mean SD

n Lithium Mean SD

n

5.5

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126

I‘. Hun&z

---_--_---

5

1

10

15

20

25

et al

Normals Non Schuophremc pattents Pattents with Schizophrenia

30

35

40

Item number Figure 1. Probability

of correct response for each item and group.

ium did perform significantly better than patients not on this medication. This difference was a result of the fact that only patients in the psychiatric control group received lithium therapy. These medication data are summarized in Table 2. For gender, no differences were found in the normal or psychiatric control groups. However, the three female schizophrenic subjects scored significantly higher than the male schizophrenic subjects (mean, = 36.7, meanM = 32.7, t = 2.20, p c 0.05). The lowest score for a woman with the diagnosis of schizophrenia was 35. Six of the male schizophrenics (40%) achieved this score or higher. The item-by-group responses are illustrated in Figure 1. These data suggest that fatigue was not a factor in the poorer performance found in patients with schizophrenia, as their performance relative to the control groups did not change over time. For two items, nos. 9 and 14, the schizophrenic group scored higher than the control groups. Whether or not the pattern of scores on these two items is probabilistic, given the total number of items in the test, or whether it represents a true reversal of performance cannot be determined at this time.

Discussion The cardinal finding of the current study is that patients with schizophrenia exhibited a deficit in olfactory discrimination in comparison to psychiatric patients not diagnosed as having schizophrenia, but receiving neuroleptics, and normal controls. Previous studies of individuals with schizophrenia have reported differences in many sensory and cognitive modalities. The two most recent observations are impairment of visual tracking, in particular, slowed responses (Iacono 1983), and impairment on the continuous performance task (Mirsky and Duncan 1986). With regard to the slowed response in visual tracking, it seems unlikely that this would result in the observed abnormalities in olfaction. However, it might be argued that the observed findings are a function of diminished attention in the schizophrenic group. The individual administration of each item by an examiner should preclude the possibility of errors due to inattention. A related potential explanation for the poorer performance in patients with schizophrenia is fatigue. However, the itemby-item responses for the patients with schizophrenia are not consistent with a fatigue effect. A second potential set of explanations is related to the current treatments (particularly

Olfactory Deficits in Schizophrenia

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neuroleptics) of schizophrenia. In an attempt to control for this factor, patients who did not have a diagnosis of schizophrenia but who received neuroleptic treatment were included in this study. The neuroleptics did not interfere significantly with olfaction in the psychia~c controls, as their ~~o~~ce was equivalent to the normal controls and in the normosmic range based on Doty et al. (1984a) standardization data. In addition, the duration of neuroleptic treatment was not correlated with SIT scores. These data suggest that neuroleptics did not significantly alter performances on the SIT. Aside from neuroleptics, there may have been an effect specific to other drugs. In reviewing the drug regimes, only three drugs were found that were prescribed to more than 20% of the patients (haloperidol, ~~yclidine, and lithium). With respect to olfaction, no deleterious effect was found that would account for the observed difference between the patients with schizophrenia and the two control groups. A third explanation for these results could be that the obtained findings are solely a function of the degree of overt psychopathology. When the two clinical groups were compared on the Global Assessment Scale, no differences were found. The ratings were performed by two independent psychiatrists, and the interrater reliability was 0.78. In addition, it seems unlikely that the observed results were secondary to institutionalization, as the patient population was young and inpatients had been hospitalized for relatively short periods (3-100 days). Finally, although olfactory discrimination has been found to correlate with age (Doty et al. 1984a) and smoking habit (Doty et al. 1985b), we could not find signific~t relationships for these variables. Therefore, these nuisance variables could not account for the reported differences. Although there were no gender differences in normal and psychiatric controls, male schizophrenic patients performed significantly worse than the female patients. This finding raises the question of whether or not the reported deficits are confined to only men with the diagnosis of schizophrenia. Given the small number of women in the schizophrenia group, this question cannot be answered by this study. The etiology and neuroanatomic basis of the microsmia found in these patients is unclear. Olfactory disturbances have been found in a variety of patient groups with confirmed lesion sites. Deficits have been found in patients with Korsakoff’s disease, which damages the mediodorsal nucleus of thalamus, and in patients who have had unilateral temporal lobectomy or lesions of the orbitofrontal cortex (Jones et al. 1975; Rausch et al. 1977; Potter and Butters 1980). Olfactory disturbances have also been found in diseases that involve specific neurotransmitter systems. Microsmia has been reported in patients with Alzheimer’s disease, which is associated with reduced choline acetyltransferase (Esiri and Wilcock 1968; Simpson et al. 1984; Warner et al. 1986), and in Parkinson’s disease, a disease involving the dopaminergic system (Ward et al. 1983; Serby et al. 1985). Potter and Butters (1980) have reported deficits in otfactory discrimination with heightened olfactory sensitivity in patients with surgical frontal lobe lesions. Therefore, Kolb (1984) has argued that the prefrontal cortex may be involved in the associative functions of olfaction. With respect to schizophrenia, Bradley (1984) has reported increases in olfactory sensitivity, whereas we found deficits in olfactory discrimination, thus suggesting possible involvement of the prefrontal cortex in schizophrenia. In addition to the neuroanatomical implications of this and other studies, the observed deficit has theoretical and practical considerations in our understanding of schizophrenia as a social process. Many of life’s pleasurable experiences hinge on olfactory discrimination. The olfactory deficit may contribute to the diminished capacity for enjoyment

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found in patients with s~~jzophre~ia, may not be detected.

1. Hutwitz

and certain noxious and potentially

et

iIi

dangerous stimu~j _.-

The authors would like to thank the faculty, residents, and clinical staff at the UBC Dept. of Psychiatry for their cooperation and aid, in particular, Dr. R. Remick, Asst. Head, Dept. of Psychiatry, HSCH.

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Doty R, Shaman P, Dann W (1984a): Development of the University of Pennsyiv~~a Smell Test: Standardized micro encapsulate test of olfactory function. Physj#i Behav 32:489-502. Doty R, Shaman P, Applebaum S, Giberson R, Sikorski L, Rosenberg L (1984b): Smeil identification ability: Changes with age. Science 226:1441-1443. Esiri M, Wilcock G (1984): The olfactory bu1b in Alzheimer’s disease. J Neural Neurosurg Psychiatry 47:56-60.

Iacono WG (1983): Psychophysiology and genetics: A key to psychopathology research. Psychoparhology 20:371-383.

Jones B, Moskowitz H, Butters W (1975): Olfactory discrimination in alcoholic Korsakoff’s patients. Neuropsychologia 13: 173-179. Kolb B (1984): Functions of the frontal cortex of the rat: A comprehensive review. Brain Rcs Rev 8:65-98.

Mirsky A, Duncan C (1986): Etiology and expression of s~hizop~enia: Neu~bioiogical chosocial factors. Ann Rev Psychol 373291-3 19.

and psy-

Pansky B, Allen D (1980): Review ofNeuruscience. New York: Macmiltan. Potter H, Butters N (1980): An assessment of olfactory deficits in patients with damage to prefrontal cortex. Neuropsychologia 18:621-628. Rausch R, Sarafetinides E, Crandall P (1977): Olfactory memory in patients with anterior temporal lobectomy. Cortex 13445-452. Serby M, Corwin S, Conrad P, Rotrosen J (1985): Olfactory dysfunction in Alzheimer’s disease and Parkinson’s disease. Am J Psychiatry 142:781-782. Simpson S, Yates, C, Gordon A, St. Clair D (1984): Olfactory tubercle choline acetyltransferase activity in Alzheimer-type dementia, Down’s syndrome and Huntington’s disease. .I Neural Neurosurg Psychiatry 47: 1138- 1139. Ward C, Hess W, Caine D (1983): Olfactory impai~ent in Parkinson’s disease. Neur~~~~ 33:943946.

Warner MD, Peabody CA, Flattery JJ, Tinkelberg JR (1986): OIfactory deficits in Alzheimer’s disease. Bid Psychiatry 2 I : 116 118.