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PubMed1998

Olfactory function in monozygotic twins discordant for schizophrenia.

OBJECTIVE: Abnormalities of olfactory identification ability have been proposed as a marker of cerebral dysfunction in schizophrenia. The authors studied the potential role of genetic factors in olfactory dysfunction by assessing monozygotic twins discordant for schizophrenia and matched comparison subjects. METHOD: The subjects were 12 pairs of monozygotic twins discordant for schizophrenia and 12 healthy subjects matched for sex and age. Each subject completed the University of Pennsylvania Smell Identification Test. RESULTS: The combined twin group scored significantly lower on smell identification than did the comparison group. The affected and unaffected twin groups did not differ from each other. CONCLUSIONS: Genetic factors may contribute to cerebral dysfunction as assessed by olfactory identification ability.

Adult↗
PubMed2000

Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's disease at follow-up.

OBJECTIVE: This study evaluated the predictive utility of olfactory identification deficits in patients with mild cognitive impairment for follow-up diagnosis of probable Alzheimer's disease. METHOD: Ninety outpatients with mild cognitive impairment were examined at 6-month intervals. Matched healthy comparison subjects (N=45) were examined annually. The University of Pennsylvania Smell Identification Test was given at baseline. RESULTS: Olfaction scores were lower in patients with mild cognitive impairment than in healthy comparison subjects. Seventy-seven patients were followed up; 19 were diagnosed with Alzheimer's disease by 2 years. Patients with low olfaction scores (< or =34 of 40), and patients with low olfaction scores who reported no subjective problems smelling, were more likely to develop Alzheimer's disease than other patients. In a Cox proportional hazards model adjusted for age, sex, modified Mini-Mental State score, and education, low olfaction scores did not predict time until development of Alzheimer's disease, but low olfaction scores accompanied by lack of awareness of olfactory deficits predicted time to development of Alzheimer's disease. This effect remained when attention or memory measures replaced modified Mini-Mental State score in the model. In patients with high Mini-Mental State scores (> or =27 of 30), low olfaction with lack of awareness remained a significant predictor of Alzheimer's disease. Olfaction scores of 30-35 showed moderate to strong sensitivity and specificity for diagnosis of Alzheimer's disease at follow-up. CONCLUSIONS: In patients with mild cognitive impairment, olfactory identification deficits, particularly with lack of awareness of olfactory deficits, may have clinical utility as an early diagnostic marker for Alzheimer's disease.

Aged↗
PubMed2001

Impaired olfactory identification in relatives of patients with familial schizophrenia.

OBJECTIVE: Impaired olfactory identification ability has previously been demonstrated in patients with schizophrenia. This study assessed olfactory function in psychotic and nonpsychotic members of multigenerational families with familial schizophrenia to determine whether deficits were present in both groups. METHOD: The University of Pennsylvania Smell Identification Test was administered birhinally to three groups of subjects aged less than 65 years: 19 psychotic and 27 nonpsychotic members of families with familial schizophrenia and 43 age- and sex-matched healthy volunteers. RESULTS: Nonpsychotic family members had significantly higher mean University of Pennsylvania Smell Identification Test scores than psychotic family members but were impaired relative to the healthy volunteer group. These group differences could not be accounted for by age, sex, or smoking habit. Fifty-eight percent of the psychotic and 34% of the nonpsychotic family members performed in the microsmic (impaired) range, compared to 9% of the healthy volunteers. CONCLUSIONS: Impaired olfactory deficits may aggregate in families with schizophrenia and may be indicative of a genetic predisposition to psychosis.

Adult↗
PubMed2002

Postoperative olfaction in chronic sinusitis: smokers versus nonsmokers.

In order to study the efficacy of surgical intervention, as well as the influence of cigarette smoking on olfaction in clinical states, we examined olfactory ability by means of the University of Pennsylvania Smell Identification Test (UPSIT). We enrolled 37 patients 21 to 60 years of age who underwent surgery for chronic sinusitis. Normosmia was defined as an UPSIT score of 30 or more. Among these patients, 31 had a disturbance in their smelling ability in the preoperative stage, and the improvement rate, defined as a rise in score of 4 or more points after surgery, was 64.5%; 11 were well healed. However, all 7 patients who were more than 40 years old at the time of surgery, and currently smoking cigarettes, had a significant deficit in olfaction in the preoperative stage and even in the postoperative stage. This study demonstrated that cigarette smoking has adverse effects on olfactory ability, especially for older patients.

Adult↗
PubMedDate not supplied

Hypogeusia, dysgeusia, hyposmia, and dysosmia following influenza-like infection.

Hypogeusia, with or without dysgenusia, and hyposmia, with or without dysosmia, followed an influenzal-like infection in 87 of 143 consecutive patients who presented at the Taste and Smell Clinic at the NIH with taste and smell abnormalities. Findings in this disease included pale nasal mucous membranes with marked patency of the nasal airway, a postive Rudolph sign, elevated detection and recognition thresholds for several tastants and odorants, disruption of the pore region of the tast dub observed on electron microscopy and infiltration of the upper lamina propria of the nasal mucous membrane wih chronic inflammatory cells observed on light microscopy. These findings, taken together, are relatively specific for the diagnosis of this surprisingly common disorder.

Adult↗
PubMedDate not supplied

Congenital anosmia: detection thresholds for seven odorant classes in hypogonadal and eugonadal patients.

Detection thresholds for a representative from each of seven odorant classes (putrid, pepperminty, ethereal, camphoraceous, pungent, musky, floral) were determined by double-blind smell testing of seven normal males, six normal females, 6 patients with uncomplicated congenital anosmia and 13 patients with the syndrome of congenital anosmia and hypogonadotropic hypogonadism (the Kallmann syndrome, olfactogenital dysplasia). The median detection thresholds did not differ significantly between hypogonadal and eugonadal anosmics for any of the odorants, suggesting that the endocrine deficit does not result from inadequate rhinencephalic input to brain centers controlling gonadotropin release. Phenylethylmethylethylcarbinol (PEMEC), a stable chemical of the floral class, was detecred at very low concentrations (10(-6) to 10(-8) M in water) by all normals tested. Since no patient with congenital anosmia was able to distinguish even undiluted PEMEC from water, we suggest that this compound is the material of choice for convenient, rapid and objective testing of the sense of smell (cranial nerve I).

Adolescent↗
PubMed2001

Regional cerebral glucose metabolism in never-medicated patients with schizophrenia.

OBJECTIVE: The purpose of this study was to assess regional cerebral glucose metabolism in patients with schizophrenia who had never received antipsychotic medication and whose olfactory identification ability had been assessed. Two hypotheses were examined. First, the patients were compared with normal controls to determine whether differences in regional cerebral metabolism were apparent. Second, regional rates of metabolism were correlated with olfactory ability and the relation between them determined. METHODS: The patient (n = 26) and control (n = 32) subjects were scanned at rest using positron emission tomography (PET) after administration of 18F-fluorodeoxyglucose (FDG). In addition, the University of Pennsylvania Smell Identification Test was administered to each patient. RESULTS: Patients with schizophrenia had reduced rates of glucose metabolism in the right and left thalamus that reached significance if not corrected for multiple comparisons. However, if a Bonferroni correction was applied over the 27 regions of interest, the differences were not significant. Scores on the Smell Identification Test were negatively correlated with 8 regions of interest. When scores were analyzed using multiple regression, the left frontal cortex and the medial parietal cortex were significant predictors. CONCLUSIONS: The finding of reduced metabolism in the thalami is consistent with some of the previous literature, whereas the negative correlations between specific regions and olfactory function are not consistent with studies using activation paradigms.

Adolescent↗
PubMed2002

Brain imaging studies of the functional organization of human olfaction.

It is believed that sensory functions are organized in a hierarchical and parallel manner. The sense of smell differs in several aspects from other senses: odors can immediately elicit emotional evocations, they are remembered after a long time, and they are difficult to label. This raises the question of whether odorous stimuli may be processed differently from the other sensory stimuli. New data from brain imaging studies suggest that this is not the case and that the specific characteristics of the sense of smell can be attributed to the engagement of limbic structures at an early stage in the signal processing.

Animals↗
PubMed2000

Activation of olfactory cortex in newborn infants after odor stimulation: a functional near-infrared spectroscopy study.

In mammals, perception of smells during the first hours of life is an essential prerequisite for adaptation of the newborn to the new extrauterine world. Functional magnetic resonance studies have shown that olfactory impression is processed in the lateral and anterior orbito-frontal gyri of the frontal lobe. Near-infrared spectroscopy (NIRS) can detect changes in oxygenated [Hb O2], and deoxygenated [Hb H] Hb during cortical activation. The aim of this study was to assess by NIRS olfactory cortex activity in newborn infants receiving olfactory stimuli. Twelve males and 11 females were studied when awake at 6 h to 8 d after birth. NIRS monitoring was carried out using two optodes placed above the left anterior orbito-frontal gyri. Each newborn was exposed for 30 s to two different smell stimuli-mother's colostrum and vanilla-and to a negative control, distilled water. Changes in Hb concentration were measured over the orbitofrontal region. During exposure to vanilla, [Hb O2] increased significantly over the left orbito-frontal area in all babies. The magnitude of the [Hb O2] increase over the illuminated region during colostrum exposure was inversely related to postnatal age. We conclude that monitoring Hb changes by NIRS can be valuable in assessing olfactory responsiveness in infants.

Aging↗
PubMed2005

CHARGE syndrome includes hypogonadotropic hypogonadism and abnormal olfactory bulb development.

CONTEXT: CHARGE (coloboma, heart defect, choanal atresia, retarded growth and development, genital hypoplasia, ear abnormalities, and/or hearing loss defect) syndrome consists of a combination of congenital malformations including genital hypoplasia and retarded growth. OBJECTIVE: The objective of the study was to study gonadotropic axis function and growth parameters in CHARGE syndrome. DESIGN: This was a retrospective study. PATIENTS: The study included 32 children with CHARGE syndrome. RESULTS: Nineteen of 20 affected boys had micropenis and/or cryptorchidism, consistent with hypogonadotropic hypogonadism during fetal life. None of the boys was of pubertal age. Seven of nine boys tested before the age of 5 months during the neonatal peak period had extremely low testosterone levels. LH response to GnRH stimulation was variable during the first year of life and not correlated with existing clinical abnormalities. None of the girls over the age of 12 yr (n = 7) had begun puberty spontaneously, and a lack of response to GnRH stimulation was documented in five of them. Olfactory evaluation (n = 10) and magnetic resonance imaging (n = 18) of the forebrain revealed defective sense of smell and abnormal olfactory bulbs in all cases. Cardiorespiratory and nutritional problems were corrected, but the mean height of the 25 children who had reached 5 yr of age was -2 +/- 0.2 sd score. Height was not correlated with birth length or body mass index. GH deficiency was diagnosed in only three children. CONCLUSION: These findings suggest that CHARGE syndrome includes the main features of Kallmann syndrome, which is defined by hypogonadotropic hypogonadism combined with a defective sense of smell and abnormal olfactory bulb development. This forebrain abnormality, if confirmed in a larger group of patients, could serve as a major new criterion for the diagnosis of CHARGE syndrome.

Body Mass Index↗
PubMed2001

Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism.

Mutations in the GnRH receptor (GNRHR) have been described as a cause of reproductive failure in a subset of patients with idiopathic hypogonadotropic hypogonadism (IHH). Given the apparent rarity of these mutations, we set out to determine the frequency and distribution of GNRHR mutations in a heterogeneous population of patients with IHH who were well characterized with respect to diagnosis, phenotype, and mode of inheritance and to define their distribution within the receptor protein. One hundred and eight probands with IHH were screened for mutations in the coding sequence of GNRHR. Forty-eight of the 108 patients had a normal sense of smell, whereas the remaining 60 had anosmia or hyposmia (Kallmann syndrome). Exon segments in the GNRHR were screened for mutations using temperature gradient gel electrophoresis, and all mutations were confirmed by direct sequencing. Five unrelated probands (3 men and 2 women), all normosmic, were documented to have changes in the coding sequence of the GNRHR. Two of these probands were from a subgroup of 5 kindreds consistent with a recessive mode of inheritance, establishing a GNRHR mutation frequency of 2 of 5 (40%) in patients with normosmic, autosomal recessive IHH. The remaining 3 probands with GNRHR mutations were from a subgroup of 18 patients without evidence of familial involvement, indicating a prevalence of 3 of 18 (16.7%) in patients with sporadic IHH and a normal sense of smell. Among the five individuals bearing GNRHR mutations, a broad spectrum of phenotypes was noted, including testicular sizes in the male that varied from prepubertal to the normal adult male range. Three probands had compound heterozygous mutations, and two had homozygous mutations. Of the eight DNA sequence changes identified, four were novel: Thr(32)Ile, Cys(200)Tyr, Leu(266)Arg, and Cys(279)TYR: COS-7 cells transiently transfected with complementary DNAs encoding the human GNRHR containing each of these four novel mutations failed to respond to GnRH agonist stimulation. We conclude that 1) the spectrum of phenotypes in patients with GNRHR mutations is much broader than originally anticipated; 2) the frequency of GNRHR mutations may be more common than previously appreciated in familial cases of normosmic IHH and infrequent in sporadic cases; and 3) functional mutations of the GNRHR are distributed widely throughout the protein.

Amino Acid Sequence↗
PubMed1988

Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration.

To explore the nature of the olfactory dysfunction associated with Parkinson's disease (PD), 81 PD patients who scored well on a cognitive screening test were administered the 40-odorant University of Pennsylvania Smell Identification Test; 38 were additionally given a forced-choice phenylethyl alcohol odor detection threshold test. Clinical ratings of 11 neurologic symptoms (three bilateral) were obtained at the time of testing, and odor identification was retested in 24 patients at intervals ranging from 5 to 39 months. Relative to matched controls, the PD patients exhibited consistent and marked decrements on both types of olfactory tests (ps less than 0.0001). The odor identification deficit was not restricted to any subset of odorants and did not evidence longitudinal change. A factor analysis of the intercorrelations among the variables yielded six easily interpretable factors: general motor, oral motor, olfactory function, cognitive function, tremor, and gender. Olfactory test scores were independent of all other measures, including disease stage and duration. Seventy-two percent of the PD patients were unaware of a smell disorder before testing; those who were aware had significantly lower test scores. A statistical comparison of PD patients' olfactory test scores to those obtained from Alzheimer's disease patients found the olfactory disorders of these diseases to be indistinguishable. The data support the hypothesis that the olfactory deficit of PD is a general and stable one which likely occurs early in the disease process.

Aged↗
PubMed1993

Olfactory testing differentiates between progressive supranuclear palsy and idiopathic Parkinson's disease.

Olfactory dysfunction occurs in most patients with idiopathic Parkinson's disease (PD). In this study, we sought to determine whether such dysfunction is also present in progressive supranuclear palsy (PSP), a condition which shares a number of motor symptoms with PD and is commonly misdiagnosed as PD. We administered the University of Pennsylvania Smell Identification Test, a standardized test of odor identification ability, to 21 PSP patients; 17 also received a forced-choice odor detection threshold test. We compared the olfactory test scores to those obtained from PD patients and normal controls matched to the PSP patients on the basis of age, sex, and smoking habits. Overall, the olfactory function of the PSP patients was markedly superior to that of the PD patients and did not differ significantly from that of the normal controls. There was no association in either the PSP or PD patient groups between (1) the olfactory test scores and (2) measures of motor symptom severity, disease stage, and medication usage. These findings demonstrate that patients with PSP and PD differ markedly in their ability to smell and suggest that olfactory testing may be useful in their differential diagnosis.

Aged↗
PubMed1999

Impaired olfaction as a marker for cognitive decline: interaction with apolipoprotein E epsilon4 status.

OBJECTIVE: To determine whether olfactory status predicts cognitive decline (CD) over a 2-year follow-up period. METHODS: The authors enrolled individuals in a community-based longitudinal study of memory and aging in the Japanese-American community in King County, WA, between 1992 and 1994. At baseline they screened 1,985 persons using the Cognitive Abilities Screening Instrument (CASI) and the 12-item Cross-Cultural Smell Identification Test (CC-SIT). Of these 1,985 people, 1,836 were found not to be demented. Two years later the authors rescreened 1,604 participants with the CASI. They defined CD as a 2-year loss of > or =5.15 points/100 on the CASI. They genotyped 69% of the 1,604 people completing both examinations for apolipoprotein E (apoE). RESULTS: After adjusting for age, CASI score at baseline, education, smoking, sex, and follow-up time, the authors determined an odds ratio (OR) for CD of 0.90 (95% CI, 0.84 to 0.97) for an increase in each correct point on the CC-SIT (range, 0 to 12). Compared with normosmics, the OR for persons with impaired olfaction (microsmics) was 1.25 (95% CI, 0.83 to 1.89) and for anosmics the OR was 1.92 (95% CI, 1.06 to 3.47). Persons who were anosmic at baseline and who had at least one APOE-epsilon4 allele had 4.9 times the risk of CD (95% CI, 1.6 to 14.9) compared with normosmics without the epsilon4 allele. The estimated relative risk among women was 9.7 (95% CI, 1.3 to 70.4), and for men the risk was 3.2 (95% CI, 0.8 to 12.6). Receiver operating characteristic (ROC) curves showed that although the area under the curve (AUC) for baseline CASI was only 0.51, the AUC for CC-SIT alone was 0.62. Adding CC-SIT to the ROC model with CASI improved the AUC curve from 0.51 to 0.62. CONCLUSIONS: Unexplained olfactory dysfunction in the presence of one or more APOE-epsilon4 alleles is associated with a high risk of cognitive decline. Cross-Cultural Smell Identification Test classifies people with cognitive decline correctly to a greater degree than a global cognitive test.

Aged↗
PubMed2005

Switch to diester preen waxes may reduce avian nest predation by mammalian predators using olfactory cues.

It has long been recognised that nest depredation by olfactory-searching mammals greatly influences the reproductive success of ground-nesting birds. Yet adaptations of birds to diminish smell during nesting have rarely been investigated. Recently, a remarkable shift in the composition of uropygial gland secretions (preen waxes) was discovered in many ground-nesting shorebirds and ducks that begin incubation, during which the usual mixtures of monoester preen waxes are replaced by mixtures of less volatile diester waxes. In this study we show experimentally that an olfactory-searching dog had greater difficulty detecting mixtures of the less volatile diesters than mixtures of monoesters. This is consistent with the hypothesis that diester preen waxes reduce birds' smell and thereby reduce predation risk.

Animals↗
PubMed1994

The effect of human olfactory biopsy on olfaction: a preliminary report.

Normal human olfactory function is subject to a wide variety of factors. Although biopsy of human olfactory neuroepithelium has been reported by several researchers, there are no studies which have evaluated the effect of this procedure on olfactory function. In this retrospective study, we sought to determine if tissue removal from the olfactory cleft has an adverse influence on the sense of smell. Nineteen subjects underwent bilateral olfactory testing and subsequent endoscopic olfactory mucosal biopsy. All subjects were retested 6 weeks to 1 year after olfactory neuroepithelial biopsy. No statistical difference was found between olfactory tests performed before or after biopsy. These data suggest that biopsy of human olfactory neuroepithelium has no discernible adverse effect on the ability to smell.

Alzheimer Disease↗
PubMed2005

Assessing the relationship between concentrations of malodor compounds and odor scores from judges.

BACKGROUND: The purpose of this review was to assess the relationship between mean organoleptic scores (using a 0-to-5 scale) and concentrations of putative odorants representative of those thought to be important in oral malodor, as well as to propose a simple model that explains the dose-response curves obtained from a group of odor judges. METHODS: The model assumes that the scale is rooted at the detection threshold (0), the maximum score (5) is fully saturating and the brain and olfactory nervous system can act as a faithful transducer of the state of binding (occupancy) of the smell receptors in the nose. The authors predicted that the response would be exponential or sigmoidal in nature. They tested this using published empirical data based on seven odor judges and eight odor compounds. RESULTS: Analysis of the data by different plotting methods showed the odorants to be significantly different from each other (P < .01 by regression analysis) with regard to thresholds and slopes. The lower the threshold, the stronger the inherent odor of the compound. The greater the slope, the greater the odor power. Volatile sulfur compounds had low smell thresholds and high odor power and were highly volatile, while indole was less volatile but had a very low threshold. Both compounds may be significant in human oral malodor. CONCLUSIONS: The authors found that the organoleptic scale was exponential in practice. These findings imply that when inhibitory agents are tested against odor-generating bacteria, a given percentage inhibition of the volatile compound production rate by a treatment (such as an antimicrobial mouthwash) will result in an equal incremental reduction on the scale, regardless of the starting position on the scale. Understanding the scale enables dental professionals to develop better ways of training, calibrating and standardizing odor judges, along with better ways of designing clinical trials and interpreting data regarding the efficacy of antiodor treatments.

Breath Tests↗
PubMed2005

Integrated neural representations of odor intensity and affective valence in human amygdala.

Arousal and valence are proposed to represent fundamental dimensions of emotion. The neural substrates for processing these aspects of stimuli are studied widely, with recent studies of chemosensory processing suggesting the amygdala processes intensity (a surrogate for arousal) rather than valence. However, these investigations have assumed that a valence effect in the amygdala is linear such that testing valence extremes is sufficient to infer responses across valence space. In this study, we tested an alternative hypothesis, namely that valence responses in the amygdala are nonlinear. Using event-related functional magnetic resonance imaging, we measured amygdala responses to high- and low-concentration variants of pleasant, neutral, and unpleasant odors. Our results demonstrate that the amygdala exhibits an intensity-by-valence interaction in olfactory processing. In other words, the effect of intensity on amygdala activity is not the same at all levels of valence. Specifically, the amygdala responds differentially to high (vs low)-intensity odor for pleasant and unpleasant smells but not for neutral smells. This implies that the amygdala codes neither intensity nor valence per se, but a combination that we suggest reflects the overall emotional value of a stimulus.

Adult↗