Olfactory deficits, cognition and negative symptoms in early onset psychosis.
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BACKGROUND: Smell identification deficits (SID) are common in adult schizophrenia, where they are associated with negative symptoms and lower intelligence. However, smell identification has not been examined in adolescents with early onset psychosis, wherein diagnosis is often obscure, and there are few prognostic predictors. METHOD: We examined smell identification, diagnosis, neuropsychological performance and symptoms in 26 well characterized adolescents with early onset psychosis, age 11-17 years. RESULTS: SID existed in the sample and were more common in patients with schizophrenia and psychotic depression than in patients with psychosis NOS and bipolar disorder. As in adults, SID were significantly associated with greater negative symptoms and lower verbal IQ. However, the associations of verbal IQ (and other verbal tasks) to smell identification in this pediatric sample were explained by the relation of both of these types of variables to negative symptoms. CONCLUSIONS: SID existed across this sample of youths with psychotic disorder, and were specifically related to typical characteristics of schizophrenia, such as negative symptoms and lower intelligence, but not to features of bipolar disorder, such as grandiosity. SID is a characteristic of early onset psychosis that may be useful for prognostic purposes. (+info)
Determinants for nasal trigeminal detection of volatile organic compounds.
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We explored the influence of methodological and chemical parameters on the detection of nasal chemesthesis (i.e., trigeminal stimulation) evoked by volatile organic compounds (VOCs). To avoid odor biases, chemesthesis was probed via nasal pungency detection in anosmics and via nasal localization (i.e., lateralization) in normosmics, in both cases using forced-choice procedures. In the experiments with anosmics, 12 neat VOCs were selected based on previous reports of lack of chemesthetic response. Although none of the VOCs reached 100% detection, detectability and confidence of detection were higher when using a glass vessel system adapted with nosepieces to fit the nostrils tightly than when using wide-mouth glass jars. Half the stimuli were detected well above chance and half were not. When the latter were tested again after being heated to 37 degrees C, that is, body temperature (from room temperature, 23 degrees C), to increase their vapor concentration, only one, octane, significantly increased its detectability. Chemesthesis gauged with normosmics mirrored that with anosmics. Gas chromatography measurements showed that, even at 23 degrees C, the saturated vapor concentrations of the undetected stimuli, except vanillin, were well above the respective calculated nasal pungency threshold (NPT) from an equation that, in the past, had accurately described and predicted NPTs. We conclude that, except for octane and perhaps vanillin, the failure of the other four VOCs to precipitate nasal chemesthesis rests on a chemical-structural limitation, for example, the molecules lack a key property to fit a receptor pocket, rather than on a concentration limitation, for example, the vapor concentration is too low to reach a threshold value. (+info)
Anosmia is very common in the Lewy body variant of Alzheimer's disease.
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BACKGROUND: Olfactory abnormalities are reported in Alzheimer's disease and Parkinson's disease. Anosmia appears to be common in dementia with Lewy bodies but not in pure Alzheimer's disease. OBJECTIVE: To determine whether anosmia improves discrimination between the Lewy body variant (LBV) of Alzheimer's disease and "pure" Alzheimer's disease. METHODS: 106 cases of necropsy confirmed pure Alzheimer's disease (n = 89) or LBV (n = 17) were reviewed. All had received butanol odour threshold testing. Anosmia was defined as a score < or = 1.0 on a 0-9 point scale. Logistic regression analysis was used to model potential predictors (for example, parkinsonism, smoking, hallucinations) of neuropathological diagnosis and anosmia. RESULTS: LBV cases had an increased prevalence of anosmia (65%) compared with Alzheimer's disease (23%; odds ratio (OR) = 6.3, p = 0.00045), or normal elderly people (6.7%). Within the dementia cases, the negative predictive value (92%) and specificity (78%) of anosmia were both good; sensitivity for detecting LBV was 65%, but the positive predictive value (PPV) was only 35%. Logistic regression models showed anosmia (OR = 5.4, p = 0.005) and visual hallucinations (OR = 7.3, p = 0.007) were strong independent predictors of Lewy body pathology. When anosmia was added as a core feature to consensus diagnostic criteria for probable Lewy body dementia, five additional cases of LBV were detected (29% increased sensitivity), but with four additional false positives (1% increased discrimination, 4% decreased specificity, 33% decreased PPV). CONCLUSIONS: Anosmia is very common in LBV. Adding anosmia as a core feature improved sensitivity for detecting LBV, but did not improve discrimination between Alzheimer's disease and LBV owing to a concomitant increase in false positives. (+info)
Electrophysiological and behavioral phenotype of insulin receptor defective mice.
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The olfactory bulb expresses one of the highest levels of insulin found in the brain. A high level of expression of the concomitant insulin receptor (IR) kinase is also retained in this brain region, even in the adult. We have previously demonstrated in a heterologous system that insulin modulates the voltage-dependent potassium channel, Kv1.3, through tyrosine phosphorylation of three key residues in the amino and carboxyl terminus of the channel protein. Phosphorylation also induces current suppression of the Kv1.3-contributed current in cultured olfactory bulb neurons (OBNs) of rodents. In order to explore the behavioral importance of this kinase-induced modulation of the channel for the olfactory ability of the animal, mice with a targeted-gene deletion of the insulin receptor were electrophysiologically and behaviorally characterized. Mice heterozygous for the insulin receptor kinase (IR+/-) gene performed the same as wild-type (+/+) mice when challenged with a traditional, non-learning-based task to test gross anosmia. There was also no significant difference across the two genotypes in tests designed to measure exploratory behavior or in a battery of systems physiology experiments designed to assess metabolic energy usage (locomotion, ingestive behaviors, weight, oxygen consumption, and respiratory quotient). Object memory recognition tests suggest that IR+/- mice have an impairment in recognition of familiarized objects; IR+/- mice demonstrate poor performance for both short-term (1 h) and long-term (24 h) memory tests in comparison to that of wild-type mice. Electrophysiological experiments indicate that mitral cell neurons cultured from both heterozygous and homozygous-null mice (IR+/- and IR-/-) have an decreased peak current amplitude compared with that recorded for wild-type (+/+) animals matched for days in vitro (DIV). These data indicate that the loss of one allele of the IR kinase gene modifies the electrical phenotype of the mitral cell neurons in the olfactory bulb without a change in gross olfactory ability. Given our findings that there are no significant changes in metabolic balance of the IR (+/-) mice but some impairment in memory retention, future experiments testing for specific olfactory behaviors or functional deficits in IR-/+ mice models of diabetes will need to either be tasks that do not require learning or will require a different model (such as diet-induced diabetes) that may evoke a stronger phenotype. (+info)
Mechanical obstruction of the olfactory cleft reveals differences between orthonasal and retronasal olfactory functions.
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Following up on recent observations in patients with nasal polyposis (NP), the present study aimed to investigate whether a mechanical obstruction of the anterior olfactory cleft (OC) would produce differential effects on orthonasal and retronasal olfactory functions. To this end, we studied 33 healthy subjects in a randomized trial. Sponges with high content of saline were either placed in the OC or on the respiratory epithelium, such that this was blinded to both subject and observer. The results indicated that orthonasal (P = 0.04) but not retronasal (P = 0.15) olfactory identification ability was lower when the OC was blocked. This confirms the idea that differences between orthonasal and retronasal olfactory functions, as observed in NP patients, are, at least to some degree, due to mechanical obstruction of the anterior portion of the OC. The present data also suggest that mechanical obstruction is a means to induce reversible hyposmia void of side effects which can be performed in a blinded fashion. This might become a valuable model of hyposmia for future investigations. (+info)
Evaluation of the validity of a maximum likelihood adaptive staircase procedure for measurement of olfactory detection threshold in mice.
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Threshold is defined as the stimulus intensity necessary for a subject to reach a specified percent correct on a detection test. MLPEST (maximum likelihood parameter estimation by sequential testing) is a method that is able to determine threshold accurately and more rapidly than many other methods. Originally developed for human auditory and visual tasks, it has been adapted for human olfactory and gustatory tests. In order to utilize this technique for olfactory testing in mice, we have adapted MLPEST methodology for use with computerized olfactometry as a tool to estimate odor detection thresholds. Here we present Monte Carlo simulations and operant conditioning data that demonstrate the potential utility of this technique in mice, we explore the ramifications of altering MLPEST test parameters on performance, and we discuss the advantages and disadvantages of using MLPEST compared to other methods for the estimation of thresholds in rodents. Using MLPEST, we find that olfactory detection thresholds in mice deficient for the cyclic nucleotide-gated channel subunit A2 are similar to those of wild-type animals for odorants the knockout animals are able to detect. (+info)
Successful treatment of idiopathic plasmacytic lymphadenopathy with polyclonal hypergammaglobulinemia.
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A 51-year-old male was admitted because of eyelid edema and anosmia, which developed in 1985. He showed bilateral cervical lymphadenopathy, with nodes larger than 2 x 2 cm, and remarkable eyelid edema. Anemia, hyperimmunoglobulinemia with hypo-albuminemia (no M-protein) and liver dysfunction were found. Bone marrow, renal function, urine analysis and LDH level were normal. Cervical lymph node biopsy showed interfollicular proliferation of plasma cells without any malignant appearance. On day 3 of oral prednisolone (PD), anosmia abruptly improved from day 7, eyelid swelling, cervical lymphadenopathy and gammopathy subsided gradually. Since PD was tapered off, no relapse has been observed thus far. (+info)
Effect of air pollution on olfactory function in residents of Mexico City.
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To our knowledge there has been no study of the effect of everyday air pollution on olfactory function. It was therefore the aim of this study to compare the olfactory performance of long-term residents of Mexico City, an environment with high air pollution, with the olfactory performance of residents of the Mexican state of Tlaxcala, a region geographically similar to Mexico City but with low air pollution. Healthy volunteers [82 Mexico City subjects (MEX), 86 Tlaxcala subjects (TLX)] 20-63 years of age and balanced for age and gender between the two localities were tested for the perception of the odors of everyday beverages presented in squeeze bottles. When tested with ascending concentrations of stimuli in a three-way oddball paradigm, residents of Tlaxcala detected the odors of instant coffee and of an orange drink at significantly lower concentrations than residents of Mexico City. They also performed significantly better in discriminating between the two similar-smelling Mexican beverages horchata and atole in an oddball test. Significant differences between the two populations in overall olfactory performance were apparent in three of the four age classes (20- to 29-, 30- to 39-, and 40- to 49-year-old subjects) but not in the 50-63 years age class. About 10% of MEX subjects compared to about 2% of TLX subjects were judged to have poor olfactory function; all were from the older age classes (mean age: 48.6 years). Thus, air pollution in Mexico City appears to have a substantial impact on olfactory function even in young and middle-aged residents. (+info)