Different patterns of N-acetylaspartate loss in subcortical ischemic vascular dementia and AD.

OBJECTIVES: 1) To determine the regional pattern of reduced N-acetylaspartate (NAA) in subcortical ischemic vascular dementia (SIVD); 2) to explore the relationship between NAA reduction and subcortical vascular disease; and 3) to test if MR spectroscopic imaging (MRSI) in combination with structural MRI improves differentiation between SIVD and Alzheimer disease (AD). METHODS: Thirteen patients with SIVD (71 +/- 8 years old) and 43 patients with AD of comparable age and dementia severity were studied using MRSI and MRI. Patients were compared to 52 cognitively normal subjects with and without lacunes. RESULTS: Compared to controls, patients with SIVD had lower NAA by 18% (p < 0.001) in frontal cortex and by 27% (p < 0.003) in parietal cortex, but no significant NAA reduction in white matter and medial temporal lobe. Compared to patients with AD, patients with SIVD had lower NAA by 13% (p < 0.02) in frontal cortex and by 20% (p < 0.002) in left parietal cortex. Cortical NAA decreased in SIVD with increasing white matter lesions (r = 0.54, p < 0.02) and number of lacunes (r = 0.59, p < 0.02). Thalamic lacunes were associated with greater NAA reduction in frontal cortex than were lacunes outside the thalamus (p < 0.02) across groups, after adjusting for cognitive impairments. Adding parietal NAA to MRI-derived hippocampal atrophy improved separation between SIVD and AD (p = 0.02) from 79 to 89%. CONCLUSIONS: These results emphasize the importance of cortical dysfunction as a factor in SIVD and indicate a characteristic pattern of metabolite change that might serve as a basis for improved diagnosis.

Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD.

BACKGROUND: Both AD and normal aging cause brain atrophy, limiting the ability of MRI to distinguish between AD and age-related brain tissue loss. MRS imaging (MRSI) measures the neuronal marker N-acetylaspartate (NAA), which could help assess brain change in AD and aging. OBJECTIVES: To determine the effects of AD on concentrations of NAA, and choline- and creatine-containing compounds in different brain regions and to assess the extent NAA in combination with volume measurements by MRI improves discrimination between AD patients and cognitively normal subjects. METHODS: Fifty-six patients with AD (mean age: 75.6 +/- 8.0 years) and 54 cognitively normal subjects (mean age: 74.3 +/- 8.1 years) were studied using MRSI and MRI. RESULTS: NAA concentration was less in patients with AD compared with healthy subjects by 21% (p < 0.0001) in the medial temporal lobe and by 13% to 18% (p < 0.003) in parietal lobe gray matter (GM), but was not changed significantly in white matter and frontal lobe GM. In addition to lower NAA, AD patients had 29% smaller hippocampi and 11% less cortical GM than healthy subjects. Classification of AD and healthy subjects increased significantly from 89% accuracy using hippocampal volume alone to 95% accuracy using hippocampal volume and NAA together. CONCLUSION: In addition to brain atrophy, NAA reductions occur in regions that are predominantly impacted by AD pathology.

Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer's disease.

OBJECTIVES: To explore volume changes of the entorhinal cortex (ERC) and hippocampus in mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with normal cognition (NC); to determine the powers of the ERC and the hippocampus for discrimination between these groups. METHODS: This study included 40 subjects with NC, 36 patients with MCI, and 29 patients with AD. Volumes of the ERC and hippocampus were manually measured based on coronal T1 weighted MR images. Global cerebral changes were assessed using semiautomatic image segmentation. RESULTS: Both ERC and hippocampal volumes were reduced in MCI (ERC 13%, hippocampus 11%, p<0.05) and AD (ERC 39%, hippocampus 27%, p<0.01) compared with NC. Furthermore, AD showed greater volume losses in the ERC than in the hippocampus (p<0.01). In addition, AD and MCI also had cortical grey matter loss (p< 0.01) and ventricular enlargement (p<0.01) when compared with NC. There was a significant correlation between ERC and hippocampal volumes in MCI and AD (both p<0.001), but not in NC. Using ERC and hippocampus together improved discrimination between AD and CN but did not improve discrimination between MCI and NC. The ERC was better than the hippocampus for distinguishing MCI from AD. In addition, loss of cortical grey matter significantly contributed to the hippocampus for discriminating MCI and AD from NC. CONCLUSIONS: Volume reductions in the ERC and hippocampus may be early signs of AD pathology that can be measured using MRI.

Region and tissue differences of metabolites in normally aged brain using multislice 1H magnetic resonance spectroscopic imaging.

Quantitative measurements of regional and tissue specific concentrations of brain metabolites were measured in elderly subjects using multislice proton magnetic resonance spectroscopic imaging ((1)H MRSI). Selective k-space extrapolation and an inversion-recovery sequence were used to minimize lipid contamination and linear regression was used to account for partial volume problems. The technique was applied to measure the concentrations of N-acetyl aspartate (NAA), and creatine (Cr)- and choline (Cho)-containing compounds in cortical gray and white matter, and white matter lesions of the frontal and the parietal lobe in 40 normal elderly subjects (22 females and 18 males, 56-89 years old, mean age 74 +/- 8). NAA was about 15% lower in cortical gray matter and 23% lower in white matter lesions when compared to normal white matter. Cr was 11% higher in cortical gray matter than in white matter, and also about 15% higher in the parietal cortex than in the frontal cortex. Cho was 28% lower in cortical gray matter than in white matter. Furthermore, NAA and Cr changes correlated with age. In conclusion, regional and tissue differences of brain metabolites must be considered in addition to age-related changes when interpreting (1)H MRSI data.

Reanalysis of multislice (1)H MRSI in amyotrophic lateral sclerosis.

The goal of this work was to reexamine previously published (1) brain spectroscopy data of abnormal metabolite ratios in amyotrophic lateral sclerosis (ALS). Toward this goal, (1)H MR spectroscopic imaging data from 10 ALS and nine control subjects were reanalyzed using improved data analysis techniques, including automated curve fitting and tissue-volume correction. In the motor cortex of ALS, N-acetyl aspartate (NAA) was 23% (P = 0.004) lower than in controls, and in the posterior internal capsule of ALS choline compounds (Cho) were 20% (P = 0.02) higher. This demonstrates that the metabolite ratio changes in ALS were due to NAA loss in the motor cortex (as expected) and Cho increase in the posterior internal capsule (not expected). Magn Reson Med 45:513-516, 2001.

Subcortical ischemic vascular dementia: assessment with quantitative MR imaging and 1H MR spectroscopy.

BACKGROUND AND PURPOSE: Subcortical ischemic vascular dementia is associated with cortical hypometabolism and hypoperfusion, and this reduced cortical metabolism or blood flow can be detected with functional imaging such as positron emission tomography. The aim of this study was to characterize, by means of MR imaging and 1H MR spectroscopy, the structural and metabolic brain changes that occur among patients with subcortical ischemic vascular dementia compared with those of elderly control volunteers and patients with Alzheimer's disease. METHODS: Patients with dementia and lacunes (n = 11), cognitive impairment and lacunes (n = 14), and dementia without lacunes (n = 18) and healthy age-matched control volunteers (n = 20) underwent MR imaging and 1H MR spectroscopy. 1H MR spectroscopy data were coanalyzed with coregistered segmented MR images to account for atrophy and tissue composition. RESULTS: Compared with healthy control volunteers, patients with dementia and lacunes had 11.74% lower N-acetylaspartate/creatine ratios (NAA/Cr) (P = .007) and 10.25% lower N-acetylaspartate measurements (NAA) in the cerebral cortex (P = .03). In white matter, patients with dementia and lacunes showed a 10.56% NAA/Cr reduction (P = .01) and a 12.64% NAA reduction (P = .04) compared with control subjects. NAA in the frontal cortex was negatively correlated with the volume of white matter signal hyperintensity among patients with cognitive impairment and lacunes (P = .002). Patients with dementia, but not patients with dementia and lacunes, showed a 10.33% NAA/Cr decrease (P = .02) in the hippocampus compared with healthy control volunteers. CONCLUSION: Patients with dementia and lacunes have reduced NAA and NAA/Cr in both cortical and white matter regions. Cortical changes may result from cortical ischemia/infarction, retrograde or trans-synaptic injury (or both) secondary to subcortical neuronal loss, or concurrent Alzheimer's pathologic abnormalities. Cortical derangement may contribute to dementia among patients with subcortical infarction.

Age-related metabolite changes and volume loss in the hippocampus by magnetic resonance spectroscopy and imaging.

Magnetic resonance imaging (MRI) studies have produced controversial results concerning the correlation of hippocampal volume loss with increasing age. The goals in this study were: 1) to test whether levels of N-acetyl aspartate (NAA, a neuron marker) change in the hippocampus during normal aging and 2) to determine the relationship between hippocampal NAA and volume changes. Proton magnetic resonance spectroscopic imaging (1H MRSI) and MRI were used to measure hippocampal metabolites and volumes in 24 healthy adults from 36 to 85 years of age. NAA/Cho decreased by 24% (r = 0.53, p = 0.01) and NAA/Cr by 26% (r = 0.61, p < 0.005) over the age range studied, whereas Cho/Cr remained stable, implying diminished NAA levels. Hippocampal volume shrank by 20% (r = 0.64, p < 0.05). In summary, aging effects must be considered in 1H MRSI brain studies. Furthermore, because NAA is considered a marker of neurons, these results provide stronger support for neuron loss in the aging hippocampus than volume measurements by MRI alone.

Reduced hippocampal N-acetylaspartate without volume loss in schizophrenia.

Quantitative magnetic resonance imaging (MRI) can measure total gray matter volume but cannot discriminate between neurons and glia. Proton magnetic resonance spectroscopic imaging (1H MRSI) measures N-acetylaspartate (NAA) which is a selective marker of neuronal loss or neuronal dysfunction. The objective of this study was to obtain quantitative measures of hippocampal volume and hippocampal NAA to determine if there was evidence for hippocampal neuronal dysfunction or neuronal loss in schizophrenia. Quantitative MRI and 1H MRSI was performed on the right and left hippocampal regions in 23 chronic schizophrenic patients and 18 control subjects. Relative to the control group, the patients with schizophrenia demonstrated no change in hippocampal volumes bilaterally, but significantly decreased NAA in the hippocampal regions bilaterally. There was also no correlation between hippocampal volumes and NAA in either the schizophrenics or controls. These findings suggest that: (1) hippocampal NAA may be a more sensitive measure of neuronal loss than volumetric measurements; and (2) reduced hippocampal NAA may be measuring neuronal dysfunction or damage rather than neuronal loss in this sample of schizophrenics.

Alzheimer disease: quantitative H-1 MR spectroscopic imaging of frontoparietal brain.

PURPOSE: To replicate previous hydrogen-1 magnetic resonance (MR) spectroscopic imaging findings of metabolic abnormalities in patients with Alzheimer disease (AD), to verify that metabolic abnormalities are not an artifact of structural variations measured at MR imaging, to determine whether metabolic changes correlate with dementia severity, and to test whether MR imaging and MR spectroscopic imaging findings together improve ability to differentiate AD. MATERIALS AND METHODS: MR spectroscopic imaging and MR imaging were performed in 28 patients with AD and 22 healthy elderly subjects. Spectroscopic imaging data were coregistered with MR imaging segmentation data to obtain volume-corrected metabolite concentrations. RESULTS: Consistent with previous results, N-acetyl aspartate (NAA) levels were statistically significantly reduced in frontal and posterior mesial cortex of AD patients, presumably due to neuronal loss. NAA level reductions were independent of structural variations measured at MR imaging and, in parietal mesial cortex, were correlated mildly with dementia severity. Spectroscopic imaging findings of NAA level combined with MR imaging measures did not improve discrimination power for AD relative to that of MR imaging alone. CONCLUSION: Reduced NAA levels in frontoparietal brain are of limited use for diagnosis of AD. However, they are not an artifact of structural variations and thus may provide useful information for the understanding of the pathologic processes underlying AD.

Changes of hippocampal N-acetyl aspartate and volume in Alzheimer's disease. A proton MR spectroscopic imaging and MRI study.

Hippocampal atrophy detected by MRI is a prominent feature of early Alzheimer's disease (AD), but it is likely that MRI underestimates the degree of hippocampal neuron loss, because reactive gliosis attenuates atrophy. We tested the hypothesis that hippocampal N-acetyl aspartate (NAA: a neuronal marker) and volume used together provide greater discrimination between AD and normal elderly than does either measure alone. We used proton MR spectroscopic imaging (1H MRSI) and tissue segmented and volumetric MR images to measure atrophy-corrected hippocampal NAA and volumes in 12 AD patients (mild to moderate severity) and 17 control subjects of comparable age. In AD, atrophy-corrected NAA from the hippocampal region was reduced by 15.5% on the right and 16.2% on the left (both p < 0.003), and hippocampal volumes were smaller by 20.1% (p < 0.003) on the right and 21.8% (p < 0.001) on the left when compared with control subjects. The NAA reductions and volume losses made independent contributions to the discrimination of AD patients from control subjects. When used separately, neither hippocampal NAA nor volume achieved to classify correctly AD patients better than 80%. When used together, however, the two measures correctly classified 90% of AD patients and 94% of control subjects. In conclusion, hippocampal NAA measured by 1H MRSI combined with quantitative measurements of hippocampal atrophy by MRI may improve diagnosis of AD.

Tissue segmentation of the brain in Alzheimer disease.

PURPOSE: To compare brain tissue in patients with Alzheimer disease with that in elderly control subjects by using high-resolution MR imaging and quantitative tissue-segmentation techniques. METHODS: MR imaging of the brain was performed in 21 patients with Alzheimer disease and 17 control subjects. A computerized segmentation program was used to quantify volumes of ventricular and sulcal cerebrospinal fluid (CSF), white matter, cortical gray matter, and white matter signal hyperintensity. Statistical analysis was performed using analysis of variance. RESULTS: We found a significant decrease in total brain tissue and cortical gray matter and an increase in the ventricular and sulcal CSF in Alzheimer patients compared with control subjects. There was no difference in the volume of white matter. More white matter signal hyperintensities were found in Alzheimer patients, and a significant interaction between age and group was noted. Neuropsychological test scores correlated significantly with sulcal CSF in patients with Alzheimer disease. CONCLUSION: Semiautomated segmentation of MR images of the brains of patients with Alzheimer disease reveals significant brain atrophy attributable to loss of cortical gray matter, which is compatible with the pathologic features of Alzheimer disease. There is also a significant increase in white matter signal hyperintensities. Tissue segmentation may increase our understanding of dementia but, as yet, when used alone, it does not play a role in the premorbid diagnosis of Alzheimer disease.

Neuropsychiatric and somatic characteristics of young adults with and without self-reported chemical odor intolerance and chemical sensitivity.

The psychological, neuropsychiatric, and somatic characteristics of young adults who have different degrees of cacosmia (i.e., feeling "ill" from the odor of xenobiotic chemicals) and who have self-described "chemical sensitivity" were examined. A total of 800 college students completed the following: a self-rating scale for frequency of odor intolerance for 10 common substances, Simon Environmental Illness Symptom Survey, the SCL-90-R, Barsky Amplification Scale, Pearlin-Schooler Mastery Scale, Cheek-Buss and Kagan Shyness scales, Marlowe-Crowne Social Desirability Scale, and a health-symptom and physician-diagnosed checklist. Two pairs of groups were compared: (1) subjects in the top 16% (i.e., cacosmics) and bottom 15% (noncacosmics) of the sample with respect to odor intolerance scale scores; and (2) subjects from the entire sample who did (28%) or did not (72%) consider themselves to be "especially sensitive to certain chemicals.¿ Cacosmics and the chemically sensitive subjects scored significantly higher on measures of psychological distress and amplification of somatic symptoms, but there was little evidence of lifestyle change, as assessed by the Simon Survey. Compared with their respective comparison groups, cacosmic and chemically sensitive groups had significantly higher incidences of illnesses associated with chemicals, alcohol intake, opiate drug use, and caffeine use, even after controlling for the psychological measures and histories of atopic allergy. Subjects with and without neuropsychiatric symptoms were differentiated with respect to chemical odor intolerance, but subjects with and without atopic allergies and possible autoimmune diseases were differentiated with respect to chemical sensitivity. Females were more cacosmic than males. Cacosmia is defined by a population subset, with or without occupational xenobiotic exposures or disability, that has distress and symptom amplification and neuropsychiatric and somatic symptoms, none of which are explained fully by psychological measures. Prospective clinical studies are possible with such individuals. The data are also consistent with a time-dependent sensitization model for illness from low-level chemical exposures.

Trait shyness in the elderly: evidence for an association with Parkinson's disease in family members and biochemical correlates.

The emergence of potential treatments to slow the progression of idiopathic Parkinson's disease (PD) has increased the need for early identification of persons at risk. Although considered controversial, some prior studies indicate that PD patients may have premorbid histories of greater trait introversion or shyness as well as increased rates of disorders associated with shyness (e.g., anxiety, affective disorders, and irritable bowel syndrome). Essential features of trait shyness include (a) inhibited and avoidant behaviors and (b) physiological hyperreactivity to the novel or unfamiliar. In parallel, (a) depression in PD patients is associated with increased harm avoidance (a possible serotonergic function), and (b) PD patients have premorbid and comorbid decreases in novelty-seeking (a possible dopaminergic function). Taken together, previous research suggests the following hypotheses: (1) given evidence for marked heritability of shyness, shy elderly should report higher rates of PD in their family members than would nonshy elderly; and (2) shy elderly without PD should exhibit psychological and biologic characteristics similar to those reported in PD. Two groups, representing the top 27% (n = 37) and bottom 31% (n = 43) of scores on a standardized shyness scale, were drawn from a larger cohort of 138 older adults (ages 50-90) living in an active retirement community. Seventeen percent of the shy versus 2% of the nonshy reported PD in a family member or self (P < .05). Shy elderly were significantly more anxious (P < .01) and depressed (P < .05) than were the nonshy.(ABSTRACT TRUNCATED AT 250 WORDS)

Psychological characteristics and subjective intolerance for xenobiotic agents of normal young adults with trait shyness and defensiveness. A parkinsonian-like personality type?

The present study examines the psychological characteristics and self-reported responses to xenobiotic agents such as tobacco smoke and pesticide of normal young adults with personality traits similar to those claimed for Parkinsonian patients. Previous research, though controversial, has suggested that persons with idiopathic Parkinson's disease (PD) have premorbid personality traits that may include shyness and repressive defensiveness. Other epidemiological evidence indicates that PD patients may have premorbidly increased prevalence of anxiety, affective, and/or somatoform disorders; decreased rates of smoking and alcohol consumption; and elevated exposure to herbicides or pesticides. A total of 783 college students enrolled in an introductory psychology course completed the Cheek-Buss Scale (shyness), the Marlowe-Crowne Social Desirability Scale (defensiveness), Symptom Checklist 90 (revised), the Mastery Scale, a health history checklist, and rating scales for frequency of illness from alcohol and 10 common environmental chemicals. Subjects were divided into four groups on the basis of above- versus below-median scores on the Cheek-Buss and Marlowe-Crowne scales (persons high in shyness and defensiveness, those high only in shyness, those high only in defensiveness, and those low in both shyness and defensiveness). The group high in shyness but low in defensiveness had the highest, whereas the group low in shyness but high in defensiveness had the lowest, total scores on the SCL-90-R; the two shyest groups were lowest in sense of mastery.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitization to early life stress and response to chemical odors in older adults.

This study examined the hypothesis that older persons who currently report illness from environmental chemical odors (cacosmia) may have experienced higher levels of stress early in life than did noncacosmic controls. The hypothesis derives from a time-dependent sensitization (TDS) model for cacosmia (Bell et al 1992) that predicts a relative interchangeability of stress and chemicals in inducing and eliciting sensitized responses in vulnerable individuals. Subjects were selected from those in the top 24% (cacosmic) and bottom 27% (noncacosmic) of a sample of 192 older adults (mean age 73.8 years) for self-reported frequency of illness form the odors of pesticide, car exhaust, paint, perfume, and new carpet. As in previous investigations, cacosmics were younger, more depressed, and more shy; cacosmics also included a higher proportion of women (83% versus 61%). As predicted, cacosmics rated themselves higher in stress for the first four decades of their lives, but not the recent past or present, even after controlling for depression, anxiety, hostility, shyness, age, and gender. Cacosmics reported increased prevalence of physician-diagnosed nasal allergies, breast cysts, hypothyroidism, sinusitis, food sensitivities, irritable bowel, and migraine headache. Only 4% of the overall sample (including 9% of the cacosmics) acknowledged the controversial physician diagnosis of "chemical sensitivity." The replicated observation of greater shyness in cacosmics is consistent with the ability of hyperreactivity to novelty to predict enhanced susceptibility to TDS from low levels of pharmacological agents in animals. The findings support a TDS model for cacosmia and suggest that cacosmia as a symptom identifies a large subset of the nonindustrial population with significant psychophysiological health problems that merit further objective examination.

Symptom and personality profiles of young adults from a college student population with self-reported illness from foods and chemicals.

Despite much debate over a presumptively somatic vs psychological etiology of nonatopic food and chemical sensitivities, little systematic research has addressed the issues. The present study investigated self-reported illness from several common foods (wheat, dairy, eggs) and chemicals (pesticide, car exhaust, paint, perfume, new carpet), symptom patterns, and psychological profiles of a sample of young adult college students (n = 490, age 19.4 +/- 2.4, 52% female/48% male). Subjects were divided into 4 groups on the basis of sample medians for frequency of illness from the foods (FI) and chemicals (CI); high FI with high CI (FI/CI), high FI alone, high CI alone, and NOILL (low FI and CI). FI was associated with more defensiveness (denial of negativity) while CI was linked with more shyness (avoidance of novelty). Women outnumbered men in all groups (FI/CI: 61%; FI: 80% CI: 55%) except the NOILL (40% women). Nevertheless, the FI/CI, FI, and/or CI groups still had significantly higher total symptom scores as well as more indigestion, headache, and memory trouble than did the NOILL group, even after depression, anxiety, shyness, defensiveness, and gender were covaried. The illness groups reported significantly more limitation of foods that mobilize endogenous opioids or generate exogenous opioids (sweets, fats, bread) as well as more illness from opiate drugs, small amounts of beverage alcohol, and late meals. Nasal symptoms from pollens or animals were more common in the FI/CI (42%) and CI (42%) than in FI (26%) or NOILL (28%) groups. Premenstrual tension syndrome and irritable bowel were also more common in the FI/CI group. The findings indicate that young adults outside the clinical setting who are relatively higher in FI and/or CI have distinctive symptom and psychological patterns. Covariate analyses suggest that important symptoms in FI and CI individuals such as indigestion, headache, and memory problems may occur in addition to rather than as simply part of emotional distress. The data are consistent with a previously hypothesized role of olfactory-limbic and hypothalamic pathways and with a time-dependent sensitization model for illness from foods and chemicals.

Possible time-dependent sensitization to xenobiotics: self-reported illness from chemical odors, foods, and opiate drugs in an older adult population.

The present paper summarizes key features of time-dependent sensitization (TDS) in neuropharmacology (progressive amplification of behavioral, neuronal, endocrine, and/or immune responses to repeated intermittent exposures to an environmental agent or cross-sensitizing agents) as a possible model for cacosmia (subjective sense of feeling ill from low levels of environmental chemical odors) in nonindustrial and industrial populations; and extends previous cacosmia research in nonpatient populations to an elderly sample. This study examined the symptom and psychological profiles of 263 older adults (aged 60-90 y, 71% women, 29% men); 57% reported that at least one chemical and 17% reported that at least four of five chemicals (pesticide, automobile exhaust, paint, new carpet, perfume) made them feel ill. Cacosmia ratings correlated weakly and negatively with age (r = -0.19, p = .001) over the whole sample. Cacosmia correlated significantly with self-reported illness from foods that may mobilize or generate opioid peptides (wheat, dairy, eggs) (r = 0.32, p < .0001) and with illness from opiate drugs (r = 0.23, p < .0001). When the sample was divided into four cells on the basis of above-versus below-median total chemical-induced illness score (CI) and total food-induced illness score (FI), the high CI and high FI, high CI only, and high FI only groups had more frequent indigestion, and the high CI group had more frequent difficulty concentrating than the groups below median for illness from both chemicals and foods (NOILL), even after covarying for age and anxiety. The most cacosmic subjects noted higher prevalence of physician-diagnosed allergies and irritable bowel than did noncacosmic subjects. In contrast with previous young adult cohort studies, the older illness groups did not differ with regard to sex distribution, depression, shyness, or repressive defensiveness. When considered with prior surveys of young adults, the present findings are consistent with the presence of previously established, time-dependent sensitization to multiple xenobiotic agents in susceptible individuals for whom psychological variables do not explain the symptom of cacosmia. If cacosmia is a symptom of TDS, then the neuropharmacology literature suggests the possibility of excitatory amino acid, hypothalamic-pituitary-adrenal axis, dopaminergic, and/or opioid involvement. Prospective studies with objective measures testing the possible induction of TDS to specific chemicals are indicated.

Self-reported illness from chemical odors in young adults without clinical syndromes or occupational exposures.

The present survey of young adult college students investigated the prevalence of self-reported illness from the smell of the five following common environmental chemicals (cacosmia): (1) pesticide, (2) automobile exhaust, (3) paint, (4) new carpet, and (5) perfume. Sixty-six percent of 643 students reported feeling ill from one or more of the five chemicals; 15% identified the smell of at least four chemicals as making them ill. Ratings of illness from pesticide correlated weakly but significantly with ratings for the largest number of individual symptoms (9 of 11); daytime tiredness and daytime grogginess both correlated at high levels of significance with illness ratings (on a 5-point scale) for four of the five chemicals. The most cacosmic group (CS) included significantly more women (79%) than the noncacosmic group (NS) (49%); women overall were more cacosmic than men (p < .001), even with the significant covariate of depression. Ratings of cacosmia correlated only weakly with scores for depression (r = 0.16), anxiety (r = 0.08), and trait shyness (r = 0.18) in the total sample. On stepwise multiple regression with cacosmia score as the dependent measure, shyness accounted for 5.8% of the variance, while depression, anxiety, sense of mastery, and repression did not enter the equation. Histories of physician-diagnosed hay fever, but not asthma, were more frequent in the CS (16%) than in the NS group (5%). Without the confounds of chronic illness or specific treatment programs, these data are similar to patterns described clinically for a subset of patients with multiple chemical sensitivities (MCS), including previous data on increased nasal resistance in MCS.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of arginine vasopressin in the development of tolerance to ethanol in normal and Brattleboro rats.

Administration of AVP and related peptide fragments following ethanol (EtOH) administration has been shown to enhance retention of tolerance to ethanol. The present studies were designed specifically to: (1) examine the influence of AVP given concurrently with EtOH on the development of tolerance to the ataxic and hypothermic effects of EtOH in Long-Evans rats, and (2) to determine if tolerance to these effects develops in Brattleboro rats which are deficient in AVP. In Experiment 1, EtOH (2.5 g/kg, 15% v/v) was administered IP to 2 groups of rats in combination with a SC injection of either AVP (6 micrograms/kg) or an equal volume of saline. Two additional control groups received IP saline injections in combination with either saline or AVP. After 13 days, EtOH-treated rats were significantly more tolerant than saline-treated animals. AVP significantly increased the hypothermic and ataxic effects of EtOH and failed to enhance tolerance development. AVP delayed the extinction of tolerance to the hypothermic (but not the ataxic) effects of ethanol when administered during the extinction phase to rats previously treated with EtOH. In Experiment 2, Brattleboro rats were injected with EtOH or an equivalent volume of saline and tested for ataxia and hypothermia. Rats receiving EtOH failed to demonstrate significant tolerance to either effect of ethanol after 12 treatment days.