Familial influence on variation in age of onset and behavioural phenotype in Alzheimer's disease.
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BACKGROUND: Alzheimer's disease manifests considerable heterogeneity, the cause of which is unknown. AIMS: To determine the familial (genotypic) influence on phenomenology (phenotype) in Alzheimer's disease. METHOD: Affected sibling pairs with Alzheimer's disease were assessed for a range of cognitive and non-cognitive symptoms. Resemblance for phenotypic characteristics was estimated using intraclass correlations for continuous traits and by pairwise concordance for dichotomous traits. The relationship between age of onset and APOE genotype was examined using linear regression analysis. RESULTS: Significant familial effects on age of onset (intraclass correlation 0.41) and mood state (intraclass correlation 0.26), and a relatively high pairwise concordance for agitation (excess concordance 0.1) were found. The APOE locus was found to account for 4% of the variance in age of onset. CONCLUSIONS: Substantial familial influence on age of onset, depression and agitation suggests that genotype does influence phenotype in Alzheimer's disease. Establishing the molecular basis for this phenotypic variation may prove relevant to other neuropsychiatric disorders. (+info)
Categorization of unilaterally presented emotional words: an ERP analysis.
(34/2819)
This study is intended to clarify the functional role of different ERP components as indicators of the processing of emotions. The effect of emotional connotation of words on hemispheric lateralization is also explored. Visual ERPs were recorded to unilaterally presented positive, negative, and neutral words that should be categorized according to their emotional connotation. The P2 amplitude was larger to positive than to negative words whereas P3 amplitude was larger to positive words compared with neutral ones. The slow positive wave (SPW) was influenced by words emotionality at anterior and posterior sites differently. The amplitude of the N1 component was larger in the left hemisphere to contralaterally presented words. The P2 and P3 components were larger over the left hemisphere whereas the N3 and N4 components were larger over the right hemisphere to ipsilateral stimulation. The results support our hypotheses on the functional role of positive ERP components in the processing of an affective words connotation: the P2 wave reflects a general evaluation of emotional significance, the P3 a task-related decision, and the SPW an additional decision control in the context of the emotional experience of an individual. Neither the "right hemisphere hypothesis" nor "valence hypothesis" on lateralization of the processing of emotions were confirmed. Each hemisphere seems to exert its effect on emotion through specific hemispheric resources that are unequally allocated along the different stages of task processing and may cause alternation of hemispheric dominance. (+info)
Comparative kinetics and response to the benzodiazepine agonists triazolam and zolpidem: evaluation of sex-dependent differences.
(35/2819)
Eighteen healthy volunteers (10 men and 8 women) participated in a single-dose, double-blind, three-way crossover pharmacokinetic and pharmacodynamic study. Treatment conditions were 0.25 mg of triazolam, a full-agonist benzodiazepine ligand; 10 mg of zolpidem, an imidazopyridine having relative selectivity for the type 1 benzodiazepine receptor subtype; and placebo. Weight-normalized clearance of triazolam was higher in women than in men (8.7 versus 5. 5 ml/min/kg), but the difference was not significant. In contrast, zolpidem clearance was lower in women than in men (3.5 versus 6.7 ml/min/kg, P <.06). Compared to placebo, both active medications produced significant benzodiazepine agonist-like pharmacodynamic effects: sedation, impaired psychomotor performance, impaired information recall, and increased electroencephalographic beta-amplitude. Effects of triazolam and zolpidem in general were comparable and less than 8 h in duration. There was no evidence of a substantial or consistent sex difference in pharmacodynamic effects or in the kinetic-dynamic relationship, although subtle differences could not be ruled out due to low statistical power. The complete dependence of triazolam clearance on CYP3A activity, as opposed to the mixed CYP participation in zolpidem clearance, may explain the differing sex effects on clearance of the two compounds. (+info)
A neurobehavioral treatment for unilateral complex partial seizure disorders: a comparison of right- and left-hemisphere patients.
(36/2819)
This study looked at the efficacy of a multi-disciplinary neurobehavioral approach for treating patients with complex partial seizure disorders. Patients with a seizure focus in either the left or right hemisphere were compared for overall effectiveness of this approach in achieving control of complex partial seizures. Patients in this study received short-term treatment based on a model of self-control developed by the Andrews/Reiter Epilepsy Research Program. This research selected all patients who met the lateralization criterion from among cases receiving short-term treatment between 1992 and 1996. Forty-four patients were identified, a group of 21 right-hemisphere subjects and a second group of 23 left-hemisphere subjects. These patients were treated in a short-term (5 consecutive days) treatment protocol and then released, with weekly phone contact for 6 months following treatment. They were then followed for an additional 19 months through the continued submission of their seizure logs and journals. Subjects in both groups kept seizure records throughout the study starting with a two-month baseline period. Other data collected allowed study of the interaction of emotional states with seizure occurrence. This project produced valuable and relevant information regarding neurobehavioral management interventions as an effective adjunctive or alternative treatment for obtaining seizure control in epilepsy patients. Overall, 79% of patients treated achieved seizure control. More than 64% identified a recognizable emotional state that triggered seizures. The emotional trigger was specific for either the right or left hemisphere. (+info)
The central role of the prefrontal cortex in directing attention to novel events.
(37/2819)
The physiological basis for the striking decrease of attention to novel events following frontal lobe injury is poorly understood. In this study, event-related potentials (ERPs) were recorded from patients with frontal lobe damage and matched subjects, who controlled the duration of viewing of background, novel and target stimuli. Frontal lobe patients did not differ from normal controls in terms of age, education, estimated IQ or mood. However, they were judged to be more apathetic as measured by self-report and informants' ratings. Patients with frontal lobe damage exhibited markedly reduced amplitude of the novelty P3 response and the duration of viewing of novel stimuli. In contrast, injury to the frontal lobes had a limited impact on P3 amplitude and behavioural responses (viewing duration and reaction time) to target stimuli. A strong correlation was found between measures of apathy and both attenuated P3 amplitude and viewing duration in response to novel but not target stimuli. Differences in amplitude of the novelty P3 response explained a large portion of the variance associated with duration of viewing of novel stimuli. After controlling for the influence of P3 amplitude, there was no association between frontal lobe injury and reduced viewing of novel stimuli. The results of this study suggest that frontal lobe damage leads to diminished visual attention to novel events through its disruption of neural processes underlying the novelty P3 response. These processes appear to regulate the allocation of attentional resources and early exploratory behaviours, and are not limited to immediate orienting responses. Damage to the frontal lobes may prevent the generation of a signal which indicates that a novel event in the environment requires additional attention due to its potential behavioural significance. The disruption of these processes is likely to contribute to the apathy observed in patients after injury to the frontal lobes. (+info)
Development of a minimum data set-based depression rating scale for use in nursing homes.
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BACKGROUND: depression is common but under-diagnosed in nursing-home residents. There is a need for a standardized screening instrument which incorporates daily observations of nursing-home staff. AIM: to develop and validate a screening instrument for depression using items from the Minimum Data Set of the Resident Assessment Instrument. METHODS: we conducted semi-structured interviews with 108 residents from two nursing homes to obtain depression ratings using the 17-item Hamilton Depression Rating Scale and the Cornell Scale for Depression in Dementia. Nursing staff completed Minimum Data Set assessments. In a randomly assigned derivation sample (n = 81), we identified Minimum Data Set mood items that were correlated (P < 0.05) with Hamilton and Cornell ratings. These items were factored using an oblique rotation to yield five conceptually distinct factors. Using linear regression, each set of factored items was regressed against Hamilton and Cornell ratings to identify a core set of seven Minimum Data Set mood items which comprise the Minimum Data Set Depression Rating Scale. We then tested the performance of the Minimum Data Set Depression Rating Scale against accepted cut-offs and psychiatric diagnoses. RESULTS: a cutpoint score of 3 on the Minimum Data Set Depression Rating Scale maximized sensitivity (94% for Hamilton, 78% for Cornell) with minimal loss of specificity (72% for Hamilton, 77% for Cornell) when tested against cut-offs for mild to moderate depression in the derivation sample. Results were similar in the validation sample. When tested against diagnoses of major or non-major depression in a subset of 82 subjects, sensitivity was 91% and specificity was 69%. Performance compared favourably with the 15-item Geriatric Depression Scale. CONCLUSION: items from the Minimum Data Set can be organized to screen for depression in nursing-home residents. Further testing of the instrument is now needed. (+info)
Impairment of neurobehavioral function and color vision loss among workers exposed to low concentration of styrene--a review of literatures.
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Recently many studies on the health effects of workers who exposed to low-concentration styrene have been published. In this paper firstly we mentioned the reasons why nervous system was critical organ for evaluating the toxicity of organic solvents both in the acute and chronic exposure phases. Then we indicated how neurobehavioral test batteries were useful to detect subclinical adverse health effects of workers exposed to organic solvents. Secondly we reviewed many epidemiological studies on the impairment of neurobehavioral function, i.e., perceptual speed, memory, cognition, personality and mood, and the loss of color vision among styrene workers. Finally, we showed our recent data on the relationship between color vision loss and the concentration of urine metabolites among styrene workers. It can conclude that styrene may cause damage on nervous system, even at the low exposure level such as 50 ppm which used to be the Threshold Limit Value (TLV) recommended by Japan Society for Occupational Health (until 1999) and American Conference of Industrial Hygienists (until 1997). (+info)
The parent-physician relationship in pediatric asthma care.
(40/2819)
OBJECTIVE: To examine the feasibility of using a behavioral coding system, the Five Minute Speech Sample (FMSS), to estimate the prevalence of relationship difficulties between parents and physicians in a pediatric asthma care setting. METHOD: The FMSS was administered to 20 parents of children with severe, chronic asthma and to the physicians they worked with during a brief day program admission. RESULTS: Rates of relationship difficulties between parents and physicians ranged from 15% to 40%, comparable to those previously identified in patient-therapist relationships in psychiatric populations. CONCLUSIONS: Although further information is needed about validity and reliability, the FMSS appears to provide clinically relevant information about the parent-physician relationship in the context of pediatric chronic illness. (+info)