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R S Kahn

Publications and source records attributed to R S Kahn.

At least 55 records · Page 3Linked to original sources
PubMed2001

Combined analysis of language tasks in fMRI improves assessment of hemispheric dominance for language functions in individual subjects.

Recent advances in functional neuroimaging techniques have prompted an increase in the number of studies investigating lateralization of language functions. One of the problems in relating findings of various studies to one another is the diversity of reported results. This may be due to differences in the tasks that are used to stimulate language processing regions and in the control tasks, as well as differences in the way imaging data are analyzed,in particular the threshold for significance of signal change. We present a simple method to assess language lateralization that allows for some variation of tasks and statistical thresholding, but at the same time yields reliable and reproducible results. Images acquired during a set of word-comprehension and -production tasks are analyzed conjointly. As opposed to the use of any one particular task, this combined task analysis (CTA) approach is geared toward identifying language regions that are involved in generic language functions rather than regions that are involved in functions that are specific to a single task. In two experiments CTA is compared to single-task analysis in healthy right-handed males. In a third experiment left-handed males were examined. Results indicate that CTA: (1) improves detection of language-related brain activity in individual subjects and (2) yields a high language laterality index (LI) in right-handed males with a small variance across subjects. The high LI matches the strong left-hemisphere dominance for language that is typical for these subjects as reported in neuropsychological and clinical tests in other studies. In the left-handed subjects dominance was found either in the left (n = 4) or the right (n = 1) hemisphere or was absent (n = 3). The LI derived from CTA is more consistent across statistical thresholds for significance of signal change in fMRI analysis than in individual-task analysis. Also, the CTA results are very similar to those obtained with conjunction analysis of the same data.

Adult↗
PubMed2001

Automatic segmentation of the ventricular system from MR images of the human brain.

An algorithm was developed that automatically segments the lateral and third ventricles from T1-weighted 3-D-FFE MR images of the human brain. The algorithm is based upon region-growing and mathematical morphology operators and starts from a coarse binary total brain segmentation, which is obtained from the 3-D-FFE image. Anatomical knowledge of the ventricular system has been incorporated into the method in order to find all constituting parts of the system, even if they are disconnected, and to avoid inclusion of nonventricle cerebrospinal fluid (CSF) regions. A test of the method on a synthetic MR brain image produced a segmentation overlap of 0.98 between the simulated ventricles ("model") and those defined by the algorithm. Further tests were performed on a large data set of 227 1.5 T MR brain images. The algorithm yielded useful results for 98% of the images. The automatic segmentations had intra-class correlation coefficients of 0.996 for the lateral ventricles and 0.86 for the third ventricle, with manually edited segmentations. Comparison of ventricular volumes of schizophrenia patients compared with those of healthy control subjects showed results in agreement with the literature.

Algorithms↗
PubMed2001

The effect of clozapine on caudate nucleus volume in schizophrenic patients previously treated with typical antipsychotics.

Typical antipsychotics have been reported to enlarge the caudate nucleus in schizophrenic patients. The atypical antipsychotic, clozapine, is associated with a decrease in caudate size in patients previously treated with typical antipsychotics. The present study investigates whether a change in caudate volume after switching from treatment with typical antipsychotics to treatment with clozapine is related to improvement in symptoms or tardive dyskinesia (TD). Twenty-six schizophrenic patients participated in this open study. Caudate nucleus volume and TD were assessed before discontinuing typical antipsychotics and after 24 weeks of treatment with clozapine. After discontinuing typical antipsychotics, symptoms were assessed in a 3 days drug-free period and subsequently once a month. Treatment with clozapine resulted in a decrease in caudate volume, improvement in symptoms and amelioration of TD. However, no difference in caudate volume changes was found between responders and non-responders to clozapine and no correlations were found between caudate volume changes and reduction of TD. In conclusion, this study replicates earlier findings that clozapine decreases caudate volume in patients previously treated with typical antipsychotics and suggests that this effect is unrelated to treatment response or to amelioration of TD.

Adult↗
PubMed2001

The effect of olanzapine treatment on monoamine metabolite concentrations in the cerebrospinal fluid of schizophrenic patients.

The mechanism of action of both typical antipsychotics and the atypical antipsychotic, clozapine, may be related to the (changing) interaction of dopamine and serotonin in schizophrenia. This study examined the effect of olanzapine in schizophrenic patients on cerebrospinal fluid (CSF) metabolites of dopamine (homovanillic acid, HVA) and serotonin (5-hydroxyindoleacetic acid, 5-HIAA). Twenty-three male schizophrenic patients, who were drug-free for at least 2 weeks (mean drug-free period of 35 days +/- 43; median 16 days), underwent a lumbar puncture (LP). Patients were subsequently treated with olanzapine 10 mg/day for 6 weeks, after which the LP was repeated. CSF was assayed for HVA and 5-HIAA concentrations. Psychiatric symptoms were rated once a week. Olanzapine significantly increased HVA concentrations and the HVA/5-HIAA ratio while 5-HIAA concentrations were not altered. These changes did not significantly correlate with treatment response. A negative correlation was found between HVA concentrations and negative symptoms after olanzapine treatment. In conclusion, olanzapine treatment increases HVA concentrations and the HVA/5-HIAA ratio in CSF of schizophrenic patients, but these changes are unrelated to its clinical efficacy.

Adult↗
PubMed2001

Effects of the atypical antipsychotic risperidone on hostility and aggression in schizophrenia: a meta-analysis of controlled trials.

Atypical antipsychotics have been hypothesized to be more effective than classical antipsychotics in the treatment of hostility and aggression, due to their characteristic pharmacological profile, involving serotonergic as well as dopaminergic systems. In the present quantitative review the published evidence regarding the effects of risperidone on hostility and aggression in schizophrenia is evaluated. Meta-analysis of seven controlled trials revealed significant differences between risperidone and classical antipsychotics and between risperidone and placebo, although the effect size was small. Additional analyses in which only methodological rigorous studies were included showed highly significant differences (risperidone versus classical antipsychotics) and the effect size approached the 'medium' range. We conclude that risperidone is superior to classical antipsychotics and placebo in the treatment of hostility and aggression in schizophrenia. Neuropharmacological mechanisms that might account for this effect are discussed, and directions for future research are outlined.

Aggression↗
PubMed2001

Quantitative genetic modeling of variation in human brain morphology.

The degree to which individual variation in brain structure in humans is genetically or environmentally determined is as yet not well understood. We studied the brains of 54 monozygotic (33 male, 21 female) and 58 dizygotic (17 male, 20 female, 21 opposite sex) pairs of twins and 34 of their full siblings (19 male, 15 female) by means of high resolution magnetic resonance imaging scans. Structural equation modeling was used to quantify the genetic and environmental contributions to phenotypic (co)variance in whole brain, gray and white matter volume of the cerebrum, lateral ventricle volume and associated variables such as intracranial volume and height. Because the cerebral cortex makes up more that two-thirds of the brain mass and almost three-quarters of its synapses, our data predominantly concerns the telencephalon. Genetic factors accounted for most of the individual differences in whole brain (90%), gray (82%) and white (88%) matter volume. Individual differences in lateral ventricle volume were best explained by a model containing common (58%) and unique (42%) environmental factors, indicating genes to be of no or minor influence. In our sample, genetic or environmental influences were not different for males and females. The same genes influenced brain volumes and intracranial volume and almost completely explained their high phenotypic correlation. Genes influencing gray and white matter overlapped to a large extent and completely determined their phenotypic correlation. The high heritability estimates that were found indicate that brain volumes may be useful as intermediate phenotypes in behavioral genetic research.

Adult↗
PubMed2001

The effect of olanzapine treatment on m-chlorophenylpiperazine-induced hormone release in schizophrenia.

In addition to dopamine, serotonin (5-hydroxytryptamine, 5-HT) has been reported to play an important role in schizophrenia. Besides blocking dopamine, atypical antipsychotics also block 5-HT receptors. The clinical efficacy of the atypical antipsychotic clozapine is associated with the 5-HT antagonistic action of the drug and a high serotonergic tone before treatment. The atypical antipsychotic olanzapine has a receptor-binding profile similar to that of clozapine. The present study investigated whether treatment with olanzapine blocks hormone release induced by the 5-HT2c agonist m-chlorophenylpiperazine (m-CPP) and, if so, whether this 5-HT antagonistic effect is related to treatment response. Eighteen male schizophrenic patients participated in this study. All patients were challenged with m-CPP (0.5 mg/kg orally) in a double-blind, randomized, placebo-controlled design after a drug-free period of at least 2 weeks. Adrenocorticotropic hormone (ACTH), cortisol, and prolactin plasma levels were measured every 30 minutes up to 210 minutes after challenge. Patients were treated for 6 weeks with 10 mg olanzapine daily in an open design, after which the challenge tests were repeated. Olanzapine significantly blocked m-CPP-induced ACTH, cortisol, and prolactin release, suggesting that it is a potent 5-HT2c antagonist in vivo. This 5-HT antagonistic effect of olanzapine was not significantly correlated with treatment response. Also, no significant correlation was found between m-CPP-induced hormone release before treatment and clinical response after treatment with olanzapine. These findings suggest that olanzapine is a potent 5-HT2c antagonist in vivo but that this is unrelated to its clinical efficacy in this nonrefractory sample of schizophrenic patients.

Adrenocorticotropic Hormone↗
PubMed2001

Effect of clozapine on caudate nucleus volume in relation to symptoms of schizophrenia.

OBJECTIVE: Studies have found that caudate volume increased after treatment with typical antipsychotics in patients with schizophrenia but decreased after treatment was changed to clozapine. In the current study the authors examined whether this volume decrease was related to clinical improvement. METHOD: Twenty-eight patients with schizophrenia who had not responded to treatment with typical antipsychotics were included in the study; 22 completed the study. Caudate volume was assessed by using magnetic resonance imaging during treatment with typical antipsychotics and after 24 weeks and 52 weeks of clozapine treatment. Symptoms were assessed just before clozapine treatment and once a month thereafter. RESULTS: Clozapine treatment resulted in a significant reduction in left caudate volume in patients who responded to the drug but not in patients who did not respond to clozapine at 52 weeks of treatment. Overall, the degree of reduction in left caudate volume was significantly related to the extent of improvement in positive and general symptoms but not in negative symptoms. CONCLUSIONS: These findings suggest that the caudate nucleus plays a role in the positive and general symptoms of schizophrenia.

Adult↗
PubMed2001

Structural brain abnormalities in chronic schizophrenia at the extremes of the outcome spectrum.

OBJECTIVE: This study investigated the relationship between outcome and structural brain abnormalities in schizophrenia. METHOD: Intracranial volume and volumes of the cerebrum, gray and white matter, lateral and third ventricles, frontal lobes, thalamus, and cerebellum were measured in 20 patients with a poor outcome, 25 with a favorable outcome, and 23 healthy comparison subjects with magnetic resonance imaging. RESULTS: Thalamic volume was significantly smaller both in poor-outcome patients and good-outcome patients. In contrast, only poor-outcome patients displayed significantly smaller cerebral gray matter, particularly prefrontal, and enlargement of the lateral and third ventricles. No significant differences were found for intracranial, cerebellar, or cortical CSF volumes. CONCLUSIONS: Smaller thalamic volumes in schizophrenia may reflect a greater susceptibility for the disorder and seem unrelated to outcome. In contrast, gray matter volume loss of the cerebrum, particularly in the frontal lobes, and lateral and third ventricular enlargement appear related to outcome in schizophrenia.

Age of Onset↗
PubMed2001

Apathy, anhedonia, and psychomotor retardation in elderly psychiatric patients and healthy elderly individuals.

Normal aging of the brain affects the basal ganglia-thalamocortical circuits. These circuits are implicated in several neuropsychiatric disorders. Normal aging may therefore influence the symptomatology of psychiatric disorders in the elderly. We investigated motivational behavior that is associated with the function of these circuits, such as apathy, anhedonia, and psychomotor retardation in healthy elderly subjects and psychiatric inpatients (age > or = 60 yr). Apathy, anhedonia, and psychomotor retardation were assessed with the Apathy Evaluation Scale, the Snaith-Hamilton Pleasure Scale, and the Widlöcher Retardation Rating Scale. Other measurements included the Comprehensive Psychopathological Rating Scale, the Mini-Mental State Examination, and the assessment of vascular risk factors. We found some evidence for age-related changes in motivational behavior. In the healthy elderly group (n = 64), increasing age was associated with anhedonia, and in the patient group (n = 62), increasing age was associated with psychomotor retardation. Motivational disturbances could be the effect of an interaction between brain aging and the neuropathology of psychiatric disorders in the elderly.

Age Factors↗
PubMed2001

Contribution of residential exposures to asthma in us children and adolescents.

CONTEXT: Residential exposures are recognized risk factors for asthma, but the relative contribution of specific indoor allergens and their overall contribution to asthma among older children and adolescents in the United States are unknown. OBJECTIVE: To estimate the relative contributions, population-attributable risks, and costs of residential risk factors for doctor-diagnosed asthma. Design. Nationally representative, cross-sectional survey conducted from 1988 to 1994. SETTING AND PARTICIPANTS: A total of 5384 children who were 6 to 16 years old and participated in the National Health and Nutrition Examination Survey III, a survey of the health and nutritional status of children and adults in the United States. MAIN OUTCOME MEASURE: Doctor-diagnosed asthma, as reported by the parent. RESULTS: Five hundred three of 5384 children and adolescents (11.4%) had doctor-diagnosed asthma. After adjusting for age, gender, race, urban status, region of country, educational attainment of the head of household, and poverty, predictors of doctor-diagnosed asthma included a history of allergy to a pet (odds ratio [OR: 2.4; 95% confidence interval [CI]: 1.7, 3.3), presence of a pet in the household (OR: 1.5; 95% CI: 1.1, 2.1), and immediate hypersensitivity to dust mite (OR: 1.5; 95% CI: 1.05, 2.0), Alternaria (OR: 1.9; 95% CI: 1.3, 2.8), and cockroach allergens (OR: 1.4; CI: 1.04, 1.9). Family history of atopy (OR: 1.7; 95% CI: 1.1, 2.7) and diagnosis of allergic rhinitis (OR: 2.1; CI: 1.1, 3.7) were also predictors for asthma. The population-attributable risk of having 1 or more residential exposures associated with doctor-diagnosed asthma was 44.4% (95% CI: 29-60), or an estimated 2 million excess cases. The attributable cost of asthma resulting from residential exposures was $405 million (95% CI: $264-$547 million) annually. CONCLUSIONS: The elimination of identified residential exposures, if causally associated with asthma, would result in a 44% decline in doctor-diagnosed asthma among older children and adolescents in the United States.

Adolescent↗
PubMed2000

State income inequality, household income, and maternal mental and physical health: cross sectional national survey.

OBJECTIVE: To examine the association of state income inequality and individual household income with the mental and physical health of women with young children. DESIGN: Cross sectional study. Individual level data (outcomes, income, and other sociodemographic covariates) from a 1991 follow up survey of a birth cohort established in 1988. State level income inequality calculated from the income distribution of each state from 1990 US census. SETTING: United States, 1991. PARTICIPANTS: Nationally representative stratified random sample of 8060 women who gave birth in 1988 and were successfully contacted (89%) in 1991. MAIN OUTCOME MEASURES: Depressive symptoms (Center for Epidemiologic Studies depression score >15) and self rated health RESULTS: 19% of women reported depressive symptoms, and 7.5% reported fair or poor health. Compared with women in the highest fifth of distribution of household income, women in the lowest fifth were more likely to report depressive symptoms (33% v 9%, P<0.001) and fair or poor health (15% v 2%, P<0. 001). Compared with low income women in states with low income inequality, low income women in states with high income inequality had a higher risk of depressive symptoms (odds ratio 1.6, 95% confidence interval 1.0 to 2.6) and fair or poor health (1.8, 0.9 to 3.5). CONCLUSIONS: High income inequality confers an increased risk of poor mental and physical health, particularly among the poorest women. Both income inequality and household income are important for health in this population.

Adolescent↗
PubMed2000

Neuropsychological dysfunctions in siblings discordant for schizophrenia.

Although cognitive impairments are well recognized in patients with schizophrenia, it is unclear which impairments are due to a genetic predisposition and which are caused by secondary disease effects or phenotype. The aim of this study is to investigate the possible relationship between genetic vulnerability to schizophrenia and cognitive functioning. Three groups of subjects were compared: 14 patients with schizophrenia, 15 healthy siblings and 32 healthy control subjects. All subjects were tested neuropsychologically. The raw test data were rescaled to standard equivalents (z-scores). Subjects' z scores on tests assessing the same cognitive domain were clustered and analyzed. Differences in cognitive functioning were found in the domains of abstraction, attention, executive functioning, spatial memory, and sensory-motor functioning. The schizophrenic probands were impaired on all these five domains whereas the healthy probands showed impairments on executive functioning and partially on sensory-motor functioning. Furthermore, for spatial memory the significant finding could mainly be attributed to impaired functioning in the patients, but not healthy siblings or control subjects, whereas for executive functioning patients and healthy siblings seemed equally impaired as compared to control subjects. The planning time of the Tower of London (TOL) and the initiation time of the Motor Planning Task (MPT) were used for measures of executive functioning, while the 'time to move of the Motor Planning Task' was used as measures of sensory motor functioning. These results suggest that the cognitive abnormalities in schizophrenia that may be related to genotype are represented in the domain of executive functioning and to some extent in the domain of sensory-motor functioning.

Adult↗
PubMed2000

Frontal lobe damage and thalamic volume changes.

The aim of this study was to investigate whether frontal lobe damage affects thalamic volume in humans. Ipsilateral and contralateral thalamic areas were measured in 0.5T T1-weighted sagittal magnetic resonance images in 12 patients, first at the time of their surgery for relief of a unilateral frontal lobe brain tumor and at follow-up approximately 2 years later. A 5% decrease in ipsilateral and 4.5% increase in contralateral thalamic area was found over time (F(1,11) = 6.15, p < 0.05). We conclude that unilateral frontal lobe damage results in a decrease in the ipsilateral thalamus and an increase in the contralateral thalamus in humans in vivo. The findings may have implications for the interpretation of the reported changes in thalamic volume in neuropsychiatric diseases.

Adolescent↗
PubMed2000

[Atypical antipsychotic drugs].

In recent years several new antipsychotics have come to market in the Netherlands (i.e. risperidone, olanzapine and quetiapine). These compounds are called atypical for their lack of the extrapyramidal side effects typical of older antipsychotics. Clozapine, which was developed earlier, is also an atypical antipsychotic drug. The new antipsychotics have proven to be more effective than the old ones in reducing the negative symptoms and in improving the cognitive deficits of schizophrenia. Moreover, they indeed induce less extrapyramidal side effects than the older antipsychotics. Head-to-head comparisons of the atypical antipsychotics are sparse. Studies comparing low-dose regimens of the typical antipsychotics with the atypical drugs as well as relapse prevention studies are needed before it can be decided whether the atypical drugs can replace the older compounds.

Antipsychotic Agents↗
PubMed2000

Specific versus nonspecific brain activity in a parametric N-back task.

In this study functional magnetic resonance imaging (fMRI) was used to examine cerebral activity patterns in relation to increasing mental load of a working memory task. Aim of the experiment was to distinguish nonspecific task-related processes from specific workload processes analytically. Twelve healthy volunteers engaged in a spatial n-back task with four levels. FMRI data were acquired with the 3D-PRESTO pulse sequence. Analysis entailed a two-step multiple regression algorithm, which was specifically designed to measure and separate load-sensitive and load-insensitive activity simultaneously, while preserving the original high spatial resolution of the fMRI signal. Load-sensitive and load-insensitive activity was found in both dorsolateral-prefrontal and parietal cortex, predominantly bilaterally, and in the anterior cingulate. As expected, the left primary sensorimotor cortex showed predominantly load-insensitive activity. Load-sensitive activity reflects specific working memory functions, such as temporary retention and manipulation of information, while load-insensitive activity reflects supportive functions, such as visual orientation, perception, encoding, and response selection and execution. Good performance was correlated with a large area of load-sensitive activity in anterior cingulate, and with a small area of load-insensitive activity in the right parietal cortex. The findings indicate that nonspecific and specific working memory processes colocalize and are represented in multiple frontal and parietal regions. Implication of this analytical strategy for application in research on psychiatric disorders is discussed.

Adult↗
PubMed2000

Selective impairments in the stress response in schizophrenic patients.

OBJECTIVE: In the vulnerability-stress concept of schizophrenia, schizophrenic patients are thought to display increased sensitivity to stress. Little is known about the biological mechanisms that are involved in stress processing in schizophrenic patients. In this study, hypothalarnic-pituitary-adrenal (HPA) function in schizophrenic patients was studied for its essential role in stress processing and adaptation to the environment. METHODS: Eighteen schizophrenic patients were compared to 21 healthy controls in their salivary cortisol response to a physical (bicycle ergometry) and a psychosocial (public speaking) stressor. Coping questionnaires were included as a measure of stress processing at the psychological level. Basal HPA function was assessed by measuring cortisol day profiles and feedback activity by using dexamethasone and hydrocortisone. RESULTS: Schizophrenic patients showed blunted cortisol responses to the psychosocial stressor, but not to the physical stressor, in spite of similar increases in heart rate. The cortisol response to the psychosocial stressor tended to be negatively correlated to the use of passive and avoidant coping strategies. Basal HPA function appeared intact in the schizophrenic patients. CONCLUSIONS: The findings show a selective impairment in the response to psychosocial stress in schizophrenic patients. This suggests the involvement of brain systems that play a role in the activation of the HPA system to psycho-social stress, like arginin-vasopressin (AVP), and cognitive processes, like coping.

Adult↗