Corticosteroid and long-acting ß-agonist therapy reduces epithelial goblet cell metaplasia.

BACKGROUND: Bronchial epithelial goblet cell metaplasia (GCM) with hyperplasia is a prominent feature of asthma, but the effects of treatment with corticosteroids alone or in combination with a long-acting ß2 -adrenergic receptor agonist (LABA) on GCM in the bronchial epithelium are unknown. OBJECTIVES: To determine whether corticosteroid alone or in combination with a LABA alters protein and gene expression pathways associated with IL-13-induced goblet cell metaplasia. RESULTS: We evaluated the effects of fluticasone propionate (FP) and of salmeterol (SM), on the response of well-differentiated cultured bronchial epithelial cells to interleukin-13 (IL-13). Outcome measures included gene expression of SPDEF/FOXa2, gene expression and protein production of MUC5AC/MUC5B and morphologic appearance of cultured epithelial cell sheets. We additionally analysed expression of these genes in bronchial epithelial brushings from healthy, steroid-naïve asthmatic and steroid-treated asthmatic subjects. In cultured airway epithelial cells, FP treatment inhibited IL-13-induced suppression of FOXa2 gene expression and up-regulation of SPDEF, alterations in gene and protein measures of MUC5AC and MUC5B and induction of GCM. The addition of SM synergistically modified the effects of FP modestly-only for gel-forming mucin MUC5AC. In bronchial epithelial cells recovered from asthmatic vs healthy human subjects, we found FOXa2 and MUC5B gene expression to be reduced and SPDEF and MUC5AC gene expression to be increased; these alterations were not observed in bronchial epithelial cells recovered after treatment with inhaled corticosteroids. CONCLUSION AND CLINICAL RELEVANCE: Corticosteroid treatment inhibits IL-13-induced GCM of the airways in asthma, possibly through its effects on SPDEF and FOXa2 regulation of mucin gene expression. These effects are modestly augmented by the addition of a long-acting ß-agonist. As we found evidence for drug treatment counteracting the effects of IL-13 on the epithelium, we conclude that further exploration into the mechanisms by which corticosteroids and long-acting ß2 -adrenergic agonists confer protection against pathologic airway changes is warranted.

A protective role for periostin and TGF-ß in IgE-mediated allergy and airway hyperresponsiveness.

BACKGROUND: The pathophysiology of asthma involves allergic inflammation and remodelling in the airway and airway hyperresponsiveness (AHR) to cholinergic stimuli, but many details of the specific underlying cellular and molecular mechanisms remain unknown. Periostin is a matricellular protein with roles in tissue repair following injury in both the skin and heart. It has recently been shown to be up-regulated in the airway epithelium of asthmatics and to increase active TGF-ß. Though one might expect periostin to play a deleterious role in asthma pathogenesis, to date its biological role in the airway is unknown. OBJECTIVE: To determine the effect of periostin deficiency on airway responses to inhaled allergen. METHODS: In vivo measures of airway responsiveness, inflammation, and remodelling were made in periostin deficient mice and wild-type controls following repeated intranasal challenge with Aspergillus fumigatus antigen. In vitro studies of the effects of epithelial cell-derived periostin on murine T cells were also performed. RESULTS: Surprisingly, compared with wild-type controls, periostin deficient mice developed increased AHR and serum IgE levels following allergen challenge without differences in two outcomes of airway remodelling (mucus metaplasia and peribronchial fibrosis). These changes were associated with decreased expression of TGF-ß1 and Foxp3 in the lungs of periostin deficient mice. Airway epithelial cell-derived periostin-induced conversion of CD4(+) CD25(-) cells into CD25(+) , Foxp3(+) T cells in vitro in a TGF-ß dependent manner. CONCLUSIONS AND CLINICAL RELEVANCE: Allergen-induced increases in serum IgE and bronchial hyperresponsiveness are exaggerated in periostin deficient mice challenged with inhaled aeroallergen. The mechanism of periostin's effect as a brake on allergen-induced responses may involve augmentation of TGF-ß-induced T regulatory cell differentiation.

The state of tranquility: subjective perception is shaped by contextual modulation of auditory connectivity.

In this study, we investigated brain mechanisms for the generation of subjective experience from objective sensory inputs. Our experimental construct was subjective tranquility. Tranquility is a mental state more likely to occur in the presence of objective sensory inputs that arise from natural features in the environment. We used functional magnetic resonance imaging to examine the neural response to scenes that were visually distinct (beach images vs. freeway images) and experienced as tranquil (beach) or non-tranquil (freeway). Both sets of scenes had the same auditory component because waves breaking on a beach and vehicles moving on a freeway can produce similar auditory spectral and temporal characteristics, perceived as a constant roar. Compared with scenes experienced as non-tranquil, we found that subjectively tranquil scenes were associated with significantly greater effective connectivity between the auditory cortex and medial prefrontal cortex, a region implicated in the evaluation of mental states. Similarly enhanced connectivity was also observed between the auditory cortex and posterior cingulate gyrus, temporoparietal cortex and thalamus. These findings demonstrate that visual context can modulate connectivity of the auditory cortex with regions implicated in the generation of subjective states. Importantly, this effect arises under conditions of identical auditory input. Hence, the same sound may be associated with different percepts reflecting varying connectivity between the auditory cortex and other brain regions. This suggests that subjective experience is more closely linked to the connectivity state of the auditory cortex than to its basic sensory inputs.

Activation of auditory cortex during silent lipreading.

Watching a speaker's lips during face-to-face conversation (lipreading) markedly improves speech perception, particularly in noisy conditions. With functional magnetic resonance imaging it was found that these linguistic visual cues are sufficient to activate auditory cortex in normal hearing individuals in the absence of auditory speech sounds. Two further experiments suggest that these auditory cortical areas are not engaged when an individual is viewing nonlinguistic facial movements but appear to be activated by silent meaningless speechlike movements (pseudospeech). This supports psycholinguistic evidence that seen speech influences the perception of heard speech at a prelexical stage.

The development of a clinically useful tool for predicting the development of psychological disorder following injury.

OBJECTIVES: To identify factors significantly associated with post-traumatic stress disorder (PTSD), anxiety, and depression at 3 months post-injury; to develop a generic model to predict the occurrence of PTSD, anxiety, and depression at 3 months post-injury; and to validate this model in a test data set of patients. DESIGN: Prospective cohort study. METHODS: Participants were 823 patients attending an emergency department (ED) following accidental injury. Baseline questionnaires were completed, with 1 and 3 months postal follow-ups. Predictor variables demonstrating significant associations with two of the three outcome measures (3-month HAD anxiety and depression scores and PTSD symptoms) were included in multivariate regression models for each outcome. Non-significant predictor variables were removed until all remaining independent variables made the most significant contribution to each of the three models. Models were validated using a test dataset. RESULTS: Previous history of mental health problems, neuroticism score and having PTSD symptoms at 1 month predicted adverse outcomes at 3 months. When used on the test datasets, the areas under the receiver operating curve (ROC) curve for the models predicting outcomes at 3 months were: PTSD=0.91 (sensitivity=88.5%); anxiety=0.87 (sensitivity=93.7%); and depression=0.87 (sensitivity=96.7%). CONCLUSIONS: The final model performed moderately well across the three outcomes and may be useful clinically as a generic rule-out tool to identify those who will not require follow up, watchful waiting or intervention.

Chronic lung disease in adult recurrent tuberculosis survivors in Zimbabwe: a cohort study.

OBJECTIVE: To examine the prevalence and magnitude of chronic lung disease (CLD) and its association with empiric anti-tuberculosis treatment (due to lack of bacteriologic confirmation) among recurrent tuberculosis (TB) survivors in a human immunodeficiency virus (HIV) prevalent setting. METHODS: Prospective cohort study of retreatment TB survivors in Harare, Zimbabwe. At median follow-up of 2 years post-treatment initiation, we characterized mortality, respiratory impairment, and mental health. RESULTS: Among 175 retreatment TB survivors, 65% of whom were HIV-positive and 21% had been empirically treated, multiparameter CLD was noted at follow-up among 14% of patients (95%CI 9.0-19.7), with a six-fold increase in age-adjusted death in the first year following treatment completion. Empirically treated TB (relative risk [RR] 3.4, 95%CI 1.4-8.3) was associated with CLD, as was the number of previous anti-tuberculosis treatment courses in dose-dependent fashion (three vs. one, RR 6.2, 95%CI 1.7-22.1). Among retreatment TB survivors, 33% (95%CI 26.0-40.1) had persistent respiratory symptoms (Chronic Obstructive Pulmonary Disease Assessment Test score 10); 26% (95%CI 19.8-33.0) significant deficits in exercise capacity (median incremental shuttle walk test distance, 550 m; Q1-Q3 440-730 m); 83% (95%CI 75.7-89.7) residual radiographic abnormalities on chest X-ray; 12% (95%CI 6.6-16.1%) moderate-to-severe obstruction on spirometry; and 13% (95%CI 7.6-17.5%) major depression. CONCLUSIONS: Despite successful treatment, retreatment TB survivors retain a substantial risk of morbidity and mortality.

Cognitive performance and grey matter density in psychosis: functional relevance of a structural endophenotype.

BACKGROUND: Structural brain changes and cognitive impairments have been identified as indicators of genetic risk for schizophrenia. However, the pattern of associations between such structural and functional liability markers has been less well investigated. METHODS: Magnetic resonance imaging data and cognitive assessments were acquired in 31 patients with psychosis, 32 non-psychotic first-degree relatives and 28 controls. The relationship between cerebral grey matter density and cognitive performance was examined using computational morphometry. RESULTS: Two out of 6 cognitive tests revealed significant associations with grey matter density in regions of the frontal lobe, basal ganglia, thalamus and cerebellum in patients and relatives. In patients, poorer executive functioning was associated with cerebellar grey matter density deficits. In relatives, poorer executive functioning was associated with increased grey matter density in the cerebellum and frontal lobe. In both patients and relatives, strategic retrieval from semantic memory was positively associated with grey matter density in basal ganglia structures. Some additional negative associations in the patients differentiated this group from relatives. CONCLUSIONS: The overlap in structure-function relationships in individuals with schizophrenia and those with liability for the disorder may suggest that regional grey matter density alterations functionally alter particular neurocircuits, which could lead to cognitive deficits. The non-overlapping structure-function correlations may reflect disease-related or compensatory mechanisms.

The anatomy of conscious vision: an fMRI study of visual hallucinations.

Despite recent advances in functional neuroimaging, the apparently simple question of how and where we see--the neurobiology of visual consciousness--continues to challenge neuroscientists. Without a method to differentiate neural processing specific to consciousness from unconscious afferent sensory signals, the issue has been difficult to resolve experimentally. Here we use functional magnetic resonance imaging (fMRI) to study patients with the Charles Bonnet syndrome, for whom visual perception and sensory input have become dissociated. We found that hallucinations of color, faces, textures and objects correlate with cerebral activity in ventral extrastriate visual cortex, that the content of the hallucinations reflects the functional specializations of the region and that patients who hallucinate have increased ventral extrastriate activity, which persists between hallucinations.

A direct demonstration of functional specialization within motion-related visual and auditory cortex of the human brain.

BACKGROUND: Physiological studies of the macaque brain have shown that there is a large expanse of visual cortex, the V5 complex, which is specialized for visual motion, and that several areas within V5 are specialized for different kinds of visual motion. In continuing work on motion-related visual cortex, we wished to chart the specialized visual motion areas in the human brain and to determine their anatomical relationship. Human subjects viewed different motion displays, and the cortical location of the increased activity produced by each stimulus was recorded. The technique of functional magnetic resonance imaging (fMRI) was used, in order to image the same subjects repeatedly. RESULTS: We found that each of the three motion stimuli activated specific parts of the V5 complex. These sites of activation overlap with V5 and, to a smaller extent, with each other. Unexpectedly, the three motion stimuli also activated neighbouring, but nonoverlapping, regions of auditory cortex that are normally activated by the perception of speech. CONCLUSIONS: The three sites of activation produced by the visual motion stimuli occupy adjacent territories within the V5 complex. Components of the V5 complex are specifically connected to regions within auditory cortex.

Dopant radiative cooling effects in indirect-drive Ar-doped capsule implosion experiments.

We present results from simulations performed to investigate the effects of dopant radiative cooling in inertial confinement fusion indirect-drive capsule implosion experiments. Using a one-dimensional radiation-hydrodynamics code that includes inline collisional-radiative modeling, we compute in detail the non-local thermodynamic equilibrium atomic kinetics and spectral characteristics for Ar-doped DD fuel. Specifically, we present results from a series of calculations in which the concentration of the Ar is varied, and examine the sensitivity of the fuel conditions (e.g., electron temperature) and neutron yield to the Ar dopant concentration. Simulation results are compared with data obtained in OMEGA indirect-drive experiments in which monochromatic imaging and spectral measurements of Ar Hebeta and Lybeta line emission were recorded. The incident radiation drive on the capsule is computed with a three-dimensional view factor code using the laser beam pointings and powers from the OMEGA experiments. We also examine the sensitivity of the calculated compressed core electron temperatures and neutron yields to the radiation drive on the capsule and to the radiation and atomic modeling in the simulations.

Sex differences among adults presenting to the emergency department with acute asthma. Multicenter Asthma Research Collaboration Investigators.

BACKGROUND: Asthma is an increasing problem worldwide, particularly among women. Sex differences in acute asthma presentation, management, or outcome would have important medical and economic implications. OBJECTIVE: To compare emergency department (ED) visits for acute asthma among women vs men. METHODS: We performed a prospective cohort study as part of the Multicenter Asthma Research Collaboration. Patients in the ED, aged 18 to 54 years, who presented with acute asthma underwent a structured interview in the ED and another by telephone 2 weeks later. The study was performed at 36 EDs in 18 states. Pregnant women with asthma were excluded (n=53). RESULTS: Of 1228 patients, 64.3% were women. Women did not differ significantly from men by age or education level, but women were more likely to be insured, have a primary care provider, and use inhaled corticosteroids. Women had a higher mean+/-SD peak expiratory flow rate than men, both early (expressed as percent predicted) (53%+/-21% vs 41%+/-18%; P<.001) and late (77%+/-24% vs 65%+/-21%; P<.001) in the ED stay. Despite this, women were more likely to be admitted to a hospital (multivariate odds ratio, 2.2; 95% confidence interval; 1.3-4.0) than men. At 2-week follow-up, women had not experienced more relapse events (odds ratio, 1.1) but were 1.5 times more likely to report an ongoing exacerbation (95% confidence interval; 1.0-2.4). CONCLUSIONS: Of adults who presented to the ED with acute asthma, women were almost twice as common as men. Although men received less outpatient care and had worse pulmonary function, women were more likely to be admitted to the hospital and to report an ongoing exacerbation at follow-up. Further studies are needed to better understand the complex relationship between sex and acute asthma.

Are auditory hallucinations the consequence of abnormal cerebral lateralization? A morphometric MRI study of the sylvian fissure and planum temporale.

BACKGROUND: Auditory verbal hallucinations (AVHs) are a characteristic feature of schizophrenia. Patients with schizophrenia have been found to have reduced volumes of a variety of brain structures as well as a reduction in right-left asymmetries, using postmortem and magnetic resonance imaging (MRI) measures. There is also evidence that patients with AVHs differ in these structural asymmetries, relative to those patients who do not hallucinate. The aim of this study was to examine whether patients with and without a prominent history of AVHs differ, both from each other and in comparison with normal subjects, in the asymmetry of the sylvian fissure (SF) and planum temporale (PT). METHODS: We recruited 74 DSM-IV male patients with schizophrenia (on the basis of their AVH history) and 32 matched normal control subjects. Thirty patients had no history of AVHs and 44 had a strong definitive history of AVHs. The SF length and PT area and volume were measured on a three-dimensional MRI spoiled GRASS volume sequence. Absolute measures and laterality coefficients were calculated. RESULTS: : All groups had the normal leftward asymmetry in both the SF and PT. Planum temporale volume and surface area and SF length were all larger in the left hemisphere. There were no significant differences in any measures between the two patient groups or between schizophrenic patients and control subjects. Greater leftward asymmetry of the SF correlated with hallucinations and thought disorder within the prominent hallucinator group. An association was found between handedness and brain size, but this did not interact with diagnosis. CONCLUSIONS: The results of this study do not confirm reports, based on smaller samples, of reduced structural asymmetries of either the SF or PT in schizophrenia, nor do they indicate a specific relationship to a propensity to experience AVHs. A modest correlation between leftward asymmetry of the SF and some positive symptomatology was found.

Meta-analysis of regional brain volumes in schizophrenia.

OBJECTIVE: The authors' goal was to determine whether patients with schizophrenia differ from comparison subjects in regional brain volumes and whether these differences are similar in male and female subjects. METHOD: They conducted a systematic search for structural magnetic resonance imaging (MRI) studies of patients with schizophrenia that reported volume measurements of selected cortical, subcortical, and ventricular regions in relation to comparison groups. They carried out a meta-analysis of the volumes of these regions in the patients with schizophrenia and the comparison subjects using a random effects model; they also used random effects regression analysis to examine the influence of gender on effect sizes. RESULTS: Fifty-eight studies were identified as suitable for analysis; these studies included 1,588 independent patients with schizophrenia. Assuming a volume of 100% in the comparison group, they found that the mean cerebral volume of the subjects with schizophrenia was smaller (98%), but the mean total ventricular volume of the subjects with schizophrenia was greater (126%). Relative to the cerebral volume differences, the regional volumes of the subjects with schizophrenia were 94% in the left and right amygdala, 94% in the left and 95% in the right hippocampus/amygdala, and 93% in the left and 95% in the right parahippocampus. Relative to the global ventricular system differences, the largest differences in ventricular subdivisions were in the right and left body of the lateral ventricle, where the volumes of schizophrenic subjects were 116% and 116%, respectively. For most regions, effect size was not significantly related to gender. CONCLUSIONS: Regional structural differences in patients with schizophrenia include bilaterally reduced volume of medial temporal lobe structures. There is a need for greater integration of results from structural MRI studies to avoid redundant research activity.

Auditory hallucinations and the temporal cortical response to speech in schizophrenia: a functional magnetic resonance imaging study.

OBJECTIVE: The authors explored whether abnormal functional lateralization of temporal cortical language areas in schizophrenia was associated with a predisposition to auditory hallucinations and whether the auditory hallucinatory state would reduce the temporal cortical response to external speech. METHOD: Functional magnetic resonance imaging was used to measure the blood-oxygenation-level-dependent signal induced by auditory perception of speech in three groups of male subjects: eight schizophrenic patients with a history of auditory hallucinations (trait-positive), none of whom was currently hallucinating; seven schizophrenic patients without such a history (trait-negative); and eight healthy volunteers. Seven schizophrenic patients were also examined while they were actually experiencing severe auditory verbal hallucinations and again after their hallucinations had diminished. RESULTS: Voxel-by-voxel comparison of the median power of subjects' responses to periodic external speech revealed that this measure was reduced in the left superior temporal gyrus but increased in the right middle temporal gyrus in the combined schizophrenic groups relative to the healthy comparison group. Comparison of the trait-positive and trait-negative patients revealed no clear difference in the power of temporal cortical activation. Comparison of patients when experiencing severe hallucinations and when hallucinations were mild revealed reduced responsivity of the temporal cortex, especially the right middle temporal gyrus, to external speech during the former state. CONCLUSIONS: These results suggest that schizophrenia is associated with a reduced left and increased right temporal cortical response to auditory perception of speech, with little distinction between patients who differ in their vulnerability to hallucinations. The auditory hallucinatory state is associated with reduced activity in temporal cortical regions that overlap with those that normally process external speech, possibly because of competition for common neurophysiological resources.

Response inhibition and impulsivity: an fMRI study.

Aggressive, suicidal and violent behaviour have been associated with impulsive personality and difficulty in inhibiting responses. We used functional magnetic resonance imaging (fMRI) of the whole brain to examine the neural correlates of response inhibition in 19 normal subjects as they performed a Go/NoGo task. Subjects completed Eysenck's Impulsivity Scale, Barratt's Impulsivity Scale (BIS) and behavioural impulsivity tasks. Associations between blood oxygen level dependent (BOLD) response, trait impulsivity, task performance and National Adult Reading Test (NART) IQ were investigated. Neural response during response inhibition was most prominent in the right lateral orbitofrontal cortex. Responses were also seen in superior temporal gyrus, medial orbitofrontal cortex, cingulate gyrus, and inferior parietal lobule, predominantly on the right side. Subjects with greater scores on impulsivity scales and who made more errors had greater activation of paralimbic areas during response inhibition, while less impulsive individuals and those with least errors activated higher order association areas. Exploratory factor analysis of orbital activations, personality measures and errors of commission did not reveal a unitary dimension of impulsivity. However, the strong association between posterior orbital activation and Eysenck's impulsivity score on a single factor suggests that greater engagement of right orbitofrontal cortex was needed to maintain behavioural inhibition in impulsive individuals. Lower IQ was more important than impulsivity scores in determining errors of commission during the task. Neuroimaging of brain activity during the Go/NoGo task may be useful in understanding the functional neuroanatomy and associated neurochemistry of response inhibition. It may also allow study of the effects of physical and psychological interventions on response inhibition in clinical conditions such as antisocial personality disorder.

Cortical activity during rotational and linear transformations.

Neuroimaging studies of cortical activation during image transformation tasks have shown that mental rotation may rely on similar brain regions as those underlying visual perceptual mechanisms. The V5 complex, which is specialised for visual motion, is one region that has been implicated. We used functional magnetic resonance imaging (fMRI) to investigate rotational and linear transformation of stimuli. Areas of significant brain activation were identified for each of the primary mental transformation tasks in contrast to its own perceptual reference task which was cognitively matched in all respects except for the variable of interest. Analysis of group data for perception of rotational and linear motion showed activation in areas corresponding to V5 as defined in earlier studies. Both rotational and linear mental transformations activated Brodman Area (BA) 19 but did not activate V5. An area within the inferior temporal gyrus, representing an inferior satellite area of V5, was activated by both the rotational perception and rotational transformation tasks, but showed no activation in response to linear motion perception or transformation. The findings demonstrate the extent to which neural substrates for image transformation and perception overlap and are distinct as well as revealing functional specialisation within perception and transformation processing systems.

Prospective multicenter study of relapse following treatment for acute asthma among adults presenting to the emergency department. MARC investigators. Multicenter Asthma Research Collaboration.

STUDY OBJECTIVE: To identify factors associated with relapse following treatment for acute asthma among adults presenting to the emergency department (ED). DESIGN: Prospective inception cohort study performed during October 1996 to December 1996 and April 1997 to June 1997, as part of the Multicenter Asthma Research Collaboration. SETTING: Thirty-six EDs in 18 states. PATIENTS: ED patients, aged 18 to 54 years, with physician diagnosis of acute asthma. For the present analysis, we restricted the cohort to patients sent home from the ED (n = 971), then further excluded patients with comorbid respiratory conditions (n = 32). This left 939 eligible subjects to have follow-up data. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Two weeks after being sent home from the ED, patients were contacted by telephone. A relapse was defined as an urgent or unscheduled visit to any physician for worsening asthma symptoms during the 14-day follow-up period. Complete follow-up data were available for 641 patients, of whom 17% reported relapse (95% confidence interval, 14 to 20). There was no significant difference in peak expiratory flow rate (PEFR) between patients who suffered relapse and those who did not. In a multivariate logistic regression analysis (controlling for age, gender, race, and primary care provider status), patients who suffered relapse were more likely to have a history of numerous ED (odds ratio [OD] 1.3 per 5 visits) and urgent clinic visits (OR 1.4 per 5 visits) for asthma in the past year, use a home nebulizer (OR 2.2), report multiple triggers of their asthma (OR 1.1 per trigger), and report a longer duration of symptoms (OR 2.5 for 1 to 7 days). CONCLUSION: Among patients sent home from the ED following acute asthma therapy, 17% will have a relapse and PEFR does not predict who will develop this outcome. By contrast, several historical features were associated with increased risk. Further research should focus on ways to decrease the relapse rate among these high-risk patients. The clinician may wish to consider these historical factors when making ED decisions.

Tear and rupture of elastomeric dental impression materials.

The curing time dependence of the tear energy, tensile strength and ultimate extension ratio of a range of characterized elastomeric impression materials was investigated. This variation of tensile strength and ultimate extension ratio was correlated with the development of the network structure. The tear energy showed only minor changes as the curing proceeded.

Stroop interference and facilitation in the cerebral hemispheres in schizophrenia.

A divided visual field presentation of the Stroop colour-word test was used to study interhemispheric (transcallosal) function in schizophrenic and normal subjects. The modified test used a colour strip paired with either an incongruent, neutral or congruent colour word. Interference and facilitation were defined as the difference between the mean reaction times for incongruent stimuli and neutral stimuli and that between neutral stimuli and congruent stimuli, respectively. The stimuli were presented tachistoscopically with the two components either separated across the midline centrally, up or down from the midpoint (bilateral presentation), or presented to a single visual half-field (unilateral presentation). The inclusion of the 'up' and 'down' bilateral conditions controlled for the reaction time advantage for central compared with unilateral stimulus presentations noted in an earlier study (David, 1993a). The difference in reaction time to an incongruent compared with a congruent colour-word pairing, the Combined Stroop Effect (CSE), was not affected significantly by stimulus presentation position (bilateral vs. unilateral) in either the control or schizophrenic group, unlike in the earlier study of David. For controls, interference was significantly greater than facilitation for both bilaterally- and unilaterally-presented stimuli. Schizophrenics had a significantly smaller interference effect for bilaterally-presented stimuli, indicating reduced interhemispheric interference in this group. For the control group, there was no significant difference between right and left CSEs, interference being significantly greater than facilitation on both visual half-field presentations. For schizophrenics, the CSE for left-presented stimuli was significantly greater than that for right-presented stimuli. In addition, left-field facilitation was significantly greater than right-field. Reduced Stroop facilitation with right-field presentations in schizophrenic subjects may reflect increased vulnerability of colour-naming by word-reading in the left hemisphere-evidence for the non-unitary nature of attentional processes and disintegration of these in schizophrenia.

A magnetic resonance imaging study of corpus callosum size in familial schizophrenic subjects, their relatives, and normal controls.

The corpus callosum is one of several brain regions thought to be abnormal in schizophrenia. We sought to investigate whether the size of the corpus callosum would be abnormally small in schizophrenic subjects from families with familial schizophrenia and their healthy relatives. We wished to determine whether an abnormal corpus callosum size is found in healthy relatives who are genetically at a greater risk than normal of developing or transmitting the disorder. Twenty-seven familial schizophrenics, 53 of their healthy first-degree relatives, and 35 normal volunteers underwent MRI brain scans. We defined 11 of the relatives as presumed 'obligate carriers', i.e. an individual who appears to be transmitting the schizophrenic gene(s). The mid-sagittal slice of the corpus callosum and the whole brain volume were measured blind to diagnostic and family group. We found no difference between schizophrenics, their relatives, and normal controls in the mid-sagittal area of the corpus callosum. There remained no difference when the relatives were divided into two groups comprising presumed 'obligate carriers' and 'non-obligate carriers'. Adjusting for age and whole brain area made no difference to the results. Families with several schizophrenic members are not associated with abnormality in the size of the corpus callosum.