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Biomedical subjects

W J Muir

Publications and source records attributed to W J Muir.

At least 19 recordsLinked to original sources
PubMed1995

Automated linkage analysis in psychiatric disorders.

A genome-wide search for linkage of microsatellite markers to chromosomal loci containing genes responsible for the major psychoses is a laborious task which can be carried out with greater speed and economy by introducing automation to several steps in the procedure. We describe the use of the Automated Linkage Preprocessor (ALP) program for the computer analysis of the waveform generated by fluorescein-labelled markers after electrophoretic separation. (To obtain a copy send a request to A.F. Brown at the below MRC address or use Anonymous FTP to ftp.hgu.mrc.ac.uk. Software is in directory pub/ALP). The program runs on a PC in the Microsoft Windows environment, and is used in conjunction with an automated laser fluorescence (ALF) sequencer (Pharmacia) and its Fragment Manager software to detect and size the PCR products, filter out peaks of fluorescence due to nonallele fragments, and generate genotypes in a format suitable for direct input to standard linkage analysis programs. The method should offer the advantages of speed, accuracy, and reduced cost. Its use in linkage studies in a large family with manic-depressive illness is discussed.

Automation↗
PubMed1995

Auditory P300 event-related potentials and neuropsychological performance in schizophrenia and bipolar affective disorder.

The auditory P300 event-related potential (ERP) and performance on neuropsychological tests were evaluated in 26 subjects with schizophrenia, 19 with bipolar affective disorder, and 27 controls. The schizophrenic and the bipolar groups were similar in having prolonged P300 latency recorded from central and temporal leads. The P300 was significantly reduced in amplitude in the schizophrenic group at midline leads and the left temporal lead but was not significantly reduced in amplitude at any electrode site when the bipolar group was compared to controls. Schizophrenics performed significantly less well than bipolars and controls on tests of verbal fluency and, within this group, a significant correlation was found between the latency of P300 and verbal fluency test scores. While the bipolar group of patients was similar to the schizophrenic group in having prolonged P300 latency, these groups differed in P300 amplitude, performance on verbal fluency tests, and the relationship between the physiological and neuropsychological variables.

Adolescent↗
PubMed1995

Identifying genes within microdissected genomic DNA: isolation of brain expressed genes from a translocation region associated with inherited mental illness.

An improved protocol has been developed for physical enrichment of cDNA sequences by hybridization to genomic DNA. When applied to microdissection recombinants derived from a translocation breakpoint region associated with inherited mental illness, a single cycle of the procedure permitted enriched cDNAs to be visualized directly by agarose gel electrophoresis. Hybridization screening of a library of clones derived from the enriched cDNAs, employing the genomic resource as a probe, led to the identification of six novel gene fragments. This general approach to the isolation of regionally encoded genes could be applied to any subchromosomal interval as a first step towards global transcription map construction.

Animals↗
PubMed1995

Direct microdissection and microcloning of a translocation breakpoint region, t(1;11)(q42.2;q21), associated with schizophrenia.

We describe the generation of large-fragment microclone libraries from the chromosomal breakpoint of a reciprocal balanced translocation linked to schizophrenia. The abnormality was visible under the phase-contrast microscope, allowing direct dissection from unstained, unbanded metaphases. Two separate microdissection experiments yielded 443 and 672 recombinants, respectively. Following complete EcoRI digestion, inserts with an average size of 0.3 kb (range, 0.2-3 kb) were obtained in the first experiment and 1.5 kb (range, 0.15-6.5 kb) in the second. FISH analysis of pooled clones "painted" back onto the derivative chromosome and assignment of microclones to somatic cell hybrids confirmed the fidelity of the method. Microdissection of chromosome regions identified by karyotype rearrangements in unstained, unbanded metaphases is a potentially powerful tool for positional cloning.

Base Sequence↗
PubMed1994

Schizophrenia and mental retardation associated in a pedigree with retinitis pigmentosa and sensorineural deafness.

A family is presented with multiple cases of mild mental retardation, schizophrenia and other functional psychoses, progressive hearing loss, and retinitis pigmentosa (RP). It closely resembles a previously reported Finnish family. We suggest that the phenotypes are not associated in this family by chance, but define a novel syndrome which may be caused by a mutant allele at a single genetic locus.

Adolescent↗
PubMed1994

Correlation of regional cerebral blood flow equivalents measured by single photon emission computerized tomography with P300 latency and eye movement abnormality in schizophrenia.

Single photon emission tomography with the intravenous blood flow marker 99mTc-exametazime was carried out in 14 acutely ill drug-free schizophrenic patients from whom P300 event-related potential, smooth eye pursuit eye tracking and verbal fluency were measured within a few days of scanning. Smooth pursuit eye movement abnormality correlated significantly with abnormal tracer uptake in superior pre-frontal cortex on the right and left and inferior pre-frontal cortex on the left. Abnormal eye movement was also associated with higher tracer uptake in left anterior cingulate and left posterior cingulate. P300 latency was significantly correlated with higher tracer uptake in left superior pre-frontal and left parietal regions. Verbal fluency performance was negatively correlated with tracer uptake in left frontal region. Eye tracking abnormality in schizophrenia is associated with bilateral frontal lobe disturbance and P300 latency increase with left-sided frontal and temporoparietal dysfunction. There was, however, a significant inverse relation between eye tracking abnormalities and abnormal perfusion in the left anterior cingulate region.

Adult↗
PubMed1992

The effects of cortisol infusion upon hormone secretion from the anterior pituitary and subjective mood in depressive illness and in controls.

The aims of this study were to determine whether the administration of cortisol has a significant effect on mood in patients with depression and whether the effects of cortisol on changes in plasma hormone concentrations are like those of synthetic corticosteroids. Twelve patients had major depression and one each had dysthymic disorder and a depressive adjustment disorder. Five were male and nine were female. All were in-patients. Eight normal subjects, two females and six males, were used as controls. Basal beta-endorphin concentrations were 2- to 3-fold higher in depressed patients than in control subjects, but there were no significant differences between the patient and control groups in the basal (pre-infusion) plasma concentrations of ACTH, cortisol, growth hormone or prolactin. Cortisol, but not saline infusion resulted in a significant improvement in self rated mood. Surprisingly, cortisol infusion at first increased plasma beta-endorphin concentrations. At later times after cortisol infusion, plasma beta-endorphin concentrations decreased as did the plasma concentrations of ACTH and growth hormone; prolactin levels were increased. These results show (i) that cortisol infusion raises mood significantly in major depression, (ii) that plasma beta-endorphin concentration is a potential marker of major depression (iii) that rather than blunting of corticosteroid effects, responses to cortisol may even be enhanced in depressive illness. The unexpected, initial increase in beta-endorphin stimulated by cortisol, suggests that the action of cortisol is not simply one of negative feedback inhibition, but may involve mineralocorticoid, as well as glucocorticoid receptors.

Adrenocorticotropic Hormone↗
PubMed1992

Eye-tracking dysfunction in the affective psychoses and schizophrenia.

Smooth pursuit eye movements to a sinusoidally moving target were recorded using the electro-oculogram in 49 subjects with bipolar disorder, 19 with major depressive disorder and 61 with definite schizophrenia, and compared with 145 normal controls. The signals were analysed in the frequency domain to yield a signal to noise ratio that is known to relate to accuracy of smooth pursuit. Smooth pursuit was found to be significantly poorer in schizophrenics than in bipolars, major depressed or controls. Eye-tracking performance was independent of the effects of neuroleptics, tricyclic antidepressants or lithium, and was not altered by the severity of depression in the affective psychoses. There was a small, but significant worsening of smooth pursuit with age in controls and schizophrenics, but this did not account for the group differences. The results support the view that among the major psychoses eye-tracking dysfunction is specific to schizophrenia.

Adolescent↗
PubMed1991

Magnetic resonance imaging in schizophrenia: altered brain morphology associated with P300 abnormalities and eye tracking dysfunction.

This study was designed to investigate whether auditory P300 event-related potential and smooth pursuit eye-movement abnormalities in schizophrenia are associated with brain structural changes measured using magnetic resonance imaging (MRI). Serial coronal MRI scans obtained from 31 schizophrenic subjects and 33 volunteer controls were analysed by a rater who had no knowledge of the subjects' diagnoses. The brain areas measured bilaterally were the temporal lobe, hippocampus, amygdala, parahippocampal gyrus, head of caudate, cingulate cortex, frontal cortex, and the lateral ventricles. The area of the third ventricle, the thickness of the corpus callosum, and the intracranial area were also measured. Auditory P300 and eye tracking performance were recorded on all subjects. There was a significant increase in the latency and a reduction in amplitude of the P300 in the schizophrenic group. Only in the schizophrenic group was P300 latency correlated negatively with the area of the right and left cingulate cortex and positively with the difference in size between the right and left amygdala. In the subgroup of schizophrenic subjects whose P300 latency was greater than 2 standard deviations above the control mean, the area of the left cingulate cortex was significantly smaller than in controls, and the absolute right-left difference in the area of the amygdala was significantly increased. Eye tracking dysfunction in schizophrenia was not related to changes in the amygdala or cingulate cortex but was significantly correlated with enlargement of the lateral ventricles. Schizophrenic subjects with poor eye tracking had significantly larger lateral ventricles than controls. Eye tracking dysfunction, but not P300 abnormality, was correlated with the severity of both positive and negative symptom of schizophrenia. These findings demonstrate that psychophysiological abnormalities are associated with altered brain structure in schizophrenia.

Arousal↗
PubMed1991

Auditory P300 and eye tracking dysfunction in schizophrenic pedigrees.

Several psychophysiological abnormalities associated with schizophrenia have been proposed as genetic trait markers of vulnerability to the disorder. Smooth pursuit eye tracking dysfunction and abnormal long latency event-related potentials are the most promising candidates. Both are independent of the effects of psychotropic medication or mental state at the time of testing, and twin studies demonstrate that each has a high level of heritability. Having recorded smooth pursuit eye tracking and event-related potentials in 20 high-density schizophrenic families, we find abnormalities in one or both measures in most of the families studied. The abnormalities, when present, occur in the family members with schizophrenia and other forms of functional psychosis, and they have a bimodal distribution with approximately half the nonschizophrenic relatives also showing eye tracking dysfunction and/or abnormal event-related potentials. Some of these relatives had psychiatric symptoms; others were normal. Our results suggest that psychophysiological examination can help to clarify the boundaries of schizophrenia spectrum disorder. By helping to decide the phenotypic status of nonschizophrenic family members, this should increase the power of DNA linkage studies.

Acoustic Stimulation↗
PubMed1991

Long-latency auditory event-related potentials in schizophrenia and in bipolar and unipolar affective disorder.

Long-latency auditory event-related potentials were examined in 96 subjects with schizophrenia, 99 with bipolar affective disorder and 48 with major depressive (unipolar) disorder, and compared with 32 in-patient and 213 normal controls. The latency of the P3 component was significantly greater in the schizophrenic and bipolar subjects compared to other groups. The difference was stable with respect to clinical state at the time of testing and was not due to age differences or the effect of psychotropic medications. The results support the clinical distinction between bipolar and unipolar affective disorders, but also show that P3 change is not specific to schizophrenia and found in bipolar but not unipolar affective disorder.

Adolescent↗
PubMed1990

Perceptual and physiological dysfunction in depression.

P300 responses to emotive words of different hedonic tones were assessed in depressed patients (unipolar major), patients recovered from the same type of depression and normal controls. Depressed patients showed a smaller amplitude of P300 in response to negatively toned words than to positive words; normal controls showed the opposite pattern and recovered patients showed a pattern of response which resembled that of depressed patients. The experimental trials comparing responses to negative and positive stimuli in relation to neutral words showed significant differences for negative as compared with neutral stimuli, but not for positive as compared with neutral stimuli. Latencies of P300 did not differentiate depressed patients from normal controls. The results are discussed within the context of the 'expectancy' theory of information processing.

Adult↗
PubMed1989

Auditory P300 does not differentiate borderline personality disorder from schizotypal personality disorder.

The P300 response to an auditory two-tone discrimination task has previously been reported to have prolonged latency and reduced amplitude in schizophrenia and borderline personality disorder. In this study, P300 was recorded from 23 subjects with borderline personality disorder, 12 subjects fulfilling criteria for both borderline and schizotypal personality, and 11 subjects with schizotypal personality. The mean P300 latency was similar in each of these groups and was significantly longer than in 32 patients with neuroses and other personality disorders and 74 nonpatient controls. These findings suggest that borderline and schizotypal patients share a similar abnormality in auditory stimulus evaluation and question whether or not these disorders are separate.

Adolescent↗
PubMed1988

The development of Alzheimer's disease in Down's syndrome assessed by auditory event-related potentials.

Several studies have reported changes in auditory event-related potentials in patients with Alzheimer's type dementia. These include an increase in latency and a reduction in amplitude of the P300 (P3) response, a late positive component generated about 300 ms after an unexpected stimulus. Alzheimer's type dementia is an almost invariable acompaniment of ageing in Down's syndrome. This study was designed to assess the usefulness of the auditory P300 response as a measure of the onset of dementia in Down's subjects, who because of poor language development may be difficult to assess by psychological tests. Auditory event-related potentials were recorded from 89 Down's subjects, aged 16-66 years. A control group of 29 mentally retarded subjects with fragile-X syndrome and 83 normal volunteer controls were also tested. Clinical psychological testing found evidence of dementia in 16 Down's subjects and none with fragile-X. Furthermore, in the Down's population but not the fragile-X or control groups, there was a marked increase in P300 latency with age starting around 37 years. In controls, the effect of age on P300 latency became significant some 17 years later around the age of 54 years. The premature effect of age on P300 in Down's syndrome was due to the prolonged P300 latency in the 16 subjects showing signs of dementia. It was confirmed that P300 latency increase reflects the development of Alzheimer's dementia in Down's subjects.

Adolescent↗