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Biomedical subjects

R M Murray

Publications and source records attributed to R M Murray.

At least 127 records · Page 7Linked to original sources
PubMed1998

Neurological abnormalities in familial and sporadic schizophrenia.

Neurological assessment was carried out on patients with schizophrenia from multiply and singly affected families, their relatives, and a normal control group (214 subjects). A systematic examination was used in which abnormal signs were divided into 'primary' and 'integrative' signs. Primary signs were elicited by a standard clinical neurological examination and included signs of focal damage to nuclei and tracts, whilst integrative signs were selected as reflecting distributed brain function. The assessments were carried out to test the hypotheses that (i) neurological abnormalities are present in schizophrenia, (ii) the pattern of abnormality is different in familial and sporadic schizophrenic subjects, and (iii) the well relatives of familial (but not sporadic) schizophrenic subjects will show neurological abnormalities. An excess of primary signs compared with the controls was demonstrated in the sporadic schizophrenic group only. Both the familial schizophrenics and their first-degree relatives (but not their sporadic counterparts) showed an increase in integrative signs. The results support the existence of different mechanisms of underlying brain dysfunction in familial and sporadic schizophrenia.

Adult↗
PubMed1998

Predictors of outcome in schizophrenia.

Several factors have been reported to be associated with poor outcome in psychosis. A prospective study was conducted to identify and subsequently assess the relative prognostic value of factors that might assist in the earlier identification of patients likely to have a poor outcome. The results confirmed that certain factors, including male gender, family history of schizophrenia, structural brain abnormalities, absence of adverse life events, and tardive dyskinesia, were indeed associated with poor outcome.

Adult↗
PubMed1998

Linkage analysis between bipolar affective disorder and markers on chromosome X.

Since 1969, several classical linkage studies suggested an X-chromosome locus for bipolar affective disorder. However, methods using highly polymorphic DNA markers have provided conflicting evidence for linkage, and an X-chromosomal locus for bipolar disorder remains controversial. More recently, Pekkarinen et al. (1995) found a maximum LOD score of 3.54 at the marker DXS994 in a large bipolar Finnish kindred. In the present study, we attempted to replicate this finding using 43 families multiply affected by bipolar affective disorder. These families were selected for the absence of male-to-male transmission of the disease, and were genotyped for two microsatellte markers, DXS1227 and DXS1062 (which is about 2 cM telomeric to DXS994). Linkage to this region was excluded either using a two-point lod score method with two plausible genetic models, or by a model-free lod score analysis which does not require specification of a particular mode of transmission. We conclude that there is no evidence of a common major gene for bipolar affective disorder at Xq25-q27 in our set of families.

Bipolar Disorder↗
PubMed1998

Minor physical anomalies in familial and sporadic schizophrenia: the Maudsley family study.

OBJECTIVES: (1) To test the hypothesis that minor physical anomalies are increased in patients with schizophrenia and (2) to investigate differences in the prevalence of minor physical anomalies in patients with familial and sporadic schizophrenia and their first degree relatives. METHODS: A weighted Waldrop assessment was carried out on 214 subjects in five groups: schizophrenic patients from multiply affected families; first degree relatives of these familial schizophrenic patients; sporadic schizophrenic patients; first degree relatives of these sporadic schizophrenic patients, and normal controls. Broad and narrow criteria for abnormality were defined based on the distribution of minor physical anomalies in the control group. RESULTS: (1) The total schizophrenic group did not have a significant increase in minor physical anomalies using a narrow criterion of abnormality, but did when a broader criterion was used. (2) A significant increase in the proportion of subjects with an abnormally high number of minor physical abnormalities was shown in the group of sporadic schizophrenic patients (uncorrected p<0.01). Separate analyses for males and females showed a significant increase in the male sporadic group (uncorrected p<0.05), and a smaller non-significant increase in the female sporadic group. Neither the familial schizophrenic group nor either group of first degree relatives showed any significant increases in the proportion of patients with high abnormality scores. CONCLUSION: This work supports prenatal developmental abnormality as a mechanism for sporadic, but not familial, schizophrenia.

Adult↗
PubMed1998

Saccadic eye movements in families multiply affected with schizophrenia: the Maudsley Family Study.

OBJECTIVE: Family studies have shown that abnormalities of smooth pursuit eye movement are increased in the adult relatives of schizophrenic probands as well as in the probands themselves. More recently, an inability of schizophrenic subjects to inhibit reflexive saccades reliably has been shown. This study aimed to test the hypothesis that the latter dysfunction is part of the extended schizophrenia phenotype. METHOD: With the use of infrared oculography, measurements of reflexive saccades and antisaccades were undertaken in 29 probands with schizophrenia, 50 of their nonpsychotic first-degree relatives, and 38 unrelated healthy volunteers. RESULTS: Probands, relatives, and healthy subjects showed no overall differences in the generation of reflexive saccades. However, in the antisaccade task, probands showed more saccadic distractibility when they were required to inhibit reflexive saccades. Analysis of corrective saccades showed that this was not due to failed comprehension or motivation. Relatives of the probands with high saccadic distractibility showed a higher distractibility rate than relatives of the probands with normal distractibility. Across all subjects, females showed a higher rate of distractibility errors than males. CONCLUSIONS: The ability to suppress reflexive saccades is an objective neurocognitive measure that is impaired in schizophrenic patients and in a proportion of their biological relatives. This antisaccade abnormality may be a vulnerability marker in a subset of schizophrenic patients and their families.

Adult↗
PubMed1998

Attenuated frontal activation during a verbal fluency task in patients with schizophrenia.

OBJECTIVE: Functional magnetic resonance imaging was used to study changes in cerebral blood oxygenation in schizophrenic patients during a verbal fluency task. METHOD: Five right-handed male schizophrenic patients and five volunteers matched on demographic variables and verbal fluency performance participated in the study. Echoplanar images were acquired over 5 minutes at 1.5 T while the subjects performed two tasks. The first involved paced silent generation of words beginning with an aurally presented cue letter. This task alternated with paced silent repetition of the aurally presented word "rest." Generic brain activation maps were constructed from individual images by sinusoidal regression and non-parametric hypothesis testing. Between-group differences in the mean power of experimental response were identified on a voxelwise basis by an analysis of covariance that controlled for between-group differences in stimulus-correlated motion. RESULTS: The comparison group showed significant responses in the left prefrontal cortex, the insula bilaterally, the midline supplementary motor area, and the medial parietal cortex. Compared to those subjects, the schizophrenic subjects showed significantly reduced power of response in the left dorsal prefrontal cortex, the inferior frontal gyrus, and the insula but significantly increased power of response in the medial parietal cortex. In both groups frontal and parietal responses were negatively correlated. CONCLUSIONS: Schizophrenic patients displayed attenuated power of response in several frontal regions during word generation but greater power of response in the medial parietal cortex during word repetition.

Adult↗
PubMed1998

First episodes of psychosis in Afro-Caribbean and White people. An 18-year follow-up population-based study.

BACKGROUND: There have been few prospective studies of the long-term outcome of psychosis in people of Afro-Caribbean origin in the UK. METHOD: We followed-up a population-based, consecutive series of 34 Afro-Caribbean and 54 White people with psychosis who had been extensively investigated during their first admission in 1973/74. Diagnoses were made by direct interview using the Present State Examination at both first admission and follow-up. RESULTS: Ninety-seven percent of the original sample were traced. A slightly greater proportion of the Afro-Caribbean people were assigned to the S+ Catego class (schizophrenia), both on first assessment and at follow-up. No difference was found between the two groups in the consistency of diagnosis over the 18 years or in the proportion of patients considered psychotic but Afro-Caribbean people tended to have fewer negative symptoms at follow-up. There were striking differences between the two groups in their experience of psychiatric care; Afro-Caribbean people were more likely to have been readmitted, to have experienced longer hospitalisations, and to have undergone more involuntary admissions than their White counterparts. CONCLUSIONS: Afro-Caribbean people who met clinical and research criteria for schizophrenia had a less satisfactory experience of, and response to, psychiatric care over 18 years than their White counterparts.

Adolescent↗
PubMed1998

Pathophysiology of 'positive' thought disorder in schizophrenia.

BACKGROUND: Formal thought disorder is a characteristic feature of psychosis, but little is known of its pathophysiology. We have investigated this in schizophrenia using positron emission tomography (PET). METHOD: Regional cerebral blood flow was measured using H2(15)O and PET while six people with schizophrenia were describing a series of 12 ambiguous pictures which elicited different degrees of thought-disordered speech. In a within-subject design, the severity of 'positive' thought disorder was correlated with cerebral blood flow across the 12 scans in each subject. RESULTS: Verbal disorganisation (positive thought disorder) was inversely correlated with activity in the inferior frontal, cingulate and left superior temporal cortex, and positively correlated with activity in the parahippocampal/anterior fusiform region bilaterally, and in the body of the right caudate (P < 0.001). The total amount of speech produced (independent of thought disorder) was positively correlated with activity in the left inferior frontal and left superior temporal cortex. CONCLUSIONS: The severity of positive thought disorder was inversely correlated with activity in areas implicated in the regulation and monitoring of speech production. Reduced activity in these regions may contribute to the articulation of the linguistic anomalies that characterise positive thought disorder. The positive correlations between positive thought disorder and parahippocampal/anterior fusiform activity may reflect this region's role in the processing of linguistic anomalies.

Adult↗
PubMed1997

The dysplastic net hypothesis: an integration of developmental and dysconnectivity theories of schizophrenia.

Two separate theories that attempt to explain different aspects of schizophrenia have recently attracted much attention. The first, the neurodevelopmental hypothesis, postulates that deviations in early development establish a neuronal phenotype that predisposes to, or, in some versions, determines the later onset of schizophrenia. The second theory proposes that schizophrenic symptoms arise from abnormalities in neuronal connectivity. Here, we suggest that the findings from these two separate lines of inquiry can be integrated into a unitary framework: the dysplastic net hypothesis. In essence, this proposes that anatomical and physiological dysconnectivity of the adult schizophrenic brain is determined by dysplastic fetal brain development. We also indicate how abnormal connectivity between brain regions constituting large-scale neurocognitive networks is expressed in both the prepsychotic and psychotic phases of schizophrenia, and we examine possible risk factors (genetic and environmental) for dysplastic formation of these networks.

Adult↗
PubMed1997

Focal signal hyperintensities in schizophrenia.

The presence of focal signal hyperintensities on MRI images of the brain was compared in 48 schizophrenic patients, 26 patients with bipolar disorder and 34 healthy controls. Significantly larger areas of brain were affected by focal signal hyperintensities, particularly in the frontal lobes, in the schizophrenic group compared to the bipolar group and the controls. Although the bipolar group had more such foci than controls, this difference did not reach statistical significance.

Adult↗
PubMed1997

Childhood laterality and later risk of schizophrenia in the 1946 British birth cohort.

An increased rate on non-righthandedness and other abnormalities of lateralization have been reported in schizophrenia. We investigated childhood hand preference and eye dominance as risk factors for adult schizophrenia among a general population birth cohort. Pre-schizophrenic children showed a significant excess of left-eye dominance at age 11 when compared with controls (OR 2.5, 1.0-5.8, p = 0.03), but there was no significant difference in hand preference between pre-schizophrenic children and controls.

Brain↗
PubMed1997

Maternal exposure to influenza and paranoid schizophrenia.

Previous research has suggested that schizophrenics exposed to influenza in the second trimester have more delusions of jealousy, delusions of reference and suspiciousness. We therefore hypothesised that the risk-increasing effect of in utero exposure to influenza would be particularly demonstrable in paranoid schizophrenia. We studied patients with an ICD diagnosis of schizophrenia in England and Wales who were born each month between 1923 and 1965 (N = 17,247. Chi-square test for trend showed that an increase in influenza exposure level during the fifth month of gestation was accompanied by an increase in the proportion of patients with paranoid schizophrenia. However, logistic regression analysis including sex, seasonality and birth period in the model resulted in the loss of any significant association between in utero exposure to influenza and the development of paranoid schizophrenia, the loss of this significance being mainly accounted for by birth period. Therefore, the association in utero exposure to influenza and subsequent development of paranoid schizophrenia we hypothesised was not supported by our data.

Adult↗
PubMed1997

No evidence for an association of affective disorders with high- or low-activity allele of catechol-o-methyltransferase gene.

Catechol-o-methyltransferase (COMT) is an enzyme that inactivates biologically active or toxic catechols. Previous studies have yielded inconsistent results on the relationship between erythrocyte COMT activity and affective disorders. Recently an amino acid change (Val-108-Met) of the COMT protein was shown to determine high- and low-activity alleles of the enzyme. Using polymerase chain reaction and the restriction enzyme NLaIII, we genotyped 107 patients with bipolar disorder, 62 with unipolar depression, and 121 controls. Neither bipolar nor unipolar patients differ significantly in the genotypic or allelic frequency from the control group. Even when the bipolar and unipolar patients were pooled into a single group, the distributions of both the genotypes and the alleles for the patient group were similar to those for the controls. We conclude that genetic variation that determines high and low activities of COMT does not have a major effect on the vulnerability to affective disorders in our sample.

Adult↗
PubMed1997

A linkage study of schizophrenia to markers within Xp11 near the MAOB gene.

A sex chromosome locus for psychosis has been considered on the basis of some sex differences in genetic risk and expression of illness, and an association with X-chromosome anomalies. Previous molecular genetic studies produced weak evidence for linkage of schizophrenia to the proximal short arm of the X-chromosome, while some other regions were not ruled out. Here we report an attempt to expand the Xp findings in: (i) a multicenter collaboration focusing on 92 families with a maternal pattern of inheritance (Study I), and (ii) an independent sample of 34 families unselected for parental mode of transmission (Study II). In the multicenter study, a parametric analysis resulted in positive lod scores (highest of 1.97 for dominant and 1.19 for recessive inheritance at a theta of 0.20) for locus DXS7, with scores below 0.50 for other markers in this region (MAOB, DXS228, and ARAF1). Significant allele sharing among affected sibling pairs was present at DXS7. In the second study, positive lod scores were observed at MAOB (highest of 2.16 at a theta of 0.05 for dominant and 1.64 at a theta of 0.00 for recessive models) and ALAS2 (the highest of 1.36 at a theta of 0.05 for a recessive model), with significant allele sharing (P = 0.003 and 0.01, respectively) at these two loci. These five markers are mapped within a small region of Xp11. Thus, although substantial regions of the X-chromosome have been investigated without evidence for linkage being found, a locus predisposing to schizophrenia in the proximal short arm of the X-chromosome is not excluded.

Chromosome Mapping↗
PubMed1997

Corpus callosum size and inter-hemispheric function in schizophrenia.

We studied the relationship between corpus callosum area and both inter-hemispheric facilitation and interference in schizophrenics and controls. Mid-sagittal sections through the corpus callosum were measured using structural magnetic resonance imaging on 42 patients and 43 normal controls, along with symptom profiles. In a sub-sample, a modified version of the Stroop Test was also performed (27 patients and 29 controls) to assess inter-hemispheric facilitation and interference of colour naming. In the larger sample (total subjects, n = 85), there were no significant differences between patients and controls in CC area but a trend towards smaller values in patients in all but the posterior segment. In the sub-sample, bilateral facilitation was greater, and interference, less in schizophrenics compared with controls. There was a positive correlation between facilitation and posterior CC area, parallelled by a negative correlation between interference and posterior CC area, in both patients and controls, which only reached statistical significance when both groups were combined. These findings suggest that the link, between CC size and neuropsychological processes involving inter-hemispheric transfer of information, is common to both schizophrenics and normal controls. There were significant negative correlations between anterior CC area and psychomotor poverty (avolition, anhedonia and affective flattening), and a suggestion that the negative correlation between age and CC size in controls was not present in patients.

Adult↗
PubMed1997

Comparison of the family history with the family study method: report from the Camberwell Collaborative Psychosis Study.

We assessed the accuracy of the family history (FH-RDC) and family study (SADS-L) methods for obtaining information about the presence of psychopathology in 274 first-degree relatives of patients with psychotic disorders. The family history method had only modest sensitivity, 40.8% for affective disorders and 58.6% for psychotic disorders, but high specificity, 94.1% for affective disorders and 98.7% for psychotic disorders. For both disorders, sensitivity was higher for relatives who had had previous psychiatric admissions. However, with the family study method, we found that relatives with affective disorder were more likely to be interviewed than those relatives with other disorders. Hence, the family study method may be prone to selection bias that distorts morbid risk estimates. We conclude that the best way of collecting information regarding family psychopathology is to interview directly as many relatives as possible and to collect supplementary family history information on unavailable relatives.

Adolescent↗