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Biomedical subjects

R M Murray

Publications and source records attributed to R M Murray.

At least 91 records · Page 5Linked to original sources
PubMed2000

Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk. Focal dysfunction and distributed disconnectivity reappraised.

BACKGROUND: PET studies of verbal fluency in schizophrenia report a failure of 'deactivation' of left superior temporal gyrus (STG) in the presence of activation of left dorsolateral prefrontal cortex (DLPFC), which deficit has been attributed to underlying 'functional disconnectivity'. AIM: To test whether these findings provide trait-markers for schizophrenia. METHOD: We used H2(15)O PET to examine verbal fluency in 10 obligate carriers of the predisposition to schizophrenia, 10 stable patients and 10 normal controls. RESULTS: We found no evidence of a failure of left STG deactivation in carriers or patients. Instead, patients failed to deactivate the precuneus relative to other groups. We found no differences in functional connectivity between left DLPFC and left STG but patients exhibited significant disconnectivity between left DLPFC and anterior cingulate cortex. CONCLUSIONS: Failure of left STG 'deactivation' and left fronto-temporal disconnectivity are not consistent findings in schizophrenia; neither are they trait-markers for genetic risk. Prefrontal functional disconnectivity here may characterise the schizophrenic phenotype.

Heterozygote↗
PubMed2000

Schizophrenia is not disappearing in south-west Scotland.

BACKGROUND: Recent work has reported a decline in the incidence of schizophrenia, but it is unclear if these findings reflect a true decrease in its incidence or are an artefact arising from methodological difficulties. AIMS: To take account of these methodological difficulties and report service-based incidence rates for schizophrenia in Dumfries and Galloway in south-west Scotland for 1979-98. METHOD: Using both clinical diagnoses and diagnoses generated from the Operational Checklist for Psychotic Disorders (OPCRIT) computer algorithm for ICD-10 and DSM-IV schizophrenia, we measured change in the incidence rates over time. We used indirect standardisation techniques and Poisson models to measure the rate ratio linear trend. RESULTS: There was a monotonic and statistically significant decline in clinically diagnosed schizophrenia. The summary rate ratio linear trend was 0.77. However, using OPCRIT-generated ICD-10 and DSM-IV diagnoses, there was no significant difference over time. CONCLUSIONS: OPCRIT-generated consistent diagnoses revealed no significant fall in the incidence of schizophrenia. Changes in diagnostic practice have caused the declining rates of clinically diagnosed schizophrenia in Dumfries and Galloway.

Factor Analysis, Statistical↗
PubMed2000

The National Adult Reading Test as a measure of premorbid IQ in schizophrenia.

OBJECTIVES: To investigate the validity of the NART as an estimate of premorbid IQ in schizophrenia. DESIGN: A within-in participants, follow-back design was adopted. METHODS: A sample of adults with schizophrenia who had presented to psychiatric services and had a measure of IQ routinely taken during childhood were traced and subject to follow-up WAIS-R and NART IQ assessment (N = 24). Measures of current IQ and NART estimated premorbid IQ were compared with the measure of IQ taken 'premorbidly', i.e. in childhood. RESULTS: There were no significant differences between childhood and adult measures of IQ. However there were significant differences between these two indices and NART estimated IQ, particularly where IQ deviated from general population means. The Vocabulary subtest of the WAIS-R performed better as an estimate of both premorbid and current IQ in the sample. CONCLUSION: Use of a word-reading test such as the NART to predict past levels of intellectual function should proceed with caution, particularly where IQ does not fall in the 'average' category. Use of more than one index of prior level of function is recommended.

Adolescent↗
PubMed1999

Schizophrenic patients and their first-degree relatives show an excess of mixed-handedness.

An excess of mixed-handedness in schizophrenia has been reported. However, it is not established whether this excess is manifest in non-schizophrenic psychoses, nor whether the underlying etiology is genetic or environmental. We investigated these issues in a group of patients with schizophrenia (n=94), affective psychosis (n=63), other psychosis (n=26); their respective first-degree relatives (total n=183) and a control group (n=85). A narrow definition of mixed-handedness was used corresponding to groups 5 and 6 as defined by the Annett Handedness Questionnaire. We found an excess of mixed-handedness in the schizophrenic group compared with controls (OR=5.2, 1.4-18.6, p<0.006). There was no difference between the other psychotic groups and controls. There was a trend for an excess of mixed-handedness in the first-degree relatives (n=99) of schizophrenic patients (p=0.055), but not in the relatives of affective or other psychotic patients. There was a striking linear trend in the proportion of mixed-handedness between controls, the relatives and the schizophrenic patients (chi2=7.0, p=0.008). There was no association between mixed-handedness and a history of pregnancy or birth complications in the schizophrenic group. There was some evidence for impaired sociability in the mixed-handed schizophrenic patients. Our results indicate that the excess of mixed-handedness in schizophrenia may have a genetic basis.

Adult↗
PubMed1999

Linkage studies of bipolar disorder with chromosome 18 markers.

Evidence consistent with the existence of genetic linkage between bipolar disorder and three regions on chromosome 18, the pericentromeric region, 18q21, and 18q22-q23 have been reported. Some analyses indicated greater evidence for linkage in pedigrees in which paternal transmission of disease occurs. We have undertaken linkage analyses using 12 highly polymorphic markers spanning these three regions of interest in a sample of 48 U.K. bipolar pedigrees. The sample comprises predominantly nuclear families and includes 118 subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM IV) bipolar I disorder and 147 subjects with broadly defined phenotype. Our data do not provide support for linkage using either parametric or nonparametric analyses. Evidence for linkage was not significantly increased by analyses that allowed for heterogeneity nor by analysing the subset of pedigrees consistent with paternal transmission.

Bipolar Disorder↗
PubMed1999

Association analysis between dopamine receptor genes and bipolar affective disorder.

We have performed a case-control analysis of dopamine D2-like receptor (DRD2, DRD3 and DRD4) gene polymorphisms in 118 Han Chinese cases with bipolar affective disorder and 196 control subjects, and replication analysis in 157 English cases and 143 control subjects. We found association between a functional DRD2 promoter variant (P = 0.03 by allele) and the DRD2 taq1A polymorphism (P = 0.001 by allele) in Chinese bipolar disorder patients. However, this finding was not replicated in the Caucasian subjects, indicating that the significant association we observed in the Chinese population is a false positive finding. An alternative explanation is that these polymorphisms are risk factors in Chinese but not Caucasian populations, a hypothesis which seems unlikely in view of the similarity of the clinical characteristics of bipolar disorder in the two populations. We also report a novel, rare one-repeat variant of the DRD4 exon 3 VNTR repeat in Chinese populations, which appears to be absent in Caucasians and is not associated with disease.

Adult↗
PubMed1999

Brain structure and neurocognitive and behavioural function in adolescents who were born very preterm.

BACKGROUND: Infants born very preterm (<33 weeks) are at increased risk of neurocognitive deficits. Their neurodevelopmental outcome up to age 8 years can be predicted by neonatal ultrasonography, but little is known of their later function. We investigated the effect of very preterm birth on brain structure and neurocognitive and behavioural functioning in adolescence. METHODS: A cohort of 105 infants born before 33 weeks of gestation in 1979-80 had ultrasonographic scans at University College Hospital, London, and were prospectively examined at 1, 4, and 8 years. At age 14-15 years, 72 of those who remained in UK (cases) and 21 age-matched full-term controls underwent brain magnetic resonance imaging (MRI), as well as neurological, cognitive, and behavioural assessment. MRI images were assessed by two neuroradiologists unaware of ultrasonographic findings or case or control status. FINDINGS: Of the 72 cases, 40 had unequivocally abnormal MRI and 15 had equivocal scans. Of the 21 controls, one had abnormal and five equivocal MRI. Abnormalities of ventricles, corpus callosum, and white matter were especially common in cases. More brain lesions were identified by MRI than by neonatal ultrasonography. The cases had significantly more reading, adjustment, and neurological impairments than controls, but their behaviour was significantly related to MRI abnormality. INTERPRETATION: Individuals born very preterm show an excess of neurocognitive and behavioural problems in adolescence, and more than half have abnormal MRI brain scans.

Adolescent↗
PubMed1999

Problem-solving and spatial working memory in patients with schizophrenia and with focal frontal and temporal lobe lesions.

Problem-solving ability was investigated in 25 DSM-IIIR schizophrenic (SC) patients using the Tower of Hanoi (TOH) task. Their performance was compared to that of: (1) 22 patients with neurosurgical unilateral prefrontal lesions, 11 left (LF) and 10 right hemisphere (RF); (2) 38 patients with unilateral temporal lobectomies, 19 left (LT) and 19 right (RT); and (3) 44 matched control subjects. Like the RT and LF group, the schizophrenics were significantly impaired on the TOH. The deficit shown by the schizophrenic group was equivalent whether or not the problems to be solved included goal-subgoal conflicts, unlike the LF group who were impaired specifically on these problems. The nature of the SC deficit was also distinct from that of the RT group, in that the problem-solving deficit remained after controlling for the effects of spatial memory performance. This study indicates, therefore, that neither focal frontal nor temporal lobe damage sustained in adult life is a sufficient explanation for the problem-solving deficits found in patients with schizophrenia.

Adult↗
PubMed1999

Attenuated frontal activation in schizophrenia may be task dependent.

UNLABELLED: Functional magnetic resonance imaging was used to examine the neural correlates of two linguistic tasks in schizophrenia. METHOD: Five dextral male schizophrenic patients and five volunteers matched for demographic variables and task performance participated. Echoplanar images were acquired over 5 min at 1.5 T while subjects performed two paced, covert tasks; (1) verbal fluency: silent generation of words beginning with an aurally presented cue letter, contrasted with silent repetition of the aurally presented word 'rest'; (2) semantic decision: deciding whether a visually presented cue word was 'living or non-living' and silently articulating the response, contrasted with rest. Both tasks entailed language processing; only verbal fluency requires the intrinsic generation of verbal material. Between-group differences in the mean power of experimental response to the semantic decision task were identified by a one-way analysis of covariance (ANCOVA), with a measure of stimulus-correlated motion as a covariate. Voxels demonstrating a significant interaction between task and group were identified using a two-way ANCOVA. RESULTS: In controls, both tasks were associated with activation of prefrontal cortex. In patients with schizophrenia there was a significantly reduced power of response in several prefrontal regions during verbal fluency relative to controls, a difference that was not evident for the semantic decision task. There was a significant group x task interaction in the left inferior frontal gyrus, left dorsolateral prefrontal cortex and the supplementary motor area at voxel and regional levels of analysis. CONCLUSIONS: Attenuation of frontal activation during cognitive task performance in schizophrenia does not represent a fixed deficit in frontal function, but may depend on the specific cognitive demands of the experimental task employed.

Adult↗
PubMed1999

Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive psychosis of early onset: case-control study.

OBJECTIVE: To examine prenatal and perinatal risk factors for subsequent development of schizophrenia and affective and reactive psychosis. DESIGN: Three population based, case-control studies conducted within a Sweden-wide cohort of all children born during 1973-9. This was done by linking individual data from the Swedish birth register, which represents 99% of all births in Sweden, to the Swedish inpatient register. SUBJECTS: Patients listed in inpatient register as having been first admitted to hospital aged 15-21 years with a main diagnosis of schizophrenia (n=167), affective psychosis (n=198), or reactive psychosis (n=292). For each case, five controls were selected. MAIN OUTCOME MEASURES: Risks of schizophrenia and affective and reactive psychosis in relation to pregnancy and perinatal characteristics. RESULTS: Schizophrenia was positively associated with multiparity (odds ratio 2.0), maternal bleeding during pregnancy (odds ratio 3.5), and birth in late winter (odds ratio 1.4). Affective psychosis was associated with uterine atony (odds ratio 2.2) and late winter birth (odds ratio 1.5). Reactive psychosis was related to multiparity (odds ratio 2.1). An increased risk for schizophrenia was found in boys who were small for their gestational age at birth (odds ratio 3.2), who were number four or more in birth order (odds ratio 3.6), and whose mothers had had bleeding during late pregnancy (odds ratio 4.0). CONCLUSIONS: A few specific pregnancy and perinatal factors were associated with the subsequent development of psychotic disorder, particularly schizophrenia, in early adult life. The association of small size for gestational age and bleeding during pregnancy with increased risk of early onset schizophrenia among males could reflect placental insufficiency.

Adult↗
PubMed1999

Mapping of grey matter changes in schizophrenia.

Studies of brain changes in schizophrenia have suggested that the disorder is associated with reductions in both global and regional grey matter. In this study, we used structural neuroimaging to differentiate between these two types of change and to examine regional grey matter throughout the whole brain. Grey matter from magnetic resonance images was segmented and transformed into stereotactic space, and patients with schizophrenia and controls were compared with respect to regional grey matter (after compensating for global grey matter differences). In two preliminary analyses to test our methodology, we demonstrated that: (1) in the transformed grey matter maps, voxel values at the location of the caudate nuclei were correlated with region-of-interest measurements of caudate area in native image space, and (2) the technique detected regional grey matter changes resulting from artificial lesions created in the native images. We then used a factorial design to examine data from two studies, comprising a total of 42 schizophrenics and 52 controls. Analysis of the main effect of schizophrenia on regional grey matter revealed significant reductions in (a) the right temporal pole, insula and amygdala, (b) the left temporal pole, insula and dorsolateral prefrontal cortex.

Adult↗
PubMed1999

Episodic memory and learning in patients with chronic schizophrenia.

This study explored the pattern of memory functioning in 58 patients with chronic schizophrenia and compared their performance with 53 normal controls. Multiple domains of memory were assessed, including verbal and non-verbal memory span, verbal and non-verbal paired associate learning, verbal and visual long-term memory, spatial and non-spatial conditional associative learning, recognition memory and memory for temporal order. Consistent with previous studies, substantial deficits in long-term memory were observed, with relative preservation of memory span. Memory for temporal order and recognition memory was intact, although significant deficits were observed on the conditional associative learning tasks. There was no evidence of lateralized memory impairment. In these respects, the pattern of memory impairment in schizophrenia is more similar in nature to that found in patients with memory dysfunction following mesiotemporal lobe lesions, rather than that associated with focal frontal lobe damage.

Adult↗
PubMed1999

Heritability estimates for psychotic disorders: the Maudsley twin psychosis series.

BACKGROUND: Previous twin studies have supported a genetic contribution to the major categories of psychotic disorders, but few of these have employed operational diagnostic criteria, and no such study has been based on a sample that included the full range of functional psychotic disorders. METHODS: A total of 224 twin probands (106 monozygotic, 118 dizygotic) with a same-sex co-twin and a lifetime history of psychosis was ascertained from the service-based Maudsley Twin Register in London, England. Research Diagnostic Criteria psychotic diagnoses were made on a lifetime-ever basis. Main-lifetime diagnoses of DSM-III-R and International Statistical Classification of Diseases, 10th Revision schizophrenia were also made. Probandwise concordance rates and correlations in liability were calculated, and biometrical model fitting applied. RESULTS: A substantial genetic contribution to variance in liability was confirmed for the major diagnostic categories except Research Diagnostic Criteria depressive psychosis and unspecified functional psychosis, where familial transmission was confirmed, but the relative contribution of genetic and common environmental factors was unclear. Heritability estimates for Research Diagnostic Criteria schizophrenia, schizoaffective disorder, mania, DSM-III-R schizophrenia, and International Statistical Classification of Diseases, 10th Revision schizophrenia were all between 82% and 85%. None of the estimates differed significantly from any other. CONCLUSIONS: Heritability estimates for schizophrenia, schizoaffective disorder, and mania were substantial and similar. Population morbid risk estimates were inferred rather than directly measured, but the results were very similar to those from studies where morbid risks were directly estimated.

Adult↗
PubMed1999

School performance in Finnish children and later development of schizophrenia: a population-based longitudinal study.

BACKGROUND: We examined whether children who are diagnosed as having schizophrenia in adulthood could be distinguished from their peers on performance in elementary school. METHODS: We used a case-control study design nested within a population-based birth cohort of all individuals born in Helsinki, Finland, between January 1, 1951, and December 31, 1960. Case ascertainment was from 3 national health care registers. Elementary school records were obtained for 400 children who were diagnosed as having schizophrenia in adulthood and for 408 controls. Results were analyzed for the 4 years of schooling (ages 7-11 years) that were common to all pupils. School subjects were entered into a principal components analysis and produced 3 factors: academic, nonacademic, and behavioral. These factors were compared between cases and controls after adjusting for sex and social group. Eligibility for high school and progression to high school were investigated among cases and controls. RESULTS: Cases performed significantly worse than controls only on the nonacademic factor (which loaded sports and handicrafts). There were no differences between the groups on the academic or behavioral factors, and there were no significant clinical correlates of factor scores. Cases were significantly less likely than controls to progress to high school, despite similar eligibility. CONCLUSIONS: Poor performance in sports and handicrafts during elementary school, which may indicate a motor coordination deficit, appears to be a risk factor for later schizophrenia. Poor academic performance in elementary school was not a risk factor for schizophrenia in this study. Lack of expected progression to high school among cases, despite good academic grades, provides evidence for deteriorating premorbid functional adjustment in schizophrenia.

Achievement↗
PubMed1999

Life events, ethnicity and perceptions of discrimination in patients with severe mental illness.

BACKGROUND: Whilst it is commonly believed that black and ethnic minority (B&EM) people living in the UK experience social disadvantage compared with the white British (WB) population, no study has specifically addressed this issue in patients with severe mental illness. We sought to test the hypothesis that B&EM patients experience more negative life events than their WB counterparts, and to examine the extent to which they attribute these events to discrimination. METHOD: Thirty-four WB, 78 African Caribbean (AC) and 35 other ethnic minority patients with psychotic illnesses, defined using Research Diagnostic Criteria, were asked to complete a Racial Life Event Questionnaire examining life events and perceptions of discrimination at baseline and 12 and 24 months later. RESULTS: African Caribbean patients experienced more 'Financial' life events across the study period, otherwise there were no significant differences between patient groups in number of life events experienced. The B&EM group collectively (n = 113), however, were significantly more likely than the WB group (n = 34) to attribute 'Assault', and 'Legal' life events to discrimination. The AC patient group were significantly more likely than the other two ethnic groups to attribute the 'Financial' and 'Health' life events they experienced to discrimination. The B&EM group was also significantly more likely, and particularly the AC patient group, to report that members of their own ethnic group are adversely affected by discrimination. Further analyses showed skin colour rather than ethnicity or nationality to be the major contributing factor to perception of discrimination; thus, the Irish (n = 11) had similar scores to the WB while Africans (n = 16) scored like the ACs. CONCLUSION: Our study shows that B&EM patients do not experience significantly more life events than WB patients; however, their perception of these events is clearly different, and significantly more often attributed to racism. It is reasonable to suppose that patients may be disinclined to utilise services they believe to be prejudiced against them on the basis of their skin colour, and service providers need to be aware of this in order to create health care services that B&EM patients feel confident to use.

Adult↗
PubMed1999

Ethnic differences in the presentation of bipolar affective disorder.

There have been repeated reports that Afro-Caribbean people living in the UK are more prone than white people to be diagnosed as having schizophrenia and mania, along with some evidence that they are less likely to receive a diagnosis of depression. We attempted to replicate these findings in a population of patients on lithium prophylaxis. We therefore assessed the clinical characteristics of people under the age of 55 from three ethnic groups attending a lithium clinic in south London, those of (1) white British (n = 88); (2) Afro-Caribbean (n = 31); and, (3) African (n = 15) origin. Nineteen of the white patients met DSM-IV criteria for unipolar depression (UP) and eight met the criteria for bipolar II disorder (BP II); in contrast, only two black patients met the criteria for unipolar depression and none met the criteria for BP II. Among patients diagnosed as BP I, Africans were significantly more likely than whites to show exclusively or mainly manic presentations while Afro-Caribbeans were more likely to have had mood-incongruent delusions. On the other hand, white patients were significantly more likely than Afro-Caribbeans to have had suicidal ideas or actions, and showed a similar but not significant excess when compared with Africans. Our findings could reflect either genuine ethnic differences in the presentation of severe affective disorder or be produced by the failure of British doctors to detect depression and deliver appropriate treatment to their black patients. The frequency with which Afro-Caribbean patients with mania present mood-incongruent delusions probably contributes to the high rates of diagnosed schizophrenia in this population.

Africa↗
PubMed1999

Factor analysis of symptoms in schizophrenia: differences between White and Caribbean patients in Camberwell.

BACKGROUND: The incidence of schizophrenia among African-Caribbeans living in Britain has been frequently reported to be increased. We sought to determine whether the symptom profile in schizophrenic patients from this group differed from that of their White counterparts. METHODS: Factor analysis was applied to symptom data obtained by the Present State Examination (PSE) from a group of White (N = 96) and Afro-Caribbean (N = 64) patients who satisfied Research Diagnostic Criteria criteria for broad schizophrenia. We identified six symptom dimensions: mania, depression, first-rank delusions, other delusions, hallucinations and one which comprised both manic and catatonic symptoms. RESULTS: The only difference between the two ethnic groups was seen on the mixed mania-catatonia dimension with the Afro-Caribbean group being over-represented. There were no other significant differences between the groups. Discriminant analysis, however, revealed no significant differences between the groups in any dimension. CONCLUSIONS: These results indicate that there are no differences between White and African-Caribbean patients with schizophrenia in terms of the core symptoms of the disorder, however, the African-Caribbean patients may present with more symptoms of a mixed affective nature.

Adolescent↗