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R M Murray

Publications and source records attributed to R M Murray.

At least 55 records · Page 3Linked to original sources

Differential activation of temporal cortex during sentence completion in schizophrenic patients with and without formal thought disorder.

The neural correlates of processing linguistic context in schizophrenic patients with formal thought disorder (FTD) were examined. Six right-handed male patients with prominent 'positive' FTD were compared with six schizophrenic patients without FTD and seven volunteers, matched for cognitive and demographic variables. Functional magnetic resonance imaging (IMRI) was used to measure cerebral activation while subjects read and completed sentence stems out loud. During a GENERATION condition, subjects were required to generate a word which completed the sentence stem appropriately. During a DECISION condition, subjects selected and articulated one of two presented terminal words. A READING condition served as baseline. The three conditions were compared with each other. Regions activated were identified in each group, and between-group differences were detected using an ANCOVA. When GENERATION was compared with READING, FTD patients showed less activation in the right superior temporal gyrus than patients without FTD or controls, but greater activation in the left inferior frontal, inferior temporal and fusiform gyri. FTD patients also showed an attenuated right temporal response when GENERATION was compared with DECISION. This differential engagement of the right temporal cortex was independent of differences in the speed or accuracy of responses, whereas the left fronto-temporal differences in activation were not evident after covarying for task errors. The attenuated engagement of right temporal cortex, which is implicated in language comprehension at the discourse level, is consistent with neuropsychological evidence linking thought disorder with deficits in processing linguistic context.

Acute Disease↗

Affected sibling pair linkage analysis of qualitative and quantitative traits for schizophrenia on chromosome 22 in a Chinese population.

We performed nonparametric linkage analysis on 136 families with two or more siblings with schizophrenia from Sichuan, southwestern China. In addition to categorical diagnosis, we used quantitative trait information from the Positive and Negative Symptom Scale and the modified Overt Aggression Scale. Categorical analysis using the diagnosis of schizophrenia and a maximum likelihood identity-by-descent method produced scores of close to 0 throughout the whole region tested. Multipoint analysis allowed exclusion of most markers with a relative risk of > 2, but did not exclude the possibility of a relative risk of < 1.5 for four of the markers. Our results provide no significant evidence for a locus for schizophrenia on chromosome 22. Quantitative linkage analysis using the PANSS-G scale score produced a maximum LOD score of approximately 1.2 with the marker D22S310, using either the Haseman-Elston method or maximum likelihood variance estimation with or without dominance. PANSS-N produced a maximum LOD score of 1.2 at the D22S283 locus. LOD score of about 1 are easily produced by chance. Thus, we conclude that under quantitative trait we also find no evidence of linkage between schizophrenia and markers on chromosome 22 in our Chinese sibling pair sample.

Adolescent↗

Transmission disequilibrium analysis of HLA class II DRB1, DQA1, DQB1 and DPB1 polymorphisms in schizophrenia using family trios from a Han Chinese population.

Our goal was to evaluate the role of HLA in the risk of developing schizophrenia, in a Han Chinese population. In several Japanese studies, there is evidence of association with DR1 and schizophrenia. A variety of other associations have been reported in other populations, including negative associations with DQbeta(*)0602 and positive associations with DR1(*)0101. Using sequence specific oligonucleotides, we genotyped four HLA markers (DRB1, DQA1, DQB1 and DPB1) in 165 family trios, consisting of Han Chinese schizophrenic subjects and their parents. Individual markers were analysed for transmission distortion in the trios using the transmission disequilibrium test. Multiple haplotype transmission was performed using the program TRANSMIT v2.5. The four markers were in strong linkage disequilibrium with each other (P value from 0.002 to 0). There was no evidence of overall transmission disequilibrium for each of the four loci. For DRB1, we did not find transmission distortion for the DRB1(*)04 and DRB1(*)08 alleles, as reported previously, but the DRB1(*)03 allele was preferentially not transmitted (P=0.009), and the DRB1(*)13 allele was preferentially transmitted from parents to schizophrenic offspring (P=0.041). Using haplotypes of pairs of markers, a significant global P value of 0.019 was achieved when using DRB1 and DQA1, mainly as a result of the excess transmission of DRB1(*)13-DQA1(*)01 (P=0.012) and a deficit in transmission of DRB1(*)03-DQA1(*)05 (P=0.002). In summary, we did not confirm any of the specific HLA allelic associations reported previously in Japanese or other populations. However, our results are compatible with the view that this region of HLA might contain a susceptibility gene which is in linkage disequilibrium with DRB1 and DQA1 genes.

Adolescent↗

Neuropsychological performance and spectrum personality traits in the relatives of patients with schizophrenia and affective psychosis.

Neuropsychological deficits are found in both schizophrenic patients and their relatives, and some studies have shown similar, but less severe, deficits in affective psychotic patients and their relatives. We set out to establish: (a) whether schizophrenia spectrum personality traits are more common in the relatives of schizophrenic patients than, in the relatives of affective psychotic patients; and (b) what the relation is between spectrum personality traits and neuropsychological deficits in these relatives. Relatives were interviewed using the International Personality Disorder Examination (IPDE), and also completed the National Adult Reading Test (NART), the Trail Making Test (TMT; Parts A and B) and Thurstone's Verbal Fluency Test (TVFT). Spectrum personality traits were equally common in 129 relatives of schizophrenic patients and 106 relatives of affective psychotic patients, but the performance of the former group was inferior to that of the latter on the NART and the TVFT. Relatives with high paranoid traits had lower NART scores than relatives without such personality traits; similarly, those with high schizoid traits took longer to complete the TMT, part B, than those without such traits; and relatives with high schizotypal traits generated significantly fewer words on the TVFT than those without such traits. We conclude that relatives of schizophrenic and affective psychotic patients share a propensity to schizophrenia spectrum traits, but relatives of the former have poorer neuropsychological performance. Furthermore, there exists an association between neuropsychological deficits and spectrum traits in both groups of relatives; in particular those with high paranoid traits have lower IQ scores than their less paranoid counterparts.

Adult↗

Schizophrenia and HLA: a review.

A number of reports of genetic association of human leucocyte antigens (HLA) and alleles with schizophrenia have recently been published. A schizophrenia locus on chromosome 6p near the HLA region has also been reported, on the basis of linkage studies. We have therefore reviewed the investigations of association of HLA with schizophrenia published from 1974 to date, and have also briefly reviewed the chromosome 6p linkage studies. Two or more groups of investigators have reported association of each of the following HLA antigens or alleles with schizophrenia - A9 or its A24 subspecificity, A28, A10, DRB1*01 and DRw6. However, these results may represent Type I errors caused by small sample size, inappropriate diagnostic, laboratory and/or statistical methodology, and/or incorrectly chosen comparison subjects. Hypothesis-driven negative associations of DRB1*04 and DQB1*0602 with schizophrenia have also been reported. Taken together, however, HLA association investigations provide only weak evidence for the existence of either resistance or susceptibility loci for schizophrenia close to the HLA region at the 6p21.3 band and, indeed, recently reported investigations that controlled for most of these confounders found no evidence of association. Linkage studies suggest that a susceptibility locus may exist and that it may be within the HLA region, but again the evidence is far from conclusive. Further HLA association investigations should employ operational diagnostic criteria, comparison subjects screened for illness and HLA genotyping, and should include both association studies of candidate alleles and transmission disequilibrium and haplotype relative risk studies.

Alleles↗

Neural correlates of formal thought disorder in schizophrenia: preliminary findings from a functional magnetic resonance imaging study.

BACKGROUND: Formal thought disorder (FTD) is a core symptom of schizophrenia, but its pathophysiology is little understood. We examined the neural correlates of FTD using functional magnetic resonance imaging. METHODS: Blood oxygenation level-dependent contrast was measured using functional magnetic resonance imaging while 6 patients with schizophrenia and 6 control subjects spoke about 7 Rorschach inkblots for 3 minutes each. In patients, varying degrees of thought-disordered speech were elicited during each "run." In a within-subject design, the severity of positive FTD was correlated with the level of blood oxygenation level-dependent contrast in the 2 runs that showed the highest variance of FTD in each patient. RESULTS: The severity of positive FTD in patients was negatively correlated (P<.001) with signal changes in the left superior and middle temporal gyri. Positive correlations were evident in the cerebellar vermis, the right caudate body, and the precentral gyrus. CONCLUSIONS: The severity of positive FTD was inversely correlated with the level of activity in the Wernicke area, a region implicated in the production of coherent speech. Reduced activity in this area might contribute to the articulation of incoherent speech. Because of the small sample size, these findings should be considered preliminary.

Adult↗

Differential frontal activation in schizophrenia and bipolar illness during verbal fluency.

INTRODUCTION: The precise nature of frontal lobe dysfunction in schizophrenia remains unclear. We have previously demonstrated, using fMRI, a task-specific attenuation of frontal activation in schizophrenic patients. By using an identical methodology in matched bipolar subjects, we sought to determine whether this finding is specific to schizophrenia or a correlate of psychosis in general. METHOD: Five dextral male bipolar patients and matching groups of schizophrenic subjects and controls were studied using fMRI. Echoplanar images were acquired while subjects performed two paced tasks: covert verbal fluency and a semantic decision task. Generic brain activation maps were constructed from individual images by sinusoidal regression analysis. Between-group differences in the mean power of experimental response were identified on a voxel-wise basis by an analysis of variance (ANOVA). RESULTS: The bipolar patients showed extensive prefrontal activation during verbal fluency which was significantly greater than in controls. There was no difference in the prefrontal BOLD response during the semantic decision task. CONCLUSIONS: These data indicate that bipolar patients show a strikingly different pattern of frontal responses compared to those with schizophrenia and provide further evidence that abnormal frontal activation in psychotic disorders is more apparent during verbal fluency than semantic decision.

Adult↗

Neuropsychological outcome at adolescence of very preterm birth and its relation to brain structure.

Neuropsychological outcome at 14 to 15 years of age of a cohort of 75 participants (39 male, 36 female) born at <33 weeks' gestation was investigated. Research was conducted parallel to a recent MRI study by Stewart and colleagues which reported that 55% of this cohort had evidence of brain abnormality. One aim of the study was to compare neuropsychological function in those very preterm children with and without MRI abnormality. Compared to a control sample of term adolescents, very preterm participants had impairment only on a measure of word production. On measures of attention, memory, perceptual skill, and visuomotor and executive function, the adolescents born very preterm performed in the normal range, whether or not they had evidence of MRI abnormality. Our findings are encouraging as the neuropsychological consequences of damage to the very preterm brain, still evident on MRI at 14 to 15 years of age, appear to be minor.

Adolescent↗

A functional study of auditory verbal imagery.

BACKGROUND: We used functional MRI to examine the functional anatomy of inner speech and different forms of auditory verbal imagery (imagining speech) in normal volunteers. We hypothesized that generating inner speech and auditory verbal imagery would be associated with left inferior frontal activation, and that generating auditory verbal imagery would involve additional activation in the lateral temporal cortices. METHODS: Subjects were scanned, while performing inner speech and auditory verbal imagery tasks, using a 1.5 Tesla magnet. RESULTS: The generation of inner speech was associated with activation in the left inferior frontal/insula region, the left temporo-parietal cortex, right cerebellum and the supplementary motor area. Auditory verbal imagery in general, as indexed by the three imagery tasks combined, was associated with activation in the areas engaged during the inner speech task, plus the left precentral and superior temporal gyri (STG), and the right homologues of all these areas. CONCLUSIONS: These results are consistent with the use of the 'articulatory loop' during both inner speech and auditory verbal imagery, and the greater engagement of verbal self-monitoring during auditory verbal imagery.

Adult↗

Verbal fluency in patients with schizophrenia and affective psychoses and their first-degree relatives.

BACKGROUND: Schizophrenic patients are known to have neuropsychological deficits including impaired verbal fluency, but it is not clear whether this latter deficit is: (a) a consequence of overall intellectual deficit; (b) shared with affective psychotic patients; or (c) shared by the relatives of schizophrenic patients; and (d) shared by the relatives of affective psychotic patients. METHODS: We administered Thurstone's Verbal Fluency Test to 45 schizophrenic patients and 72 of their relatives, and 30 affective psychotic patients and 53 of their relatives. Subjects were asked to generate as many words as possible beginning with the letters 'C' and 'S' and the total was taken as the dependent variable. Subjects also completed the National Adult Reading Test (NART) to provide a measure of (pre-morbid) IQ. RESULTS: Schizophrenic patients generated significantly fewer words than affective psychotic patients, however adjusting for NART this became non-significant. Schizophrenic (but not affective psychotic) patients generated significantly fewer words than their relatives; again adjusting for NART this became non-significant. Patients who had been exposed to obstetric complications (OC+) and those who had not (OC-) had similarly poor verbal fluency scores. Relatives of OC+ schizophrenic patients had superior verbal fluency than relatives of OC- schizophrenic patients and this remained significant after adjustment for NART. CONCLUSIONS: The results suggest that some families transmit impairment in verbal fluency as part of a pattern of lower overall IQ. However, in other families, relatives show largely normal neuropsychological function, and the poorer verbal performance of the schizophrenic member appears to have arisen secondary to his/her exposure to OCs.

Adult↗

Neuropsychological performance of psychotic patients in community care: results from the UK700 study.

OBJECTIVE: To compare cognitive performance in chronic schizophrenic and affective psychotic patients maintained in community care. METHOD: We studied a sample of community-based patients (n = 707) with chronic psychotic disorders. Neuropsychological assessment was completed using the National Adult Reading Test (NART) and the Trail Making Test (TMT). RESULTS: Affective psychotic patients had higher premorbid IQ than schizophrenic patients before adjustment for confounding factors (P=0.03); however, after adjustment for ethnic group and social class this became non-significant (P=0.19). There were no significant differences between groups on the TMT, parts A or B. CONCLUSION: Unlike studies suggesting that schizophrenic patients are more cognitively impaired than affective psychotic patients, our study suggests a degree of cognitive homogeneity between those patients who develop a chronic illness. Measures of premorbid IQ suggest that this cognitive homogeneity exists prior to the onset of illness.

Adult↗

Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term.

Individuals born before 33 weeks' gestation are at risk of brain lesions, which have the potential to disrupt subsequent neurodevelopment. As a result they manifest an increased incidence of neuromotor signs and cognitive deficits, which can still be detected in adolescence. The cerebellum is known to be involved in both the co-ordination of movement and in cognitive processes. We therefore set out to establish whether cognitive and motor impairments in adolescents born very pre-term are associated with abnormalities of the cerebellum as revealed by volumetric analysis of brain MRI scans. The volume of the whole cerebellum was determined manually using a PC-based Cavalieri procedure in 67 adolescents born very pre-term and 50 age-matched, full-term born controls. Cognitive and neurological assessments were performed at 1, 4, 8 and 14-15 years of age as part of the long-term follow-up of the pre-term subjects. The pre-term-born subjects had significantly reduced cerebellar volume compared with term-born controls (P<0.001). This difference was still present after controlling for potential confounders. There was no association between cerebellar volume and motor neurological signs. However, there were significant associations between cerebellar volume and several cognitive test scores, in particular the Wechsler Intelligence Scale for Children-Revised, the Kaufman Assessment Battery for Children and the Schonnel reading age. This provides further evidence implicating the cerebellum in cognition and suggests that cerebellar abnormalities may underlie some of the cognitive deficits found in individuals born very pre-term.

Adolescent↗

Modality specific neural correlates of auditory and somatic hallucinations.

Somatic hallucinations occur in schizophrenia and other psychotic disorders, although auditory hallucinations are more common. Although the neural correlates of auditory hallucinations have been described in several neuroimaging studies, little is known of the pathophysiology of somatic hallucinations. Functional magnetic resonance imaging (fMRI) was used to compare the distribution of brain activity during somatic and auditory verbal hallucinations, occurring at different times in a 36 year old man with schizophrenia. Somatic hallucinations were associated with activation in the primary somatosensory and posterior parietal cortex, areas that normally mediate tactile perception. Auditory hallucinations were associated with activation in the middle and superior temporal cortex, areas involved in processing external speech. Hallucinations in a given modality seem to involve areas that normally process sensory information in that modality.

Adult↗

Cognitive neuropsychiatric models of persecutory delusions.

OBJECTIVE: The major cognitive theories of persecutory delusion formation and maintenance are critically examined in this article. METHOD: The authors present a comprehensive review of the literature, citing results of relevant functional neuroimaging and neural network studies. RESULTS: People with persecutory delusions selectively attend to threatening information, jump to conclusions on the basis of insufficient information, attribute negative events to external personal causes, and have difficulty in envisaging others' intentions, motivations, or states of mind. Presence of the "reality distortion" cluster of psychotic symptoms correlates with cerebral blood flow in the left lateral prefrontal cortex, ventral striatum, superior temporal gyrus, and parahippocampal region. Social cognitive processing (selective attention to threat, attribution of causation or mental states) in normal subjects involves similar areas. Neural network models of persecutory delusions highlight the importance of disordered neuromodulation in their formation and of disordered neuroplasticity in their maintenance. CONCLUSIONS: Further studies examining the interaction of these cognitive processes, cross-sectionally and longitudinally, at cognitive psychological, neural network, and functional neuroanatomical levels are warranted to establish a comprehensive cognitive neuropsychiatric model of the persecutory delusion.

Attention↗

Obstetric complications and schizophrenia: prenatal underdevelopment and subsequent neurodevelopmental impairment.

BACKGROUND: Many studies have shown an association between obstetric complications and schizophrenia. AIMS: To investigate the possible relationship between prenatal underdevelopment, neurodevelopmental abnormality and subsequent schizophrenia. METHOD: The literature was reviewed. In particular, by pooling data from recently published reports, we examined whether low birthweight (< 2500 g) is a risk factor for schizophrenia. RESULTS: Low birthweight was significantly more common for subjects with schizophrenia than for control subjects: P < 0.00001, odds ratio 2.6 (95% CI 2.0 to 3.3). Individuals born prematurely are at greater risk of perinatal brain damage and subsequent neurodevelopmental abnormalities, which may constitute vulnerability to the development of schizophrenia. Patients with schizophrenia who had low birthweights also tended to have poor premorbid psychosocial adjustment. CONCLUSIONS: Low birthweight is a modest, but definite, risk factor for schizophrenia. Brain damage associated with prenatal underdevelopment has a role in the pathogenesis of poor premorbid functioning and subsequent neurodevelopmental impairment in some cases of schizophrenia.

Brain↗

Understanding the excess of psychosis among the African-Caribbean population in England. Review of current hypotheses.

BACKGROUND: Increased rates of schizophrenia continue to be reported among the African-Caribbean population in England. AIMS: To evaluate the competing biological, psychological and social explanations that have been proposed. METHOD: Literature review. RESULTS: The African-Caribbean population in England is at increased risk of both schizophrenia and mania; the higher rates remain when operational diagnostic criteria are used. The excess of the two psychotic disorders are probably linked: African-Caribbean patients with schizophrenia show more affective symptoms, and a more relapsing course with greater social disruption but fewer chronic negative symptoms, than White patients. No simple hypothesis explains these findings. CONCLUSIONS: More complex hypotheses are needed. One such links cultural variation in symptom reporting, the use of phenomenological constructs by psychiatrists and social disadvantage.

Attitude to Health↗

Predictors of later schizophrenia and affective psychosis among attendees at a child psychiatry department.

BACKGROUND: Schizophrenia has been linked with psychological problems in childhood but there is little information on precursors of affective psychosis. AIMS: To compare childhood psychological antecedents of adult schizophrenia and affective psychosis. METHOD: Childhood item sheets, which give standardised information on signs and symptoms of mental illness in the year preceding assessment are completed for all attendees at the children's department of the Maudsley and Bethlem Royal Hospital. We examined item sheet data on individuals with an adult diagnosis of schizophrenia (n=59) or affective psychosis (n=27) and a comparison group with no adult mental illness (n=86) (all had attended the department). RESULTS: Abnormal suspiciousness or sensitivity and relationship difficulties with peers are associated with later schizophrenia. In contrast, affective psychosis is associated with childhood hysterical symptoms and disturbances in eating. CONCLUSIONS: Childhood psychological precursors for schizophrenia and affective psychosis differ and do not simply reflect non-specific psychiatric disturbance in adolescence.

Adolescent↗