Biomedical subjects

R M Murray

Publications and source records attributed to R M Murray.

At least 37 records · Page 2Linked to original sources

PubMed2004

Lateralisation of language function in young adults born very preterm.

OBJECTIVE: To explore, using functional magnetic resonance imaging (MRI), the functional organisation of phonological processing in young adults born very preterm. SUBJECTS: Six right handed male subjects with radiological evidence of thinning of the corpus callosum were selected from a cohort of very preterm subjects. Six normal right handed male volunteers acted as controls. METHOD: Blood oxygenation level dependent contrast echoplanar images were acquired over five minutes at 1.5 T while subjects performed the tasks. During the ON condition, subjects were visually presented with pairs of non-words and asked to press a key when a pair of words rhymed (phonological processing). This task alternated with the OFF condition, which required subjects to make letter case judgments of visually presented pairs of consonant letter strings (orthographic processing). Generic brain activation maps were constructed from individual images by sinusoidal regression and non-parametric testing. Between group differences in the mean power of experimental response were identified on a voxel wise basis by analysis of variance. RESULTS: Compared with controls, the subjects with thinning of the corpus callosum showed significantly reduced power of response in the left hemisphere, including the peristriate cortex and the cerebellum, as well as in the right parietal association area. Significantly increased power of response was observed in the right precentral gyrus and the right supplementary motor area. CONCLUSIONS: The data show evidence of increased frontal and decreased occipital activation in male subjects with neurodevelopmental thinning of the corpus callosum, which may be due to the operation of developmental compensatory mechanisms.

Adolescent↗

PubMed2004

Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia.

BACKGROUND: High rates of osteoporosis in schizophrenia may result from the prolactin-raising effects of some antipsychotic medication. Aims To examine bone mineral density in relation to relevant endocrine variables in patients with schizophrenia taking prolactin-raising antipsychotics. METHOD: Fifty-five patients who had been receiving prolactin-raising antipsychotic medication for >10 years underwent dual-energy X-ray absorptiometry of their lumbar and hip bones. Among the endocrine variables assessed were plasma prolactin and sex hormones. RESULTS: Age-related reduced bone mineral density measures were found in 17 (57%) of the male and 8 (32%) of the female patients. Higher doses of the female patients. Higher doses of medication were associated with increased rates of both hyperprolactinaemia and bone mineral density loss. Bone loss for the whole group was correlated with medication dose, and for men was inversely correlated with testosterone values. CONCLUSIONS: These results suggest that patients with schizophrenia on long-term prolactin-raising antipsychotic medication are at high risk of developing reduced bone mineral density as a consequence of hyperprolactinaemia-induced hypogonadism.

Adult↗

PubMed2003

Episodic memory in schizophrenic patients and their relatives.

BACKGROUND: Memory dysfunction among healthy relatives of patients with schizophrenia suggests that genetic liability to the disorder can also be manifested as cognitive impairment. This study was designed to further elucidate the nature of the memory dysfunction being transmitted. METHOD: Memory function was assessed in 62 schizophrenic patients, 98 of their healthy relatives and 66 controls. Material-specific immediate/delayed recall and percentage retention were investigated using the Logical Memory and Visual Reproduction tests of the Wechsler Memory Scale (WMS). A third subtest of the WMS, the Associate Learning and a visual analogue of it, the Abstract Paired Associates, were used to measure verbal and visual learning. Current general intellectual function was assessed using a five-subtest short-form of the Wechsler Adult Intelligence scale-Revised (WAIS-R). RESULTS: Schizophrenic patients performed significantly worse than controls on nearly all measures. Their relatives also showed significant deficit on the immediate and delayed recall of the Logical Memory, immediate recall of the Visual Reproduction, and the Abstract Paired Associates tests. Logical memory was substantially more impaired than the other measures for both patients and relatives. The deficit in immediate recall of the Logical Memory remained significant even after excluding those relatives with an Axis I diagnosis and schizotypal personality disorder. These findings were despite the relatives having an equivalent level of general intellectual function to that of controls. CONCLUSION: Familial, presumed genetic, liability to schizophrenia may be expressed as dysfunction in verbal memory.

Adolescent↗

PubMed2003

Self-responsibility and the self-serving bias: an fMRI investigation of causal attributions.

We use causal attributions to infer the most likely cause of events in the social world. Internal attributions imply self-responsibility for events. The self-serving bias describes the tendency of normal subjects to attribute the causation of positive events internally ("I am responsible em leader ") and negative events externally ("Other people or situational factors are responsible em leader "). The self-serving bias has been assumed to serve a positive motivational function by enhancing self-esteem. Abnormalities of attributional style have been implicated in both depression and psychosis. We examined the neural basis of both self-responsibility and the self-serving bias using functional magnetic resonance imaging during the performance of attributional decision tasks. We found that the determination of self-responsibility recruits areas previously implicated in action simulation (bilateral premotor cortex and cerebellum), suggesting that such higher order social cognition is related to simpler internal models of goal-directed action. The dorsal striatum, previously implicated in motivated behavior, mediates the self-serving bias.

Adult↗

PubMed2003

A quantitative genetic analysis of schizotypal personality traits.

BACKGROUND: Previous twin studies investigating the heritability of schizotypy have often had limited power and have failed to measure the disorganization/social anxiety component. METHOD: Seven hundred and thirty-three female twin pairs, drawn from the Institute of Psychiatry Volunteer Twin Register, completed the Oxford-Liverpool Inventory of Feelings and Experiences and the Peters et al. Delusions Inventory. Structural equation modelling was carried out on scores for MZ and DZ twin pairs. RESULTS: The best fitting models for all scales comprised additive genetic and unique environmental effects. Heritability was estimated at approximately 50% for most scales, although it was lower at 37% for the PDI scale. Multivariate structural equation model fitting revealed a best-fitting model in which additive genetic and unique environmental influences act through a single common pathway for Cognitive Disorganization, Unusual Experiences and the PDI, and through a separate common pathway for Cognitive Disorganization and Introvertive Anhedonia. CONCLUSIONS: The various components of schizotypy are moderately heritable. Multivariate model fitting indicates that at least two latent factor structures are required to account for the covariation between the various components of schizotypy. The positive and negative components of schizotypy are relatively genetically independent, although each in turn may be related to Cognitive Disorganization.

Adolescent↗

PubMed2003

Pre-morbid characteristics and co-morbidity of methamphetamine users with and without psychosis.

BACKGROUND: The long-term use of methamphetamine (MAMP) can result in psychosis but it is not clear why some individuals develop psychotic symptoms, while others use MAMP regularly over long periods and remain unscathed. We set out to characterize MAMP users and to examine the relationship of pre-morbid personality, pre-morbid social function and other psychiatric disorders to MAMP psychosis. METHOD: Four hundred and forty-five amphetamine users were recruited from a psychiatric hospital and a detention centre in Taipei, and were assessed with the Diagnostic Interview for Genetic Studies (DIGS). Their parents were interviewed with the Premorbid Schizoid and Schizotypal Traits (PSST) and the Premorbid Social Adjustment (PSA) schedules. Pre-morbid characteristics and psychiatric co-morbidity were compared between the MAMP users with a lifetime diagnosis of MAMP psychosis and those without. RESULTS: The MAMP users with psychosis presented a clinical picture which mimicked the positive symptoms of schizophrenia: 85% had auditory hallucinations; 71% persecutory delusions; 63% delusions of reference. Compared with their non-psychotic counterparts, these MAMP users were younger at first MAMP use, used larger amounts of MAMP, had a significantly higher mean PSST score, and higher rates of major depressive disorder, alcohol dependence and antisocial personality disorder. CONCLUSIONS: Earlier and larger use of MAMP was associated with increased risk of psychosis. Our data are also compatible with the view that pre-morbid schizoid/schizotypal personality predisposes MAMP users to develop psychosis, and that the greater the personality vulnerability, the longer the psychosis will persist.

Adolescent↗

PubMed2003

beta-1,3-Glucuronyltransferase-1 gene implicated as a candidate for a schizophrenia-like psychosis through molecular analysis of a balanced translocation.

We have mapped and sequenced both chromosome breakpoints of a balanced t(6;11)(q14.2;q25) chromosome translocation that segregates with a schizophrenia-like psychosis. Bioinformatics analysis of the regions revealed a number of confirmed and predicted transcripts. No confirmed transcripts are disrupted by either breakpoint. The chromosome 6 breakpoint region is gene poor, the closest transcript being the serotonin receptor 1E (HTR1E) at 625 kb telomeric to the breakpoint. The chromosome 11 breakpoint is situated close to the telomere. The closest gene, beta-1,3-glucuronyltransferase (B3GAT1 or GlcAT-P), is 299 kb centromeric to the breakpoint. B3GAT1 is the key enzyme during the biosynthesis of the carbohydrate epitope HNK-1, which is present on a number of cell adhesion molecules important in neurodevelopment. Mice deleted for the B3GAT1 gene show defects in hippocampal long-term potentiation and in spatial memory formation. We propose that the translocation causes a positional effect on B3GAT1, affecting expression levels and making it a plausible candidate for the psychosis found in this family. More generally, regions close to telomeres are highly polymorphic in both sequence and length in the general population and several studies have implicated subtelomeric deletions as a common cause of idiopathic mental retardation. This leads us to the hypothesis that polymorphic or other variation of the 11q telomere may affect the activity of B3GAT1 and be a risk factor for schizophrenia and related psychoses in the general population.

Base Sequence↗

PubMed2003

Incidence of schizophrenia in south-east London between 1965 and 1997.

BACKGROUND: There has been much debate about changes in the incidence of schizophrenia. AIMS: To identify any changes in incidence of schizophrenia in Camberwell, south-east London, between 1965 and 1997. METHOD: Research Diagnostic Criteria and DSM-III-R diagnoses were generated for all first contacts by the OPCRIT computer program, and incidence rates of schizophrenia in seven time periods were measured. Indirect standardisation and Poisson models were used to measure the effect of time period and to examine interactions with age and gender. RESULTS: There was a continuous and statistically significant increase in the incidence of schizophrenia, which was greatest in people under 35 years of age and was not gender-specific. CONCLUSIONS: The incidence of schizophrenia has doubled in south-east London over the past three decades.

Adult↗

PubMed2003

Pregnancy and birth complications in patients with schizophrenia in Trinidad and London.

It has been shown that an excess of pregnancy and birth complications (PBCs) does not contribute to the excess rates of schizophrenia reported for the population of Caribbean origin in Britain compared with the native Caucasian British population. We therefore attempted to compare the rate of PBCs between a sample of schizophrenics in Britain with that of a sample from Trinidad where some of the Caribbean migrants to Britain originated. First contact patients with schizophrenia according to the CATEGO system diagnosis were identified in Trinidad and London. Their mothers, where available, were interviewed using the Lewis-Murray scale for pregnancy and birth complications. Data from Trinidad and Tobago concerning 56 patients were compared with those of the Caucasian (n = 61) and African-Caribbean (n = 50) patients in London. The rate of PBCs was similar for the Caucasian British patients (24.6%) and the patients in Trinidad and Tobago (21.7%). The rates were lowest in the African-Caribbean patients in London (14.0%), though this difference was not statistically significant. These findings suggest that pregnancy and birth complications are a risk factor for a substantial minority of patients with schizophrenia in Trinidad and London. It also confirms that the excess rates of schizophrenia reported for the Caribbean population in Britain are not due to these complications.

Adolescent↗

PubMed2002

Genetic contributions to regional variability in human brain structure: methods and preliminary results.

Twin studies provide one approach for investigating and partitioning genetic and environmental contributions to phenotypic variability in human brain structure. Previous twin studies have found that cerebral volume, hemispheric volume, ventricular volume, and cortical gyral pattern variability were heritable. We investigated the contributions of genetic and environmental factors to both global (brain volume and lateral ventricular volume) and regional (parcellated gray matter) variability in brain structure. We examined MR images from 10 pairs of healthy monozygotic and 10 pairs of same-sex dizygotic twins. Regional gray matter volume was estimated by automated image segmentation, transformation to standard space, and parcellation using a digital atlas. Heritability was estimated by path analysis. Estimated heritability for brain volume variability was high (0.66; 95% confidence interval 0.17, 1.0) but the major effects on lateral ventricular volume variability were common and unique environmental factors. We constructed a map of regional brain heritability and found large genetic effects shared in common between several bilateral brain regions, particularly paralimbic structures and temporal-parietal neocortex. We tested three specific hypotheses with regard to the genetic control of brain variability: (i) that the strength of the genetic effect is related to gyral ontogenesis, (ii) that there is greater genetic control of left than of right hemisphere variability, and (iii) that random or fluctuating asymmetry in bilateral structures is not heritable. We found no evidence in support of the first two hypotheses, but our results were consistent with the third hypothesis. Finally, we used principal component (PC) analysis of the genetic correlation matrix, to identify systems of anatomically distributed gray matter regions which shared major genetic effects in common. Frontal and parietal neocortical areas loaded positively on the first PC; some paralimbic and limbic areas loaded negatively. Bilateral insula, some frontal regions, and temporal neocortical regions functionally specialized for audition and language loaded strongly on the second PC. We conclude that large samples are required for powerful investigation of genetic effects in imaging data from twins. However, these preliminary re. sults suggest that genetic effects on structure of the human brain are regionally variable and predominantly symmetric in paralimbic structures and lateral temporal cortex.

Algorithms↗

PubMed2002

Does schizophrenia result from developmental or degenerative processes?

The debate as to whether schizophrenia is a neurodevelopmental or a neurodegenerative disorder has its roots in the latter part of the 19th century when authorities such as Clouston (1891) posited that at least some insanities were "developmental" in origin. These views were soon eclipsed by Kraepelin's (1896) concept of dementia praecox as a degenerative disease, and the latter view carried not only the day but also much of the 20th century. Then, in the 1980s several research groups again began to speculate that schizophrenia might have a significant developmental component (Feinberg, 1982-1983; Schulsinger et al., 1984; Murray et al., 1985; Murray and Lewis, 1987; Weinberger et al., 1987). What became known as the "neurodevelopmental hypothesis" received support from neuropathological studies implicating anomalies in early brain development such as aberrant migration of neurons. Unfortunately, these studies proved difficult, if not impossible, to replicate (Harrison, 1999). The pendulum, therefore, began to swing again, and in the latter part of the 1990s came renewed claims that the clinical progression of the illness was accompanied by continued cerebral ventricular enlargement and reduction in the volumes of certain brain structures. Nevertheless, since few doubt that there is a developmental component to schizophrenia, the question which we will address in this paper is whether schizophrenia is a) simply the final consequence of a cascade of increasing developmental deviance (Bramon et al., 2001), or b) whether there is an additional brain degeneration following onset of psychosis which is superimposed on the developmental impairment (Lieberman, 1999).

Brain↗

PubMed2002

Reversed lateralization of temporal activation during speech production in thought disordered patients with schizophrenia.

BACKGROUND: Formal thought disorder is a core symptom of schizophrenia. It is associated with a reversed lateralization of the superior temporal cortex volume, an area that is implicated in lexical retrieval. We investigated the neural correlates of word retrieval during continuous speech in patients with formal thought disorder using functional magnetic resonance imaging (fMRI). METHODS: Blood oxygenation level dependent (BOLD) contrast was measured with fMRI while six patients with schizophrenia and six healthy control subjects spoke about seven Rorschach inkblots for 3 min each. Subjects produced varying amounts of speech during each run. In a within subject design, the number of words produced was correlated with the BOLD contrast in the two runs in each participant who showed the highest variance of speech output. RESULTS: In control subjects, the amount of speech produced was mainly correlated with activation in the left superior temporal gyrus. In the patient group, the main correlations were in the right superior temporal gyrus. CONCLUSIONS: During the production of continuous speech, patients with formal thought disorder showed a reversed laterality of activation in the superior temporal cortex. This is consistent with findings of perturbed hemispheric interaction in schizophrenia, particularly in patients with formal thought disorder.

Adult↗

PubMed2002

Do schizophrenic patients who managed to get to university have a non-developmental form of illness?

BACKGROUND: Many people who develop schizophrenia have impairments in intellectual and social functioning that are detectable from early childhood. However, some patients do not exhibit such deficits, and this suggests that they may have suffered less neurodevelopmental damage. We hypothesized that the aetiology and form of schizophrenia may differ in such patients. We therefore studied a group of schizophrenic patients who were functioning well enough to enter university prior to illness onset. METHODS: The casenotes of 46 university-educated patients and 48 non-university-educated patients were rated on several schedules including the OPCRIT checklist, and the two groups were compared using univariate statistical techniques. Principal components analysis was then performed using data from all patients, and the factor scores for each principal component were compared between groups. RESULTS: Univariate analyses showed the university-educated patients had an excess of depressive symptoms, and a paucity of core schizophrenic symptoms. Four principal components emerged in the principal components analysis: mania, biological depression, schizophrenic symptoms, and a reactive depression. University-educated patients scored significantly higher on the reactive depression principal component, and lower on the schizophrenic symptoms principal component, than the non-university-educated patients.

Adjustment Disorders↗

PubMed2002

Lower prevalence of pre-morbid neurological illness in African-Caribbean than White psychotic patients in England.

BACKGROUND: It has been suggested that the increased incidence of psychosis in African-Caribbeans living in England may be due to illnesses in which social stress plays an important aetiological role. If this is the case, the prevalence of factors associated with psychosis that predate illness onset such as obstetric complications, pre-morbid neurological illness and poor childhood social adjustment may be expected to be lower in African-Caribbean than Whites psychotic patients. METHOD: Details of obstetric complications, pre-morbid neurological illness, and pre-morbid social adjustment were obtained for 337 psychotic patients by patient interview, interviews of mothers and chart review. The proportions of patients with each 'risk factor' in the African-Caribbean (N = 103) and White (N = 184) groups were compared using regression analysis; age, sex, social class, diagnosis and referral status were possible explanatory variables. RESULTS: African-Caribbean patients were less likely to have suffered a pre-morbid neurological disorder than their White counterparts (odds ratio 0.19, 95% CI 0.06-0.61). There was no significant difference in pre-morbid social adjustment or obstetric complications between the two groups, though fewer obstetric complications were reported in the African-Caribbean group (21.5%) than the White group (30.9%). CONCLUSIONS: African-Caribbean patients with psychosis have experienced less pre-morbid neurological illness.

Black or African American↗

PubMed2002

IQ in childhood psychiatric attendees predicts outcome of later schizophrenia at 21 year follow-up.

OBJECTIVE: Preschizophrenic children who merit psychiatric referral are claimed to have a particularly malevolent illness when the psychosis develops later. The 21 years outcome of a sample of such children was investigated. METHOD: Fifty-one children who attended psychiatric services, and were later diagnosed as having schizophrenia, were followed up a mean of 21 years later. Baseline childhood demographic, clinical and putative aetiological characteristics were identified from the case notes. Follow-up assessment evaluated clinical symptoms, social functioning and service utilization. The predictive value of baseline factors on outcome was examined. RESULTS: Outcome was poor, and seven (14%) of the subjects were deceased. Childhood IQ was strongly predictive of social outcome (F=5.1, P=0.01) and service utilization (F=5.2, P=0.01), but not clinical symptoms. No other factors predicted outcome. CONCLUSION: Low childhood IQ had an unfavourable impact on social outcome and service utilization once schizophrenia developed.

Age of Onset↗

PubMed2002

The functional significance of perinatal corpus callosum damage: an fMRI study in young adults.

We used functional MRI (fMRI) to establish the functional significance of corpus callosum damage in young adults who had been born very preterm. Seven subjects from a cohort of individuals who had been born at <33 weeks gestation and who had sustained callosal damage visualized on structural MRI were compared while they carried out auditory and visual tasks requiring callosal transfer with nine very preterm subjects with corpora callosa of normal appearance on structural MRI, and with seven full-term controls. The very preterm subjects with damaged corpora callosa had significantly different activation patterns compared with the two control groups. In the visual task, additional activity was seen in the right dorsolateral prefrontal cortex of the damaged callosum group, possibly because the task was accomplished by storing information in working memory. On the auditory task, a deficit of activity was seen in the right temporal lobe of the callosum group. The findings reveal a plasticity of function compensating for early damage to the corpus callosum.

Adolescent↗

PubMed2002

Functional imaging of the mechanisms underlying the bilateral field advantage.

Visual stimulus comparisons across the vertical meridian are faster and more accurate than those restricted to a single hemifield (the bilateral field advantage). We set out to investigate the cerebral mechanisms underlying this effect using functional magnetic resonance imaging. Seven normal volunteers were presented pairs of shape stimuli bilaterally across the vertical meridian and unilaterally within a single hemifield. We found a network of additional areas activated in the unilateral condition over the bilateral condition which have been related to working memory in previous studies. The results suggest different processing strategies with different temporal characteristics in the bilateral and unilateral conditions, providing a novel explanation for the bilateral field advantage.

Adolescent↗

PubMed2001

Incidence of schizophrenia in ethnic minorities in London: ecological study into interactions with environment.

OBJECTIVE: To determine whether the incidence of schizophrenia among people from non-white ethnic minorities is greater in neighbourhoods where they constitute a smaller proportion of the total population. DESIGN: Ecological design including retrospective study of case records to calculate the incidence of schizophrenia in the ethnic minority population across electoral wards and multi-level analysis to examine interaction between individuals and environment. SETTING: 15 electoral wards in Camberwell, South London. PARTICIPANTS: All people aged 16 years and over who had contact with psychiatric services during 1988-97. MAIN OUTCOME MEASURE: Incidence rates of schizophrenia according to Research Diagnostic Criteria. RESULTS: The incidence of schizophrenia in non-white ethnic minorities increased significantly as the proportion of such minorities in the local population fell. The incidence rate ratio varied in a dose-response fashion from 2.38 (95% confidence interval 1.49 to 3.79) in the third of wards where non-white ethnic minorities formed the largest proportion (28-57%) of the local population to 4.4 (2.49 to 7.75) in the third of wards where they formed the smallest proportion (8-22%). CONCLUSION: The incidence of schizophrenia in non-white ethnic minorities in London is greater when they comprise a smaller proportion of the local population.

Ethnicity↗