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Biomedical subjects

R M Murray

Publications and source records attributed to R M Murray.

At least 73 records · Page 4Linked to original sources
PubMed2001

Twin study of symptom dimensions in psychoses.

BACKGROUND: Symptomatology in psychoses can be summarised as quantitative symptom dimensions, but their genetic basis is unknown. AIMS: To investigate whether genes make an important contribution to symptom dimensions. METHOD: A total of 224 probandwise twin pairs (106 monozygotic, 118 same-gender dizygotic) where probands had psychosis were ascertained from the Maudsley Twin Register in London. Factor analysis was performed on lifetime symptoms rated on the Operational Checklist for Psychotic Disorders (OPCRIT). Correlations of dimension scores within monozygotic and dizygotic pairs concordant for Research Diagnostic Criteria psychoses were performed. Relationships between dimension scores and genetic loading for psychoses were assessed using logistic regression. RESULTS: Patterns of familial aggregation consistent with a genetic effect were found for the disorganised dimension and for some measures of the negative, manic and general psychotic dimensions. Disorganised dimension scores were related significantly to genetic loading for psychoses. CONCLUSIONS: The disorganised dimension, and possibly other symptom dimensions, may be useful phenotypes for molecular genetic studies of psychoses.

Diseases in Twins↗
PubMed2001

Comparison of the incidence of schizophrenia in rural Dumfries and Galloway and urban Camberwell.

BACKGROUND: Being born or living in urban areas is associated with high rates of schizophrenia. However, few studies have compared the incidence in urban/rural areas using the same methodology. AIMS: To compare service-based incidence rates for schizophrenia in rural Dumfries and Galloway in south-west Scotland with urban Camberwell in south-east London. METHOD: Using Research Diagnostic Criteria diagnoses from the OPCRIT computer algorithm, we compared the incidence of schizophrenia over 12 years (1979-1984 and 1992-1997) using indirect standardisation techniques and Poisson regression modelling. RESULTS: The incidence was 61% higher in urban Camberwell than in rural Dumfries and Galloway (standardised incidence ratio (SIR)=1.61; 95% CI=1.42-1.81). There was no difference in incidence when we compared the White population in Camberwell with Dumfries and Galloway (SIR=1.12; 95% CI=0.86-1.43). CONCLUSIONS: The incidence of schizophrenia in urban Camberwell was higher than that in rural Dumfries and Galloway; the high incidence of non-Whites in Camberwell largely explains the urban/rural difference.

Adolescent↗
PubMed2001

Hypocalcemic and normocalcemic hyperparathyroidism in patients with advanced prostatic cancer.

PTH and ionized calcium levels were measured in 131 patients with advanced prostate cancer, all of whom had received at least first-line hormone therapy. Patients were classified into those in remission, those with stable disease, or those with progressive disease according to their prostate-specific antigen response and their clinical status. Thirty-four percent of all patients had PTH levels above the upper level of normal for controls of similar age (7.0 pmol/liter), and in 44% of these patients this was associated with a normal ionized calcium. Patients with proven bone metastases had significantly higher PTH levels than those without. (7.3 +/- 0.5 vs. 4.3 +/- 0.4 pmol/liter, P < 0.0005). There was evidence for a difference in the PTH levels between the three response groups. The PTH levels tended to be higher in patients with progressive disease. Thirty-seven of 65 patients (57%) with both progressive disease and proven bone metastases had elevated PTH levels. Mean levels of urinary deoxypyridinoline and cAMP were significantly greater in patients with high PTH than in those with a normal PTH. Treatment with oral calcium supplements in 32 patients with a high PTH seemed to have only a transient effect on elevated PTH or low ionized calcium levels. These data show that secondary hyperparathyroidism occurs frequently in patients with advanced prostate cancer, particularly in those with both progressive disease and bone metastases. The increased PTH levels are associated with an increase in bone resorption markers. These findings raise important questions about the role of PTH in progression of prostatic cancer in bone and the potential limitations of the use of bisphosphonates in patients with a raised PTH or low serum calcium.

Aged↗
PubMed2000

Childhood schizotypy and positive symptoms in schizophrenic patients predict schizotypy in relatives.

BACKGROUND: Schizotypy is one phenotypic expression of the familial-genetic liability to schizophrenia, but its precise relationship to frank psychotic symptoms remains unclear. We, therefore, set out to examine the relationships between (a) premorbid personality in schizophrenic patients, (b) the psychopathology they showed, and (c) schizotypal traits in their relatives. METHOD: Ninety consecutively admitted schizophrenic patients were interviewed with the Present State Examination (PSE). Their mothers were interviewed concerning their childhood personality and social adjustment, and 121 of their well relatives were evaluated with three different schizotypal scales. Factor analyses were carried out on (a) the nine main psychotic symptoms from the patients' PSE interview, and on (b) the schizotypal features derived from the scales completed by the first-degree relatives. Correlation coefficients were calculated between premorbid personality traits, and factor scores in probands and in relatives. RESULTS: No relationship was found between childhood schizoid-schizotypal personality traits and any particular dimension of psychopathology in patients. The positive syndrome in patients was correlated with higher scores for relatives on the three schizotypy scales, but did not predict any specific pattern of schizotypy in the relatives. Premorbid schizoid-schizotypal traits were also correlated with schizotypy in the relatives. CONCLUSIONS: Schizotypy in relatives has a familial relationship with schizoid-schizotypal traits in the childhood, and with positive symptoms during the illness, of schizophrenic patients.

Adolescent↗
PubMed2000

Pharmacogenetic prediction of clozapine response.

We did association studies in multiple candidate genes to find the combination of polymorphisms that give the best predictive value of response to clozapine in schizophrenic patients. A combination of six polymorphisms in neurotransmitter-receptor-related genes resulted in 76.7% success in the prediction of clozapine response (p=0.0001) and a sensitivity of 95% (+/- 0.04) for satisfactory response. These results will form the basis for a simple test to enhance the usefulness of clozapine in psychiatric treatment.

Alleles↗
PubMed2000

A magnetic resonance imaging study of corpus callosum size in familial schizophrenic subjects, their relatives, and normal controls.

The corpus callosum is one of several brain regions thought to be abnormal in schizophrenia. We sought to investigate whether the size of the corpus callosum would be abnormally small in schizophrenic subjects from families with familial schizophrenia and their healthy relatives. We wished to determine whether an abnormal corpus callosum size is found in healthy relatives who are genetically at a greater risk than normal of developing or transmitting the disorder. Twenty-seven familial schizophrenics, 53 of their healthy first-degree relatives, and 35 normal volunteers underwent MRI brain scans. We defined 11 of the relatives as presumed 'obligate carriers', i.e. an individual who appears to be transmitting the schizophrenic gene(s). The mid-sagittal slice of the corpus callosum and the whole brain volume were measured blind to diagnostic and family group. We found no difference between schizophrenics, their relatives, and normal controls in the mid-sagittal area of the corpus callosum. There remained no difference when the relatives were divided into two groups comprising presumed 'obligate carriers' and 'non-obligate carriers'. Adjusting for age and whole brain area made no difference to the results. Families with several schizophrenic members are not associated with abnormality in the size of the corpus callosum.

Adult↗
PubMed2000

Premorbid IQ in patients with functional psychosis and their first-degree relatives.

Numerous studies have found deficits in premorbid IQ in schizophrenic patients, but it is not clear whether this deficit is shared by (a) patients with other functional psychoses, and (b) relatives of these patients. Ninety-one schizophrenic patients, 66 affective psychotic patients (29 schizoaffective and 37 manic or depressed), and 50 normal control subjects were administered the National Adult Reading Test (NART) which provides an estimate of premorbid IQ. The NART was also completed by 85 first-degree relatives of schizophrenic patients and by 65 first-degree relatives of affective psychotic patients. After adjustments were made for sex, social class, ethnicity and years of education, schizophrenic patients had significantly lower premorbid IQ than their relatives, the affective psychotic patients and controls. Manic and depressed patients had significantly lower NART scores than their first-degree relatives, but schizoaffective patients did not, and neither group differed significantly from controls. There was no significant difference in premorbid IQ between patients who had experienced obstetric complications (OC+) and those who had not (OC-). Both OC+ and OC- schizophrenic patients differed significantly from their relatives, but the disparity was greatest between OC+ patients and their relatives. Relatives of OC+ schizophrenic patients had significantly higher IQ than relatives of OC- schizophrenic patients.

Adult↗
PubMed2000

Mapping auditory hallucinations in schizophrenia using functional magnetic resonance imaging.

BACKGROUND: Perceptions of speech in the absence of an auditory stimulus (auditory verbal hallucinations) are a cardinal feature of schizophrenia. Functional neuroimaging provides a powerful means of measuring neural activity during auditory hallucinations, but the results from previous studies have been inconsistent. This may reflect the acquisition of small numbers of images in each subject and the confounding effects of patients actively signaling when hallucinations occur. METHODS: We examined 6 patients with schizophrenia who were experiencing frequent auditory hallucinations, using a novel functional magnetic resonance imaging method that permitted the measurement of spontaneous neural activity without requiring subjects to signal when hallucinations occurred. Approximately 50 individual scans were acquired at unpredictable intervals in each subject while they were intermittently hallucinating. Immediately after each scan, subjects reported whether they had been hallucinating at that instant. Neural activity when patients were and were not experiencing hallucinations was compared in each subject and the group as a whole. RESULTS: Auditory hallucinations were associated with activation in the inferior frontal/insular, anterior cingulate, and temporal cortex bilaterally (with greater responses on the right), the right thalamus and inferior colliculus, and the left hippocampus and parahippocampal cortex (P<.0001). CONCLUSIONS: Auditory hallucinations may be mediated by a distributed network of cortical and subcortical areas. Previous neuroimaging studies of auditory hallucinations may have identified different components of this network.

Auditory Perception↗
PubMed2000

What risk factors tell us about the causes of schizophrenia and related psychoses.

Genetic, epidemiologic, and molecular studies concur that liability to schizophrenia is transmitted through the inheritance of a number of genes of relatively small effect, some of which are shared with other psychoses. Each of these susceptibility genes causes minor deviations that are relatively innocent in themselves, for example, increased lateral ventricular volume, schizotypal personality, or subtle cognitive difficulties. However, when an individual is unlucky enough to inherit several of these traits, their cumulative effect, often compounded by environmental hazards, propels that person over a threshold for the expression of frank psychosis. Early environmental risk factors for schizophrenia include urban and winter birth, fetal malnutrition and hypoxia, and possibly prenatal viral infections; these early hazards have only a modest risk-increasing effect, and operate in the context of genetic risk. Preschizophrenic children are more likely to have minor psychomotor and cognitive problems; low IQ has a linear relationship with risk for schizophrenia. However, schizophrenia is not simply a neurodevelopmental disorder, because risk factors have been identified that have their effects proximal to the onset of psychosis: drug abuse, immigrant status, and social adversity and isolation. Both genetic and environmental risk factors appear to operate across diagnostic categories and therefore support a dimensional model of psychosis.

Brain↗
PubMed2000

Early and late environmental risk factors for schizophrenia.

Although a high proportion of liability to schizophrenia is under genetic control, a number of environmental risk factors have been identified. The earliest of these are complications of pregnancy and birth, though whether these cause or reflect disturbed brain development is not absolutely clear. Neurodevelopmental deviance is also indicated by neurological dysfunction, social, behavioural and cognitive deficits during childhood. Immigrant status is a significant risk factor, especially prominent among the African Caribbean population in England, though the mechanism is unknown. Later environmental risk factors include adverse life events and substance abuse. An additive model of multiple genetic and environmental risk factors of small effect may be too simplistic and an interactive model where genetic predisposition is compounded by environmental effects is more in keeping with current evidence. The nature of such interactions can be explored more fully when susceptibility genes for schizophrenia are identified.

Brain↗
PubMed2000

Intra-uterine physical growth in schizophrenia: evidence confirming excess of premature birth.

BACKGROUND: Many studies have suggested a possible aetiological role for obstetric complications in the development of schizophrenia. We focused on prenatal physical growth in schizophrenia, a contentious issue in the literature. METHODS: We compared gestational age at birth, birth weight (BW) and birth head circumference (BHC) between 312 schizophrenics and 517 controls, and between 187 schizophrenics and their matched healthy siblings. Information on obstetric histories was obtained from the Maternal and Child Health Handbooks (i.e. contemporaneous records). RESULTS: Gestational age at birth was significantly earlier in the schizophrenics than in the controls (P = 0.017). Pre-term birth (gestational age of 36 weeks or less) was more common in schizophrenics than in controls (8.0% v. 3.4%, P = 0.005, odds ratio 2.5). Low BW (2500 g or less) was more frequent in schizophrenics than in controls (9.6% v. 4.6%, P = 0.005, odds ratio 2.2). The schizophrenics had significantly lighter BW (P = 0.0003) and tended to have smaller BHC (P = 0.081) compared with controls. However, multiple regression analysis showed that there was no significant difference in BW or BHC between the schizophrenics and controls when gestational age and maternal weight were controlled. There was no significant difference in BW or BHC between schizophrenics and their siblings, although the schizophrenics tended to be born at earlier gestational age than their siblings. CONCLUSIONS: Our results suggest that prematurity at birth is associated with a risk of developing schizophrenia in adulthood. When gestational age and maternal body weight were allowed for, there was no evidence that schizophrenics tend to have lower mean BW or smaller BHC.

Adult↗
PubMed2000

Imaging attentional and attributional bias: an fMRI approach to the paranoid delusion.

BACKGROUND: The pathophysiology of auditory hallucinations and delusions of control has been elucidated using functional imaging. Despite their clinical importance, there have been few similar attempts to investigate paranoid delusions. We have examined two components of social cognition (attentional and attributional biases) that contribute to the formation and maintenance of paranoid delusions, using functional magnetic resonance imaging (fMRI). METHOD: Normal subjects performed tasks requiring attentional and attributional judgements. We investigated the neural response particularly associated with attention to threatening material relevant to self and with the 'self-serving' attributional bias. RESULTS: The determination of relevance to self of verbal statements of differing emotional valence involved left ventrolateral prefrontal cortex (left inferior frontal gyrus, BA 47), right caudate and right cingulate gyrus (BA 24). Attention to threatening material relevant to self differentially activated a more dorsal region of the left inferior frontal gyrus (BA 44). Internal attributions of events, where the self was viewed as an active intentional agent, involved left precentral gyrus (BA 6) and left middle temporal gyrus (BA 39). Attribution of events in a non 'self-serving' manner required activation of the left precentral gyrus (BA 6). CONCLUSIONS: Anomalous activity or connectivity within these defined regions may account for the attentional or attributional biases subserving paranoid delusion formation. This provides a simple model for paranoid delusion formation that can be tested in patients.

Adult↗
PubMed2000

Family-based linkage disequilibrium mapping using SNP marker haplotypes: application to a potential locus for schizophrenia at chromosome 22q11.

Family-based linkage disequilibrium mapping using SNP markers is expected to be a major route to the identification of susceptibility alleles for complex diseases. However there are a number of methodological issues yet to be resolved, including the handling of extended haplotype data and analysis of haplotype transmission in sib-pair or family trio samples. In the present study, we have analysed two dinucleotide repeat and six SNP markers at the COMT locus at chromosome 22q11, a region implicated in psychosis, for transmission distortion in 198 Chinese schizophrenic family trios. When individual markers were analysed using the TDT, two showed modest evidence of transmission distortion (186C/T, P = 0.04; Val158Met, P = 0.01). Using haplotypes of paired markers analysed by the program TRANSMIT, the most significant P value was 0.001, for the Met158Val and 900ins/delC polymorphisms in the COMT gene. The global P value for the haplotypes of all six SNP markers tested was 0.004, largely a result of the excess transmission of two extended haplotypes which differed at the marker 408C/G. The exclusion of this marker from the analysis gave a global P value of 0.002 and produced a five marker haplotype system which was significant at P = 0.0006. This haplotype consisted of the alleles -287G:186C:Val158:900insC:ARVCF930C, which may represent a background haplotype for the transmission of a schizophrenia susceptibility allele at chromosome 22q11. Our results support the hypotheses that either COMT is itself a susceptibility gene, or more likely that this region of chromosome 22 contains a susceptibility gene that is in linkage disequilibrium with COMT alleles. Molecular Psychiatry (2000) 5, 77-84.

Adolescent↗
PubMed2000

Risk factors for the deficit syndrome of schizophrenia.

Previous studies have found two risk factors associated with the deficit syndrome of schizophrenia: an increase in summer births, compared to others with schizophrenia; and a higher risk of schizophrenia in relatives. In data from the Camberwell Register Psychosis Series, a population-based sample that approximated a treated-incidence sample, the deficit/nondeficit categorization was made using a previously validated proxy method. Associations were found between the deficit syndrome and both summer birth and a family history of schizophrenia. In contrast, nondeficit schizophrenia was associated with a family history of psychiatric problems other than schizophrenia. The deficit group also had poorer insight. An early age of onset was associated with disorganization, but not with the deficit or nondeficit group. The deficit/nondeficit differences could not be attributed to confounding by demographic features or the severity of hallucinations, delusions, or formal thought disorder.

Age of Onset↗
PubMed2000

Meta-analysis of regional brain volumes in schizophrenia.

OBJECTIVE: The authors' goal was to determine whether patients with schizophrenia differ from comparison subjects in regional brain volumes and whether these differences are similar in male and female subjects. METHOD: They conducted a systematic search for structural magnetic resonance imaging (MRI) studies of patients with schizophrenia that reported volume measurements of selected cortical, subcortical, and ventricular regions in relation to comparison groups. They carried out a meta-analysis of the volumes of these regions in the patients with schizophrenia and the comparison subjects using a random effects model; they also used random effects regression analysis to examine the influence of gender on effect sizes. RESULTS: Fifty-eight studies were identified as suitable for analysis; these studies included 1,588 independent patients with schizophrenia. Assuming a volume of 100% in the comparison group, they found that the mean cerebral volume of the subjects with schizophrenia was smaller (98%), but the mean total ventricular volume of the subjects with schizophrenia was greater (126%). Relative to the cerebral volume differences, the regional volumes of the subjects with schizophrenia were 94% in the left and right amygdala, 94% in the left and 95% in the right hippocampus/amygdala, and 93% in the left and 95% in the right parahippocampus. Relative to the global ventricular system differences, the largest differences in ventricular subdivisions were in the right and left body of the lateral ventricle, where the volumes of schizophrenic subjects were 116% and 116%, respectively. For most regions, effect size was not significantly related to gender. CONCLUSIONS: Regional structural differences in patients with schizophrenia include bilaterally reduced volume of medial temporal lobe structures. There is a need for greater integration of results from structural MRI studies to avoid redundant research activity.

Adult↗