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Biomedical subjects

Robin Murray

Publications and source records attributed to Robin Murray.

At least 37 records · Page 2Linked to original sources
PubMed2004

A controlled study of brain structure in monozygotic twins concordant and discordant for schizophrenia.

BACKGROUND: We examined monozygotic twins concordant and discordant for schizophrenia to clarify the role of genetic and environmental factors in determining brain abnormalities. METHODS: Magnetic resonance imaging brain scans were obtained from 14 monozygotic twin pairs concordant and 10 monozygotic pairs discordant for schizophrenia, as well as 17 pairs of monozygotic control twins. Twenty-two discordant sibling-pairs and 56 pairs of unrelated control subjects were included to assess the extent of genetic control over these structures. RESULTS: Within-pair similarities for whole brain volume increased as pair members were more closely related genetically (monozygotic twins > siblings > unrelated control subjects). Schizophrenic twins, whether from concordant or discordant pairs, had smaller whole brain volumes than control twins. The probands of discordant pairs showed more abnormalities in hippocampal, third and lateral ventricular volumes than concordant twins. CONCLUSIONS: Whole brain volume is under high genetic control and smaller whole brain volume is a reflection of the genetic liability to develop schizophrenia. The variation in hippocampal and ventricular volumes within discordant monozygotic pairs indicates a role for environmental factors in determining these volume abnormalities in schizophrenia. Such factors may also underlie the more extensive morphometric deviations in patients from monozygotic discordant twins than in their counterparts from concordant twins.

Adolescent↗
PubMed2004

Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer.

In a placebo-controlled randomized clinical trial, zoledronic acid (4 mg via a 15-minute infusion every 3 weeks for 15 months) reduced the incidence of skeletal-related events (SREs) in men with hormone-refractory metastatic prostate cancer. Among 122 patients who completed a total of 24 months on study, fewer patients in the 4-mg zoledronic acid group than in the placebo group had at least one SRE (38% versus 49%, difference = -11.0%, 95% confidence interval [CI] = -20.2% to -1.3%; P =.028), and the annual incidence of SREs was 0.77 for the 4-mg zoledronic acid group versus 1.47 for the placebo group (P=.005). The median time to the first SRE was 488 days for the 4-mg zoledronic acid group versus 321 days for the placebo group (P =.009). Compared with placebo, 4 mg of zoledronic acid reduced the ongoing risk of SREs by 36% (risk ratio = 0.64, 95% CI = 0.485 to 0.845; P =.002). Patients in the 4-mg zoledronic acid group had a lower incidence of SREs than did patients in the placebo group, regardless of whether they had an SRE prior to entry in the study. Long-term treatment with 4 mg of zoledronic acid is safe and provides sustained clinical benefits for men with metastatic hormone-refractory prostate cancer.

Aged↗
PubMed2004

Predicting violence in schizophrenia: a prospective study.

BACKGROUND: People with schizophrenia are more violent than the general population, but this increased risk is attributable to the actions of a small subgroup. Identifying those at risk has become an essential part of clinical practice. AIMS: To estimate the risk factors for assault in patients with schizophrenia. METHODS: Two hundred seventy-one patients with schizophrenia were interviewed using an extensive battery of instruments. Assault was measured from multiple data sources over the next 2 years and criminal records were obtained. Multiple sociodemographic and clinical variables measured at baseline were examined as possible predictors of assault during follow-up. RESULTS: Sixty-nine (25%) patients committed assault during the 2-year follow-up. The model that best predicted assault included a history of recent assault (OR 2.33, 95% CI 1.17-4.61), a previous violent conviction (OR 2.02, 95% CI 1.04-3.87), having received special education (OR 2.76, 95% CI 1.22-6.26) and alcohol abuse (OR 3.55, 95% CI 1.24-10.2). CONCLUSIONS: Previously established risk factors including a history of violence and alcohol abuse are replicated in this study. Although low premorbid IQ did not predict violence, a need for special education did.

Adolescent↗
PubMed2004

Reliability of brain volumes from multicenter MRI acquisition: a calibration study.

Multicenter studies can provide additional information over single center studies because of their increased statistical power. Because similar acquisition protocols are being used internationally for structural magnetic resonance imaging (MRI) studies of the human brain, volumetric MRI data studies seem suitable for this purpose. Possible systematic differences between sites should be avoided, however, particularly when subtle differences in tissue volume are being searched for, such as in neuropsychiatric diseases. In this calibration study, the brains of six healthy volunteers were (re)scanned with MR scanners from four different manufacturers at five different sites, using the local acquisition protocols. The images were segmented at a central reference site. The intraclass correlation coefficient (ICC) was determined for the whole brain, gray and white matter, cerebellum, and lateral and third ventricle volumes. When required, the processing algorithms were calibrated for each site. Calibration of the histogram analysis was needed for segmentation of total brain volume at one site and for gray and white matter volume at all sites. No (additional) calibration was needed for cerebellum and ventricle volumes. The ICCs were > or = 0.96 for total brain, > or = 0.92 for cerebellum, > or = 0.96 for lateral ventricle, > or = 0.21 for third ventricle, > or = 0.84 for gray matter, and > or = 0.78 for white matter volume. Calibration of segmentation procedures allows morphologic MRI data acquired at different research sites to be combined reliably in multicenter studies.

Adult↗
PubMed2004

The cerebellum and decision making under uncertainty.

This study aimed to identify the neural basis of probabilistic reasoning, a type of inductive inference that aids decision making under conditions of uncertainty. Eight normal subjects performed two separate two-alternative-choice tasks (the balls in a bottle and personality survey tasks) while undergoing functional magnetic resonance imaging (fMRI). The experimental conditions within each task were chosen so that they differed only in their requirement to make a decision under conditions of uncertainty (probabilistic reasoning and frequency determination required) or under conditions of certainty (frequency determination required). The same visual stimuli and motor responses were used in the experimental conditions. We provide evidence that the neo-cerebellum, in conjunction with the premotor cortex, inferior parietal lobule and medial occipital cortex, mediates the probabilistic inferences that guide decision making under uncertainty. We hypothesise that the neo-cerebellum constructs internal working models of uncertain events in the external world, and that such probabilistic models subserve the predictive capacity central to induction.

Adolescent↗
PubMed2004

Effects of very low birthweight on brain structure in adulthood.

Very-low-birthweight (VLBW) individuals are at high risk of brain injury in the perinatal period. We wished to determine how such early brain lesions affect brain structure in adulthood. Thirty-two VLBW adults (20 female, 12 male) and 18 term, normal birthweight sibling control individuals (nine female, nine male) underwent structural MRI at a mean age of 23 years 4 months (range 17 to 33 years; SD 3.4). Images were analyzed using an automated tissue segmentation algorithm in order to estimate whole brain tissue class volumes in native space. Images were then warped to a template image in standard space. There was no significant between-group difference in whole brain, grey matter, white matter, or total cerebral spinal fluid (CSF) volumes. However, lateral ventricular volume was significantly increased by 41% in those with VLBW. The ratio of grey to white matter was also significantly increased (by 10%) in those with VLBW. Group comparison maps showed widespread changes in the distribution of grey and white matter, and relative excess of ventricular CSF, in the brains of VLBW individuals. Increased ventricular volume predicted decreased grey matter in subcortical nuclei and limbic cortical structures, and decreased periventricular white matter. We conclude that these diffuse abnormalities of grey and white matter are a consequence of the interaction of perinatal brain injury and ongoing neurodevelopmental processes.

Adolescent↗
PubMed2004

Predictors of antisocial personality. Continuities from childhood to adult life.

BACKGROUND: Antisocial behaviour in adult life has its roots in childhood. AIMS: To explore the independent and joint effects of childhood characteristics on the persistence of antisocial behaviour into adult life. METHOD: A clinical sample of twins who were systematically ascertained in childhood was followed up 10-25 years later. A total of 225 twins were interviewed regarding childhood and adult psychiatric disorder, psychosocial functioning, and psychosocial and cognitive risk factors. RESULTS: In univariate analyses, childhood hyperactivity and conduct disorder showed equally strong prediction of antisocial personality disorder (ASPD) and criminality in early and mid-adult life. Lower IQ and reading problems were most prominent in their relationships with childhood and adolescent antisocial behaviour. In multivariate modelling childhood conduct disorder and hyperactivity predicted adult ASPD even when intervening risk factors were accounted for. The number of hyperactive and conduct symptoms also predicted adult outcome. CONCLUSIONS: Childhood disruptive behaviour has powerful long-term effects on adult antisocial outcomes, which continue into middle adulthood. The importance of number of symptoms, the presence of disruptive disorder, and intermediate experiences highlight three areas where interventions might be targeted.

Adolescent↗
PubMed2004

Pituitary volume in psychosis.

BACKGROUND: Patients with psychosis have activation of the hypothalamic-pituitary-adrenal (HPA) axis during the acute phase of the psychosis. Whether this has any morphological consequences for the pituitary gland is currently unknown. AIMS: To examine pituitary volume variation in people at different stages of psychotic disorder. METHOD: Pituitary volume was measured using 1.5 mm, coronal magnetic resonance images in 24 people with first-episode psychosis, 51 with established schizophrenia and 59 healthy controls. RESULTS: Compared with the control group, the people with first-episode psychosis had pituitary volumes that were 10% larger, whereas those with established schizophrenia had pituitary volumes that were 17% smaller. In both of the groups with psychosis, there was no difference in pituitary volume between those receiving typical antipsychotic drugs and those receiving atypical antipsychotics. CONCLUSIONS: The first episode of a psychosis is associated with a larger pituitary volume, which we suggest is due to activation of the HPA axis. The smaller pituitary volume in the group with established schizophrenia could be the consequence of repeated episodes of HPA axis hyperactivity.

Acute Disease↗
PubMed2004

Brain volumes in adult survivors of very low birth weight: a sibling-controlled study.

OBJECTIVES: To establish whether adults who were born very low birth weight (VLBW) show altered volumes of certain brain structures. METHODS: Unmatched case-control study was conducted of 33 individuals from a cohort of VLBW (<1500 g) infants who were born between 1966 and 1977 and 18 of their normal birth weight siblings. Whole brain, gray matter, ventricular, corpus callosum, and hippocampal volumes were measured on structural magnetic resonance imaging scans. RESULTS: VLBW individuals had a 46% increase in total ventricular volume and a 17% reduction in posterior corpus callosum volume. No differences in whole brain, gray matter, or hippocampal volumes were observed. CONCLUSION: Specific differences exist in the volumes of certain brain structures in adults who were born VLBW compared with their normal birth weight siblings.

Adult↗
PubMed2003

Suicide and attempted suicide among people of Caribbean origin with psychosis living in the UK.

BACKGROUND: A report from a 1980s cohort claimed that suicidal behaviour was four times less common in UK-resident people of Caribbean origin with psychosis than in British Whites. Since then, evidence has accumulated that the rate of suicide and suicidal ideation has been increasing. Aims To compare rates of suicidal behaviour in people of Caribbean and British White origin in a large multi-centre sample of patients with psychosis. METHOD: A secondary analysis of 708 patients with psychosis followed up for 2 years. Outcome measures of reported suicide and attempted suicide were adjusted for socio-economic and clinical differences between groups at baseline. RESULTS: People of Caribbean origin had a lower risk of suicidal behaviour than British Whites (odds ratio adjusted for age and gender 0.49, 95% CI 0.26-0.92). There was a strong negative interaction between ethnic group and age: suicidal acts were four times less likely in people of Caribbean origin aged over 35 years compared with British Whites, but there was no large or significant difference in those under 35. CONCLUSIONS: The previously reported lower relative risk of suicidal behaviour in people of Caribbean origin with psychosis is restricted to those over 35 years, suggesting that the protective effect of Caribbean origin is disappearing in younger generations.

Adult↗
PubMed2003

Childhood origins of violent behaviour in adults with schizophreniform disorder.

BACKGROUND: People with psychosis have an elevated risk of violence. AIMS: To examine whether violent behaviour in adults with psychosis can be accounted for by psychotic symptoms or physical aggression in childhood. METHOD: We used data from a prospective longitudinal study of a complete birth cohort born in New Zealand. When cohort members were 26 years old, information was obtained on past-year psychiatric diagnosis of schizophreniform disorder and on violent behaviour. Childhood psychotic symptoms were measured at age 11 years using a diagnostic interview, and childhood physical aggression was assessed by teachers when cohort members were aged 7, 9 and 11 years. RESULTS: Participants with schizophreniform disorder were more likely to be violent than participants without, even after controlling for sociodemographic variables and concurrent substance dependence disorders. Childhood psychotic symptoms were a strong risk factor for violence in adults with schizophreniform disorder, as was childhood physical aggression, although to a lesser extent. CONCLUSIONS: Violence by individuals with schizophreniform disorder could be prevented by monitoring early signs of psychotic symptoms and by controlling childhood physical aggression.

Adult↗
PubMed2002

A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma.

BACKGROUND: Bone metastases are a common cause of morbidity in patients with prostate carcinoma. We studied the effect of a new bisphosphonate, zoledronic acid, which blocks bone destruction, on skeletal complications in prostate cancer patients with bone metastases. METHODS: Patients with hormone-refractory prostate cancer and a history of bone metastases were randomly assigned to a double-blind treatment regimen of intravenous zoledronic acid at 4 mg (N = 214), zoledronic acid at 8 mg (subsequently reduced to 4 mg; 8/4) (N = 221), or placebo (N = 208) every 3 weeks for 15 months. Proportions of patients with skeletal-related events, time to the first skeletal-related event, skeletal morbidity rate, pain and analgesic scores, disease progression, and safety were assessed. All statistical tests were two-sided. RESULTS: Approximately 38% of patients who received zoledronic acid at 4 mg, 28% who received zoledronic acid at 8/4 mg, and 31% who received placebo completed the study. A greater proportion of patients who received placebo had skeletal-related events than those who received zoledronic acid at 4 mg (44.2% versus 33.2%; difference = -11.0%, 95% confidence interval [CI] = -20.3% to -1.8%; P =.021) or those who received zoledronic acid at 8/4 mg (38.5%; difference versus placebo = -5.8%, 95% CI = -15.1% to 3.6%; P =.222). Median time to first skeletal-related event was 321 days for patients who received placebo, was not reached for patients who received zoledronic acid at 4 mg (P =.011 versus placebo), and was 363 days for those who received zoledronic acid at 8/4 mg (P =.491 versus placebo). Compared with urinary markers in patients who received placebo, urinary markers of bone resorption were statistically significantly decreased in patients who received zoledronic acid at either dose (P =.001). Pain and analgesic scores increased more in patients who received placebo than in patients who received zoledronic acid, but there were no differences in disease progression, performance status, or quality-of-life scores among the groups. Zoledronic acid at 4 mg given as a 15-minute infusion was well tolerated, but the 8-mg dose was associated with renal function deterioration. CONCLUSION: Zoledronic acid at 4 mg reduced skeletal-related events in prostate cancer patients with bone metastases.

Adenocarcinoma↗
PubMed2002

Personality dimensions and neuropsychological performance in first-degree relatives of patients with schizophrenia and affective psychosis.

Several studies have found a significant increase in the prevalence of some personality disorders in the first-degree relatives of patients with schizophrenia; other studies have found subtle neuropsychological deficits in these relatives. However, little is known about the specificity of the personality traits reported or about the relationship between these traits and the neuropsychological deficits.One-hundred first-degree relatives of patients with schizophrenia (SR) and 88 first-degree relatives of affective psychotic patients (APR) completed the Eysenck Personality Questionnaire which measures extraversion, neuroticism, and psychoticism; they were also administered the National Adult Reading Test (NART), the Trail Making Test (TMT) and a Verbal Fluency Test (VFT). The male relatives of patients with schizophrenia scored significantly higher on the psychoticism scale than the male relatives of affective psychotic patients. In the SR group, there were significant correlations between the TMT performance and the extraversion scores and, between the IQ scores and the psychoticism scores. However, when logistical regression analyses were performed, none of the three personality scores predicted any of the neuropsychological performance in either the SR or the APR group. These results indicate some specificity as well as sex differences in the psychoticism dimension. Moreover, the relationship between the personality dimensions and the neuropsychological performance could indicate that psychoticism increases vulnerability to psychosis whereas extraversion decreases it.

Adult↗
PubMed2002

The relationship between predisposing factors, premorbid function and symptom dimensions in psychosis: an integrated approach.

BACKGROUND: Increasing evidence suggests psychosis may be more meaningfully viewed in dimensional terms rather than as discrete categorical states and that specific symptom clusters may be identified. If so, particular risk factors and premorbid factors may predict these symptom clusters. AIMS: (i) To explore, using principal component analysis, whether specific factors for psychotic symptoms can be isolated. (ii) To establish the predictors of the different symptom factors using multiple regression techniques. METHOD: One hundred and eighty-nine inpatients with psychotic illness were recruited and information on family history, premorbid factors and current symptoms obtained from them and their mothers. RESULTS: Seven distinct symptom components were identified. Regression analysis failed to identify any developmental predictors of depression or mania. Delusions/hallucinations were predicted by a family history of schizophrenia and by poor school functioning in spite of normal premorbid IQ (F = 6.5; P < 0.001); negative symptoms by early onset of illness, developmental delay and a family history of psychosis (F = 4.1; P = 0.04). Interestingly disorganisation was predicted by the combination of family history of bipolar disorder and low premorbid IQ (F = 4.9; P = 0.003), and paranoia by obstetric complications (OCs) and poor school functioning (F = 4.2; P = 0.01). CONCLUSION: Delusions and hallucinations, negative symptoms and paranoia all appeared to have a developmental origin though they were associated with different childhood problems. On the other hand, neither mania nor depression was associated with childhood dysfunction. Our most striking finding was that disorganisation appeared to arise when a familial predisposition to mania was compounded by low premorbid IQ.

Adolescent↗
PubMed2002

The effects of antipsychotic-induced hyperprolactinaemia on the hypothalamic-pituitary-gonadal axis.

Hyperprolactinaemia is commonly induced by antipsychotic medications that have dopamine-blockade as their main mechanism of action. The purpose of this study was to assess the effect of antipsychotic-induced hyperprolactinaemia on hypothalamic-pituitary-gonadal axis (HPG) function.HPG axis function was assessed in 67 consecutive outpatients who were diagnosed with schizophrenia and stabilized for a period of not less than 2 years on typical antipsychotic medication, by means of clinical history, relevant questionnaires and measurement of plasma prolactin, estradiol, progesterone, testosterone, LH, FSH, sex hormone binding globulin, and TSH levels. Normative laboratory data were used to assess whether hormone levels fell within the reference range for a normal population. There was a significant correlation between dose of medication and plasma prolactin levels for the total group (P<0.001). Prolactin levels were significantly negatively associated with sex hormone levels in females (P<0.05). Males taking antipsychotic medication had a mean prolactin level of 404.1m/IU and mean gonadotrophin and sex hormone levels that fell within normal limits. The results of this study indicate that neuroleptic-induced prolactin secretion is a dose-related side effect and, in females, the level of hyperprolactinaemia is correlated with the degree of suppression of the HPG axis. Women taking long-term prolactin-raising antipsychotic medications are likely to be hyperprolactinaemic and have an associated hypogonadal state. In males, prolactin levels remain within normal limits, but at the upper end, with no apparent disturbance of reproductive hormones.

Adult↗
PubMed2002

Patients' perceptions of intensive case management.

OBJECTIVE: The authors examined patients' perceptions of their case management care and the factors that influenced those perceptions. METHODS: A nine-item patients' perceptions questionnaire was administered to 225 patients with severe psychosis who were enrolled in a randomized controlled trial evaluating the efficacy of intensive versus standard case management. RESULTS: Factor analysis of the responses to the perceptions questionnaire revealed two principal components: quality of care received (including relationship and contact with the case manager) and overall perception of case management. Patients had a better overall perception of intensive case management compared with standard case management, but no significant differences were noted in perceived quality of care. Patients with female case managers had more positive perceptions of the quality of the care they received than those with male case managers. Several clinical and social variables were strongly associated with perceived quality of care but less so with overall perception of case management. CONCLUSIONS: Patients' general perceptions of intensive case management seemed more favorable than patients' general perceptions of standard case management, but no difference was noted in their perceptions of quality of care.

Adult↗
PubMed2002

Psychosis in high-security and general psychiatric services: report from the UK700 and special hospitals' treatment resistant schizophrenia groups.

BACKGROUND: Serious violence is an unusual but significant correlate of psychosis, and leads to the need for specialist secure psychiatric services. Most such service users have previously used general psychiatric services. AIMS: To examine diagnostic and socio-demographic differences between high-security psychiatric service users from their peers in community services. METHOD: Two groups of patients with psychosis were compared: a national sample of high-security hospital residents, and a sample of patients in contact with general psychiatric services. RESULTS: Schizophrenia was the almost invariable diagnosis for all special hospital patients. White patients in the community sample were significantly more likely to have affective components to their illness compared with African-Caribbean patients; unlike those in special hospitals. There was a small excess in the proportion of African-Caribbean patients in the special hospital group, controlling for diagnosis, gender and locality. Men were overrepresented in this group. CONCLUSIONS: Among patients with psychosis, having a diagnosis of schizophrenia and being male increase the likelihood of special hospital admission. Suggestions that ethnic minority patients are much more likely to have engaged in serious violence and need high-security placement were not borne out.

Adolescent↗