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Showing papers by "Robin M. Murray published in 2000"


Journal ArticleDOI
TL;DR: In this article, the authors 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.
Abstract: 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. (Am J Psychiatry 2000; 157:16‐25)

1,644 citations


Journal ArticleDOI
TL;DR: These findings provide the first evidence for continuity of psychotic symptoms from childhood to adulthood, and the link between child and adult psychotic symptoms was not the result of general childhood psychopathology.
Abstract: Background Childhood risk factors for the development of adult schizophrenia have proved to have only modest and nonspecific effects, and most seem unrelated to the adult phenotype. We report the first direct examination of the longitudinal relationship between psychotic symptoms in childhood and adulthood. Methods We analyzed prospective data from a birth cohort (N = 761), in which children were asked about delusional beliefs and hallucinatory experiences at age 11 years, and then followed up to age 26 years. Structured diagnostic interviews were employed at both ages and self-report of schizophreniform symptoms was augmented by other data sources at age 26 years. Results Self-reported psychotic symptoms at age 11 years predicted a very high risk of a schizophreniform diagnosis at age 26 years (odds ratio, 16.4; 95% confidence interval, 3.9-67.8). In terms of attributable risk, 42% of the age-26 schizophreniform cases in the cohort had reported 1 or more psychotic symptoms at age 11 years. Age-11 psychotic symptoms did not predict mania or depression at age 26 years, suggesting specificity of prediction to schizophreniform disorder. The link between child and adult psychotic symptoms was not simply the result of general childhood psychopathology. Conclusion These findings provide the first evidence for continuity of psychotic symptoms from childhood to adulthood.

1,110 citations


Journal ArticleDOI
TL;DR: Auditory hallucinations may be mediated by a distributed network of cortical and subcortical areas that is associated with activation in the inferior frontal/insular, anterior cingulate, and temporal cortex bilaterally and may have identified different components of this network.
Abstract: 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 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.

614 citations


Journal ArticleDOI
TL;DR: A combination of six polymorphisms in neurotransmitter-receptor-related genes resulted in 76.7% success in the prediction of clozapine response and a sensitivity of 95% (+/- 0.04) for satisfactory response in schizophrenic patients.

338 citations


Journal ArticleDOI
TL;DR: Failure of left STG ‘deactivation’ and left fronto-temporal disconnectivity are not consistent findings in schizophrenia; neither are they trait-markers for genetic risk.
Abstract: Background PET studies of verbal fluency in schizophrenia report a failure of ‘deactivation’ of left superior temporal gyrus (STG) in the presence of activation of left dorsolateral prefrontal cortex (DLPFC), which deficit has been attributed to underlying ‘functional disconnectivity’. Aim To test whether these findings provide trait-markers for schizophrenia. Method We used H215O PET to examine verbal fluency in 10 obligate carriers of the predisposition to schizophrenia, 10 stable patients and 10 normal controls. Results We found no evidence of a failure of left STG deactivation in carriers or patients. Instead, patients failed to deactivate the precuneus relative to other groups. We found no differences in functional connectivity between left DLPFC and left STG but patients exhibited significant disconnectivity between left DLPFC and anterior cingulate cortex. Conclusions Failure of left STG ‘deactivation’ and left fronto-temporal disconnectivity are not consistent findings in schizophrenia; neither are they trait-markers for genetic risk. Prefrontal functional disconnectivity here may characterise the schizophrenic phenotype.

192 citations


Journal ArticleDOI
TL;DR: Patients with schizophrenia who were prone to auditory hallucinations show attenuated activation when processing inner speech in areas implicated in verbal self-monitoring.
Abstract: Cognitive models propose that auditory verbal hallucinations are derived from inner speech misidentified as external by means of defective self-monitoring (1). This suggests that the functional neuroanatomy of monitoring inner speech may be abnormal in patients who are prone to auditory verbal hallucinations. Both covert articulation and imagining another person’s speech involve the generation of inner speech, but imagining speech (auditory verbal imagery) places greater demands on verbal self-monitoring (2). We used functional magnetic resonance imaging (fMRI) to compare the neural correlates of inner speech and auditory verbal imagery in patients with schizophrenia who were predisposed to hallucinations and comparison subjects. We predicted that 1) both patients and volunteers would show activation in the left inferior frontal gyrus or insula when generating inner speech (2) and 2) patients, in relation to comparison subjects, would show attenuated activation in the temporal cortices and supplementary motor area during auditory verbal imagery, reflecting defective monitoring of inner speech (2, 3).

184 citations


Journal ArticleDOI
TL;DR: Although a high proportion of liability to schizophrenia is under genetic control, a number of environmental risk factors have been identified and an interactive model where genetic predisposition is compounded by environmental effects is more in keeping with current evidence.

158 citations


Journal ArticleDOI
TL;DR: The results support the hypotheses that either COMT is itself a susceptibility gene, or more likely that this region of chromosome 22 contains a susceptibility genes that is in linkage disequilibrium with COMT alleles.
Abstract: 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.

136 citations


Journal ArticleDOI
TL;DR: Testing for linkage between markers in this region of chromosome 15q and schizophrenia in a sample of 15 multiply affected and 5 single case families with schizophrenia drawn from the Bantu-speaking black population of South Africa showed positive though non-significant results.
Abstract: Recent reports have strongly linked markers near the alpha-7 nicotinic cholinergic receptor subunit gene on human chromosome 15q13-q14 to a sensory gating deficit common in schizophrenics, and have shown positive though non-significant results linking this region to the primary phenotype of schizophrenia in a sample of North American families. We therefore tested for linkage between markers in this region of chromosome 15q and schizophrenia in a sample of 15 multiply affected and 5 single case families with schizophrenia drawn from the Bantu-speaking black population of South Africa. An initial replication using markers from the original study gave an affected-only LOD score maximum of 1.08 under a recessive model at Theta=0.00 for D15S1360, a dinucleotide polymorphism found on the same YAC as the alpha-7 receptor gene. Nonparametric affected-only multipoint analysis gave a Z-score of 1. 29, P=0.098, for D15S1360, and Z=1.45, p=0.075 for D15S118. We then increased the resolution of the map with an extended set of 20 markers. Again, two peaks were observed, with NPL scores of 1.81, p=0.037, at D15S1043 and 1.79 at D15S1360 and 1.80 at D15S1010, both p=0.037. Transmission disequilibrium testing of data from D15S1360 gave an allele-wise and genotype-wise chi(2) of 6.59, 2 df, p=0.037. Haplotype transmission disequilibrium testing using a restricted allele and haplotype set from D15S1043 and D15S1360 gave a global chi(2) of 10.647, 4 df, P=0.007, and a maximum chi(2) of 6.567, 1 df, P=0.004 for excess transmission of the 1.2 haplotype into affected offspring. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:196-201, 2000.

124 citations


Journal ArticleDOI
TL;DR: 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 and associations were found between the deficit syndrome and both summer birth and a family history of schizophrenia.
Abstract: 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.

102 citations


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

Journal ArticleDOI
TL;DR: The neural response particularly associated with attention to threatening material relevant to self and with the ‘self-serving’ attributional bias is investigated, providing a simple model for paranoid delusion formation that can be tested in patients.
Abstract: 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.

Journal ArticleDOI
TL;DR: The results demonstrated no association between the AlwNI RFLP at the GABAAα6 receptor subunit gene and alcohol dependence (P = 0.059), however, the NciI RFLp at theGABAAγ2 receptor sub unit gene was associated with alcohol dependence comorbid with antisocial personality disorder (P″=‬0.021).
Abstract: Recent investigations suggest that genetic susceptibility to alcohol dependence may be conferred by GABA(A) receptor subunit genes. In this study, three RFLPs at the GABA(A)beta2, GABAAalpha6, GABA(A)alpha1 and two at the GABA(A)gamma2 receptor subunit genes, were examined for association with alcohol dependence in 189 subjects meeting DSM-III-R criteria for this disorder and 152 unrelated controls from a Japanese population. The results demonstrated no association between the AlwNI RFLP at the GABA(A)alpha6 receptor subunit gene and alcohol dependence (P = 0.059). However, the NciI RFLP at the GABA(A)gamma2 receptor subunit gene was associated with alcohol dependence comorbid with antisocial personality disorder (P = 0.021). This supports a recent finding reporting an association between the GABA(A)gamma2 receptor subunit gene and alcohol dependence with criminal record in a Finnish population. Taking into account the effects of multiple comparisons, this result should be interpreted with caution pending replication.

Journal ArticleDOI
TL;DR: The results suggest that prematurity at birth is associated with a risk of developing schizophrenia in adulthood, and there was no evidence that schizophrenics tend to have lower mean BW or smaller BHC.
Abstract: 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.

Journal ArticleDOI
08 Jan 2000
TL;DR: Results showed that non-speech sound could be used in a simple share-dealing scenario to present a “sound graph” of share prices, which allowed participants to reduce the workload they had to invest in share-price monitoring as they could listen to the graph whilst they worked in a share accumulation window.
Abstract: A problem with mobile computing devices is the output of dynamic information owing to their small screens. This paper describes an experiment to investigate the use of non-speech sounds to present dynamic information without using visual display space. Results showed that non-speech sound could be used in a simple share-dealing scenario to present a “sound graph” of share prices. This allowed participants to reduce the workload they had to invest in share-price monitoring as they could listen to the graph whilst they worked in a share accumulation window.

Journal ArticleDOI
TL;DR: Schizotypy in relatives has a familial relationship with schizoid-schizotypal traits in the childhood, and with positive symptoms during the illness, of schizophrenic patients.

Journal ArticleDOI
TL;DR: It is found that families with several schizophrenic members are not associated with abnormality in the size of the corpus callosum, and there remained no difference when the relatives were divided into two groups comprising presumed 'obligate carriers' and 'non-obligates'.

Journal ArticleDOI
TL;DR: Failure of left STG 'deactivation' and left fronto-temporal disconnectivity are not consistent findings in schizophrenia; neither are they trait-markers for genetic risk.

Journal ArticleDOI
TL;DR: Findings support the view that the cerebral structural abnormalities found in patients with schizophrenia are the result of an early pathologic process affecting the development of fetal ectodermal structures.

Journal ArticleDOI
TL;DR: The Kraepelinian Dichotomy: Evidence from Developmental and Neuroimaging Studies shows clear links to major depressive disorder, particularly in young people aged under the age of 18.
Abstract: Received October 19, 1999; revised February 16, 2000; accepted April 18, 2000. From the Department of Psychiatry, Institute of Psychiatry (King’s College), De Crespigny Park, London, SE5 8AF, United Kingdom. Send correspondence to Dr. Curtis at the above address; e-mail: v.curtis@iop.kcl.ac.uk Copyright 2000 American Psychiatric Press, Inc. The Kraepelinian Dichotomy: Evidence From Developmental and Neuroimaging Studies

Journal ArticleDOI
TL;DR: Both genetic and environmental risk factors appear to operate across diagnostic categories and therefore support a dimensional model of psychosis.
Abstract: 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

Journal ArticleDOI
TL;DR: Mental health teams frequently use, and even more frequently claim to use, psychosocial treatments in the care of people with schizophrenia but there remains a suspicion, particularly among patients' and relatives' groups, that such treatments are not as widely available as they ought to be.
Abstract: Mental health teams frequently use, and even more frequently claim to use, psychosocial treatments in the care of people with schizophrenia. Yet there remains a suspicion, particularly among patients' and relatives' groups, that such treatments are not as widely available as they ought to be. This failure to take up psychosocial treatments may be partly because they are not marketed by powerful organizations like drug companies. However, another reason is that psychiatrists are often skeptical whether psychosocial treatments are effective and whether they have been tested as rigorously as new drugs. Sadly, there have been some grounds for this skepticism. Only too often a new social therapy has been compared with standard treatment and found to be superior, hi many cases, however, the team that applied the innovative therapy has been led by an enthusiastic young researcher highly committed to the therapy under test. In comparison, the standard treatment has been that offered by an elderly psychiatrist practicing as he has done for the previous 30 years while dreaming of retirement and ways to poison the head of his hospital. Under such circumstances, the fact that the new treatment is found to be superior cannot be taken as indicating that its benefits are generalizable!

Journal ArticleDOI
TL;DR: In this paper, the authors used functional MRI to examine the neural correlates of cognitive processes putatively relevant to auditory hallucinations, and auditory hallucinations themselves, and found that hallucinations were associated with activation in a network that resembled that engaged during imagining speech, except that there was an absence of activation in the SMA and cerebellum.


Journal ArticleDOI
TL;DR: There were no significant differences between groups of relatives based on age at onset of psychosis in the proband, however, relatives of patients exposed to obstetric complications completed Trails A in a shorter time and relatives of schizophrenic patients showed more indicators of left hemisphere damage.
Abstract: Numerous studies have found deficits in executive functioning in schizophrenic patients, but it is not clear whether these deficits are shared by patients with affective psychoses, or by the relati...