Biomedical subjects

R M Murray

Publications and source records attributed to R M Murray.

At least 145 records · Page 8Linked to original sources

PubMed1997

Seasonality of birth in schizophrenia: the effect of regional population density.

It has been suggested that winter birth in urban areas may be associated with an increased risk of schizophrenia. Data on 4139 patients with a hospital diagnosis of schizophrenia were obtained from a survey of public departments of psychiatry in metropolitan France. Place of birth was classified according to the administrative subdivision of French territory into 95 'départements'. Density of population in the decade and in the département of birth was identified using successive census data. A 20% excess (OR, 1.20; 95% CI, 1.03-1.40; p = 0.02) of winter births (January-March) was found among patients born in highly densely populated areas (> 136 inhabitants/km2) compared to those born in other areas. These results suggest that seasonal early environmental risk factor(s) linked to schizophrenia predominantly operate in urban areas.

Adolescent↗

PubMed1997

Developmental insanity or dementia praecox: was the wrong concept adopted?

Over a century ago, the Scottish psychiatrist Thomas Clouston proposed the idea of a developmental or adolescent insanity. He characterised the condition as having a male predominance and a poor outcome, and noted the frequency of a family history and of minor anomalies of the palate; he considered it a disorder of cortical development and the onset of psychotic symptoms due to maturation during adolescence "of certain parts of the brain which had lain dormant before". Clouston's idea was subsequently eclipsed by the broader dementia-praecox espoused by Kraepelin and Bleuler, but recent epidemiological, neuroimaging, and neuropathological research supports the existence, within the schizophrenia syndrome of a group of patients with a severe, early onset, developmental psychosis. This disorder, re-christened as neurodevelopmental schizophrenia, is associated with childhood language and speech difficulties which render subjects more likely to later misinterpret their own inner speech as external voices; like all developmental disorders of language, it is commoner in males. Predisposing factors include the inheritance of abnormal cerebral asymmetry, and early environmental hazards of brain development such as prenatal exposure to maternal viral infection and perinatal complications.

Adolescent↗

PubMed1997

The Maudsley Family Study, II: Endogenous event-related potentials in familial schizophrenia.

Auditory event-related potentials (ERPs) were obtained from 33 schizophrenics, from 16 families multiply affected with schizophrenia, 57 of their non-schizophrenic first-degree relatives and 32 unrelated healthy controls. Transmission of schizophrenia in these families appeared unilinear with one parent only transmitting the disorder. Consequently, we were able to identify 10 presumed obligate carriers and study eight of them. Schizophrenic patients showed latency prolongation and amplitude reduction of the N100, N200 and P300 waves compared to controls. Their relatives showed similar abnormalities compared to controls. There was a trend for bimodal distribution of the P300 latency in the relatives, with 20 (35%) of them falling outside two standard deviations of the mean of the controls. These included six of the eight obligate carriers. Our results suggest that ERP abnormalities may serve as markers of genetic vulnerability in schizophrenia and may be useful in genetic linkage studies.

Adult↗

PubMed1997

In vivo effects on striatal dopamine D2 receptor binding by the novel atypical antipsychotic drug sertindole--a 123I IBZM single photon emission tomography (SPET) study.

The novel antipsychotic drug sertindole has an atypical pharmacological profile. We have estimated striatal D2 dopamine binding in schizophrenic patients treated with sertindole using 123I iodobenzamide (IBZM) SPET. Patients were recruited from a clinical trial of sertindole's tolerability and efficacy. Striatal D2 binding in sertindole-treated patients (n = 5), was compared with previously reported data from clozapine (n = 10); olanzapine (n = 6); typical antipsychotic responsive (n = 10); and risperidone (n = 6)-treated groups. Mean PANSS (structured clinical interview for the positive and negative syndrome scale) scores showed clinical improvement in the sertindole group. Few extrapyramidal side effects (EPS) were recorded [average Simpson-Angus (SAS) score = 2.6]. Sertindole-treated patients had mean D2 binding indices (+/-SE) significantly lower than clozapine-treated patients (1.19 +/- 0.04) versus (1.49 +/- 0.04), and olanzapine-treated patients (1.41 +/- 0.06); and similar to those of risperidone (1.24 +/- 0.04) and typical antipsychotic responsive (1.25 +/- 0.05) treated patients. In this patient sample the preliminary evidence suggests that sertindole's decreased tendency to induce EPS at clinically therapeutic doses is not due to limited occupancy of striatal D2 receptors in vivo, and as is the case for risperidone, patients are protected from EPS by some other intrinsic effect of the drug.

Adult↗

PubMed1997

Do noradrenergic reuptake inhibitors affect serotonergic function in depression?

d-Fenfluramine, a specific 5-HT releasing agent without the catecholamine effects of d,l-fenfluramine, was used as a serotonergic neuroendocrine challenge in subjects with unipolar major depression. Prolactin and cortisol responses to 30 mg d-fenfluramine were measured in patients at baseline. Patients were then randomly assigned to treatment for 6 weeks with a specific noradrenergic reuptake inhibitor, a tricyclic antidepressant, or placebo. Response to antidepressant treatment was assessed, and patients underwent further testing with d-fenfluramine. Prolactin responses were increased by treatment, but this was independent of whether or not patients' depression responded to treatment. Seven patients were treated with a specific noradrenergic reuptake inhibitor. These patients showed a significant rise in 5-HT-mediated cortisol responses after treatment, independent of whether their depression improved. We conclude that antidepressants which selectively modify noradrenergic function also have effects on 5-HT function as measured by neuroendocrine testing.

Adrenergic Uptake Inhibitors↗

PubMed1997

Serotonergic function and negative and depressive symptomatology in schizophrenia and major depression.

BACKGROUND: Serotonergic abnormalities are found in both major depressive disorder (MDD) and schizophrenia. Depressive symptoms commonly occur alongside the negative or defect symptoms in schizophrenia and antiserotonergic drugs may be particularly effective in their treatment. We wished to explore whether these symptoms could be distinguished biologically by directly comparing serotonergic function in these two illnesses. METHOD: Fifteen patients with MDD and 13 patients with schizophrenia underwent testing with the specific serotonin releasing agent D-fenfluramine (D-FEN). Prolactin and cortisol responses were measured to ascertain central serotonergic function. Individual patient results were compared with their own carefully matched control to correct for the effect of age, sex, weight and menstrual cycle, before the two patient groups were then compared. RESULTS: Prolactin responses differed significantly between the two patient groups, being lower in MDD patients and higher in schizophrenia patients than their individually matched controls. Cortisol responses did not differ. Within the schizophrenia group, increased serotonergic function correlated positively with depressive symptoms, but there was no such correlation with defect symptoms. Depressive scores were negatively correlated with the presence of negative symptoms in the schizophrenic group. CONCLUSIONS: Schizophrenia and MDD have distinct and opposite neuroendocrine responses to D-FEN. There is no evidence that depressive symptoms in these two conditions have a common serotonergic basis. Moreover, these responses distinguished between negative and depressive symptoms in our schizophrenic group.

Adult↗

PubMed1997

Structural brain abnormalities in male schizophrenics reflect fronto-temporal dissociation.

BACKGROUND: Many studies have separately reported abnormalities of frontal and temporal lobe structures in schizophrenia, but little is known of structural fronto-temporal associations in this condition. We investigated whether male patients with chronic schizophrenia would show abnormal patterns of correlation between regional brain volumes. METHODS: Structural magnetic resonance images of the brain in 42 patients were compared with 43 matched unaffected controls. We explored the pattern of association between regional brain volumes by correlational analyses, and non-parametrically tested for significance of between-group differences by randomization. RESULTS: The schizophrenics demonstrated significant volume deficits in several brain regions (left temporal lobe and hippocampus, right dorsolateral prefrontal cortex), and significant volume increases in the ventricular system (third ventricle and left temporal horn of the lateral ventricle). Controls demonstrated large positive correlations (r > 0.4) between prefrontal and temporal lobe regions. By contrast, inter-regional correlations significantly reduced in schizophrenics included those between prefrontal, anterior cingulate and temporal regions, and between posterior cingulate and hippocampus (P < 0.05). The most salient abnormality in patients was a dissociation between prefrontal and superior temporal gyrus volumes (P < 0.01). CONCLUSIONS: These results support the existence of a relative 'fronto-temporal dissociation' in schizophrenia which we suggest may be due to lack of mutually trophic influences during frontal and temporal lobe development.

Chronic Disease↗

PubMed1997

Association analysis of the dopamine D4 gene exon III VNTR and heroin abuse in Chinese subjects.

Although social and cultural influences are clearly important, family, twin and adoption studies indicate that genes contribute significantly to substance abuse. Substance abuse is associated with novelty seeking, a heritable human personality trait which may be influenced by alleles of the dopamine D4 (DRD4) gene exon III VNTR. Consequently Kotler et al analysed the DRD4 VNTR in opiate-dependent subjects from Israel, and found a significant excess of the 7-repeat allele. We have attempted to replicate this finding using a Han Chinese case-control sample of 121 heroin-dependent subjects and 154 normal controls. We found two 7-repeat alleles which occurred exclusively in the patient group, and overall there was an excess of longer alleles, which did not reach significance (chi 2 = 7.04; P = 0.07). When the D4 VNTR was divided into 'long' (5-7 repeats) and 'short' (2-4 repeats), a significant excess of long alleles was observed in the patient group (P = 0.023, one-tailed), with an odds ratio of 2.30 (95% CI 1.07-4.93). We conclude that our findings support the hypothesis that alleles of the DRD4 exon III VNTR are susceptibility factors for heroin abuse.

Adolescent↗

PubMed1997

Catechol-O-methyltransferase polymorphisms and schizophrenia: a transmission disequilibrium study in multiply affected families.

Catechol-O-methyltransferase (COMT) metabolizes catecholamines such as dopamines, noradrenaline and adrenaline. It exists as common high and low activity alleles in the population (determined by a valine 158 methionine polymorphisms), and high red blood cell activity of COMT has previously been associated with schizophrenia. To examine the relationship between COMT and schizophrenia genetically, the transmission disequilibrium test was performed on 22 multiply affected Caucasian and Japanese families genotyped for val158met and a second, silent, polymorphism (C256G), using PCR based assays. The high activity val158 allele was transmitted from parents to the affected individuals more frequently than the low activity met158 allele, although this was not statistically significant. Combining this data with a previous study using Chinese family trios with schizophrenia (Li et al., 1996) gave a highly significant result (p = 0.0015). The G256 allele was also transmitted preferentially to the affected offspring, and this was statistically significant when schizophrenia, schizoaffective disorder and unspecified functional psychosis were included in the definition of the affected phenotype (p = 0.03). Overall, these findings may indicate an effect of COMT alleles on susceptibility to schizophrenia, or reflect linkage disequilibrium with a different causative polymorphism in the vicinity. Other reported associations of COMT with obsessive compulsive and rapid cycling bipolar disorder indicate that the COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders.

Amino Acid Substitution↗

PubMed1997

Observations on switching patients with schizophrenia to risperidone treatment. Risperidone Switching Study Group.

This study examined one possible strategy for switching patients to treatment with risperidone involving immediate cessation of current neuroleptics and gradual withdrawal of anticholinergic treatments. All patients received risperidone monotherapy for at least 4 weeks. Side-effects and symptoms were rated and successful switching was defined as completion of the study with no consistent worsening in any rating scales. Of the 41 patients entered, five withdrew for reasons unconnected with the study. Of the remaining 36 patients, 64% (23 patients) were switched successfully. Overall, the rating scales showed significant improvements (mean score on Krawiecka scale, 11.0 to 6.6, P < 0.001), and side-effects decreased (mean score on Simpson & Angus scale, 5.1 to 2.9, P = 0.004). The strategy appeared to be successful for most patients, especially those who had previously received depot medication. However, more gradual withdrawal of previous treatments, including anticholinergics, may be advisable in some cases.

Adolescent↗

PubMed1997

Schizophrenia: developmental disturbance of brain and mind?

Schizophrenia is the most severe of the mental illnesses and affects approximately 0.8% of the population in Western societies. Postmortem and neuroimaging studies show that patients with schizophrenia have slightly larger cerebral ventricles than normal and a decrease in cortical volume, most markedly in the left temporal lobe. These changes are present at diagnosis and appear to show little change over extended periods of follow-up. Associated findings such as lack of normal cerebral asymmetry and cytoarchitectonic changes suggestive of impaired migration of cortical neurons implicate aberrant neurodevelopment. Schizophrenics also show an excess of pregnancy and birth complications, and an association with prenatal exposure to maternal influenza. These and reports of abnormal psychological development in pre-schizophrenic children add further support to the theory that the disorder has neurodevelopmental origins.

Brain↗

PubMed1997

Premorbid social functioning in schizophrenia and bipolar disorder: similarities and differences.

OBJECTIVE: This research examined social functioning in childhood and adolescence among patients with schizophrenia and patients with bipolar disorder compared with healthy subjects and investigated the relation between premorbid adjustment and risk factors for psychosis. METHOD: Maternal recall was used to assess the premorbid adjustment of patients with schizophrenia (N = 70) and patients with bipolar disorder (N = 28) recruited from a survey of consecutive hospital admissions for psychosis and of healthy comparison subjects (N = 100) drawn from the same catchment area. RESULTS: The patients with schizophrenia had significantly poorer premorbid adjustment in childhood and adolescence than the comparison subjects and were impaired in both sociability and school adjustment. The patients with bipolar disorder exhibited poorer social impairment in adolescence than the comparison subjects, though to a lesser degree than the schizophrenic subjects, but functioned well at school. There were significant linear trends in the risk of psychosis with worsening premorbid functioning, which was most marked in the schizophrenic group, and a specific linear relation between low birth weight and poor premorbid adjustment among the schizophrenic patients. CONCLUSIONS: Impaired premorbid social functioning is not specific to schizophrenia and is seen also in bipolar disorder. The data support the view that poor premorbid social adjustment is one manifestation of vulnerability to adult psychotic disorders. These results are consistent with other findings pointing to early developmental deficits in patients who subsequently develop psychosis.

Adolescent↗

PubMed1997

Auditory hallucinations and the temporal cortical response to speech in schizophrenia: a functional magnetic resonance imaging study.

OBJECTIVE: The authors explored whether abnormal functional lateralization of temporal cortical language areas in schizophrenia was associated with a predisposition to auditory hallucinations and whether the auditory hallucinatory state would reduce the temporal cortical response to external speech. METHOD: Functional magnetic resonance imaging was used to measure the blood-oxygenation-level-dependent signal induced by auditory perception of speech in three groups of male subjects: eight schizophrenic patients with a history of auditory hallucinations (trait-positive), none of whom was currently hallucinating; seven schizophrenic patients without such a history (trait-negative); and eight healthy volunteers. Seven schizophrenic patients were also examined while they were actually experiencing severe auditory verbal hallucinations and again after their hallucinations had diminished. RESULTS: Voxel-by-voxel comparison of the median power of subjects' responses to periodic external speech revealed that this measure was reduced in the left superior temporal gyrus but increased in the right middle temporal gyrus in the combined schizophrenic groups relative to the healthy comparison group. Comparison of the trait-positive and trait-negative patients revealed no clear difference in the power of temporal cortical activation. Comparison of patients when experiencing severe hallucinations and when hallucinations were mild revealed reduced responsivity of the temporal cortex, especially the right middle temporal gyrus, to external speech during the former state. CONCLUSIONS: These results suggest that schizophrenia is associated with a reduced left and increased right temporal cortical response to auditory perception of speech, with little distinction between patients who differ in their vulnerability to hallucinations. The auditory hallucinatory state is associated with reduced activity in temporal cortical regions that overlap with those that normally process external speech, possibly because of competition for common neurophysiological resources.

Adult↗

PubMed1997

Schizophrenia and the myth of intellectual decline.

OBJECTIVE: The authors' goal was to investigate the issue of intellectual deterioration in schizophrenia. METHOD: They examined the childhood IQs of adult patients with schizophrenia who had attended a child psychiatry service where measurement of intelligence was routine. Follow-up IQs of 34 of these patients were obtained an average of 19.4 years later. RESULTS: The mean child and adult IQs were greater than one standard deviation lower than those of the general population. There were no significant differences between the child and adult IQs, however, suggesting that the impairment in intelligence during childhood was stable over the follow-up period. CONCLUSIONS: The deficit in intellectual function observed in these patients, and reported in the literature, is lifelong and predates the onset of schizophrenia.

Adolescent↗

PubMed1997

Obstetric complications and age at onset in schizophrenia: an international collaborative meta-analysis of individual patient data.

OBJECTIVE: An excess of obstetric complications in the histories of schizophrenic patients is a well-replicated finding, but less consistent results have been found concerning the relationships between obstetric complications and family history of schizophrenia, age at onset of schizophrenia, and gender. Small sample size limited the power of previous studies that attempted to assess such relationships. The aim of this study was to use data on individual patients from all available studies to examine the links between a history of obstetric complications and family history of schizophrenia, age at onset, and gender. METHOD: Raw data from 854 schizophrenic patients concerning history of obstetric complications rated according to the Lewis and Murray scale were obtained from 11 different research groups. Weighted average estimates were calculated with the use of regression techniques. RESULTS: A significant association was found between age at onset of schizophrenia and obstetric complications: the earlier the age at onset, the more likely the history of obstetric complications. Subjects with onset of schizophrenia before age 22 were 2.7 times more likely than those with onset at a later age to have had a history of abnormal presentation at birth and 10 times more likely to have had a history of complicated Cesarean birth. No association was found between obstetric complications and family history of schizophrenia or gender. CONCLUSIONS: The association between obstetric complications and early age at onset of schizophrenia indicates that the pathophysiology of early-onset schizophrenia involves neurodevelopmental impairment.

Adolescent↗

PubMed1997

The Maudsley Family Study. 4. Normal planum temporale asymmetry in familial schizophrenia. A volumetric MRI study.

BACKGROUND: Loss or reversal of the normal asymmetry of the planum temporale (PT) has been reported in schicophrenia, and may be due to aberations in the gene(s) controlling the development of brain asymmetries. We tested this hypothesis in a sample of schizophrenics and their relatives from families multiply affected with the disorder. METHOD: We compared 32 schizophrenics and 55 of their non-schizophrenic first-degree relatives with 39 matched community controls. Volumetric measurements of the cortical volume beneath the PT were obtained using the Cavalieri method from three-dimensionally reconstructed magnetic resonance imaging images. RESULTS: PT volume asymmetry coefficients from patients and their relatives did not differ significantly from those of the controls. Gender-specific analysis did not revealany differences. CONCLUSIONS: Abnormalities in PT volume asymmetry are not present in familial schizophrenia, where genetic factors appear to predominate.

Adult↗

PubMed1997

Grey matter correlates of syndromes in schizophrenia. A semi-automated analysis of structural magnetic resonance images.

BACKGROUND: Symptoms in schizophrenia cluster into syndromes, each of which may be associated with a particular pattern of cerebral blood flow. We sought to investigate whether these syndromes are also related to neuroanatomical changes. METHOD: A semi-automated method was used to examine structural magnetic resonance images in 12 patients with schizophrenia. The relationship between the relative regional grey matter volume and ratings of the syndromes of psychomotor poverty, disorganisation and reality distortion was investigated. RESULTS: There was a significant negative correlation between psychomotor poverty score and the relative volume of the left ventro-medial prefrontal grey matter, and a significant positive correlation between disorganisation and the relative volumes of the hippocampus, and the parahippocampal/fusiform gyrus bilaterally. CONCLUSION: The correlation between psychomotor poverty and left prefrontal grey matter volume resembles that previously seen with prefrontal blood flow in the same patient, suggesting that this functional abnormality is related to an underlying anatomical change.

Adult↗

PubMed1997

Increased rate of psychosis among African-Caribbeans in Britain is not due to an excess of pregnancy and birth complications.

BACKGROUND: It has been suggested that the increased rate of psychotic illness among African-Caribbeans living in Britain is due to an excess of pregnancy and birth complications (PBCs). METHOD: We therefore compared the frequency of PBCs in a group of White psychotic patients (n = 103) and a comparable group of patients of African-Caribbean origin (n = 61); the latter consisted of 30 first-generation (born in the Caribbean) and 31 second-generation (born in Britain) individuals. RESULTS: White psychotic patients were more than twice as likely to have a history of PBCs as their African-Caribbean counterparts (odds ratio = 2.34, 95% confidence interval (CI) 0.88-6.47, P = 0.062). The same trend was observed among patients with a DSM-III diagnosis of schizophrenia (odds ratio = 1.65, 95% CI 0.56-4.97, P = 0.32). The rate of PBCs was similar among the first- and second-generation Caribbean psychotic patients. CONCLUSIONS: The increased rate of psychotic illness that has been reported among the African-Caribbean population in Britain is not due to an increased prevalence of PBCs.

Adult↗