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Biomedical subjects

R M Murray

Publications and source records attributed to R M Murray.

At least 199 records · Page 11Linked to original sources

Abnormal monitoring of inner speech: a physiological basis for auditory hallucinations.

Auditory verbal hallucinations ("voices") are thought to arise from a disorder of inner speech (thinking in words). We examined the neural correlates of tasks which involve inner speech in subjects with schizophrenia who hear voices (hallucinators), subjects with schizophrenia who do not (nonhallucinators), and normal controls. There were no differences between hallucinators and controls in regional cerebral blood flow during thinking in sentences. However, when imagining sentences being spoken in another person's voice--which entails both the generation and monitoring of inner speech--hallucinators had a normal left frontal response, but reduced activation in the left middle temporal gyrus and the rostral supplementary motor area, regions which were activated by both normal subjects and nonhallucinators (p < 0.001). These findings suggest that a predisposition to verbal hallucinations is associated with a failure to activate areas concerned with the monitoring of inner speech.

Adult↗

Contrasting neuroendocrine responses in depression and chronic fatigue syndrome.

Hypothalamic-pituitary-adrenal (HPA) axis and central 5-HT function were compared in chronic fatigue syndrome (CFS), depression and healthy states. 10 patients with CFS and 15 patients with major depression were matched for age, weight, sex and menstrual cycle with 25 healthy controls. Baseline-circulating cortisol levels were highest in the depressed, lowest in the CFS and intermediate between the two in the control group (P = 0.01). Prolactin responses to the selective 5-HT-releasing agent d-fenfluramine were lowest in the depressed, highest in the CFS and intermediate between both in the healthy group (P = 0.01). Matched pair analysis confirmed higher prolactin responses in CFS patients than controls (P = 0.05) and lower responses in depressed patients than controls (P = 0.003). There were strong inverse correlations between prolactin and cortisol responses and baseline cortisol values. These data confirm that depression is associated with hypercotisolaemia and reduced central 5-HT neurotransmission and suggest that CFS may be associated with hypocortisolaemia and increased 5-HT function. The opposing responses in CFS and depression may be related to reversed patterns of behavioural dysfunction seen in these conditions. These findings attest to biological distinctions between these disorders.

Adult↗

Does prenatal exposure to influenza in mice induce pyramidal cell disarray in the dorsal hippocampus?

Epidemiological studies point to an association between prenatal exposure to influenza and later schizophrenia. Such studies are consistent with neuropathologic reports demonstrating cytoarchitectural abnormalities in the hippocampus and parahippocampal gyrus suggestive of second trimester developmental anomalies. The hypothesis that prenatal exposure to influenza in the second trimester may induce hippocampal pyramidal cell disarray in mice was investigated. Between days 9-16 of pregnancy, 35 Balb/c mice were intranasally inoculated with either a mouse-adapted or non mouse-adapted pool of Influenza A/Singapore/1/57 (H2N2), and 10 controls were inoculated with normal saline. Offspring were sacrificed on day 21 postpartum. Microscopic examination of the CA1-CA2 junctional areas in the offspring of mice exposed to influenza failed to demonstrate excess pyramidal cell disarray when compared with influenza-free, age matched controls. There was evidence that disarray was greater among those exposed on day 13 of pregnancy. Analyses of the data by sex and severity of maternal infection failed to reveal any significant effects.

Animals↗

Linkage studies on chromosome 22 in familial schizophrenia.

As part of a systematic search for a major genetic locus for schizophrenia we have examined chromosome 22 using 14 highly polymorphic markers in 23 disease pedigrees. The markers were distributed at an average distance of 6.6 cM, covering 70-80% of the chromosome. We analyzed the data by the lod score method using five plausible genetic models ranging from dominant to recessive, after testing the power of our sample under the same genetic parameters. The most positive lod score found was 1.51 under a recessive model for the marker D22S278, which is insufficient to conclude linkage. However, an excess of shared alleles in affected siblings (P < .01) was found for both D22S278 and D22S283. For D22S278, the A statistic was equal to the lod score (1.51) and therefore did not provide additional evidence for linkage allowing for heterogeneity, but the Liang statistic was more significant (P = .002). Our results suggest the possibility that the region around D22S278 and D22S283 contains a gene which contributes to the aetiology of schizophrenia.

Alleles↗

A voxel-based method for the statistical analysis of gray and white matter density applied to schizophrenia.

We describe a novel technique for characterizing regional cerebral gray and white matter differences in structural magnetic resonance images by the application of methods derived from functional imaging. The technique involves automatic scalp-editing of images followed by segmentation, smoothing, and spatial normalization to a symmetrical template brain in stereotactic Talairach space. The basic idea is (i) to convert structural magnetic resonance image data into spatially normalized images of gray (or white) matter density, effected by segmenting the images and smoothing, and then (ii) to use Statistical Parametric Mapping to make inferences about the relationship between gray (or white) matter density and symptoms (or other pathophysiological measures) in a regionally specific fashion. Because the whole brain sum of gray (or white) matter indices is treated as a confound, the analysis reduces to a characterization of relative gray (or white) matter density on a voxel by voxel basis. We suggest that this is a powerful approach to voxel-based statistical anatomy. Using the technique, we constructed maps of the regional cerebral gray and white matter density correlates of syndrome scores (distinct psychotic symptoms) in a group of 15 schizophrenic patients. There was a negative correlation between the score for the reality distortion syndrome and regional gray matter density in the left superior temporal lobe (P = 0.01) and regional white matter density in the corpus callosum (P < 0.001). These abnormalities may be associated with functional changes predisposing to auditory hallucinations and delusions. This method permits the detection of structural differences within the entire brain (as opposed to selected regions of interest) and may be of value in the investigation of structural gray and white matter abnormalities in a variety of brain diseases.

Adult↗

Premorbid abnormalities in mania, schizomania, acute schizophrenia and chronic schizophrenia.

The aim of this study was to examine the hypothesis that differences in outcome among affective and non-affective psychoses are associated with differences in the degree of developmental deviance. We conducted a retrospective survey of first contact cases treated over a 20-year period in a psychiatric hospital serving a catchment area in South London. All patients with non-depressive functional psychosis residing in the catchment area who received their first psychiatric treatment between 1965 and 1984 were included in the study. Cases were classified according to the relative chronicity of their illness into four non-overlapping groups: mania, schizomania, acute schizophrenia and chronic schizophrenia. There was a linear trend in the association between illness chronicity and proxy measures of development deviance, such as premorbid unemployment, single status and poor academic achievement. Compared to individuals with mania, schizophrenic patients had a 3-6 times increased risk of premorbid abnormality. For patients with schizomania and acute schizophrenia, the risk was 1.5-3 times greater than for manic subjects. We conclude that the prevalence of premorbid abnormalities is highest among chronic schizophrenia, but similar disturbances also occur, to a lesser degree, in less disabling affective and non-affective psychotic disorders.

Acute Disease↗

Prenatal exposure to influenza epidemics and risk of mental retardation.

This study was undertaken to determine whether prenatal exposure to influenza epidemics increases the risk of mental handicap. The monthly birth frequencies of 827 first-admission individuals (mean age at admission 13 years) with a primary diagnosis of non-specific mental retardation, discharged from psychiatric hospitals in England and Wales, were examined in relation to the monthly death rates from influenza over the period 1953-1980. The relative risk of developing mental handicap when exposed to influenza epidemics during mid-gestation was assessed by a generalized linear model. Increased death rates from influenza, a measure of prevalence of the infection, were significantly associated with an increase in births of mentally handicapped individuals 6 months later. For every 1000 female deaths from influenza there was a 17% increase in births of mentally handicapped individuals 6 months later. Maternal exposure to influenza at approximately the third to fourth month of gestation may be risk factor for developing mental handicap.

Adult↗

Genetic and environmental factors in premenstrual symptom reporting and its relationship to depression and a general neuroticism trait.

Previous work has indicated a genetic contribution to premenstrual symptom reporting, regularity and menarche but no genetic contribution to cycle length, and no consistent genetic contribution to premenstrual symptom reporting. This paper reports the results (n = 634) of multivariate genetic analysis in which premenstrual symptom reporting is included in a general personality factor along with extroversion (E), neuroticism (N) and depression (D). The results showed that N, E, D and PMS all fitted on a common personality factor. There was no evidence for a specific genetic contribution of depression or premenstrual symptom reporting over and above those shown in the common personality factor. There were, however, unique/specific environmental contributions for PMS. For E and N, in contrast, both unique genetic and environmental contributions were apparent.

Adolescent↗

Problem solving in schizophrenia: a specific deficit in planning ability.

The study investigated problem solving ability in schizophrenia. Thirty DSM-IIIR schizophrenic patients and 27 matched normal controls were tested on the Three-Dimensional Computerised Tower of London Test (3-D CTL Test) (Morris et al., 1993). The patients took significantly more moves to solve a series of problems and solved significantly fewer problems in the predetermined minimum number of moves. The patients response times, as measured using a control version of the task (the 3-D CTL Control), were longer than those of the controls. However, when latencies were adjusted to take into account the slower responses overall, the patients planning times were not significantly increased. Inaccurate planning, as defined by taking more moves, did not correlate with either positive or negative symptoms, but the response times tended to be longer in patients who had more negative symptoms. The findings suggest that there is a deficit in problem solving activity in schizophrenia that may be associated with translating 'willed intentions' into action, independent of slower motor speed.

Adult↗

Morbid risk of schizophrenia for relatives of patients with cannabis-associated psychosis.

Twenty-three patients admitted with acute psychosis who were cannabis positive on urinary screening were each matched, with respect to sex, with two psychotic controls who screened negatively for all substances. The lifetime morbid risk of psychiatric disorder was estimated among the first degree relatives of cases and controls, using RDC-FH criteria to define diagnoses, and Weinberg's shorter method of age correction. The cases had a significantly greater familial morbid risk of schizophrenia (7.1%) than the controls (0.7%), while the risks of other psychoses, and of non-psychotic conditions were similar. The same pattern of familial risk was evident when the analysis was restricted to patients with DSM-III schizophrenia. The data suggest that the development or recurrence of acute psychosis in the context of cannabis use may be associated with a genetic predisposition to schizophrenia.

Adult↗

Minor physical anomalies in psychoses: associations with clinical and putative aetiological variables.

This study of patients with functional psychoses set out to examine associations between minor physical anomalies (MPAs) and demographic, clinical, CT scan measures, and putative aetiological variables. 157 psychotic patients had minor physical anomalies assessed using a modified Waldrop scale. RDC diagnoses for these patients were: schizophrenia (n = 79), schizoaffective disorder (n = 31), mania (n = 24), major depression (n = 13), unspecified functional psychosis (n = 8), other organic psychosis (n = 2). 63 healthy white controls were also assessed with the modified Waldrop scale. Minor physical anomalies were not associated with any particular diagnosis. For white subjects, patients had significantly more MPAs than well controls. Anomalies of the palate were the most frequent item reported in patients and controls. For males, there was a weak association between the presence of MPAs and positive family history of a major psychiatric disorder. Those with MPAs required more frequent and longer psychiatric admissions, and showed impaired ability on a test sensitive to left parietal system function. Within the patient group, there were no associations between MPAs and gender, age at onset, negative symptoms, premorbid level of functioning, estimated premorbid intelligence, pregnancy and birth complications, and selected CT variables. Minor physical anomalies are found in a range of functional psychoses. There may be overlap between the various genes that predispose to psychiatric illness (especially in males) and those genes that predispose to developmental instability.

Adult↗

Dysfunctional attitudes in depressed and recovered depressed patients and their first-degree relatives.

A series of depressed probands and their first-degree relatives were categorized as follows: (a) currently depressed; (b) recovered depressed; and (c) never-ill relatives. Their scores on a subscaled version of the Dysfunctional Attitude Scale (the DAS-24) were compared. The DAS total scores mirrored previous findings in that the total scores for recovered individuals returned to normal or near-normal levels. However, the dependency subscale scores remained elevated for the recovered depressed group. It is proposed that these results support the conclusion that self-report measures of cognitive vulnerability should focus on specific rather than global effects, if progress is to be made in the search for true vulnerability factors.

Achievement↗

Gender differences in schizophrenia: hormonal effect or subtypes?

Compared with their male counterparts, females with schizophrenia, on average, show better premorbid functioning, later onset, and a more benign course of illness. They are also more likely to have a family history of schizophrenia and/or affective illness, to exhibit "atypical" and affective features, and to show a seasonal pattern of hospital admission that mimics that of patients with mania. However, there exists a paradox. Although schizophrenia in females has much in common with affective disorder, the "schizophrenogenic" effect of maternal influenza also appears to be more significant in female than in male schizophrenia. Perhaps females with a predisposition to affective psychosis who have also been subject to the effects of maternal viral infection during gestation develop some subtle neurodevelopmental damage that renders their psychosis schizophrenia-like.

Female↗

Chromosome 22 markers demonstrate transmission disequilibrium with schizophrenia.

Previously we reported evidence for genetic linkage between markers on chromosome 22q12 and schizophrenia in 23 multiply affected pedigrees. As part of further investigation of this region, we have applied the transmission disequilibrium test (TDT) to the genotype data. The TDT is a test for both linkage and linkage disequilibrium, and is based on the unequal probability of transmission of two different marker alleles from parents to affected offspring. We obtained significant results for the marker D22S283 (chi 2 = 35.9, 14 df, p = 0.001), D22S278 (chi 2 = 16.5, 6 df, p = 0.01) and F8VWFP (chi 2 = 13.1, 4 df, p = 0.01). Application of the Bonferonni correction for testing multiple markers renders the results for marker D22S278 and F8VWFP non-significant (from p = 0.01 to p = 0.14), while the result for D22S283 remains modestly significant at p < 0.02. Overall, our findings strengthen the suggestion that the region around D22S283 contains a susceptibility gene for schizophrenia.

Chromosome Mapping↗

No association between prenatal exposure to influenza and autism.

We examined the relationship between the number of autistic patients, obtained from the register of the National Autism Society (NAS), born each month between January 1953 and December 1988 in England, and the occurrence of influenza epidemics one to nine months before birth. The relative risk of developing autism, for exposure to influenza during gestation, was assessed by a Poisson regression model. Our results indicate that exposure to influenza epidemics during gestation is not associated with autism.

Adolescent↗

Maternal influenza, obstetric complications, and schizophrenia.

OBJECTIVE: Epidemiologic studies have reported an association between prenatal exposure to influenza and adult schizophrenia. The authors studied this association in individual patients with schizophrenia and also investigated the relationship of obstetric complications, another postulated risk factor, to adult schizophrenia. METHOD: Using a structured interview instrument, the authors assessed infections during pregnancy, obstetric complications, gestational age, and birth weight by interviewing the mothers of 121 patients with DSM-III-R schizophrenia. RESULTS: Significantly more infections were reported in the second trimester of the patients' gestations than in the combined first and third trimesters. Influenza accounted for 70% of second-trimester infections. Patients with schizophrenia whose mothers reported having influenza during the second trimester were almost five times more likely to experience at least one definite obstetric complication than were patients who were not exposed to influenza during the second trimester; the exposed patients weighed a mean of 210 g less at birth than the unexposed patients. CONCLUSIONS: Maternal influenza during the second trimester may impair fetal growth and predispose to obstetric complications and lower birth weight in a proportion of individuals destined to develop schizophrenia.

Adult↗