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R M Murray

Publications and source records attributed to R M Murray.

At least 181 records · Page 10Linked to original sources
PubMed1996

Imaging as a tool in exploring the neurodevelopment and genetics of schizophrenia.

Neuroimaging has enabled us to address questions about the timing and origin of brain abnormalities in schizophrenia. First episode and longitudinal computed tomography (CT) and magnetic resonance imaging (MRI) studies of schizophrenic patients have shown that the brain abnormalities are present at onset of psychosis and are non-progressive. Such findings support the idea that schizophrenia is a developmental rather than a degenerative condition. Furthermore, the presence of ventriculomegaly and diminished hemispheric asymmetry in familial schizophrenics and in those of their relatives who appear to be transmitting the disorder, implies involvement of the genes controlling neurodevelopment. However, genetic factors do not fully account for the development of schizophrenia; early environmental insults such as obstetric complications are also important and may interact with genetic predisposition. Brain development continues postnatally and profound maturational events also occur in adolescence and early adulthood. Magnetic resonance spectroscopy (MRS) studies allow the investigation of the developmental biochemistry of the living brain and are being used to explore the role of maturational brain events in determining the onset of psychosis.

Brain↗
PubMed1996

Prenatal exposure to influenza and increased cerebrospinal fluid spaces in schizophrenia.

Several epidemiological studies have suggested that maternal exposure to influenza during midgestation is a risk factor for schizophrenia. In exploring the possible pathogenic mechanism, we examined the relationship between computed tomography structural brain measures in 83 schizophrenia patients and 113 controls and also their risk of maternal exposure to influenza. Four brain measures of the cerebrospinal fluid (CSF) spaces (lateral ventricle, maximum third ventricle, sulcal fluid, and sylvian fissure) were investigated in relation to the risk exposure level. In schizophrenia patients, these measures, in particular sylvian fissures, were found to increase with higher levels of risk exposure to influenza during the susceptible period (i.e., midgestation); no such effect was found in controls. These results indicate that risk for midgestational influenza exposure is associated with generalized enlargement of the CSF spaces, especially in the region of the temporal lobe. The findings suggest that certain morphological abnormalities of the brain frequently reported in schizophrenia patients may be partly attributable to antenatal exposure to influenza.

Adult↗
PubMed1996

Perinatal complications and schizophrenia. Data from the Maternal and Child Health Handbook in Japan.

A number of studies have shown that schizophrenics have increased obstetric complications compared with controls, but conflicting negative results have also been reported. Similarly, some studies found that obstetric complications were more frequently observed among male or nonfamilial schizophrenics than their female or familial schizophrenic counterparts, but others reported negative or inverse results. Since 1948 in Japan, every pregnant woman has been assigned a Maternal and Child Health Handbook in which obstetricians have been obliged to fill in obstetric data. In the current study, perinatal complications assessed using the scale of Parnas et al. (1982), based on information from the maternal and child health handbook were compared between DSM-III-R-diagnosed schizophrenics (N = 59), their healthy siblings (N = 31), and controls (N = 108). We found that female schizophrenics had experienced significantly more perinatal complications than siblings and controls. We could not detect any significant association between perinatal complications and family history.

Comorbidity↗
PubMed1996

Linkage analysis of the fragile X gene FMR-1 and schizophrenia: no evidence for linkage but report of a family with schizophrenia and an unstable triplet repeat.

We have examined 23 families multiply affected with schizophrenia for linkage to the FMR-1 gene on the X chromosome. Alleles at the FMR-1 CGG triplet repeat were analysed by the polymerase chain reaction, and methylation status at the FMR-1 locus in individuals with evidence of expanded or unstable repeats was analysed by Southern hybridization. Two-point LOD score analyses with a range of X-linked single gene models and a non-parametric affected sib-pair method revealed no evidence for linkage. In one family, however, a fragile X premutation was found, and one individual with schizophrenia and developmental delay was a mosaic for the full and premutation. We conclude that although mutations within the FMR-1 gene do not have a major aetiological role in schizophrenia in our collection of pedigrees, it is possible that FMR-1 mutations can modify the clinical phenotype of schizophrenia.

Adolescent↗
PubMed1996

Preferential transmission of the high activity allele of COMT in schizophrenia.

Catechol-O-methyl transferase (COMT) metabolizes a variety of catecholamines such as dopamine, adrenaline and noradrenaline. It exists in common high and low activity forms. The low activity form is the result of an amino acid substitution (val-108-met) which reduces the thermostability of the enzyme [Lotta et al. (1994) Biochemistry, 34, 4202-4210]. We have genotyped this polymorphism in 178 trios consisting of Han Chinese schizophrenic subjects and their parents in order to test the hypothesis that the high activity allele is transmitted more often to affected subjects. The data were analysed using the transmission disequilibrium test (TDT), a robust method of detecting linkage in the presence of allelic associations. Of the 131 parents heterozygous at this locus, 80 transmitted the high activity allele (val-108) to affected offspring, while the remaining 51 transmitted the low activity allele (p = 0.005, one-tailed). Combining this result with that of a previous TDT study of the same polymorphism in familial schizophrenia [Kunugi et al. (1996) submitted] gives significant evidence for linkage disequilibrium (p = 0.0015). However, val-108 is frequent in the Han Chinese population, and in the present sample, 239 of the 350 non-transmitted parental alleles were val-108 (68%). It is therefore unlikely that val-108 allele of COMT has a major effect on susceptibility to schizophrenia. Our results suggest that either val-108 is a minor risk factor for schizophrenia, that the COMT gene has additional polymorphisms with greater effect on risk, or that this region of chromosome 22 contains a susceptibility gene which is in linkage disequilibrium with the COMT gene.

Adolescent↗
PubMed1996

A factor analytic study of symptoms in acute schizophrenia.

The three-syndrome model of schizophrenic phenomenology has been well established in chronic illness. We report an attempt to replicate this concept in a sample of acutely unwell schizophrenic patients. Factor analysis was performed using PSE data collected within a week of admission from 114 patients who met DSMIII(R) diagnostic criteria for schizophrenia. Four main factors accounted for 58% of the variance. The first two factors closely resembled Liddle's disorganisation and psychomotor poverty syndromes. Hallucinations and delusions loaded separately under the third and fourth factors. To examine the validity of these four syndromes, the relationships between factor scores and other clinical data were examined. The disorganisation syndrome was associated with a history of multiple past admissions and a longer lifetime duration of in-patient treatment.

Acute Disease↗
PubMed1996

Genetic association of the HLA DRB1 gene locus on chromosome 6p21.3 with schizophrenia.

OBJECTIVE: The authors investigated the human leukocyte antigen (HLA) DRB1*04 gene in schizophrenic patients because it is positively associated with rheumatoid arthritis, an autoimmune disease that exhibits a strong negative association with schizophrenia. The HLA DQB1*0602 allele was also studied because of previous reports of genetic association between it and schizophrenia. Maternal HLA was investigated because of the reported association between prenatal influenza and schizophrenia and the central role of HLA molecules in the immune response to viral infections. METHOD: Polymerase chain reactions and sequence-specific oligonucleotide probes were used to genotype 94 unrelated patients with DSM-III-R schizophrenia, 92 mothers of schizophrenic offspring who were not related either to each other or to the 94 patients, and 177 healthy comparison subjects. RESULTS: The frequency of DRB1*04 alleles was significantly lower in both the schizophrenic patients and the unrelated mothers of schizophrenic offspring than in the healthy comparison subjects. No significant differences were found for DQB1*0602. CONCLUSIONS: DRB1*04 alleles may partially account for the genetic predisposition to schizophrenia. The association reported here may be explained by genetic linkage or by an autoimmune pathophysiology for a proportion of schizophrenia cases. Alternatively, it may be that maternal B lymphocytes that do not express the DR4 antigen encoded by DRB1*04 respond to influenza virus by producing antibodies that perturb neurodevelopment, thus underpinning a proportion of schizophrenia cases.

Chromosomes, Human, Pair 6↗
PubMed1996

Enhancement of the prolactin response to d-fenfluramine in drug-naive schizophrenic patients.

BACKGROUND: We wished to investigate central serotonergic function in untreated schizophrenia. METHOD: Thirteen drug-naive, DSM-III-R schizophrenic patients were compared with sex, race, age, weight and menstrual phase matched controls. Plasma prolactin and cortisol responses to a specific serotonergic probe, d-fenfluramine, were measured along with BPRS ratings. RESULTS: Prolactin responses were enhanced in schizophrenic patients compared to controls (P < 0.05) and were correlated positively with BPRS items for depression, anxiety and guilt. Baseline cortisol was also raised in those with schizophrenia (P < 0.001). CONCLUSIONS: Central serotonergic tone may be raised in acute, drug-naive schizophrenia and may be associated with the presence of affective symptomatology.

Adult↗
PubMed1996

Mixed-handedness in patients with functional psychosis.

BACKGROUND: An excess of non-right-handedness has been shown among patients with schizophrenia. However it is not clear whether this finding can be accounted for by an increase in left-handedness, mixed-handedness or both. It is not known whether atypical patterns of hand preferences occur in other functional psychotic illnesses. METHOD: The Annett hand preference questionnaire was administered to patients with schizophrenia (n = 120); affective psychosis (n = 55); schizoaffective psychosis (n = 41), and control subjects (n = 86). Handedness was classified into three categories: right, mixed and left-handedness. RESULTS: The hand preference patterns of patients with functional psychotic illnesses were not significantly different from controls. Patients with schizophrenia showed a non-significant excess of mixed-handedness compared with controls. Patients with schizophrenia and affective psychosis showed a non-significant decrease in left-handedness compared with controls. CONCLUSIONS: Although our results showed a trend in the hypothesised direction, we failed to demonstrate that patients with psychotic illness differed from controls on self-reported hand preference patterns.

Adult↗
PubMed1996

Prenatal exposure to the 1957 influenza epidemic and adult schizophrenia: a follow-up study.

BACKGROUND: We investigated the hypothesis that prenatal exposure to the 1957 A2 influenza increases the risk of schizophrenia in adulthood. METHOD: We traced a cohort of individuals known to have been exposed to the 1957 influenza epidemic during gestation and an unexposed cohort matched for period of gestation and hospital of birth. Follow-up information on psychiatric illness in subjects was sought from two sources: maternal interview and psychiatric hospital admission data. RESULTS: Follow-up information was obtained on 54% of the sample: 238 subjects from the influenza-exposed group and 287 subjects from the unexposed group. There was no increased risk of schizophrenia among the exposed cohort compared to the unexposed cohort (relative risk 1.1; 95% Cl 0.41-2.95), although there was an increase in depressive illness (relative risk 1.59; 95% Cl 1.15-2.19). CONCLUSIONS: The association between prenatal influenza and an increased risk of schizophrenia in adulthood has thus far been found only in population-based data and is not supported by the present observational study which has information about exposure and outcome in individuals.

Cohort Studies↗
PubMed1996

The neural correlates of inner speech and auditory verbal imagery in schizophrenia: relationship to auditory verbal hallucinations.

BACKGROUND: Auditory verbal hallucinations are thought to arise from the disordered monitoring of inner speech (thinking in words). We tested the hypothesis that a predisposition to verbal auditory hallucinations would be associated with an abnormal pattern of brain activation during tasks which involved the generation and monitoring of inner speech. METHOD: The neural correlates of tasks which engaged inner speech and auditory verbal imagery were examined using positron emission tomography in (a) schizophrenic patients with a strong predisposition to auditory verbal hallucinations (hallucinators), (b) schizophrenic patients with no history of hallucinations (nonhallucinators), and (c) normal controls. RESULTS: There were few between-group differences in activation during the inner speech task. However, when imagining sentences spoken in another person's voice, which entails the monitoring of inner speech, hallucinators showed reduced activation in the left middle temporal gyrus and the rostral supplementary motor area, regions which were strongly activated by both normal subjects and nonhallucinators (P < 0.001). Conversely, when nonhallucinators imagined speech, they differed from both hallucinators and controls in showing reduced activation in the right parietal operculum. CONCLUSIONS: A predisposition to verbal hallucinations in schizophrenia is associated with a failure to activate areas implicated in the normal monitoring of inner speech, whereas the absence of a history of hallucinations may be linked to reduced activation in an area concerned with verbal prosody.

Adult↗
PubMed1996

Morbid risk of schizophrenia in first-degree relatives of white and African-Caribbean patients with psychosis.

BACKGROUND: The high rate of schizophrenia among the second-generation African-Caribbean population in Britain has prompted much concern and speculation. Sugarman and Craufurd have reported that the morbid risk in the siblings of second-generation African-Caribbean schizophrenic patients was unusually high compared with that of the siblings of White patients. METHOD: We sought to replicate these findings by comparing the morbid risk for schizophrenia in the first-degree relatives of 111 White and 73 African-Caribbean psychotic probands. The latter comprised 35 first-generation (born in the Caribbean) and 38 second-generation (born in Britain) probands. RESULTS: The morbid risk for schizophrenia was similar for the parents and siblings of White and first-generation African-Caribbean patients, and for the parents of the second-generation African-Caribbean probands. However, the siblings of second-generation African-Caribbean psychotic probands had a morbid risk for schizophrenia that was seven times that of their White counterparts (P = 0.007); similarly, the siblings of second-generation African-Caribbean schizophrenic probands had a morbid risk for schizophrenia that was four times that of their White counterparts (P = 0.05). CONCLUSIONS: These findings replicate those of the earlier report of Sugarman and Craufurd, and suggest either that the second-generation African-Caribbean population in Britain is particularly vulnerable to some environmental risk factors for schizophrenia, or that some environmental factors act selectively on this population in Britain.

Adult↗
PubMed1996

The neurodevelopmental theory of schizophrenia: evidence concerning structure and neuropsychology.

Severe schizophrenics as a group show subtle abnormalities of cerebral structure. Cerebral ventricular enlargement is the best replicated finding, and this tends to be associated with impairment of neuropsychological performance. The idea that these abnormalities have a neurodevelopmental origin gains indirect support from the, admittedly less consistent, evidence of abnormalities of cerebral asymmetry and of neuronal migration in adult schizophrenics, as well as from the better established behavioural, psychomotor, and cognitive impairments reported in preschizophrenic children. However, the relationship between childhood and adult neuropsychological and brain structural findings has not been proven, and we don not know whether only some schizophrenia has a developmental origin, or whether patients differ only in the degree of developmental impairment that they show.

Adult↗
PubMed1996

A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders.

The serotonin transporter (5-HTT) is a candidate locus for aetiological involvement in affective disorders. Biochemical studies in suicides and depressed patients suggest that 5-HT uptake function is frequently reduced in affective illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such as fluoxetine. We have performed an association study of a short variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional activity of the 5-HTT promoter leading to low functional expression of the 5-HTT, in 454 patients with bipolar or unipolar affective disorder and 570 controls, derived from three European Centres (London, Milan and Würzburg). In all three centres, the frequency of the low activity allele was higher in patients than in controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Würzburg). Although these differences were not individually significant, a stratified analysis of all three samples gave a significant overall odds ratio of 1.23 (95% confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low-activity genotype among the patients was even greater (odds ratio 1.53, 95% confidence interval 1.04-2.23, P = 0.02), suggesting partial recessively of the low-activity allele. Given the functional role of 5-HTT, our findings suggest that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential genetic susceptibility factor for affective disorders. If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.

Alleles↗
PubMed1995

No evidence for linkage between the X-chromosome marker DXS7 and schizophrenia.

DeLisi et al. (1994b) have examined the X and Y chromosomes for linkage to schizophrenia in 126 small families and report a small positive LOD score for the marker DXS7, adjacent to the MAO locus at Xp11.4-11.3. Because of this, we have examined the DXS7 for linkage to schizophrenia using 17 pedigrees in which male-to-male transmission of schizophrenia was absent. Alleles at DXS7 were genotyped using the PCR and LOD scores calculated using five models of inheritance, including classical dominant recessive and intermediate models. LOD scores were substantially negative for all models examined and analysis for linkage heterogeneity using the LOD2 method showed no significance. Analysis by the nonparametric affected sib-pair method likewise indicated no linkage. We conclude that DXS7 is not a major locus for schizophrenia in our collection of pedigrees.

Family↗