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Biomedical subjects

R M Murray

Publications and source records attributed to R M Murray.

At least 235 records · Page 13Linked to original sources
PubMed1993

Schizophrenia: genetics and the maternal immune response to viral infection.

Thirty years ago, Eliot Slater suggested that the reason schizophrenia was not progressively eliminated from the population was that the responsible gene also conveyed a compensatory advantage in terms of increased resistance to infection. If this selective advantage lies in the antibody response to certain viral infections, this could explain recent studies suggesting that exposure to influenza in the second trimester of gestation increases the risk of later schizophrenia. We propose that prenatal exposure to influenza induces maternal antibodies which then cross-react with proteins in the developing foetal brain, becoming foetal autoantibodies. Thus an immunogenetic response by the mother results in aberrant foetal neurodevelopment, the biological substrate for a proportion of adult schizophrenia. Initial research strategies to test this hypothesis are proposed.

Antibodies, Viral↗
PubMed1993

Does social deprivation during gestation and early life predispose to later schizophrenia?

We employed a case-control study design to investigate whether schizophrenic patients differed from non-psychotic psychiatric patients in terms of place of birth and paternal occupation. "Cases" were first-contact schizophrenic patients ascertained from the Camberwell Cumulative Psychiatric Case Register. "Controls" were the next (non-psychotic) patient on the Register matched for age and sex. In comparison with controls, cases were more likely to have: (1) been born in the deprived inner-city Camberwell catchment area (odds ratio 2.3), and (2) had fathers who had "manual" as opposed to "non-manual" occupations (odds ratio 2.1). The results were compatible with the notion that socio-economic deprivation during gestation and early life predisposes to later schizophrenia.

Case-Control Studies↗
PubMed1993

Puberty and the onset of psychosis.

According to the neurodevelopmental hypothesis of schizophrenia, maturational events in the brain at puberty interact with congenital defects to produce psychotic symptoms. As girls reach puberty at a younger age than boys, we predicted that (i) females would show earlier onset of psychotic illness arising around puberty, and (ii) onset of psychosis in females would be related to menarche. Analysis of epidemiological data regarding admission to psychiatric units in (a) England over the period 1973-1986, (b) France over the period 1975-1980, as well as examination of 97 psychotic adolescents referred to an adolescent unit over a 14 year period, supported both these propositions.

Adolescent↗
PubMed1993

Reduction of cortical volume in schizophrenia on magnetic resonance imaging.

The MRI scans of 48 schizophrenic patients, fulfilling RDC criteria, were compared to those of 34 healthy controls matched for age, ethnicity and parental social class. The volume of the frontal and anterior parietal lobes was significantly reduced in the schizophrenic group as a result of a selective decrease in cortical volume, with a corresponding increase in the volume of sulcal fluid. Reduction in the volume of the temporal grey matter was more marked on the right, but was not in excess of the loss of volume observed in other areas of the cortex. MRI abnormalities correlated poorly with clinical parameters, although both unemployment and poor pre-morbid adjustment predicted reduced cerebral volume and increased sulcal volume. These results question whether the medial temporal lobes are the only site of structural pathology in schizophrenia.

Adult↗
PubMed1993

Antipsychotic medication, D2 dopamine receptor blockade and clinical response: a 123I IBZM SPET (single photon emission tomography) study.

The hypothesis that poor response to antipsychotic medication is due to inadequate occupancy of central D2 receptors was tested in vivo. We assessed striatal D2 dopamine receptor availability for binding with the specific ligand 123I IBZM by single photon emission tomography (SPET) in two groups of DSM-III-R diagnosed schizophrenic patients on typical antipsychotic medication, and a group of healthy controls (N = 20). Patients were characterized by clinical ratings as antipsychotic responders (N = 10) or non-responders (N = 8). Dynamic single slice SPET, at a slice chosen to include the basal ganglia, began immediately following intravenous injection of 185 MBq 123I IBZM. Semiquantitative analysis generated indices of D2 receptor availability for binding. There was no difference in striatal D2 receptor availability between the patient groups, both showing a similar degree of occupancy by antipsychotic medication compared to the control group. Thus, poor clinical response does not appear to be accounted for by differential blockade, or inadequate occupancy of striatal dopamine D2 receptors by antipsychotic medication.

Adult↗
PubMed1993

Genetic influences on eating attitudes in a normal female twin population.

The Eating Attitudes Test (EAT) and the Eating Disorder Inventory (EDI) were administered to a female volunteer twin population aged 18 to 45 years. Both members of 147 monozygotic (MZ) and 99 dizygotic (DZ) twin pairs completed the questionnaires. Thirty-five subjects scored over the cut-off point of the EAT-26. Interviews of these high-scoring twins and their co-twins identified three subjects with a past history of anorexia nervosa, and three others with a history of a partial syndrome. A heritability value of 41% was obtained for the overall EAT scores, while factor analysis produced a 'dieting' factor with a heritability of 42%. The 'body dissatisfaction' and 'drive for thinness' subscales of the EDI had heritability values of 52 and 44% respectively. The genetic contribution to the variance in body mass index in the twin sample was estimated at 64%. For all the above phenotypes, an environmental model of transmission with heritability constrained to be zero, could be rejected. Conversely, we were unable to reject a purely additive genetic model with shared environmental variance constrained at zero, suggesting that family environment has little or no effect on the transmission of many of these traits.

Adolescent↗
PubMed1993

Long-term glycemic control and the rate of progression of early diabetic kidney disease.

In this prospective study of 11.9 years duration (range 9 to 14), we examined the progression of albuminuria prior to and after the onset of microalbuminuria [albumin excretion rate (AER): 20 to 200 micrograms/minute]. Glycated hemoglobin (HbA1), AER and blood pressure were measured every six months. Twenty-two (13 type I, 9 type II) patients were identified in whom AER increased progressively (progressors). These patients were compared with 22 others matched for age, duration and type of diabetes in whom AER did not change significantly during the study period (non-progressors). In the progressors, the rate of increase in AER correlated with mean HbA1 for the study period in patients with type I (r = 0.68, P < 0.01) and type II diabetes (r = 0.71, P < 0.05). Furthermore, AER began increasing well before the conventional 20 micrograms/minute threshold of microalbuminuria had been reached and within the first five years of diagnosis of type I diabetes. We conclude that in predisposed diabetic patients, long-term glycemic control is correlated with the rate of development of early renal abnormalities. Repeated measurements of AER from the time of diagnosis may be useful in the early detection of patients who will develop microalbuminuria and ultimately overt diabetic nephropathy.

Adolescent↗
PubMed1993

Schizophrenia: a neurodevelopmental perspective.

The role of aberrant neurodevelopment in the etiology of schizophrenia is reviewed in light of recent neuropathologic, neurochemical, and neuroimaging evidence of cerebral abnormalities in schizophrenic patients. There may exist some genetic defect in the control of brain development. Clinical epidemiologic surveys highlight the importance of obstetric complications, and prenatal exposure to influenza epidemics in contributing to these abnormalities. It is suggested that such environmental hazards and aberrations in the control of early brain development produce the neuronal phenotype that manifests as schizophrenia with early age of onset of symptoms associated with soft neurologic signs and is more common in young males.

Brain Chemistry↗
PubMed1993

The epidemiology of late-onset schizophrenia.

We report an analysis of a large catchment area sample of patients with nonaffective functional psychoses presenting across all ages at onset. The male:female ratio was 1.56:1 in the 16-25-year age group; it reached unity around 30 years of age and declined to 0.38:1 in the 66-75-year group. Contrary to expectation, a higher proportion of patients with onset of illness after 45 years than of younger onset patients fulfilled DSM-III-R criteria for schizophrenia (52% vs. 38%). The distribution by age at onset was much the same irrespective of stringency of diagnosis. The highest rates were in the 16-25-year age group, with a slight second peak in the 46-55-year group, and a third (more emphatic) peak in the over-65 group. A closer analysis of demographic and phenomenologic variables revealed distinct differences between patients with early and late (after 44 years) onset of illness.

Adolescent↗
PubMed1993

ADH and ALDH genotype profiles in Caucasians with alcohol-related problems and controls.

Eighty-two Caucasian patients receiving treatment for alcohol-related problems and eighty four controls were DNA typed for variants in the alcohol dehydrogenase (ADH2 and ADH3) and mitochondrial aldehyde dehydrogenase (ALDH2) gene loci. No association was observed between individual, or combined gene frequencies and the presence of alcohol-related problems.

Adult↗
PubMed1993

A case-control study of family history and cerebral cortical abnormalities in schizophrenia.

The relationship between family history of psychosis and cortical sulcal widening on CT scans was investigated. Forty-two schizophrenic subjects with a positive family history were individually matched to 42 schizophrenics with no documented family history and 42 healthy controls. Abnormally wide sulci, as defined on the basis of the normal control data, were significantly more common in the family history negative group (9/42) than in the family history positive group (1/42) or the controls (2/36). No significant correlation was found between cerebral cortical ratings and ventricular size.

Case-Control Studies↗
PubMed1993

Does prenatal influenza divert susceptible females from later affective psychosis to schizophrenia?

We examined the relationship between influenza epidemics and the number of schizophrenic and affective psychotic individuals born each month between 1938 and 1965 in England and Wales. Increased death rates from influenza were followed 5 months later by a significant increase in schizophrenic births and a concurrent fall in the number of births of affective psychotic individuals. When the sexes were examined separately, both the positive effect of influenza on schizophrenic births and its negative effect on affective psychotic births were evident for females but not for males. Furthermore, during February to June in high influenza years, there was an inverse relationship between the number of female schizophrenic and affective psychotic births. The explanation for these surprising findings may be that prenatal exposure to influenza impairs the neurodevelopment of some females with a predisposition to affective psychosis, in such a way that their later illness shows schizophrenic rather than affective features.

Adult↗
PubMed1993

Premorbid social underachievement in schizophrenia. Results from the Camberwell Collaborative Psychosis Study.

In an investigation of the timing and precursors of social decline in schizophrenia and affective psychosis, 195 subjects from the Camberwell Collaborative Psychosis Study were currently of lower social class than were their fathers. A comparison between father's occupation and proband's best premorbid occupational level indicated underachievement confined to DSM-III schizophrenia, there being no such effect in affective psychosis. Decline in social status following onset of psychosis, analysed by comparing best premorbid occupation with current occupation, was marked in both schizophrenia and affective psychosis, indicating a non-specific effect. Schizophrenic patients who failed to achieve their fathers' social status had poorer educational qualifications than those who equalled or bettered their paternal social class, despite similar premorbid IQ (NART) scores and age at onset of psychosis. These results indicate that schizophrenia may be manifest before the onset of psychosis, and lend weight to the notion of a developmental origin to this disorder.

Adolescent↗
PubMed1993

Sex and schizophrenia: effects of diagnostic stringency, and associations with and premorbid variables.

In a case-record study, all first-contact patients with non-affective functional psychosis from a defined area over 20 years were diagnosed according to operational criteria of varying stringency and emphasis, and incidence rates for each set of criteria determined by sex and age at onset; data on premorbid adjustment were also analysed by sex and age at onset. The overall first-contact incidence of non-affective functional psychosis was approximately equal in men and women; however, the ratio of male to female incidence rates rose progressively when RDC (1.2), DSM-III-R (1.3), DSM-III (2.2), and Feighner (2.5) criteria for schizophrenia were applied. Schizophrenia was most common in young males and least common in older males, with females occupying an intermediate position. Schizophrenia in young males, particularly when stringently defined, was especially likely to be associated with single status, poor work and social adjustment, and premorbid personality disorder. The results suggest that schizophrenia syndrome is heterogeneous, and young males are especially prone to a severe neurodevelopmental form of illness associated with premorbid deficits.

Adult↗
PubMed1993

Schizophrenia: prenatal influenza and autoimmunity.

The schizophrenic syndrome may represent a stereotyped response by the developing brain to various insults, including micro-organisms. We review studies that have examined the association between schizophrenia and infectious agents, and examine the current evidence for the hypothesis that exposure to influenza during fetal life increases the risk of later schizophrenia. A prenatal autoimmune basis for some cases of schizophrenia is proposed.

Autoimmune Diseases↗