Cities, winter birth, and schizophrenia.
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Female↗
Biomedical subjects
R M Murray
Publications and source records attributed to R M Murray.
Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia.
According to the dopamine hypothesis of schizophrenia, D2 receptor blockade is essential for a drug to have antipsychotic potency, and antipsychotic potency and D2 blockade are linearly related in vitro. To test this assumption in vivo, we have compared clinical response with central D2 dopamine receptor availability measured by 123I-iodobenzamide single photon emission tomography in two groups of schizophrenic patients. 6 patients were on typical antipsychotic drugs and 10 were on the atypical antipsychotic clozapine, including 2 patients from the first group. The patients on typical antipsychotics showed poor therapeutic response despite D2 receptor blockade. Significant clinical improvement occurred in all patients on clozapine, but at a lower level of D2 blockade by the drug. These findings suggest a more complex relation between D2 blockade and clinical efficacy than was previously thought.
Adult↗
Genes, viruses and neurodevelopmental schizophrenia.
Recent neuroimaging and neuropathological studies suggest a developmental origin for schizophrenia. Some cases may, therefore, be caused by a genetic defect in the specification of brain development. Early environmental hazards such as obstetric complications, and maternal exposure during pregnancy to influenza epidemics, have also been found to increase the risk of later schizophrenia. The relationship between the prevalence of influenza and birth date has been found more consistently for female than male schizophrenics. Female schizophrenia is also associated with a higher risk of schizophrenia in first degree relatives. This raises the question of whether part of the genetic predisposition to schizophrenia may comprise an abnormal reaction to maternal influenza.
Brain Damage, Chronic↗
A developmental perspective on the pathology and neurochemistry of the temporal lobe in schizophrenia.
Neuropathological, neuroimaging, clinical and epidemiological evidence suggests that many cases of schizophrenia are developmental in origin. Dysplastic changes in the medial temporal lobes appear to be of particular importance. However, research implicating a neurodevelopmental origin for schizophrenia has proceeded largely in isolation from knowledge concerning the neurochemistry of the disorder. This paper attempts to integrate these disparate lines of research, and examines the role of trophic mechanisms in the formation of the hippocampus. Those neurotransmitters which have been most consistently found to be abnormal in the temporal lobes of schizophrenics (excitatory amino acids and CCK), are involved in the control of hippocampal development. We suggest that these neurotransmitter findings are the residue of abnormalities in their role as trophic factors in foetal or neonatal life, and that the latter contribute to the developmental aberrations considered fundamental to schizophrenia.
Adult↗
A neurodevelopmental approach to the classification of schizophrenia.
The conventional distinction between schizophrenia and manic depression has received little objective support from recent studies of phenomenology, outcome, or familial homotypy. Instead, much clinical, epidemiological, and morphological evidence suggests that within the broad range of Schneiderian schizophrenia there exists one form (congenital schizophrenia) that can be distinguished from other types, the manifestations of which are confined to adult life. We hypothesize that congenital schizophrenia is a consequence of aberrant brain development during fetal and neonatal life. Such patients show structural brain changes and cognitive impairment, and in their male predominance, early onset, and poor outcome, they reflect Kraepelin's original description of dementia praecox. We contend that adult-onset schizophrenia is itself heterogeneous. One important component is a relapsing and remitting disorder that is more frequent in females than in males, exhibits positive but not negative symptoms, and has much in common etiologically with affective psychosis. There also exists a very-late-onset group in which degenerative brain disorder is implicated.
Bipolar Disorder↗
Cortical volume reduction in schizophrenia using MRI.
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Cerebral Cortex↗
Schizophrenia following pre-natal exposure to influenza epidemics between 1939 and 1960.
We examined the relationship between the dates of births of schizophrenic patients admitted to hospitals for the first time in England and Wales between 1970 and 1979, and the occurrence of influenza epidemics between 1939 and 1960. Our results indicate that exposure to influenza epidemics between the third and seventh month of gestation is associated with schizophrenia in adult life. The hypothesis that maternal viral infection is an important cause of schizophrenia can explain many aspects of the enigmatic epidemiology of the condition.
Adult↗
The relationship of environmental temperature to the incidence and outcome of schizophrenia.
This paper presents new analyses of data from two multicentre studies carried out by the WHO. The morbid risk of developing schizophrenia, as broadly defined by the Determinants of Outcome Study, was positively related to the mean daily range of temperature. The outcome of schizophrenia, as determined by the International Pilot Study of Schizophrenia, was found to be positively related to mean environmental temperature. Further studies are needed to examine the relationship of geographical and climatic variables to schizophrenia in order to complement what is already known about the role of sociocultural factors.
Adolescent↗
Circulating PTH and PTHrP levels before and after treatment of tumor induced hypercalcemia with Pamidronate Disodium (APD).
The effect of lowering ionized calcium on circulating parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) was assessed in twenty patients with hypercalcemia of malignancy following treatment with Pamidronate Disodium. Ionized calcium levels fell rapidly in all treated patients. PTH concentrations were initially suppressed below normal in 18 patients, but rose from 0.48 +/- 0.42 pmol/L to 3.63 +/- 3.13 pmol/L (p less than 0.01) after treatment, reaching higher than normal values in some patients even in the presence of persistent hypercalcemia. PTHrP concentrations did not change significantly after treatment. These findings are consistent with an increased sensitivity of parathyroid tissue to changes in ionized calcium following prolonged exposure to hypercalcemia. Regulation of tumor secretion of PTHrP by calcium was not apparent within the range of calcium concentrations in this study.
Calcium↗
Schizophrenia and neurodevelopment.
Schizophrenia is characterised by the psychotic symptoms of hallucinations and delusions, accompanied by variable degrees of loss of insight. Whilst there is heterogeneity in the clinical profile, and presumably in the pathogenesis of what is currently called 'schizophrenia', it has become absolutely clear over the past decade that schizophrenic symptoms are consequent upon serious brain dysfunction. This new perspective has laid to rest a variety of 'crazy' theories, including the notion that mental illness was a myth, or that schizophrenia could be caused by faulty child rearing. The use of dopamine-blocking drugs has led to an improvement in symptom control, and diminished the need for prolonged hospital stays. It was hoped that the clear relationship between antipsychotic activity and dopamine blockade would help to elucidate the pathophysiology of schizophrenia, but to date no consistent abnormalities of the dopamine system have been found. Nevertheless, we have learned much about both the aetiology of schizophrenia and the origin of particular symptoms. Much of this has stemmed from increased understanding of the brain abnormalities underlying the disorder.
Adolescent↗
The familial transmission of alcoholism.
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Alcoholism↗
Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic.
The birth dates of schizophrenic inpatients in eight health regions in England and Wales were reviewed for any effect of the 1957 A2 influenza epidemic. 5 months after the peak infection prevalence, the number of births of individuals who later developed schizophrenia was 88% higher than the average number of such births in the corresponding periods of the 2 previous and the next 2 years. This finding is in accordance with a study from Helsinki and with clinical and neuropathological evidence of aberrant fetal brain development in the pathogenesis of schizophrenia.
Adult↗
Do different subtypes of hospitalized depressives have different long-term outcomes?
In 1965 and 1966, a consecutive series of 89 patients admitted to the Maudsley Hospital, London, England, with depressive illness were interviewed, and various personality questionnaires were administered; 18 years later, they were followed up and reinterviewed. Then, on the basis of the index data alone and without knowledge of their eventual outcomes, they were subtyped according to the Research Diagnostic Criteria, DSM-III, Newcastle Index, and Present State Examination diagnostic criteria. Patients who met the various subtype criteria at index were compared with those who did not in respect to their long-term outcome. Subtyping had little prognostic utility except for three endogenous criteria that were all associated with poor outcome. In addition, DSM-III melancholia had an interactive effect with the personality measure neuroticism, so that those melancholic patients who at index had high neuroticism scores were very likely to have a poor outcome.
Adolescent↗
Fetal brain development and later schizophrenia.
Computed tomography and magnetic resonance imaging studies have shown cerebral ventricular enlargement and a decreased volume of temporal lobe structures in a proportion of schizophrenic patients. Neuropathological investigations confirm these findings and also show diminished volume of the hippocampus and abnormal pre-alpha cell clusters in the parahippocampal gyrus. Compared with controls, schizophrenic patients are more likely to have minor physical anomalies, to have a history of obstetric complications, and to have been born in the late winter. Together the evidence regarding structural brain abnormalities and epidemiology suggests that a significant proportion of cases of schizophrenia have their origins in fetal or neonatal life. The mechanisms involved in the aberrant neurodevelopment remain obscure but some impairment of neuronal migration is an appealing hypothesis.
Brain↗
Tyrosine hydroxylase polymorphisms and bipolar affective disorder.
A reported genetic association between bipolar affective disorder and DNA polymorphisms at the tyrosine hydroxylase gene is not confirmed by the present study. The combined allele frequencies in the patients, from studies published to date, are significantly different from the frequencies in the controls for the TY7/BglII polymorphism.
Alleles↗
Can future suicidal behaviour in depressed patients be predicted?
The determinants of suicidal behaviour over 18 years were examined in a series of 89 depressed in-patients, using index data on clinical features, personality, and history of past loss. Seven variables were selected from univariate analyses and their relationship with (1) the presence or absence, (2) frequency, (3) intent, and (4) medical threat of suicidal behaviour was then explored by generalised linear modelling. Severe dysphoria, past alcoholism and chronic physical illness were most predictive of suicidal attempting; however, different variables predicted the frequency, degree of intent and severity of medical threat of subsequent suicidal attempts. Thus, our results suggest that different aspects of long-term suicidal behaviour have different determinants.
Adolescent↗
The neurodevelopmental basis of sex differences in schizophrenia.
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Brain Damage, Chronic↗
Does recurrent depression lead to a change in neuroticism?
The hypothesis that recurrent or chronic depressive illness produces a long-term change in neuroticism was examined in a sample (N = 34) from a consecutive series of 89 depressed patients admitted to the Maudsley Hospital in 1965/6. The Eysenck Personality Inventory (EPI) was administered at the time of the index illness both when the patients were depressed and on recovery, and then again at follow-up 18 years later. The change in the neuroticism (N) score over the 18-year-period was compared in good and poor outcome groups defined variously by a global rating of outcome, frequency of episodes, extent of subsequent hospitalization and the presence or absence of subsequent chronicity. The mean N score for the sample as a whole did not change significantly over the 18 years, and no differential change in the N score was observed between any of the good and poor outcome groups. Thus, the hypothesis was not supported.
Adolescent↗