Biomedical subjects

R M Murray

Publications and source records attributed to R M Murray.

At least 163 records · Page 9Linked to original sources

PubMed1997

Schizophrenia with onset at the extremes of adult life.

OBJECTIVE: To define the epidemiology, phenomenology, premorbid and risk factors in patients with the first manifestation of a schizophrenia-like illness after the age of 60 years, and compare them with patients with an onset before the age of 25 years. DESIGN/SETTING/SUBJECTS: All contacts for a non-affective psychotic illness across all ages of onset were ascertained through a psychiatric case register; patients were rediagnosed according to operationalized criteria for psychotic illness, and those with a very early and very late onset compared. MAIN OUTCOMES MEASURES: Phenomenological, premorbid and aetiological parameters were compared in the two groups, using risk ratios and 95% confidence intervals. RESULTS: Very late onset patients (N = 72) were, compared to their very early onset counterparts (N = 192), more likely to be female, have good premorbid functioning and development history, and to exhibit persecutory delusions and hallucinations; they were less likely to have negative schizophrenic symptoms, to have a positive family history of schizophrenia, or have suffered pregnancy or birth complications. CONCLUSIONS: The results highlight premorbid, aetiological and phenomenological differences between patients with the onset of a schizophrenia-like illness at the extremes of adult life, and suggest it is premature to consider the two groups to be merely different manifestations of the same illness.

Adult↗

PubMed1996

Linkage studies in bipolar affective disorder with markers on chromosome 21.

Straub et al. (1994: Nature Genet. 8. 291-296) have suggested that a susceptibility gene for bipolar affective disorder is located at chromosome 21q22.3, on the basis of linkage analysis in one large family. This result has been supported by Gurling et al. (1995: Nature Genet. 10, 8-9) who also found some evidence for linkage to this region under locus heterogeneity. In order to investigate the validity of these results and to estimate how broadly applicable they are, we performed a linkage study between bipolar affective disorder and two DNA markers (D21S171 and PFKL) from 21q22.3 using 60 bipolar pedigrees from three European centres and Brazil. The most positive result obtained was a maximised admixture lod score of 1.2 for the marker PFKI, under the assumption of locus heterogeneity, dominant transmission and a diagnostic classification which included recurrent unipolar depression. However, since lod scores obtained for both markers were substantially negative overall, we conclude that there is no common major gene for bipolar affective disorder at 21q22.3. It remains possible that a gene of major effect in this region operates in a minority of families.

Bipolar Disorder↗

PubMed1996

Relationship between in utero exposure to influenza epidemics and risk of schizophrenia in Denmark.

Several recent epidemiological studies suggest that exposure to influenza during gestation increases the risk of later developing schizophrenia. Inconsistency exists, however, particularly in studies that have examined the relationship between the prevalence of influenza and the monthly number of schizophrenic births, over many years. Our sample (N = 9462) was obtained from a Danish computerized case register, and consisted of schizophrenia patients born between 1915 and 1970, and first admitted to Danish psychiatric hospitals between 1971 and 1991. The study sample was chosen to represent "incidence cases" to allow us to calculate the population attributable risk fraction (PAF). The temporal correlation of fluctuations in the prevalence of influenza and fluctuations in the monthly number of preschizophrenic births was examined using a Poisson regression analysis. Exposure to influenza 4 months prior to birth (i.e., about the 6th month of gestation) was significantly associated with an increased risk of later schizophrenia, especially for narrowly defined schizophrenia. The number of schizophrenic births was found to have risen by 12% (95% confidence interval: 1-24%) for every 100,000 cases of influenza in the 4th month before birth. Our model indicates the PAF to be 1.4%, that is, only 1.4% of the whole schizophrenic sample is attributed to prenatal exposure to influenza. Although maternal exposure to influenza during midgestation is not a major risk factor for schizophrenia, the elucidation of its causal mechanism may open the avenue to understanding the neurodevelopmental origins of the disease.

Adult↗

PubMed1996

A linkage study of schizophrenia with DNA markers from chromosome 8p21-p22 in 25 multiplex families.

Two recent genome-wide searches for linkage (Lasseter et al., 1994; Moises et al., 1995) suggested that a susceptibility gene for schizophrenia might be located at chromosome 8p21-p22. We attempted to replicate these findings by performing a linkage study of schizophrenia with four DNA markers from this region using 25 multiply affected families. Neither the lod score method nor non-prametric extended sib-pair analysis yielded any evidence for linkage, even under the assumption of locus heterogeneity. We conclude that there is unlikely to be a major gene in the 8p21-p22 region which confers susceptibility to schizophrenia in our set of families. However we cannot exclude the possibility of a major gene present in other families, or of a susceptibility gene with a moderate but widespread effect which we cannot detect.

Autoradiography↗

PubMed1996

Relationship of birth season to clinical features, family history, and obstetric complication in schizophrenia.

Birth in late winter and spring has been consistently shown to be a risk factor of schizophrenia. The relationship of late winter/spring birth to clinical characteristics and other putative risk factors, such as family history and obstetric complications, may provide clues to etiology. Data relating to season of birth, clinical features, family history, and obstetric complications were analyzed for 192 patients with schizophrenia as defined by Research Diagnostic Criteria (including schizoaffective disorder). There was no significant association of season of birth with any of the psychopathological dimensions nor was there a significant association with obstetric variables or family history. However, winter-born schizophrenic patients who had a negative family history were more likely to have a history of obstetric complications. These findings suggest that obstetric complications associated with schizophrenia are perhaps the result of some seasonal risk factors important in those without a family history of the disorder.

Adolescent↗

PubMed1996

The serotonin transporter is a potential susceptibility factor for bipolar affective disorder.

The serotonin transporter is a strong candidate for aetiological involvement in affective disorders and psychosis. We analysed a VNTR in intron 2 of the human serotonin transporter gene (hSERT) for allelic association with bipolar affective disorder, unipolar depression and schizophrenia. An increased frequency of allele 12 of the VNTR was observed in subjects with bipolar affective disorder (n = 191; chi 2 p = 0.00048 by allele) but not unipolar depression (n = 86; chi 2 p = 0.18, ns) or schizophrenia (n = 129; chi 2 p = 0.08, ns), although a trend towards an excess of allele 12 was observed for the latter. There was also a significant difference in the frequency of allele 12 between bipolar affective disorder and unipolar depression (p = 0.0087). The relative risk for bipolar affective disorder with respect to allele 12 was 1.84 (95% CI 0.97-3.56) for heterozygotes, and 3.10 (95% CI 1.60-6.07) for homozygotes, with evidence for a gene-dosage effect. Because allele 12 is common in the population, the attributable risk is 50.8% (95% CI 14.5%-73.3%). We hypothesize that either the VNTR affects regulation of expression of hSERT at the transcriptional level or it is in linkage disequilibrium with another functional polymorphism in the gene, and this results in an increased risk for the development of bipolar affective disorder.

Alleles↗

PubMed1996

Autoimmune diseases in the pedigrees of schizophrenic and control subjects.

Autoimmune diseases aggregate in individuals and within pedigrees, and it has been postulated that autoimmune mechanisms may account for a proportion of schizophrenia. Structured questionnaires were used to interview the mothers of 121 DSM-III-R schizophrenic patients and the mothers of 116 controls in order to determine the prevalence of schizophrenia and of autoimmune diseases in their pedigrees. Patients with a schizophrenic first degree relative were significantly more likely to also have a parent or sibling with an autoimmune disease (60% vs. 20%, OR = 6.1, 95% CI = 2.3-6.5, p = 0.0003). A significant excess of insulin dependent diabetes mellitus (IDDM) was present in the parents and siblings of schizophrenic patients (OR = 9.65, 95% CI = 1.3-429.2, p = 0.009). These findings suggest that autoimmune mechanisms may play a role in the aetiology of schizophrenia, particularly familial schizophrenia. Associations have been established between autoimmune diseases and the HLA encoding genes of the major histocompatibility complex on chromosome six, and it may be that some of the genetic liability to schizophrenia involves these genes.

Adult↗

PubMed1996

Plasma homovanillic acid profile at different phases of the ovulatory cycle in healthy women.

Variation in some central monoamine levels has been shown to be influenced by cyclical changes in gonadal hormones in women; however, there is less consensus about how the human menstrual cycle affects turnover of dopamine. Fluctuations in plasma homovanillic acid (HVA) are thought to represent changes in central dopamine turnover and activity and, some suggest, may be used to monitor the response to neuroleptic medication or to predict those more likely to respond to antipsychotic treatment. We have measured the effect of fluctuations in gonadal hormones on the level of plasma HVA at four consecutive points across the menstrual cycles of 30 healthy volunteers. We found no significant change in plasma HVA over the cycle and there was no correlation with either estradiol or progesterone levels. This study suggests that peripheral markers of central dopamine function do not change significantly with physiological changes in gonadal hormones levels.

Adult↗

PubMed1996

The incidence of mania: time trends in relation to gender and ethnicity.

In order to investigate conflicting reports about possible changes in the incidence of mania, we established first contact rates for mania in the defined area of Camberwell between 1965 and 1984. There was some evidence for an increase in the first contact rate of mania, especially in females. This rise may be associated with the influx into Camberwell of individuals of Afro-Caribbean origin who showed significantly higher rates than the white group [adjusted rate ratio 3.1; 95% confidence interval (CI) 1.4-6.9] and more often displayed mixed manic and schizophrenic symptomatology (risk ratio 2.2; 95% CI 1.1-4.3). We conclude that the incidence of mania has not decreased and may actually have increased. High rates of mental illness among members of ethnic minorities are not specific to schizophrenia, suggesting that a risk factor common to both manic and schizophrenic illness is more prevalent among these groups.

Adolescent↗

PubMed1996

Parasuicide in Camberwell-ethnic differences.

Over a 6-month period, this study compared referral rates amongst different ethnic groups to an inner city deliberate self-harm (DSH) team, using native British (in the remainder of this paper referred to as whites) as standard and age-standardized referral ratios as the measure of effect. Indian female rates were 2.6 times those of whites. Amongst United Kingdom born Indian females, (crude) rates were 7.8 times those of United Kingdom born white females. Unemployment was associated with a 9 times increased referral rate amongst whites and a 3 times increased referral rate amongst ethnic minorities, suggesting that ethnicity modifies the association between unemployment and DSH rates. This study suggested that ethnic minority and white DSH differ in important respects; DSH teams serving multicultural communities may need to develop special expertise to meet the needs of minority ethnic groups.

Adolescent↗

PubMed1996

Reduced prolactin and cortisol responses to d-fenfluramine in depressed compared to healthy matched control subjects.

d-Fenfluramine, a specific 5-HT releasing agent without the catecholamine effects of d,l-fenfluramine, was used as a neuroendocrine challenge in 19 subjects with major depression and 19 healthy controls. Patients and controls were matched for age, sex, weight, and menstrual status. 5-HT-mediated prolactin and cortisol responses were both significantly attenuated in the depressed group. Patients with a history of a suicide attempt had lower cortisol responses than those without. Peak cortisol responses were inversely related to baseline cortisol levels. There were also significant relationships between hormone responses and both age and weight. These findings replicate those of a previous study using this challenge and reiterate the role of reduced 5-HT activity in suicide. They also reinforce the need for careful matching in neuroendocrine studies.

Adult↗

PubMed1996

Family history of autoimmune diseases in psychosis.

The mothers of 101 psychotic patients and 116 normal controls were interviewed using a semi-structured questionnaire designed to determine the presence or absence of autoimmune disorders in first degree relatives of the probands. Thyrotoxicosis and insulin-dependent diabetes mellitus were significantly more common in the relatives of the psychotic patients than in the control relatives; in particular thyrotoxicosis was more frequent in the mothers of patients (11%) than the mothers of controls (2.6%). None of the examined characteristics of the patients, including RDC-diagnosis, family history of psychosis, age at onset of psychosis and winter birth, was predictive of thyrotoxicosis and insulin-dependent diabetes mellitus in relatives.

Adolescent↗

PubMed1996

Do obstetric complications cause the earlier age at onset in male than female schizophrenics?

We compared the age at onset of 184 patients with functional psychoses with and without a history of obstetric complications (OCs) as defined by the scale of Lewis et al. (1989). OCs had no significant influence on the age at onset in those patients who had affective psychoses or were non-white. There were 73 white patients with a DSM-III-R diagnosis of schizophrenia. The mean age at onset of those 25 who had a history of at least one definite OC was 2.6 years earlier than that of the 48 patients with no history of OCs. This effect was entirely due to the male patients with histories of OCs who had, on average, a 3.5 years earlier age at onset. There were no gender differences in age at onset among schizophrenics without a history of OCs. We suggest that a subgroup of male patients with a history of OCs is responsible for the earlier age at onset in male compared to female schizophrenics.

Black or African American↗

PubMed1996

Further exploration of a latent class typology of schizophrenia.

We previously derived a typology of schizophrenia from a latent class analysis of 447 first-contact non-affective functional psychotic patients from a defined catchment area. Here, using the same sample, we show that the three subtypes, 'neurodevelopmental' (Type A), 'paranoid' (Type B) and 'schizoaffective' (Type C) have different premorbid, phenomenological and treatment response characteristics. A canonical variate analysis of the three subtypes achieved partial separation between the first two subtypes, but the 'schizoaffective' type was less distinct.

Adult↗

PubMed1996

Small head circumference at birth in schizophrenia.

The growing evidence for neurodevelopmental basis to schizophrenia has focused attention on the prenatal development of individuals who later develop the illness. Several previous studies have shown reduced birth weight (BW) in schizophrenics and one recently reported smaller birth head circumference (BHC). The current study compared 67 DSM-III-R schizophrenics and a general population group of 1640, using information obtained from contemporaneous birth records. When gestational age and gender were controlled for, no significant difference was found in BW between the schizophrenics and the comparison population. However, the preschizophrenics showed significantly smaller BHC for gestational age, suggestive of slower fetal brain growth.

Adult↗

PubMed1996

Functional anatomy of inner speech and auditory verbal imagery.

The neural correlates of inner speech and of auditory verbal imagery were examined in normal volunteers, using positron emission tomography (PET). Subjects were shown single words which they used to generate short, stereotyped sentences without speaking. In an inner speech task, sentences were silently articulated, while in an auditory verbal imagery condition, subjects imagined sentences being spoken to them in an another person's voice. Inner speech was associated with increased activity in the left inferior frontal gyrus. Auditory verbal imagery was associated with increases in the same region, and in the left premotor cortex, the supplementary motor area and the left temporal cortex. The data suggest that the silent articulation of sentences involves activity in an area concerned with speech generation, while imagining speech is associated with additional activity in regions associated with speech perception.

Adult↗

PubMed1996

Psychotic illness in ethnic minorities: clarification from the 1991 census.

Age and sex-adjusted first admission rates for operationally-defined schizophrenia and other non-affective psychosis in different ethnic groups were calculated over the period 1988-1992 in a defined catchment area in South London. Standardized rates for schizophrenia, corrected for age- and gender-related under-reporting in the 1991 census and a 20% underestimate of the size of the ethnic minority populations in the area, were not only higher in the Afro-Caribbean group (SMR: 3.1; 95% C1:2.0-4.7), but also in the African group (SMR: 4.2; 95% C1: 2.8-6.2). It was further found that higher rates were not specific to schizophrenia. These findings suggest that some common factor associated with ethnic minority membership is important in producing an excess of psychotic illness.

Adolescent↗

PubMed1996

Age-period-cohort analysis of the incidence of schizophrenia in Scotland.

Studies examining a possible decline in the incidence of schizophrenia over the last two to three decades have paid little attention to the possible role of birth cohort effects. We collected data on a Scottish national sample of all schizophrenic patients, admitted for the first time between 1966 and 1990 (N = 11348; male = 6301). In an Age-Period-Cohort analysis, a full model, incorporating three factors, had a substantially better fit to the data than other models (especially, an Age-Period model), providing clear evidence of the presence of a cohort effect. After adjustment for the effects of age and period, there was a 55% reduction in the rate of schizophrenia in men and a 39% fall in the number of women over the 50-year birth period from 1923 to 1973. The marked decline in the first admission rates observed in Scotland cannot, however, be attributed entirely to this cohort effect. Rather, a greater proportion of the declining first admission rates (88%) is ascribed to the period effect (i.e. artefactual or causally related cross-sectional effects). Nevertheless, the fact that a birth-cohort effect accounts for part of the declining incidence, suggests that causal environmental factors operating early in life have been diminishing in intensity.

Adolescent↗