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Biomedical subjects

R M Murray

Publications and source records attributed to R M Murray.

At least 217 records · Page 12Linked to original sources
PubMed1994

Growth hormone responses to pyridostigmine in schizophrenia: evidence for cholinergic dysfunction.

The hypothesis that increased central cholinergic neurotransmitter function may be present in schizophrenic illness and may underlie negative symptoms was tested using a neuroendocrine challenge approach. The cholinergic challenge used was the anticholinesterase pyridostigmine, thought to cause the release of growth hormone (GH) from the anterior pituitary by diminishing inhibitory somatostatin tone. Eleven patients, six neuroleptic-naive and five neuroleptic-free, satisfying DSM-III-R criteria for schizophrenia and 11 matched controls took part. Subjects received pyridostigmine (120 mg orally) and blood was sampled at 0, 60, 90, 120, and 180 min for GH estimation. Peak GH responses were significantly increased in the schizophrenic group compared to controls. There was no relationship between individual peak GH values and negative symptom ratings (Scale for the Assessment of Negative Symptoms). Neither could a relationship be established between other aspects of psychopathology or dyskinesias and GH responses. An increased pyridostigmine/GH response is also found in affective disorders and could be related to nonspecific symptoms common to all these diagnostic groups. This study suggests that schizophrenia may be associated with increased cholinergic neurotransmitter function but the relationship between this cholinergic dysfunction and schizophrenia may involve psychopathology not specific to schizophrenia.

Adult↗
PubMed1994

Failure to find linkage between a functional polymorphism in the dopamine D4 receptor gene and schizophrenia.

We report the results of a linkage study in 24 families multiply affected with schizophrenia using a polymorphic DNA sequence encoding the third cytoplasmic loop of the dopamine D4 receptor. Two-point LOD score analyses with a range of single gene models ranging from near dominant to near recessive revealed no evidence for linkage. In addition, we examined the data by non-parametric sib-pair analysis and found no excess sharing of alleles between affected sib-pairs. We therefore conclude that mutations within the dopamine D4 receptor gene do not have a major aetiological role in schizophrenia in our collection of pedigrees.

Alleles↗
PubMed1994

Genetic mapping of 14 short tandem repeat polymorphisms on human chromosome 22.

We have constructed a linkage map of 14 short tandem repeat polymorphisms (11 with heterozygosity > 70%) on the long arm of human chromosome 22 using 23 non-CEPH pedigrees. Twelve of the markers could be positioned uniquely with a likelihood of at least 1,000:1, and distributed at an average distance of 6.62 cM (range 1.5-16.1 cM). The sex-combined map covers a total of 79.6 cM, the female map 93.2 cM and the male map 64.6 cM. Based on comparisons between physical maps and other genetic maps, we estimate that our map covers 70%-80% of the chromosome. The map integrates markers from previous genetic maps and uniquely positions one marker (D22S307). Data from physical mapping on the location of four genetic markers correlates well with our linkage map, and provides information on an additional marker (D22S315). This map will facilitate high resolution mapping of additional polymorphic loci and disease genes on chromosome 22, and act as a reference for building and verifying physical maps.

Chromosome Mapping↗
PubMed1994

Schizophrenia and the influenza epidemics of 1954, 1957 and 1959: a southern hemisphere study.

The dates of birth of patients who were admitted with schizophrenia to public hospitals in Queensland between the years 1972 and 1988 were examined for associations between risk of schizophrenia and influenza epidemics. The hypothesis that infants born between four and six months after an influenza epidemic onset have increased risk of schizophrenia was examined for the 1954, 1957 and 1959 epidemics. After the 1954 epidemic there was a significant excess of male schizophrenia births four months after the onset of the epidemic. In 1957, there was a significant excess of female schizophrenia births in the fifth month after the onset of the epidemic. The 1959 epidemic was not associated with any significant excess.

Adult↗
PubMed1994

Cannabis and acute psychosis.

The Present State Examination was used to assess the psychopathology of 23 psychotic patients who were cannabis positive on urinary screening, and 46 matched drug-free controls. Cases and controls were indistinguishable in terms of psychopathology, DSMIII diagnoses, onset of recent illness, the proportion of first admissions, ethnicity, and socio-economic class, differing only in their histories of substance use. These data suggest that psychosis which develops or recurs in the context of cannabis use does not have a characteristic psychopathology or mode of onset, and is not restricted to a particular ethnic or socio-demographic group. There is thus little evidence to support the validity of 'cannabis psychosis' as a diagnostic entity.

Acute Disease↗
PubMed1994

The subtyping of schizophrenia in men and women: a latent class analysis.

Latent class analysis on an epidemiologically based series of 447 first contact patients with a broad diagnosis of schizophrenia revealed evidence for two subtypes: a 'neurodevelopmental' type characterized by early onset, poor pre-morbid social adjustment, restricted affect and a male:female ratio of 7:3; and a 'paranoid' type characterized by later onset, persecutory delusions and an almost equal sex ratio. A third 'schizoaffective' subtype, whose existence was less clear cut, was almost entirely confined to females and characterized by dysphoria and persecutory delusions, and had negligible familial risk of schizophrenia. The aetiological, biological and clinical significance of this typology remains to be tested.

Adolescent↗
PubMed1994

Volumetric MRI measurements in bipolars compared with schizophrenics and healthy controls.

Twenty-six patients with RDC bipolar disorder were compared with a previously reported group of 48 RDC schizophrenics and 34 healthy controls, using volumetric MRI measurements of cerebral, cortical and sulcal volumes. The bipolar group appeared no different from the controls, and both of these groups had significantly larger cerebral and cortical volumes than the schizophrenics. Our previous report of a significantly reduced cortical volume in the schizophrenic group, with a corresponding increase in the volume of sulcal fluid is, therefore, not a generalized feature of psychotic illness but may be more specific to schizophrenia.

Adult↗
PubMed1994

Cerebral ventricle dimensions as risk factors for schizophrenia and affective psychosis: an epidemiological approach to analysis.

A case-control study was undertaken of volumetric computerized tomographic scan measures in 216 consecutive admissions for functional psychosis and 67 healthy community controls. Odds ratio analysis demonstrated significant linear trends in the association between increasing lateral and third ventricle volumes, and both RDC schizophrenia (N = 121) and schizo-affective disorder (N = 41); cases were consistently associated with larger volumes than controls. There was an association between larger third, but not lateral, ventricle size in affective psychoses (N = 54). These associations were statistically independent of intracranial volume, sex, social class and ethnicity, factors which were significantly associated with ventricular measures in the controls. There was no evidence of a threshold corresponding to the notion of normal versus enlarged ventricles. Within the schizophrenia group, there were no large or significant associations between ventricle dimensions and age at onset, duration of illness or pre-morbid social functioning. Neither obstetric complications nor a family history of schizophrenia or other psychiatric illness was associated with large ventricles in these cases.

Adolescent↗
PubMed1994

Genetics of alcohol misuse.

Family, twin, and adoption studies demonstrate the genetic contribution to alcoholism but also confirm an important environmental component. The current rapid developments in genetics are providing candidate genes that can be assessed for a role in alcoholism, and a reported association with the DRD2 receptor gene is still being examined. Alcoholism is a complex behaviour which may be more amenable to genetic studies when dissected into its constituent parts. It is probable that multiple genes contribute to the genetic vulnerability to alcoholism and, hopefully, the effect of some will be of sufficient size so that they can be identified. Identification of these vulnerability factors will allow targeting of preventative efforts but before genetic tests are used clinically the full ethical implications will need to be considered carefully.

Adoption↗
PubMed1994

Twin concordance for congenital and adult-onset psychosis: a preliminary study of the validity of a novel classification of schizophrenia.

As a test of the hypothesis that the psychoses can be divided into congenital and adult-onset forms, we applied operational criteria for these two disorders to the case summaries of 24 monozygotic and 33 dizygotic schizophrenic twin pairs. Our results indicate that the reliability and validity of this novel classification are comparable with the best of the existing systems and support further investigation of the hypothesis.

Adult↗
PubMed1994

Prenatal exposure to influenza and the development of schizophrenia: is the effect confined to females?

The question of whether prenatal exposure to influenza epidemics is associated with an increased risk of later schizophrenia remains controversial. The authors examined this relationship, using data on the dates of birth and gender of 3,827 schizophrenic patients born in England and Wales between 1938 and 1965 and first admitted to hospitals in the 1980s, the numbers of live births between 1938 and 1965, and the numbers of deaths attributed to influenza between 1937 and 1965. The analysis showed that females, but not males, exposed to influenza epidemics 5 months before birth had a significantly greater rate of adult schizophrenia.

Adult↗
PubMed1994

D2 dopamine receptor binding in the basal ganglia of antipsychotic-free schizophrenic patients. An 123I-IBZM single photon emission computerised tomography study.

We used SPECT to examine striatal D2 receptor binding in 20 antipsychotic-free DSM-III-R schizophrenic patients and 20 age- and sex-matched normal controls. Dynamic single-slice SPECT, at a slice chosen to include the basal ganglia, began immediately following intravenous injection of 185 MBq of 123I-IBZM. A semiquantitative approach was used to generate indices of specific D2 receptor binding in the basal ganglia. There was no overall elevation of D2 receptor binding between patients and controls. A male sex-specific left lateralised asymmetry of striatal D2 receptor binding was found in the patient group. Age-dependent decline of striatal D2 receptors was confirmed in controls, but not in patients. These results suggest that alterations in striatal D2 receptor distribution and density do occur in schizophrenia, and possibly reflect wider disruptions in prefrontal-striatal-limbic circuits.

Adolescent↗
PubMed1994

Which patients with non-affective functional psychosis are not admitted at first psychiatric contact?

BACKGROUND: We wished to explore the sociodemographic and clinical characteristics associated with admission to hospital in patients with a non-organic non-affective psychosis. METHOD: Subjects were 484 first-contact patients with a non-affective functional psychosis from an inner-city catchment area over 20 years from the mid-1960s. Sociodemographic and clinical characteristics associated with admission to hospital were analysed. RESULTS: Around 20% of patients were not admitted, and the proportion did not change significantly over the years. Ethnicity, sex, and marital and employment status did not predict admission. Factors associated with admission included police involvement, and violence to self or others. A diagnosis of schizoaffective disorder, and persecutory delusions, auditory hallucinations, and bizarre behaviour were all more common in patients admitted to hospital. CONCLUSIONS: The study indicates biases which might arise in research based exclusively on patients admitted to hospital.

Adolescent↗
PubMed1994

The relationship of schizophrenic births to 16 infectious diseases.

BACKGROUND: Recently, several investigators have reported an association between influenza epidemics and increased birth rates of 'preschizophrenic' individuals some four to six months later. Here we examine whether maternal exposure to other infectious diseases can also predispose the foetus to later schizophrenia. METHOD: Two independent sets of dates of birth of first admission schizophrenic patients, born between 1938 and 1965 in England and Wales, were obtained from the Mental Health Enquiry in England and Wales. Data on the number of deaths per month from 16 infectious diseases between 1937 and 1965 in England and Wales were also collected. We used a Poisson regression model to examine the relationship between deaths from infectious diseases and schizophrenic births. RESULTS: In the two separate data sets, increased national deaths from bronchopneumonia preceded, by three and five months respectively, increased numbers of schizophrenic births. We did not find any other significant associations between schizophrenic births and any of the other 15 infectious diseases. CONCLUSIONS: The association between deaths from bronchopneumonia and increased schizophrenic births some months later may be a reflection of the fact that bronchopneumonia deaths increase markedly during influenza epidemics.

Adult↗
PubMed1994

Neurodevelopmental schizophrenia: the rediscovery of dementia praecox.

Many people with severe schizophrenia have increased cerebral ventricular size and diffuse reduction in cortical volume; recent attention has focused on subtle malformations of the cytoarchitecture in the hippocampus and parahippocampal cortex. Sufferers also show an excess of dermatoglyphic and minor physical abnormalities, and a significant proportion had psychomotor deficits, cognitive or behavioural problems as children. Such findings suggest that the form of schizophrenia most akin to Kraepelin's original description of dementia praecox results from neurodevelopmental impairment. This may have its origin in genetic defects in the control of early brain growth, or in early environmental hazards such as prenatal exposure to maternal influenza or perinatal complications. How foetal or neonatal lesions produce hallucinations and delusions two or three decades later remains a mystery, but maturational changes in the brain may be important.

Adult↗
PubMed1993

Increased blood flow in Broca's area during auditory hallucinations in schizophrenia.

Verbal auditory hallucinations are common in schizophrenia but little is known about how they arise. We have used single photon emission tomography (SPET) to measure regional cerebral blood flow with the aim of identifying brain areas that are especially active during auditory hallucinations. We scanned twelve men with schizophrenia while they were experiencing hallucinations. The subjects were rescanned under identical conditions when their hallucinations had resolved (mean 19 weeks later). Blood flow was significantly greater during hallucinations than in the non-hallucinating state in Broca's area (mean count density on SPET 1.18 [SD 0.04] vs 1.13 [0.06]; p < 0.001); flow was also higher during hallucinations in the left anterior cingulate cortex and regions in the left temporal lobe, but these differences did not achieve significance. The increased flow in Broca's area was not accounted for by changes in other clinical variables nor by changes in the dose of neuroleptic drugs. These findings suggest that the production of auditory hallucinations in schizophrenia is associated with increased activity in a network of cortical areas specialised for language.

Adolescent↗