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P Sham

Publications and source records attributed to P Sham.

At least 91 records · Page 5Linked to original sources
PubMed1995

Analysis of clozapine response and polymorphisms of the dopamine D4 receptor gene (DRD4) in schizophrenic patients.

We have examined the hypothesis that a variable number of tandem repeats in the third cytoplasmic loop of the dopamine D4 receptor influences clinical response to clozapine using a sample of 189 schizophrenic patients. Alleles of the 48-bp repeat, which range from two to ten copies in the normal human population, were analysed by the polymerase chain reaction using genomic DNA as template. Association between these alleles and response to clozapine was tested using the difference in pre- and post-treatment GAS scores as a measure of response. We found no statistically significant variation between genotypic groups and response by analysis of variance. We conclude that the variation of the number of 48-bp repeats alone does not determine response to clozapine. Larger studies are underway to determine if there is a more subtle relationship with sequence variation within the repeats or at other polymorphic sites within the gene that may provide evidence for a component of clozapine's action being at D4 receptors.

Alleles↗
PubMed1995

Neuroticism: a vulnerability marker for depression evidence from a family study.

INTRODUCTION: We investigated the relationship between depressive illness and personality traits from the Eysenck Personality Inventory (EPI) using data from a family study. METHODS: The first-degree relatives of a series of 89 probands with RDC major depression (MD) were subdivided by their lifetime RDC diagnosis into: (1) relatives recovered from MD (n = 34); (2) never-ill relatives (n = 45). The neuroticism (N) and extraversion (E) scores of these two groups were compared using a multilevel linear model, allowing for potential confounders. The relationship between age of onset and recurrence of MD and N scores in group 1 was also examined. RESULTS: (1) Raised N scores were associated with a past history of major depression. (2) There was no such relationship for E scores. (3) Current depressive symptoms were also associated with an increased N score but this did not explain the relationship between previous major depression and N scores. (4) Recurrent episodes of major depression in the recovered MD relatives were significantly associated with increased N scores. CONCLUSION: These data suggest that raised N may be a vulnerability marker for major depression.

Adult↗
PubMed1995

Schizophrenia and the androgen receptor gene: report of a sibship showing co-segregation with Reifenstein syndrome but no evidence for linkage in 23 multiply affected families.

Crow et al. [1993: Am J Med Genet (Neuropsychiatr Genet) 48:159-160] have reported excess sharing of alleles by male sibling pairs with schizophrenia, at a triplet repeat marker within the androgen receptor gene, indicating that mutations at or near this gene may be a risk factor for males. In this report, we describe a pair of male siblings concordant for both schizophrenia and Reifenstein syndrome, which is caused by a mutation in this gene. This provides support for the hypothesis that the androgen receptor may contribute to liability to develop schizophrenia. Because of this, we have examined a collection of 23 pedigrees multiply affected by schizophrenia for linkage to the androgen receptor. We have found no evidence for linkage by both the LOD score and affected sibling-pair methods, under a range of genetic models with a broad and narrow definition of phenotype, and when families with male-to-male transmission are excluded. However, because of the small number of informative male-male pairs in our sample, we cannot confirm or refute the excess allele sharing for males reported by Crow.

Adolescent↗
PubMed1995

Systematic search for major genes in schizophrenia: methodological issues and results from chromosome 12.

We describe a method of systematically searching for major genes in disorders of unknown mode of inheritance, using linkage analysis. Our method is designed to minimize the probability of missing linkage due to inadequate exploration of data. We illustrate this method with the results of a search for a locus for schizophrenia on chromosome 12 using 22 highly polymorphic markers in 23 high density pedigrees. The markers span approximately 85-90% of the chromosome and are on average 9.35 cM apart. We have analysed the data using the most plausible current genetic models and allowing for the presence of genetic heterogeneity. None of the markers was supportive of linkage and the distribution of the heterogeneity statistics was in accordance with the null hypothesis.

Chromosomes, Human, Pair 12↗
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↗
PubMed1995

Does prenatal exposure to influenza in mice induce pyramidal cell disarray in the dorsal hippocampus?

Epidemiological studies point to an association between prenatal exposure to influenza and later schizophrenia. Such studies are consistent with neuropathologic reports demonstrating cytoarchitectural abnormalities in the hippocampus and parahippocampal gyrus suggestive of second trimester developmental anomalies. The hypothesis that prenatal exposure to influenza in the second trimester may induce hippocampal pyramidal cell disarray in mice was investigated. Between days 9-16 of pregnancy, 35 Balb/c mice were intranasally inoculated with either a mouse-adapted or non mouse-adapted pool of Influenza A/Singapore/1/57 (H2N2), and 10 controls were inoculated with normal saline. Offspring were sacrificed on day 21 postpartum. Microscopic examination of the CA1-CA2 junctional areas in the offspring of mice exposed to influenza failed to demonstrate excess pyramidal cell disarray when compared with influenza-free, age matched controls. There was evidence that disarray was greater among those exposed on day 13 of pregnancy. Analyses of the data by sex and severity of maternal infection failed to reveal any significant effects.

Animals↗
PubMed1995

Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder.

We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significant only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant.

Alleles↗
PubMed1995

Association between clozapine response and allelic variation in 5-HT2A receptor gene.

We report allelic association between a polymorphism (T102C) within the coding region of the 5-HT2A gene (HTR2A, 13q14-21) and response to clozapine in schizophrenic patients. Homozygosity for the C102 allele was more frequent (30/57, 53%) among patients who did not respond to clozapine than in those who responded (23/92, 25%). This finding is evidence that allelic variation of genes which encode neurotransmitter receptors can influence clinical response to antipsychotic drugs.

Alleles↗
PubMed1995

Linkage studies of bipolar disorder in the region of the Darier's disease gene on chromosome 12q23-24.1.

We have recently described a family in which there is cosegregation of major affective disorder with Darier's disease and have mapped this autosomal dominant skin disorder to 12q23-q24.1. This has provided an interesting candidate region for genetic studies of bipolar disorder. We have studied the segregation of seven markers spanning the Darier's disease locus in 45 bipolar disorder pedigrees and found modest evidence in support of linkage under heterogeneity for 5 of these markers. Nonparametric analyses were suggestive of linkage with a marker at the gene encoding a secretory form of phospholipase A2. Our sample has relatively low power to detect linkage under heterogeneity and independent researchers should examine markers from this region in further samples of bipolar pedigrees.

Alleles↗
PubMed1995

Linkage studies on chromosome 22 in familial schizophrenia.

As part of a systematic search for a major genetic locus for schizophrenia we have examined chromosome 22 using 14 highly polymorphic markers in 23 disease pedigrees. The markers were distributed at an average distance of 6.6 cM, covering 70-80% of the chromosome. We analyzed the data by the lod score method using five plausible genetic models ranging from dominant to recessive, after testing the power of our sample under the same genetic parameters. The most positive lod score found was 1.51 under a recessive model for the marker D22S278, which is insufficient to conclude linkage. However, an excess of shared alleles in affected siblings (P < .01) was found for both D22S278 and D22S283. For D22S278, the A statistic was equal to the lod score (1.51) and therefore did not provide additional evidence for linkage allowing for heterogeneity, but the Liang statistic was more significant (P = .002). Our results suggest the possibility that the region around D22S278 and D22S283 contains a gene which contributes to the aetiology of schizophrenia.

Alleles↗
PubMed1995

Cytochrome P4502D6 genotype does not determine response to clozapine.

1. The atypical antipsychotic drug clozapine, used in the treatment of resistant schizophrenia, is metabolized partly by the hepatic cytochrome P450 enzyme CYP2D6. Two phenotypes with respect to the activity of the enzyme are recognized (extensive metabolisers (EM) and poor metabolisers (PM)), resulting from allelic variation in the gene, CYP2D6. 2. Genotype was determined in 123 schizophrenic patients currently being treated with clozapine, in order to determine if EM or PM status influences response to this drug. Patients were divided into responders and non-responders using the Global Assessment Scale, and genotyped for the A and B poor metaboliser mutations by digesting PCR products with HpaII or BstNI. 3. Fifty-nine patients were heterozygous for allele B and for allele A. Eight patients were determined as poor metabolisers since they were homozygous either for A and B. Poor metabolisers were equally distributed between responders and nonresponders and no correlation between CYP2D6 alleles and response to clozapine was found. 4. The results are consistent with recent findings showing that CYP1A2, rather than CYP2D6, is the major enzyme responsible for the metabolism of clozapine.

Alleles↗
PubMed1994

Further evidence for anomalies in the hand-prints of patients with schizophrenia: a study of secondary creases.

Finger and palm prints from 46 ICD-9 schizophrenic patients and 43 age and sex matched normal controls were examined independently and blind to diagnosis, by four raters. Seven prints were judged to have very high densities of secondary creases. These abnormal prints were all from the schizophrenic group. Patients with high densities of creases were more severely ill, having had more than five admissions to hospital and higher doses of neuroleptic medication. There was a trend for such patients to have had a complicated obstetric history and an earlier onset of their illness.

Adult↗
PubMed1994

The influence of life events on the subsequent course of psychotic illness. A prospective follow-up of the Camberwell Collaborative Psychosis Study.

Fifty-nine psychotic patients with acute onset of illness, who had been interviewed about their experience of stressful life events before the episode, were followed up for an average of 42 months. Thirty patients (51%) had experienced a stressful life event in the 3 months immediately before onset (EV+), 29 had not (EV-). In patients with an RDC diagnosis of affective disorder or unspecified functional psychosis, the presence of stressful life events was associated subsequently with milder symptom severity, less time spent in hospital, more treatment for depressive symptoms and less for psychotic symptoms. In schizophrenia, differences were less apparent, but patients with event associated episodes had less need of anti-psychotic maintenance medication over the follow-up period and tended to have spent more time in complete remission. EV+ schizophrenic subjects also had higher morbid risk for schizophrenia in their first degree relatives, and tended to be female and to have less typical symptoms than EV- schizophrenic patients.

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↗
PubMed1993

Statistics and the nature of depression.

A critical examination is made of the role that statistical methods have played in the understanding of depression. The development of instruments for measuring depression is illustrated by reference to the Beck Depression Inventory and the Hamilton Rating Scale. The controversy over the existence of one or two types of depression is examined from the perspective of the statistical tools used. Some of the problems in studies of the heritability of depression are outlined. The development of clinical trials of depression is examined, with particular reference to ECT and maintenance therapy, and the role of meta-analysis is discussed.

Data Interpretation, Statistical↗