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Biomedical subjects

Pak Sham

Publications and source records attributed to Pak Sham.

49 records · Page 3Linked to original sources
PubMed2003

A randomized controlled study of cognitive therapy for relapse prevention for bipolar affective disorder: outcome of the first year.

BACKGROUND: Despite the use of mood stabilizers, a significant proportion of patients with bipolar affective disorder experience frequent relapses. A pilot study of cognitive therapy (CT) specifically designed to prevent relapses for bipolar affective disorder showed encouraging results when used in conjunction with mood stabilizers. This article reports the outcome of a randomized controlled study of CT to help prevent relapses and promote social functioning. METHODS: We randomized 103 patients with bipolar 1 disorder according to the DSM-IV, who experienced frequent relapses despite the prescription of commonly used mood stabilizers, into a CT group or control group. Both the control and CT groups received mood stabilizers and regular psychiatric follow-up. In addition, the CT group received an average of 14 sessions of CT during the first 6 months and 2 booster sessions in the second 6 months. RESULTS: During the 12-month period, the CT group had significantly fewer bipolar episodes, days in a bipolar episode, and number of admissions for this type of episode. The CT group also had significantly higher social functioning. During these 12 months, the CT group showed less mood symptoms on the monthly mood questionnaires. Furthermore, there was significantly less fluctuation in manic symptoms in the CT group. The CT group also coped better with manic prodromes at 12 months. CONCLUSION: Our findings support the conclusion that CT specifically designed for relapse prevention in bipolar affective disorder is a useful tool in conjunction with mood stabilizers.

Adaptation, Psychological↗
PubMed2003

The heritability of bipolar affective disorder and the genetic relationship to unipolar depression.

BACKGROUND: Twin studies of bipolar affective disorder (BPD) have either been small or have not used explicit diagnostic criteria. There has been little use of genetic model fitting and no analyses to explore the etiological overlap with unipolar depression (UPD). METHODS: Sixty-seven twin pairs, 30 monozygotic and 37 dizygotic, in which the proband had BPD were ascertained, and lifetime diagnoses were made using DSM-IV criteria. Univariate models were applied to estimate the contribution of additive genetic and environmental effects. Bipolar data were then combined with those from 68 monozygotic and 109 dizygotic pairs in which the proband had UPD. Two models were explored: a classic 2-threshold approach, in which BPD and UPD occupy the same continuum of liability but differ in severity, and a correlated liability model of mania and depression. RESULTS: Heritability of BPD was estimated at 85% (95% confidence interval [CI], 0.73-0.93) using narrow concordance and 89% (95% CI, 0.61-1.0) using broad concordance, with no shared environmental effects detected. A 2-threshold model was an unsatisfactory fit. Fitting a correlated liability model revealed a genetic correlation of 0.65 (95% CI, 0.58-0.75) between mania and depression and a correlation of 0.59 (95% CI, 0.15-0.84) for nonfamilial environment. Approximately 71% of the genetic variance for mania was not shared with depression. CONCLUSIONS: As defined by the DSM-IV, BPD is highly heritable. There are substantial genetic and nonshared environmental correlations between mania and depression, but most of the genetic variance in liability to mania is specific to the manic syndrome.

Bipolar Disorder↗
PubMed2002

Brain volumes in familial and non-familial schizophrenic probands and their unaffected relatives.

Structural brain abnormalities are consistently reported in schizophrenic subjects but the etiology of these abnormalities remains unclear. We tested the contribution of genetic predisposition and obstetric complications to the structural brain abnormalities found in schizophrenic probands and their relatives. MRI scans were carried out on 35 schizophrenic probands from families multiply affected with the disorder, and 63 of their unaffected relatives, including 10 parents who appeared to transmit genetic risk to their children; as well as 31 schizophrenic probands from families with no other affected members, 33 of their unaffected relatives; and finally 68 controls. Volumetric measurements of whole brain, lateral ventricles, third ventricle, cerebellum, and temporal lobes were completed for each subject. The impact of obstetric complications on brain structure was assessed across the gradient of presumed genetic predisposition. Both groups of schizophrenic probands displayed enlargement of the lateral and third ventricles, and there was a gradient of ventricular enlargement amongst the unaffected relatives in proportion to their likelihood of carrying schizophrenic genes. Ventricular enlargement was largely confined to males in both probands and unaffected relatives. Obstetric complications were associated with ventricular enlargement only in the familial probands. Non-familial probands displayed reduced volume of the temporal lobes bilaterally. In families with several schizophrenic members, ventricular enlargement is a marker for genetic liability, particularly in males. Individuals inheriting the susceptibility to schizophrenia appear particularly prone to develop ventricular enlargement in response to obstetric complications.

Adolescent↗
PubMed2002

Soluble interleukin 2 receptor levels in families of people with schizophrenia.

BACKGROUND: Several authors have reported increased soluble interleukin 2 receptor (sIL2Ralpha) concentrations in schizophrenia. The aim of this work was to examine serum sIL2Ralpha in the first degree relatives of patients with schizophrenia. METHODS: We sampled 51 first degree relatives of patients with DSM IIIR schizophrenia. These relatives were unaffected by psychosis and included nine fathers, thirteen mothers, seventeen sisters and twelve brothers. They were compared to 126 controls who were not pregnant, had no known autoimmune disorder and no intercurrent illness. Neither the controls, nor their first degree relatives, suffered from a psychotic illness. Serum sIL2Ralpha was analysed using a commercial ELISA preparation (Quantikine sIL2Ralpha immunoassay - R and D Systems, Inc.). We used non-parametric Mann Whitney U test and Spearman correlation throughout. SIL2Ralpha levels were adjusted for higher levels in females and with increasing age. RESULTS: Adjusted mean sIL2Ralpha values of unaffected siblings, averaged within their families, were higher than controls (n=14, one-tailed p=0.027). There was no difference in sIL2Ralpha values between fathers or mothers and controls following regression for age and sex. CONCLUSION: Soluble interleukin 2 receptoralpha levels are increased in siblings of patients with schizophrenia.

Adult↗
PubMed2002

The relationship between predisposing factors, premorbid function and symptom dimensions in psychosis: an integrated approach.

BACKGROUND: Increasing evidence suggests psychosis may be more meaningfully viewed in dimensional terms rather than as discrete categorical states and that specific symptom clusters may be identified. If so, particular risk factors and premorbid factors may predict these symptom clusters. AIMS: (i) To explore, using principal component analysis, whether specific factors for psychotic symptoms can be isolated. (ii) To establish the predictors of the different symptom factors using multiple regression techniques. METHOD: One hundred and eighty-nine inpatients with psychotic illness were recruited and information on family history, premorbid factors and current symptoms obtained from them and their mothers. RESULTS: Seven distinct symptom components were identified. Regression analysis failed to identify any developmental predictors of depression or mania. Delusions/hallucinations were predicted by a family history of schizophrenia and by poor school functioning in spite of normal premorbid IQ (F = 6.5; P < 0.001); negative symptoms by early onset of illness, developmental delay and a family history of psychosis (F = 4.1; P = 0.04). Interestingly disorganisation was predicted by the combination of family history of bipolar disorder and low premorbid IQ (F = 4.9; P = 0.003), and paranoia by obstetric complications (OCs) and poor school functioning (F = 4.2; P = 0.01). CONCLUSION: Delusions and hallucinations, negative symptoms and paranoia all appeared to have a developmental origin though they were associated with different childhood problems. On the other hand, neither mania nor depression was associated with childhood dysfunction. Our most striking finding was that disorganisation appeared to arise when a familial predisposition to mania was compounded by low premorbid IQ.

Adolescent↗
PubMed2002

DNA Pooling: a tool for large-scale association studies.

DNA pooling is a practical way to reduce the cost of large-scale association studies to identify susceptibility loci for common diseases. Pooling allows allele frequencies in groups of individuals to be measured using far fewer PCR reactions and genotyping assays than are used when genotyping individuals. Here, we discuss recent developments in quantitative genotyping assays and in the design and analysis of pooling studies. Sophisticated pooling designs are being developed that can take account of hidden population stratification, confounders and inter-loci interactions, and that allow the analysis of haplotypes.

Animals↗
PubMed2002

Optimal selection strategies for QTL mapping using pooled DNA samples.

The cost of large-scale association studies may be reduced substantially by analysis of pooled DNA from multiple individuals. Here we examine the optimal symmetric and asymmetric designs for pooling experiments for quantitative traits under a range of assumptions about the underlying genetic model and the sources of experimental errors in allele frequency estimation. The results indicate that, in the absence of experimental errors and for common alleles with additive effects, a symmetric pooling scheme comparing the top 27% with the bottom 27% of the trait distribution is optimal, extracting 80% the total information available. A symmetric design is not optimal for rare or recessive alleles, which require asymmetric (or other) pooling strategies. Allele frequency measurement errors reduce the optimal pooling fraction as well as the overall efficiency of the pooling design. In contrast, random variation in the amount of DNA contributed by individuals to a pool reduces only the overall efficiency of the pooling design. Our results emphasize the importance of minimising experimental errors and suggest a pooling fraction of around 20%.

Analysis of Variance↗
PubMed2002

Family-based association tests for quantitative traits using pooled DNA.

Interest in whole-genome QTL mapping has spurred efforts to reduce the cost of studies now based primarily on individual genotyping. Pooled DNA tests are a possible solution, and understanding how measurement error affects test power could assist in study design. Here we describe pooled tests explicitly optimised for measurement error, including family-based tests robust to population stratification. Our results suggest that pooled DNA whole-genome screens may be feasible with current instruments.

Chromosome Mapping↗
PubMed2002

Haplotype and linkage disequilibrium analysis to characterise a region in the calcium channel gene CACNA1A associated with idiopathic generalised epilepsy.

Idiopathic generalised epilepsy (IGE) is a common form of epilepsy, including several defined and overlapping syndromes, and likely to be due to the combined actions of mutations in several genes. In a recent study we investigated the calcium channel gene CACNA1A for involvement in IGE, unselected for syndrome, by means of association studies using several polymorphisms within the gene. We reported a highly significant case/control association with a silent single nucleotide polymorphism (SNP) in exon 8 that we confirmed by within-family analyses. In this present study we screened the gene for novel SNPs within 25 kb of exon 8, which have enabled us to define the critical region of CACNA1A in predisposing to IGE. Several intronic SNPs were identified and three, within 1.5 kb of exon 8 and in strong linkage disequilibrium with each other and with the original SNP, were significantly associated with IGE (P=0.00029, P=0.0015 and P=0.010). The associations were not limited to an IGE syndrome or other subgroup. Another SNP, 25 kb away, in intron 6 was also significantly associated with IGE (P=0.0057) but is not in linkage disequilibrium with the SNPs around exon 8. Haplotype predictions revealed even more significant associations (3-marker haplotype: P<10(-6)). Logistic regression showed that all the data can be explained by two of the SNPs, which is consistent with two functionally significant variants being responsible for all five associations, although a single variant cannot be excluded. The functionally significant variant(s) are unlikely to be exonic and suggests an effect on expression or alternative splicing.

Adolescent↗
PubMed2002

Variance components models for gene-environment interaction in quantitative trait locus linkage analysis.

Gene-environment interaction (G x E) is likely to be a common and important source of variation for complex behavioral traits. Gene-environment interaction, or genetic control of sensitivity to the environment, can be incorporated into variance components twin and sib-pair analyses by partitioning genetic effects into a mean part, which is independent of the environment, and a part that is a linear function of the environment. An approach described in a companion paper (Purcell, 2002) is applied to sib-pair variance components linkage analysis in two ways: allowing for quantitative trait locus by environment interaction and utilizing information on any residual interactions detected prior to analysis. As well as elucidating environmental pathways, consideration of G x E in quantitative and molecular studies will potentially direct and enhance gene-mapping efforts.

Computer Simulation↗
PubMed2002

Validation of single nucleotide polymorphism quantification in pooled DNA samples with SNaPIT. A glycosylase-mediated methods for polymorphism detection method.

Association studies using genome scans to identify quantitative trait loci for multifactorial disorders, with anything approaching reasonable power, have been compromised by the need for a very dense array of genetic markers and large numbers of affected individuals. These requirements impose enormous burdens on the genotyping capacity for most laboratories. DNA pooling has been proposed as a possible approach to reduce genotyping costs and effort. We report on the application of the SNaPIT technology to evaluate allele frequencies in pooled DNA samples and conclude that it offers a cost effective, efficient and accurate estimator and provides several advantages over competing technologies in this regard.

Chromosome Mapping↗
PubMedDate not supplied

Familiality of clinical characteristics in schizophrenia.

Few studies have assessed the familiality of clinical characteristics in schizophrenia. Therefore, we set out to investigate the familiality of the following characteristics; age of onset, course of disorder, employment status at onset, impairment during disorder, marital status at onset, mode of onset and premorbid functioning. Clinical characteristics were recorded using the Operational Criteria Checklist for Psychotic Illness for 155 subjects with an RDC diagnosis of schizophrenia, schizoaffective disorder, or psychosis of unknown origin, from 61 families multiply affected by schizophrenia. Age of onset, course of disorder, impairment during disorder, mode of onset, and premorbid functioning were shown to be familial. The familiality of these clinical characteristics supports their use in the delineation of homogeneous subsets for future genetic studies.

Adult↗