Biomedical subjects

Pak Sham

Publications and source records attributed to Pak Sham.

At least 37 records · Page 2Linked to original sources

PubMed2005

Relapse prevention in patients with bipolar disorder: cognitive therapy outcome after 2 years.

OBJECTIVE: In a previous randomized controlled study, the authors reported significant beneficial effects of cognitive therapy for relapse prevention in bipolar disorder patients up to 1 year. This study reports additional 18-month follow-up data and presents an overview of the effect of therapy over 30 months. METHOD: Patients with DSM-IV bipolar I disorder (N=103) suffering from frequent relapses were randomly assigned into a cognitive therapy plus medication group or a control condition of medication only. Independent raters, who were blind to patient group status, assessed patients at 6-month intervals. RESULTS: Over 30 months, the cognitive therapy group had significantly better outcome in terms of time to relapse. However, the effect of relapse prevention was mainly in the first year. The cognitive therapy group also spent 110 fewer days (95% CI=32 to 189) in bipolar episodes out of a total of 900 for the whole 30 months and 54 fewer days (95% CI=3 to 105) in bipolar episodes out of a total of 450 for the last 18 months. Multivariate analyses of variance showed that over the last 18 months, the cognitive therapy group exhibited significantly better mood ratings, social functioning, coping with bipolar prodromes, and dysfunctional goal attainment cognition. CONCLUSIONS: Patients in the cognitive therapy group had significantly fewer days in bipolar episodes after the effect of medication compliance was controlled. However, the results showed that cognitive therapy had no significant effect in relapse reduction over the last 18 months of the study period. Further studies should explore the effect of booster sessions or maintenance therapy.

Adaptation, Psychological↗

PubMed2005

Regional volume deviations of brain structure in schizophrenia and psychotic bipolar disorder: computational morphometry study.

BACKGROUND: It is unclear whether schizophrenia and psychotic bipolar disorder are associated with similar deviations of brain morphometry. AIMS: To assess volumetric abnormalities of grey and white matter throughout the entire brain in individuals with schizophrenia or with bipolar disorder compared with the same control group. METHOD: Brain scans were obtained by magnetic resonance imaging from 25 people with schizophrenia, 37 with bipolar disorder who had experienced psychotic symptoms and 52 healthy volunteers. Regional deviation in grey and white matter volume was assessed using computational morphometry. RESULTS: Individuals with schizophrenia had distributed grey matter deficit predominantly involving the fronto-temporal neocortex, medial temporal lobe, insula, thalamus and cerebellum, whereas those with bipolar disorder had no significant regions of grey matter abnormality. Both groups had anatomically overlapping white matter deficits in regions normally occupied by major longitudinal and interhemispheric tracts. CONCLUSIONS: Schizophrenia and psychotic bipolar disorder are associated with distinct grey matter deficits but anatomically coincident white matter abnormalities.

Adult↗

PubMed2005

Cognitive style in bipolar disorder.

BACKGROUND: Abnormalities of cognitive style in bipolar disorder are of both clinical and theoretical importance. AIMS: To compare cognitive style in people with affective disorders and in healthy controls. METHOD: Self-rated questionnaires were administered to 118 individuals with bipolar I disorder, 265 with unipolar major recurrent depression and 268 healthy controls. Those with affective disorder were also interviewed using the Schedules for Clinical Assessment in Neuropsychiatry and case notes were reviewed. RESULTS: Those with bipolar disorder and those with unipolar depression demonstrated different patterns of cognitive style from controls; negative self-esteem best discriminated between those with affective disorders and controls; measures of cognitive style were substantially affected by current levels of depressive symptomatology; patterns of cognitive style were similar in bipolar and unipolar disorder when current mental state was taken into account. CONCLUSIONS: Those with affective disorder significantly differed from controls on measures of cognitive style but there were no differences between unipolar and bipolar disorders when current mental state was taken into account.

Adult↗

PubMed2005

The value of four mental health self-report scales in predicting interview-based mood and anxiety disorder diagnoses in sibling pairs.

Questionnaire-based dimensional measures are often employed in epidemiological studies to predict the presence of psychiatric disorders. The present study sought to determine how accurately 4 dimensional mental health measures, the 12-item General Health Questionnaire (GHQ-12), Neuroticism (EPQ-N), the high positive affect and anxious arousal scales from the Mood and Anxiety Symptoms Questionnaire (MASQ-HPA and MASQ-AA) and a composite of all 4, predicted psychiatric caseness as diagnosed by the University of Michigan Composite International Diagnostic Interview (UM-CIDI). Community subjects were recruited through general practitioners; those who agreed to participate were sent a questionnaire containing the above measures. Subsequently, the UM-CIDI was administered by telephone to 469 subjects consisting of sibling pairs who scored most discordantly or concordantly on a composite index of the 4 measures. Logistic Regression and Receiver Operating Characteristic (ROC) curve analyses were carried out to assess the predictive accuracy of the dimensional measures on UM-CIDI diagnosis. A total of 179 subjects, 62 men and 117 women with an average age of 42 years, were diagnosed with at least one of the following psychiatric disorders: depression, dysthymia, generalized anxiety disorder (GAD), social phobia, agoraphobia and panic attack. The six disorders showed high comorbidity. EPQ-N and the Composite Index were found to be very strong and accurate predictors of psychiatric caseness; they were however unable to differentiate between specific disorders. The results from the present study therefore validated the four mental health measures as being predictive of psychiatric caseness.

Adult↗

PubMed2004

Parental phenotypes in family-based association analysis.

Family-based association designs are popular, because they offer inherent control of population stratification based on age, sex, ethnicity, and environmental exposure. However, the efficiency of these designs is hampered by current analytic strategies that consider only offspring phenotypes. Here, we describe the incorporation of parental phenotypes and, specifically, the inclusion of parental genotype-phenotype correlation terms in association tests, providing a series of tests that effectively span an efficiency-robustness spectrum. The model is based on the between-within-sibship association model presented in 1999 by Fulker and colleagues for quantitative traits and extended here to nuclear families. By use of a liability-threshold-model approach, standard dichotomous and/or qualitative disease phenotypes can be analyzed (and can include appropriate corrections for phenotypically ascertained samples), which allows for the application of this model to analysis of the commonly used affected-proband trio design. We show that the incorporation of parental phenotypes can considerably increase power, as compared with the standard transmission/disequilibrium test and equivalent quantitative tests, while providing both significant protection against stratification and a means of evaluating the contribution of stratification to positive results. This methodology enables the extraction of more information from existing family-based collections that are currently being genotyped and analyzed by use of standard approaches.

Female↗

PubMed2004

A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder.

Schizophrenia and mania have a number of symptoms and epidemiological characteristics in common, and both respond to dopamine blockade. Family, twin and molecular genetic studies suggest that the reason for these similarities may be that the two conditions share certain susceptibility genes. On the other hand, individuals with schizophrenia have more obvious brain structural and neuropsychological abnormalities than those with bipolar disorder; and pre-schizophrenic children are characterised by cognitive and neuromotor impairments, which are not shared by children who later develop bipolar disorder. Furthermore, the risk-increasing effect of obstetric complications has been demonstrated for schizophrenia but not for bipolar disorder. Perinatal complications such as hypoxia are known to result in smaller volume of the amygdala and hippocampus, which have been frequently reported to be reduced in schizophrenia; familial predisposition to schizophrenia is also associated with decreased volume of these structures. We suggest a model to explain the similarities and differences between the disorders and propose that, on a background of shared genetic predisposition to psychosis, schizophrenia, but not bipolar disorder, is subject to additional genes or early insults, which impair neurodevelopment, especially of the medial temporal lobe.

Amygdala↗

PubMed2004

Meta-analysis of the P300 and P50 waveforms in schizophrenia.

OBJECTIVE: To determine whether patients with schizophrenia have abnormalities in the P300 and P50 waves and to quantify the magnitude of any differences from controls. METHOD: We conducted a systematic search for articles published between January 1994 and August 2003 that reported P50 or P300 measures in schizophrenic patients and controls. Metaregression analyses were performed using a random effects model. The pooled standardised effect size (PSES) was calculated as the difference between the means of the two groups divided by the common standard deviation. RESULTS: We identified 46 studies suitable for analysis of P300 measures, including 1443 patients and 1251 controls. There were 20 P50 studies including 421 patients and 401 controls. The PSES for the P300 amplitude was 0.85 (95% CI: 0.65 to 1.05; p<0.001), and for the P300 latency was -0.57 (95% CI: -0.75 to -0.38; p<0.001). The PSES of the P50 ratio was -1.56 (95% CI: -2.05 to -1.06; p<0.001). There were no significant differences between patients and controls in P50 latency. Across-study variations in filters, task difficulty, antipsychotic medication and duration of illness did not influence the PSES significantly. CONCLUSIONS: This meta-analysis confirms the existence of ERP deficits in schizophrenia. The magnitude of these deficits is similar to the most robust findings reported in neuroimaging and neuropsychology in schizophrenia.

Antipsychotic Agents↗

PubMed2004

Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder.

BACKGROUND: Several studies assessing volumetric measurements of regional brain structure in bipolar disorder have been published in recent years, but their results have been inconsistent. Our aim was to complete a meta-analysis of regional morphometry in bipolar disorder as assessed using magnetic resonance imaging (MRI). METHODS: We conducted a systematic literature search of MRI studies of bipolar disorder and identified studies which reported volume measurements in a selected number of regions. Twenty-six studies comprising volumetric measurements on up to 404 independent patients with bipolar disorder were included. A meta-analysis was carried out comparing the volumes of regions in bipolar disorder to comparison subjects using a random effects model. RESULTS: Patients with bipolar disorder had enlargement of the right lateral ventricle, but no other regional volumetric deviations which reached significance. Strong heterogeneity existed for several regions, including the third ventricle, left subgenual prefrontal cortex, bilateral amygdala and thalamus. CONCLUSIONS: Regional volume of most structures we studied is preserved in bipolar disorder as a whole, which was significantly associated only with right-sided ventricular enlargement. However the extensive heterogeneity detected indicates the need for further studies to establish if consistent regional brain volume deviation exists in bipolar disorder or in specific clinical subsets of the illness.

Algorithms↗

PubMed2004

A controlled study of brain structure in monozygotic twins concordant and discordant for schizophrenia.

BACKGROUND: We examined monozygotic twins concordant and discordant for schizophrenia to clarify the role of genetic and environmental factors in determining brain abnormalities. METHODS: Magnetic resonance imaging brain scans were obtained from 14 monozygotic twin pairs concordant and 10 monozygotic pairs discordant for schizophrenia, as well as 17 pairs of monozygotic control twins. Twenty-two discordant sibling-pairs and 56 pairs of unrelated control subjects were included to assess the extent of genetic control over these structures. RESULTS: Within-pair similarities for whole brain volume increased as pair members were more closely related genetically (monozygotic twins > siblings > unrelated control subjects). Schizophrenic twins, whether from concordant or discordant pairs, had smaller whole brain volumes than control twins. The probands of discordant pairs showed more abnormalities in hippocampal, third and lateral ventricular volumes than concordant twins. CONCLUSIONS: Whole brain volume is under high genetic control and smaller whole brain volume is a reflection of the genetic liability to develop schizophrenia. The variation in hippocampal and ventricular volumes within discordant monozygotic pairs indicates a role for environmental factors in determining these volume abnormalities in schizophrenia. Such factors may also underlie the more extensive morphometric deviations in patients from monozygotic discordant twins than in their counterparts from concordant twins.

Adolescent↗

PubMed2004

Evidence that RNA editing modulates splice site selection in the 5-HT2C receptor gene.

Adenosine to inosine editing of mRNA from the human 5-HT2C receptor gene (HTR2C) occurs at five exonic positions (A-E) in a stable stem-loop that includes the normal 5' splice site of intron 5 and is flanked by two alternative splice sites. Using in vitro editing, we identified a novel editing site (F) located in the intronic part of the stem-loop and demonstrated editing at this site in human brain. We have shown that in cell culture, base substitutions to mimic editing at different combinations of the six sites profoundly affect relative splicing at the normal and the upstream alternative splice site, but splicing at the downstream alternative splice site was consistently rare. Editing combinations in different splice variants from human brain were determined and are consistent with the effects of editing on splicing observed in cell culture. As RNA editing usually occurs close to exon/intron boundaries, this is likely to be a general phenomenon and suggests an important novel role for RNA editing.

Aged↗

PubMed2004

Normal cerebral asymmetry in familial and non-familial schizophrenic probands and their unaffected relatives.

Loss of normal fronto-occipital cerebral asymmetry has been reported in patients with schizophrenia and also in their well relatives from multiply affected families, suggesting a relationship with susceptibility genes. We sought to confirm this relationship in a family study of patients with schizophrenia and their unaffected relatives of presumed differing genetic risk. MRI scans were carried out on 25 probands from families multiply affected with the disorder, and 36 of their unaffected relatives, 34 probands from families with no other affected members, 42 of their unaffected relatives, and 76 controls. Volumetric measurements of prefrontal, premotor, sensorimotor and occipitoparietal regions were obtained from which a measure of fronto-occipital torque was derived. There were no significant differences in measurements of fronto-occipital torque between the subject groups. Both schizophrenic probands and their relatives displayed the normal pattern of cerebral asymmetry, with larger right than left frontal regions and a larger left than right occipitoparietal region. Our findings failed to confirm an association between loss of fronto-occipital torque and genetic liability for schizophrenia and also failed to replicate the previously reported association between loss/reversal of fronto-occipital asymmetry and schizophrenia.

Adult↗

PubMed2004

Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

Adjusting for covariates in variance components QTL linkage analysis.

Variance components modeling has emerged as a powerful method for quantitative trait loci (QTL) linkage analysis. However, the power to detect a gene of minor effect is low. Many complex traits are affected by environmental as well as genetic factors, and one strategy to increase power is to reduce nongenetic phenotypic variance by adjusting for environmental covariates. In this paper, we investigate the power of three approaches to covariate adjustment in variance components linkage analysis: (i) incorporate covariates in the means model, (ii) incorporate covariates in the covariance matrix, and (iii) perform analysis on residual statistics. These approaches are compared to an analysis without adjustment. The results show that in the absence of correlation between the covariate and the QTL effect, adjusting for covariates indeed increases power to detect an underlying QTL. As this correlation increases, however, the power decreases. In the presence of a causal association between QTL and covariates, not adjusting for covariates appeared to be more powerful. The three approaches for adjusting for covariate: residual statistics, the means model, and the covariance model, had equal power to detect a QTL.

Analysis of Variance↗

PubMed2004

Parental familial vulnerability, family environment, and their interactions as predictors of depressive symptoms in adolescents.

OBJECTIVE: Familial risk for depression results from both biological and social influences. These may also be associated with other characteristics, including alcohol use, smoking, and body mass index (BMI), and with environmental risks such as social problems, life events, and educational level, all of which may be associated with depression in offspring. The authors examined the links between (1) parental familial vulnerability to depression and (2) the role of associated parental characteristics on severe adolescent depressive symptoms. Third, the authors explored the influence of family environment variables. Fourth, the authors sought interactions between parental familial vulnerability and family environment. METHOD: Questionnaires were obtained from 1,294 parents of 1,818 adolescent offspring. RESULTS: The odds of severe adolescent depressive symptoms increased by a factor of 1.5 per standard deviation increase in parental familial vulnerability to depression (odds ratio [OR] = 1.50). Parental BMI (OR = 1.05) and educational level (OR = 2.60) had significant influences independent of parental vulnerability. Analyses indicated a significant interaction such that those with high parental familial vulnerability, whose parents also had no qualifications, had a threefold risk of severe depressive symptoms. CONCLUSIONS: Adolescents with a family history of depression whose parents also lack qualifications may be a target for intervention.

Adolescent↗

PubMed2004

Properties of structured association approaches to detecting population stratification.

OBJECTIVE: To examine the properties of the structured association approach for the detection and correction of population stratification. METHOD: A method is developed, within a latent class analysis framework, similar to the methods proposed by Satten et al. (2001) and Pritchard et al. (2000). A series of simulations illustrate the relative impact of number and type of loci, sample size and population structure. RESULTS: The ability to detect stratification and assign individuals to population strata is determined for a number of different scenarios. CONCLUSION: The results underline the importance of careful marker selection.

Algorithms↗

PubMed2004

The contribution of risk factors to blood pressure heritability estimates in young adults: the East flanders prospective twin study.

The heritability of blood pressure estimated in previous studies may be confounded by the influence of potential blood pressure risk factors. We applied the classical twin design to estimate the contribution of these covariates to blood pressure heritability. The study consisted of 173 dizygotic and 251 monozygotic twin pairs aged 18-34 years, randomly selected from the East Flanders Prospective Twin Survey. In a standardized examination, blood pressure and anthropometry was measured, a questionnaire was completed, and a fasting blood sample was taken. In univariate and bivariate modeling, diastolic and systolic heritability were estimated both unadjusted and adjusted for potential risk factors. Also, covariate interaction was modeled. Bivariate analysis gave heritability estimates of 0.63 (95%CI 0.55-0.59), 0.74 (95%CI: 0.68-0.79), and 0.78 (95%CI: 0.70-0.84) for diastolic, systolic, and cross-trait heritability, respectively. The remaining variances could be attributed to unique environmental influences. These heritability estimates did not change substantially in univariate analyses or after adjustment for risk factors. A sex-limitation model showed that the heritability estimates for women were significantly higher than for men, but the same genetic factors were operating across sexes. Sex and cigarette smoking appeared to be statistically significant interaction terms. The heritability of blood pressure is relatively high in young adults. Potential risk factors of blood pressure do not appear to confound the heritability estimates. However, gene by sex by smoking interaction is indicated.

Adolescent↗

PubMed2003

CHIP: Defining a dimension of the vulnerability to attention deficit hyperactivity disorder (ADHD) using sibling and individual data of children in a community-based sample.

We are taking a quantitative trait approach to the molecular genetic study of attention deficit hyperactivity disorder (ADHD) using a truncated case-control association design. An epidemiological sample of children aged 5 to 15 years was evaluated for symptoms of ADHD using a parent rating scale. Individuals scoring high or low on this scale were selected for further investigation with additional questionnaires and DNA analysis. Data in studies like this are typically complicated. In the study reported on here, individuals have from 1 to 4 questionnaires completed on them and the sample is composed of a mixture of singletons and siblings. In this paper, we describe how we used a genetic hierarchical model to fit our data, together with a twin dataset, in order to estimate genetic factor loadings. Correlation matrices were estimated for our data using a maximum likelihood approach to account for missing data. We describe how we used these results to create a composite score, the heritability of which was estimated to be acceptably high using the twin dataset. This score measures a quantitative dimension onto which molecular genetic data will be mapped.

Adolescent↗

PubMed2003

Hippocampal volume in familial and nonfamilial schizophrenic probands and their unaffected relatives.

BACKGROUND: There is evidence for hippocampal volume loss in schizophrenia, but the etiology of this remains unclear. The aim of our study was to assess the contribution of familial liability and obstetric complications to hippocampal volume reduction in schizophrenia. METHODS: Hippocampal volumes were obtained using stereological methods from magnetic resonance scans performed on 35 schizophrenic probands from multiply affected families and 63 of their unaffected relatives, as well as 31 schizophrenic probands from families with no other affected members, 33 of their unaffected relatives, and 68 control subjects. RESULTS: Probands with schizophrenia, regardless of family history, had significant volume reduction of the left hippocampus. Hippocampal volume was not significantly reduced in either group of relatives. Obstetric complications were associated with left hippocampal volume reduction. CONCLUSIONS: We failed to find evidence that hippocampal volume loss is associated with familial liability to schizophrenia but have confirmed the association between hippocampal volume reduction and exposure to obstetric complications.

Adolescent↗