Publications by authors named "McGuffin P"

Recent developments in the classification of major depressive disorder are reviewed in light of the predictions made by Kendell in the 1970s. Particularly, the institution of operational diagnoses along with the contentious issues of subdividing major depressive disorder and its characterisation on a dimensional as opposed to a categorical scale.

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Attention deficit hyperactivity disorder (ADHD) is a discrete clinical syndrome characterized by the triad of inattention, hyperactivity, and impulsivity in the context of marked impairments. Molecular genetic studies have been successful in identifying genetic variants associated with ADHD, particularly with DSM-IV inattentive and combined subtypes. Quantitative trait locus (QTL) approaches to linkage and association mapping have yet to be widely used in ADHD research, although twin studies investigating individual differences suggest that genetic liability for ADHD is continuously distributed throughout the population, underscoring the applicability of quantitative dimensional approaches.

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Cigarette consumption and smoking cessation are influenced in part by genes. Personality traits have also been implicated in the aetiology of smoking. Neuroticism, a personality trait with a heritable component, correlates well with anxiety and depression, increasing the risk of being a smoker and decreasing the chance of smoking cessation.

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Unipolar major depressive disorder (MDD) is a complex disorder thought to result from multiple genes in combination with environmental and developmental components. The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) has been implicated in MDD in a meta-analysis of association studies and is within a linkage region suggested by a recent study of affected sib pairs. A single base mutation in the MTHFR gene (C677T) results in the production of a mildly dysfunctional thermolabile enzyme.

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Childhood depressive conditions have been explored from multiple theoretical approaches but with few empirical attempts to address the interrelationships among these different domains and their combined effects. In the present study, the authors examined different pathways through which social, cognitive, and genetic risk factors may be expressed to influence depressive symptoms in 300 pairs of child twins from a longitudinal study. Path analysis supported several indirect routes.

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Less is known about depression in children than in adults. This study integrates fields by combining cognitive and interpersonal research investigating childhood depression symptoms through the use of a genetic framework. Three research questions are addressed.

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Background: It is widely held that there are no differences in the symptom profile of male and female depression. Studies to date that have found differences have used different methodologies and had inconsistent findings. Here we compare the clinical profile of major depression for men and women from a sample of almost 600 well-characterized individuals with recurrent major depressive disorder (MDD).

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Monozygotic (MZ) twins may be subject to epigenetic modifications that could result in different patterns of gene expression. Several lines of evidence suggest that epigenetic factors may underlie mental disorders such as bipolar disorder (BD) and schizophrenia (SZ). One important epigenetic modification, of relevance to female MZ twins, is X-chromosome inactivation.

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We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

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The objectives of this study were to examine sex differences in depressive symptom patterns in 475 sib pairs with well-defined recurrent major depression and to test the hypotheses that (a) symptom patterns show higher intraclass correlations within same sex sib pairs versus mixed sex sib pairs; and (b) symptoms more associated with women, e.g. atypical depressive and anxiety symptoms, account for differences between male and female siblings within the same family.

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Background: A number of scales are used to estimate the severity of depression. However, differences between self-report and clinician rating, multi-dimensionality and different weighting of individual symptoms in summed scores may affect the validity of measurement. In this study we examined and integrated the psychometric properties of three commonly used rating scales.

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There is strong evidence for an association between maternal smoking in pregnancy and psychological problems in offspring. The problems most frequently associated are attention problems, hyperactivity, and conduct problems, although there is some evidence for an association with substance use problems as well. The nature of this association is unclear, but it is likely the result of a number of different mechanisms.

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Gene-environmental interaction (G x E) between a common functional polymorphism in the promoter region of the serotonin transporter gene (5-HTT) and environmental adversity on the onset of depression in humans has been found in fifteen independent studies. It is supported by evidence from animal experiments, pharmacological challenge and neuroimaging investigations. However, negative findings have been reported in two large samples.

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Anxiety and depression share genetic influences, and have been associated with similar cognitive biases. Psychological theories of anxiety and depression highlight threat interpretations of ambiguity. Little is known about whether genes influence cognitive style, or its links to symptoms.

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Gene polymorphisms and behavior.

Pediatr Blood Cancer

June 2007

Genetics has a entered golden post genomic era that promises to greatly improve our understanding of the etiology of complex familial disorders. Many forms of behavior are familial but Mendelian disorders are rare, and common conditions have complex inheritance. Twin and adoption studies confirm that major psychiatric disorders such as schizophrenia and bipolar affective disorder are highly heritable.

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Purpose Of Review: Molecular genetic studies of bipolar affective disorder are beginning to show some positive and reproducible findings. The most relevant of these will be reviewed.

Recent Findings: Obtaining consistent findings from whole genome scans has been hampered by small sample sizes and phenotypic heterogeneity.

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Objectives: Associations between sleep and internalizing problems are complex and poorly understood. To better understand these covarying difficulties, genetic and environmental influences were estimated by using a twin design.

Methods: Three hundred 8-year-old twin pairs reported on their anxiety and depression by completing the Screen for Childhood Anxiety Related Emotional Disorders and the Children's Depression Inventory.

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Objective: The authors previously reported strong evidence for familial aggregation of postpartum (puerperal) psychotic episodes in women with bipolar disorder. The authors here examine whether vulnerability to postpartum triggering of depressive episodes aggregates in families and assess how this aggregation varies with the definition of postpartum onset.

Method: Postpartum depression occurrence was studied in the female members of 120 sibling pairs recruited at a site within an international multicenter study of sibling pairs with recurrent unipolar depression.

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Both childhood trauma (CT) and genetic factors contribute to the pathophysiology of depression. We studied the relationship of CT to age of onset (AO) of depression, personality traits, and expression of symptom dimensions in 324 adults with recurrent unipolar depression. Subjects received structured psychiatric interviews and completed CT, depressive symptom, and personality rating questionnaires.

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Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes.

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Background: Demonstrating differences between euthymic bipolar subjects and healthy controls in response to positive (happy) mood induction may help elucidate how mania evolves. This pilot study evaluates the Go task in a reward paradigm as a method for inducing a happy mood state and compares the response of euthymic bipolar subjects and healthy controls.

Method: The Sense of Hyperpositive Self Scale, the Tellegen positive and negative adjectives, the Global-Local task and a visual analogue scale for measuring positive affect were administered to 15 euthymic bipolar subjects and 19 age-and-sex-matched healthy control subjects before and after they had performed the Go task in a reward paradigm.

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This article gives an overview of genetic research approaches and their application to delusional disorder. Most studies have been based on small samples and have had other methodological limitations, so it is not clear whether there is a genetic contribution to the aetiology of delusional disorder. It is unlikely that delusional disorder is strongly related genetically to affective disorder or schizophrenia, but more subtle relationships cannot be ruled out.

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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.

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Genome-wide linkage analysis was carried out in a sample of 497 sib pairs concordant for recurrent major depressive disorder (MDD). There was suggestive evidence for linkage on chromosome 1p36 where the LOD score for female-female pairs exceeded 3 (but reduced to 2.73 when corrected for multiple testing).

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