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Biomedical subjects

Peter McGuffin

Publications and source records attributed to Peter McGuffin.

At least 19 recordsLinked to original sources
PubMed2007

Interrelationship of childhood trauma, neuroticism, and depressive phenotype.

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. Experience of at least one type of trauma was reported by 79.9% of subjects, and the most common forms of trauma were physical neglect, emotional abuse, and emotional neglect. There was an earlier AO of depression in the groups that reported CT compared to those that reported none, with earliest AO occurring in those who had experienced the highest levels of CT. There were no significant correlations between overall CT scores and neuroticism or extraversion. Total CT was a significant (P=.008) predictor of the Mood symptom dimension, mostly accounted for by emotional abuse (P=.019), and physical neglect predicted the Anxiety symptom dimension (P=.002). All types of CT are commonly reported in individuals with depression, and emotional abuse and physical neglect, though previously less well identified, appear to have an important role in the pathogenesis of depressive disorders. The effect of CT on individuals with an underlying genetic vulnerability to depression may result in differences in depressive phenotype characterized by earlier AO of depression and the expression of specific depressive symptom dimensions.

Adolescent↗
PubMed2007

The genetics of bipolar affective disorder.

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. Recently, there have been concerted efforts to overcome these problems by combining data for meta-analysis. What has become increasingly clear is that several regions that are likely to contain genes contributing to bipolar affective disorder are also relevant to schizophrenia, a finding supported by recent twin data. Studies to date have implicated the D-amino acid oxidase activator complex (also known as G72/G30), disrupted in schizophrenia-1 and neuregulin, and have pointed to several promising linkage regions in which the genes have not yet been identified. In addition, there is some evidence to support the involvement of genetic variants in catechol-o-methyl transferase and brain-derived neurotrophic factor in the aetiology of bipolar affective disorder. SUMMARY: Molecular genetic research in bipolar affective disorder may lead to the development of new diagnostic paradigms for classifying the psychoses and affective states. In addition, determining the functional significance of the susceptibility genes will pave the way for enhanced diagnostic accuracy and improved treatments.

Amino Acid Oxidoreductases↗
PubMed2006

A pilot study of positive mood induction in euthymic bipolar subjects compared with healthy controls.

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. RESULTS: Significant differences were found between subjects and controls on several measures at each time-point but there were no differences across the groups across time except for the visual analogue scales, where subjects had a more sustained duration in self-reported happiness compared with controls. CONCLUSIONS: This pilot study has shown that a positive affect can be induced in bipolar subjects and controls which can be demonstrated by changes in scores on several tasks. However, only the visual analogue scales showed a significant difference between cases and controls over time. Such tests may prove valuable in furthering understanding about the evolution of manic mood states.

Adult↗
PubMed2006

Genetics and delusional disorder.

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. The rarity of multiply affected families prohibits linkage studies and, to date, molecular genetic investigations have been mainly limited to small association studies of dopamine receptor polymorphisms. A range of considerably larger, epidemiologically rigorous studies is required, but the uncommonness and other features of the disorder put strong limitations on the prospects for ascertaining adequate samples.

Adoption↗
PubMed2006

Familiality of postpartum depression in unipolar disorder: results of a family study.

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. Employing a range of definitions of postpartum onset, the authors examined concordance for postpartum episode status between sisters. RESULTS: Episodes of depression with onset within 4 weeks of delivery clustered in families, but there was no significant evidence of familial clustering of broadly defined postpartum depression (onset within 6 months). Among women with a family history of narrowly defined postpartum episodes, 42% experienced depression following their first delivery, whereas only 15% of women with no such family history experienced depression following first delivery. The evidence for familiality maximized with a postpartum onset definition of 6-8 weeks. CONCLUSIONS: These results implicate familial factors in susceptibility to the triggering of narrowly defined postpartum depressive episodes in women with recurrent major depression. They suggest that a postnatal onset definition of within 6-8 weeks of delivery may be optimal in studies of the triggering of depressive illness by childbirth.

Adult↗
PubMed2006

Associations between sleep problems, anxiety, and depression in twins at 8 years of age.

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. Parents reported on their children's sleep problems by completing the Child Sleep Habits Questionnaire. RESULTS: Children reported by their parents to have different types of sleep problems self-reported more depression symptoms than those without. The correlation between total sleep-problem score and depression was moderate. That between sleep problems and anxiety was smaller and was not examined further. The association between sleep problems and depression was mainly explained by genes, and there was substantial overlap between the genes influencing sleep problems and those influencing depression. There was smaller influence from environmental factors making family members alike, and environmental factors making family members different decreased the association between sleep problems and depression. CONCLUSIONS: A range of sleep difficulties are associated with depression in school-aged children, and the overall association between the 2 difficulties may be largely influenced by genes.

Anxiety Disorders↗
PubMed2005

Whole genome linkage scan of recurrent depressive disorder from the depression network study.

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). The region includes a gene, MTHFR, that in previous studies has been associated with depressive symptoms. Two other regions, on chromosomes 12q23.3-q24.11 and 13q31.1-q31.3, showed evidence for linkage with a nominal P < 0.01. The 12q peak overlaps with a region previously implicated by linkage studies of unipolar and bipolar disorders and contains a gene, DAO, that has been associated with both bipolar disorder and schizophrenia. The 13q peak lies within a region previously linked strongly to panic disorder. A fourth modest peak with an LOD of greater than 1 on chromosome 15q lies within a region that showed genome-wide significant evidence of a recurrent depression locus in a previous sib-pair study. Both the 12q and the 15q findings remained significant at genome-wide level when the data from the present study and the previous reports were combined.

Adolescent↗
PubMed2005

Family dysfunction interacts with genes in the causation of antisocial symptoms.

There is emerging evidence of gene-environment interaction effects on conduct problems, both from adoption studies and from a study using a measured genotype. An association between non-violent family dysfunction and conduct problems has also been reported, although not in the context of gene-environment interaction studies. The aim of this study was to examine the interaction of genes and family dysfunction in contributing to conduct problems in young people. Parents of 278 monozygotic and 378 dizygotic twin pairs, aged 5-18, from the CaStANET birth cohort twin register were questioned about zygosity, conduct problems and family environment. Using structural equation modeling we tested for main and interactive effects of genes and family dysfunction modelled as an environmental "moderator variable". Both main and gene-environment interaction effects were highly significant. It was concluded that a risk genotype conferring susceptibility to family dysfunction is responsible for most of the variance in antisocial symptoms in childhood and adolescence.

Antisocial Personality Disorder↗
PubMed2005

Personality as a determinant of social functioning in depression.

BACKGROUND: The Social Adaptation Self-Evaluation Scale (SASS) is an instrument for measuring drive-based aspects of social functioning and has been used in trials of antidepressants. It has been suggested that social adaptation may be akin to a personality trait. We investigated the personality dimensions of neuroticism and extraversion as determinants of social functioning measured by SASS in patients with depression. METHODS: Patients seen at a tertiary mood disorders unit were assessed using SASS, Eysenck Personality Questionnaire (EPQ), Inventory of Depressive Symptoms-Self-Rated (IDS-SR) and Mood Disorders Questionnaire (MDQ). RESULTS: In a sample of 80 depressed outpatients, we found that extraversion made the largest unique contribution to social functioning followed by self-rated severity of depression. Neuroticism and other clinical and demographic variables were not significant predictors. CONCLUSIONS: Social functioning as measured by SASS is predicted by extraversion and severity of depression. Personality traits should be taken into account when assessing social functioning in depression.

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↗
PubMed2004

The Depression Network (DeNT) Study: methodology and sociodemographic characteristics of the first 470 affected sibling pairs from a large multi-site linkage genetic study.

BACKGROUND: The Depression Network Study (DeNt) is a multicentre study designed to identify genes and/or loci linked to and/or associated with susceptibility to unipolar depression in Caucasian families. This study presents the method and socio-demographic details of the first 470 affected sibling pairs recruited from 8 different sites in Europe and the United States of America. METHODS: Probands fulfilling either the Diagnostic and Statistical Manual 4th edition (DSM-IV) or the International Classification of Diseases 10th edition (ICD-10) criteria for recurrent unipolar depression of moderate or severe degree and who had at least one similarly affected sibling were eligible for the study. Detailed clinical and psychological assessments were undertaken on all subjects including an interview using the Schedules for Clinical Assessment in Neuropsychiatry. Blood samples were collected from all participants to extract DNA for linkage analysis. RESULTS: The different sites used different recruitment strategies depending on local health care organisation but despite this there was remarkable similarity across sites for the subjects recruited. Although the Bonn site had significantly older subjects both for age of onset and age at interview, for the sample as a whole, subjects were interviewed in their mid-40s and had experienced the onset of their recurrent depression in their 20s. Preliminary genome screening was able to include 929 out of the 944 subjects (98.4%) typed at 932 autosomal and 544 X chromosome markers. CONCLUSIONS: This paper describes the methodology and the characteristics of the subjects from the 414 families included in the first wave of genotyping from the multi-site DeNT study. Ultimately the study aims to collect affected sibling pairs from approximately 1200 families.

Age of Onset↗
PubMed2004

Functional effects of a tandem duplication polymorphism in the 5'flanking region of the DRD4 gene.

BACKGROUND: Several polymorphisms have been identified in the 5'flanking region of the human dopamine D(4) receptor gene (DRD4), including a tandem duplication polymorphism. This comprises a 120-base-pair repeat sequence that is known to have different allele frequencies in various populations around the world. Furthermore, various studies have revealed evidence of linkage to attention-deficit/hyperactivity disorder and association with schizophrenia and methamphetamine abuse. The location of the polymorphism in the 5'regulatory region of the DRD4 gene and the fact that it consists of potential transcription factor binding sites suggest that it might confer differential transcriptional activity of the alleles. METHODS: We investigated the functional effects of this gene variant with transient transfection methods in four human cell lines and then assessed transcriptional activity with luciferase reporter gene assays. RESULTS: The longer allele has lower transcriptional activity than the shorter allele in SK-N-MC, SH-SY5Y, HEK293, and HeLa cell lines. CONCLUSIONS: This evidence suggests that the duplication might have a role in regulating the expression of the DRD4 gene and provides an understanding of the biological mechanisms underlying the etiology of neuropsychiatric disorders such as ADHD, schizophrenia, and metamphetamine abuse.

5' Flanking Region↗
PubMed2004

Genome-wide linkage analysis of a composite index of neuroticism and mood-related scales in extreme selected sibships.

There is considerable evidence to suggest that the genetic vulnerabilities to depression and anxiety substantially overlap and quantitatively act to alter risk to both disorders. Continuous scales can be used to index this shared liability and are a complementary approach to the use of clinical phenotypes in the genetic analysis of depression and anxiety. The aim of this study (Genetic and Environmental Nature of Emotional States in Siblings) was to identify genetic variants for the liability to depression and anxiety after the application of quantitative genetic methodology to a large community-based sample (n = 34,371), using four well-validated questionnaires of depression and anxiety. Genetic model fitting was performed on 2658 unselected sibships, which provided evidence for a single common familial factor that accounted for a substantial proportion of the genetic variances and covariances of the four scales. Using the parameter estimates from this model, a composite index of liability (G) was constructed. This index was then used to select a smaller--but statistically powerful--sample for DNA collection (757 individuals, 297 sibships). These individuals were genotyped with more than 400 microsatellite markers. After the data were checked and cleaned, linkage analysis was performed on G and the personality scale of neuroticism using the regression-based linkage program MERLIN-REGRESS. The results indicated two potential quantitative trait loci (QTL): one on chromosome 1p (LOD 2.2) around 64 cM (43-70 cM) near marker D1S2892 and another on chromosome 6p (LOD 2.7) around 47 cM (34-63 cM) near marker D6S1610. Further exploratory sex-specific analyses suggested that these QTLs might have sex-limited effects.

Adolescent↗
PubMed2004

Do aggressive and non-aggressive antisocial behaviors in adolescents result from the same genetic and environmental effects?

Antisocial behavior (ASB) in adolescents can broadly be separated into two forms; aggressive and non-aggressive. Both are heritable and it has been suggested that aggressive ASB is more heritable. The extent to which genes contribute to the correlation between the two is unknown. Structural equation modeling was applied to a population-based twin sample of 258 twins pairs aged 11-18 to estimate the heritability of each form of ASB and to estimate the extent to which the phenotypic correlation was the consequence of shared genes and environmental factors. Non-shared environment and genetic factors substantially influenced both forms of ASB. The heritability of aggressive (but not non-aggressive) ASB was significantly higher in girls than in boys. Combining both sexes, a model in which the genetic effects on aggressive and non-aggressive ASB were identical could be rejected. Our results suggest a partial genetic overlap with a specific genetic effect contributing to the variance of aggressive ASB and a stronger genetic effect on aggression in females than in males.

Adolescent↗