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Biomedical subjects

Peter McGuffin

Publications and source records attributed to Peter McGuffin.

At least 37 records · Page 2Linked to original sources
PubMed2004

Familiality of symptom dimensions in depression.

BACKGROUND: Depression is a clinically heterogeneous disorder thought to result from multiple genes interacting with environmental and developmental components. A dimensional rather than a categorical approach to depressive phenotype definition may be more useful for identification of susceptibility genes. OBJECTIVES: To perform an exploratory factor analysis on a range of depressive and anxiety symptoms in a large, well-defined sample of depressed siblings, as well as a confirmatory factor analysis in a separate large group of unrelated depressed subjects, and to analyze correlations of identified symptom dimensions between depressed siblings. DESIGN: Subjects (N = 1034), including 475 sibling pairs, with a history of at least 2 depressive episodes were recruited from the Depression Network Study, a large-scale multicenter collection of families affected by recurrent unipolar depression. Subjects were interviewed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and diagnosed according to the DSM-IV and the International Classification of Diseases, 10th Revision, using a computerized scoring program (CATEGO5). Factor analysis was carried out on 26 depression symptom items, including 4 anxiety screening items. Confirmatory factor analysis was performed on an independent sample of 485 depressed individuals. RESULTS: Four interpretable factors were identified: (1) mood symptoms and psychomotor retardation; (2) anxiety; (3) psychomotor agitation, guilt, and suicidality; and (4) appetite gain and hypersomnia. For each symptom group, a quantitative scale was constructed, and correlations between siblings were calculated. There was a moderate degree of sibling homotypia for some depressive symptoms, and factors 1, 2, and 3 showed significant positive familial correlation (0.145 [P =.001], 0.335 [P<.001], and 0.362 [P<.001], respectively). CONCLUSIONS: This is the first study of large, well-defined samples of depressed subjects in whom symptom dimensions have been derived and then confirmed using independent material. The significant correlations between siblings for 3 of the dimensions suggest substantial familial, perhaps genetic, etiologies.

Adult↗
PubMed2004

Conduct problems in children and adolescents: a twin study.

BACKGROUND: Evidence supports a genetic influence on conduct problems as a continuous measure of behavior and as a diagnostic category. However, there is a lack of studies using a genetically informative design combined with several different informants and different settings. OBJECTIVES: To examine genetic and environmental influences on conduct problems rated by parent and teacher reports and self-reports and to determine whether their ratings reflect a common underlying phenotype. DESIGN: A twin study design was used to examine conduct problem scores from ratings by teachers, parents, and twins themselves. SETTING: General community. PARTICIPANTS: Twins aged 5 to 17 years participating in the Cardiff Study of All Wales and North England Twins (CaStANET) project. MAIN OUTCOME MEASURES: Conduct problem scale from the Strengths and Difficulties Questionnaire. RESULTS: Conduct problem scores were significantly heritable based on parent and teacher reports and self-reports. Combining data from all 3 informants showed that they are rating a common underlying phenotype of pervasive conduct problems that is entirely genetic, while teacher ratings show separate genetic influences that are not shared with other raters. CONCLUSIONS: Conduct problems are significantly heritable based on parent and teacher reports and self-reports, and are also influenced by environmental effects that impinge uniquely on children from the same family. There is a cross-situational conduct problems' phenotype, underlying the behavior measured by all informants, that is wholly genetic in origin. No significant influence of shared environmental effects was found.

Adolescent↗
PubMed2004

The Social, Genetic and Developmental Psychiatry Centre: its origins, conception and initial accomplishments.

BACKGROUND: The Social, Genetic and Developmental Psychiatry Centre was established by the Medical Research Council, in partnership with the Institute of Psychiatry, King's College London, in 1994. METHOD AND RESULTS: The paper describes the origins of the Centre; the reasons why a new initiative was needed in the early 1990s; the thinking that led to the proposal for a major interdisciplinary research centre that integrated social, genetic and developmental research perspectives; the approach to international recruitment of world leaders; and the initial research accomplishments with respect to the basic goal of understanding nature-nurture interplay. CONCLUSIONS: The structure and interdisciplinary approach of the Centre have proved a success and the initial accomplishments have begun to meet the objectives of showing how nature-nurture interplay is involved in the development of psychiatric disorders.

Child Psychiatry↗
PubMed2004

The genetic relationship between social cognition and conduct problems.

Studies of children and adolescents with conduct problems suggest both genetic and environmental influences on population variance. Any genetic influence is likely to be complex and to act via mediating attributes of personality or cognitive style. One potential mediating attribute is social cognitive ability, as conduct problems have been shown to be associated with deficient social cognitive skills. The current investigation has examined the correlation between conduct problems and social cognition and has investigated the genetic and environmental influences on these measures and their covariation using a twin design. A population-based sample of twins aged 5-17 was used to examine the genetic relationship between conduct problems and social cognition using parent-report questionnaires. Conduct problems and social cognition were found to be highly correlated and to share common genetic influences that accounted for about half the covariation in scores. Each phenotype was subject to its own environmental influences that were not shared.

Adolescent↗
PubMed2004

Commingling analysis of intraocular pressure and glaucoma in an older Australian population.

PURPOSE: To test the hypothesis of a major genetic determinant of intraocular pressure (IOP) under the mixed genetic model in a defined population, and to elucidate the relationship between IOP and glaucoma. METHODS: IOP was measured in 3654 persons attending the Blue Mountains Eye Study. A commingling analysis on IOP was performed using a new program, SKUDRIVER. The goodness of fit of 1-, 2- and 3-distribution models was measured. This was repeated after the glaucoma cases had been removed from the dataset, and further repeated on the glaucoma cases in the dataset. RESULTS: The best model was 3-distribution with no evidence for Hardy-Weinberg disequilibrium. The proportion of variance explained by this major effect was 0.18. When glaucoma cases were removed, the best model had 2 distributions. There was no evidence of admixture in glaucoma patients. CONCLUSIONS: The findings of this study are consistent with the presence of a major gene accounting for 18% of the variance of IOP, which could therefore influence the risk of glaucoma, in this population. These findings suggest methods of optimizing strategies for family and association studies to identify quantitative trait loci for IOP. No evidence for distinct IOP-dependent and IOP-independent subgroups of glaucoma was found.

Adult↗
PubMed2004

Nature and nurture interplay: schizophrenia.

There is compelling evidence from family, twin and adoption studies of a substantial genetic contribution to schizophrenia. The mode of transmission is complicated and very rarely if ever involves a single gene. Rather schizophrenia results from multiple genes of small effect and their interplay with the environment. Perhaps because the overall size of the genetic effect is large, accounting for about 80 % of variance, definite environmental factors have been difficult to pin down. It has even been suggested that "the environment" consists entirely of epigenetic or stochastic phenomena that can never be detected by a standard epidemiological methods. Nevertheless, a variety of social stressors, including high expressed emotion in relatives and life events affect the course of illness and certain physical factors such as obstetric complications and cannabis smoking have been implicated in contributing to liability to the disorder. The recent discovery of several positional candidate genes that have been replicated as being associated with liability to schizophrenia holds considerable promise not just for a better understanding of the neurobiology but also for improved knowledge about risk prediction and gene-environment interplay.

Diseases in Twins↗
PubMed2004

The development of prosocial behaviour in children and adolescents: a twin study.

BACKGROUND: Childhood psychopathology is associated with both high and low levels of prosocial behaviour. It has been proposed that the development of prosocial behaviour shows emerging and consolidating individual differences as children grow older. The influences on these individual differences have not previously been examined in children and adolescents using multiple raters in a genetically informative design. METHODS: Twin data from 682 families based on parent and teacher reports were used to examine the genetic and environmental influences on prosocial behaviour in 5-16-year-olds. Effects of sex, age and rater were examined. RESULTS: There were no significant differences in the magnitude of genetic and environmental influence on male and female prosocial behaviour. Declining common environment and increasing genetic influences were seen with age. This emerged as a trend in parent data and reached statistical significance in teacher data. When parent and teacher data were examined together in a rater bias model significant bias acting on the parent ratings emerged, in keeping with previous discrepancies between parental and observational measures. There was overlap in the phenotype rated by parents and teachers, with a highly heritable common underlying phenotype. CONCLUSIONS: The influences on the distribution of prosocial behaviour in children and adolescents show declining shared environmental and increasing genetic influences with age. Parental assessments of prosocial behaviour show significantly higher scores than teacher reports and whilst there is overlap in the phenotype rated by parents and teachers, parents show significant bias in their ratings.

Adolescent↗
PubMed2003

A sib-pair study of the Temperament and Character Inventory scales in major depression.

BACKGROUND: Certain aspects of the personality may be associated with the vulnerability to develop depression. A sib-pair method has been used to examine the familiality of the 7 scales of the Temperament and Character Inventory (TCI) and whether this could be related to the genetic vulnerability to develop depression. METHODS: Probands with depression and their nearest-aged siblings from Wales were compared with healthy control probands and their nearest-aged siblings on the TCI and measures of depressed mood. RESULTS: All 7 scales of the TCI were familial, and scores on 6 of the scales were similar to US population scores. However, the Welsh subjects' scores on the self-transcendence scale were markedly lower than the US mean, suggesting strong cultural or national influences on this measure. Harm avoidance scores were substantially influenced by current and past depression, but this scale also showed stable traitlike characteristics that are likely related to the genetic vulnerability to depression. Novelty seeking and self-directedness were also partly state-dependent and were negatively correlated with low mood; high scorers may be resilient to the development of depression. High reward dependence may also protect against the development of depression and is unrelated to mood state. The cooperativeness, persistence, and self-transcendence scales appear to have a limited relationship with the development of depression. CONCLUSIONS: Harm avoidance, reward dependence, novelty seeking, and self-directedness have traitlike characteristics that are related to the familiality of depression. Cooperativeness, self-transcendence, and persistence are also familial, but this appears to be unrelated to depression.

Adult↗
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↗
PubMed2003

Linkage and association studies of schizophrenia.

Recent twin studies confirm that schizophrenia is highly heritable, but attempts to locate and identify genes have proved to be difficult. This is largely because major genes appear to be rare or nonexistent. Instead, genetic liability almost certainly results from the combined effects of multiple susceptibility loci and most studies have been under-equipped to detect such effects. Nevertheless, several regions of the genome have been implicated by more than one linkage study and chromosome 22q has been implicated by linkage and by studies of patients with microdeletions. Recent work attempting to refine regions of interest using linkage dysequilibrium mapping has identified four promising and novel "positional candidates;" they are neuregulin-1 on chromosome 8p-p21, G72 located at chromosome 13q34, dysbindin at 6p22.3, and proline dehydrogenase, which is a gene that maps to chromosome 22q11. In addition, there is renewed interest in a fifth gene, catechol-O-methyltransferase, also on chromosome 22q11.

Carrier Proteins↗
PubMed2003

Humiliation, loss and other types of life events and difficulties: a comparison of depressed subjects, healthy controls and their siblings.

BACKGROUND: It has been proposed that adverse life events involving loss or humiliation are particularly potent in provoking depressive episodes. We have also previously suggested that experiencing high rates of non-severe events may play a role in the development of resilience to the impact of severe threatening events when these occur. METHOD: The Life Events and Difficulties Schedule (LEDS) (Brown & Harris, 1978) was used to record the life events experienced by 108 depressed probands and their nearest aged siblings as well as 105 healthy control subjects and their nearest aged siblings. All subjects were interviewed using the Schedule for the Clinical Assessment of Neuropsychiatry (SCAN) (Wing et al. 1990). RESULTS: Depressed probands were significantly more likely to have experienced a severe threatening event, loss event, or a humiliation event compared to the other subjects. These events also made up a greater proportion of the total number of events, in the depressed probands. Humiliation events were more frequent in depressed men than depressed women. There were no differences between the four groups for experiencing a non-severe event, although depressed probands also experienced more difficulties than the other three groups. Fifty-six healthy subjects who had not become depressed despite having experienced at least one severe and threatening event, had significantly more non-severe events, than the 116 subjects who were depressed at the time of interview. CONCLUSIONS: The findings support the hypothesis that loss and humiliation events are particularly depressogenic. Experiencing a high rate of non-severe events may be associated with resilience to becoming depressed in the face of a threatening event.

Adaptation, Psychological↗
PubMed2003

Fifty years of the double helix and its impact on psychiatry.

OBJECTIVE: To discuss the impact of Watson and Crick's double helix discovery on the field of psychiatry. METHOD: Psychiatric research studies using molecular genetic techniques are summarized. The implications of these findings in terms of our understanding and treatment of mental illness are discussed. RESULTS: There now exists growing evidence of candidate gene sites for a variety of psychiatric disorders ranging from schizophrenia to reading disability. CONCLUSIONS: The field of psychiatric genetics has become one of the most vital and productive areas of psychiatric research. New findings are continually coming to light, bringing us ever closer to understanding these complex disorders at a molecular level. Such knowledge could lead to improved drug treatments, screening of at-risk individuals and even a reduction in the stigma attached to psychiatric disorders.

Bipolar Disorder↗
PubMed2003

Age and birth cohort effects on rates of alcohol dependence.

BACKGROUND: Epidemiological studies of traits such as alcohol dependence and depression have often found lifetime rates in younger individuals exceeding those found in older individuals. This suggests additional influences of birth cohort or period effects so that individuals in later-born cohorts have an increased lifetime risk. METHODS: Data from the Collaborative Study on the Genetics of Alcoholism were used to investigate secular trends for alcoholism and related conditions and to examine risk predictors while taking the cohort effect into account. We used data on 4099 interviewed parents and siblings of alcohol-dependent subjects and 1054 members of control families. We used survival analysis techniques and the Cox proportional hazards regression model to estimate the relative risk for demographic covariates. We used the relative sample to predict risk in the sibling of the proband and family history information to determine whether there was a bias when deceased individuals were excluded from analysis. RESULTS: In the control sample, we observed a 1.8% lifetime rate of DSM-III-R alcohol dependence in women born before 1940, as contrasted to a 13% rate in women born after 1960, and a 15% lifetime rate in men born before 1940, contrasted with a 28% rate in men born after 1960. As expected, lifetime rates in relatives were increased when compared with controls. Highly significant risk ratios (RR) were observed for gender (RR, 2.3), cohort of birth (RR, 1.5 over a decade), daily smoking (RR, 2.0), heavy smoking (RR, 3.0), and comorbid diagnoses of antisocial personality (RR, 2.2) and depression (RR, 1.6). Analysis of the family history data indicated higher rates of alcohol dependence in relatives who were deceased compared to those who were living. CONCLUSIONS: Marked cohort differences were observed and may reflect real changes over time, or artifacts of memory recall, differential mortality, or public awareness. The analysis of all relatives (living or deceased) indicates that associated mortality may, in part, explain the secular trends seen when analyses are restricted to living, personally interviewed individuals.

Adolescent↗
PubMed2003

Depressive symptoms in children and adolescents: changing aetiological influences with development.

BACKGROUND: Evidence suggests that depressive symptoms become increasingly heritable as children grow into adolescence. However, the literature is not entirely consistent in this respect and existing longitudinal twin studies have examined changes within adolescence only. METHOD: Parent and self-report questionnaire data were used to examine the genetic and environmental influences on depressive symptoms in a UK sample of 670 twin pairs aged 5-17. Age effects were examined cross-sectionally and longitudinally using data collected over a 3-year period. RESULTS: Cross-sectional analyses showed that shared environmental effects had significant influence in younger children but not in adolescence, when depression scores were significantly more heritable. The results of these cross-sectional analyses were supported when two waves of parent-report data collected over three years were analysed. Significant new genetic influences emerged in adolescence but no new shared environmental influences. Some sex differences were found, with girls showing greater genetic influence than boys, but only from parent-report data. CONCLUSIONS: These findings support and extend earlier work which has shown increasing genetic influence on depressive symptoms as children grow into adolescence.

Adolescent↗
PubMed2002

Psychopathology in the postgenomic era.

We are rapidly approaching the postgenomic era in which we will know all of the 3 billion DNA bases in the human genome sequence and all of the variations in the genome sequence that are ultimately responsible for genetic influence on behavior. These ongoing advances and new techniques will make it easier to identify genes associated with psychopathology. Progress in identifying such genes has been slower than some experts expected, probably because many genes are involved for each phenotype, which means the effect of any one gene is small. Nonetheless, replicated linkages and associations are being found, for example, for dementia, reading disability, and hyperactivity. The future of genetic research lies in finding out how genes work (functional genomics). It is important for the future of psychology that pathways between genes and behavior be examined at the top-down psychological level of analysis (behavioral genomics), as well as at the bottom-up molecular biological level of cells or the neuroscience level of the brain. DNA will revolutionize psychological research and treatment during the coming decades.

Animals↗
PubMed2002

Association of DRD4 in children with ADHD and comorbid conduct problems.

Recent family and twin study findings suggest that ADHD when comorbid with conduct problems may represent a particularly familial and heritable form of ADHD. Although several independent groups have shown association between the DRD4 7 repeat allele and ADHD, others have failed to replicate this finding. Previous TDT analyses of UK and Eire samples had also been negative. We set out to further examine the role of DRD4 but selecting a subgroup of children with ADHD and comorbid conduct problems. Families were recruited from Manchester, Ireland, Birmingham and London clinics. From these, 67 children who fulfilled diagnostic criteria for ADHD and who displayed conduct disorder symptoms were selected. TDT analysis, which had previously yielded negative results for the total sample, showed evidence of association between DRD4 and "ADHD with conduct problems" (7 repeat allele-24 transmissions, 13 non-transmissions; one-tailed P=0.05). These results provide further support for the role of DRD4 in ADHD. Furthermore, these results when considered together with family and twin study findings, suggest that those children with ADHD and comorbid conduct problems may be particularly informative for molecular genetic studies of ADHD. Further work is needed to examine these phenotype issues.

Adolescent↗