Biomedical subjects

A Pickles

Publications and source records attributed to A Pickles.

At least 19 recordsLinked to original sources

PubMed2006

Familial loading in specific language impairment: patterns of differences across proband characteristics, gender and relative type.

There is now little doubt that both environmental factors and genes are likely to make important contributions to the aetiology of specific language impairment (SLI). The most commonly proposed model for understanding these influences is the multifactorial model. In the present study we examine two expectations based on this model: that there will be a systematic relationship between the severity of proband language scores and the rate and severity of SLI in relatives and that relatives will be more strongly affected if they are relatives of a proband of the more rarely affected gender (female) because the latter require a higher genetic liability to become equally impaired. Ninety-three probands and their 300 first-degree relatives participated in this study. Results showed a relationship between proband severity at age 14 and an increased rate of SLI in relatives. This relationship was strong for child siblings and was significant with respect to both rate of SLI and severity over a range of language and literacy measures. In contrast, higher levels of SLI among relatives of female rather than male probands was entirely disproved.

Adolescent↗

PubMed2005

Making sense of informant disagreement for overanxious disorder.

A community sample of 2798 8-17-year-old twins and their parents completed a personal interview about the child's current psychiatric history on two occasions separated by an average of 18 months. Parents also completed a personal interview about their own lifetime psychiatric history at entry to the study. Results indicate that informant agreement for overanxious disorder (OAD) was no better than chance, and most cases of OAD were based on only one informant's ratings. Disagreement about level of OAD symptoms or presence of another disorder (mostly phobias or depression) accounted for most cases of informant disagreement: 60% of cases based only on child interview, 67% of cases based only on maternal interview, and 100% of cases based only on paternal interview. OAD diagnosed only by maternal interview was also distinguished by an association with maternal alcoholism and increasingly discrepant parental reports of marital difficulties. Given the substantial overlap in case assignments for DSM-III-R OAD and DSM-IV GAD, these findings may identify sources of informant disagreement that generalize to juvenile GAD.

Adolescent↗

PubMed2005

[Use of telepathology to provide rapid diagnosis of neurosurgical specimens].

To determine whether still digital images of neurosurgical specimens sent by e-mail are an effective and safe way of obtaining an emergency pathological diagnosis, representative images from 48 neurosurgical smear specimens were digitized, compressed and sent by electronic mail to our consultant neuropathologist with relevant clinical and radiological information. The time to select, digitize, compress and send the images for each case was recorded. Comparison was made between diagnosis made from digital images (DI) and historical smear (HS) using the original permanent section (PS) diagnosis as the gold standard. A diagnosis of normal vs. abnormal, neoplastic vs. non-neoplastic, primary vs. secondary and tumor grade was made in each case. The mean time for selection and digitalization of each case was 9.51 minutes. The number of correct pathological diagnosis was 41/48 using DI and 48/48 using HS, giving an accuracy rate of 85.4% and 100% respectively. DI was 100% sensitive in recognizing neoplastic tissue but only 98% specific. Most inaccuracies were in grading and caused by problems with field selection and familiarity with the technique. We conclude that static digital images are reliable and safe method of interpreting tissue during neurosurgical procedures. This corresponds with the findings of previous studies.

Brain Neoplasms↗

PubMed2005

Influence of serotonin transporter gene polymorphisms on cognitive decline and cognitive abilities in a nondemented elderly population.

Dysfunction of the serotonergic pathway disrupts normal cognitive functioning and is believed to be the underlying basis for a variety of psychiatric disorders. Two functional polymorphisms within the serotonin transporter (SLC6A4) gene (promoter 44 bp insertion/deletion (HTTLPR) and an intron two 16 or 17 bp variable number tandem repeat (VNTR2)) have been extensively studied in psychiatric conditions but not in the cognitive functioning of normal individuals. We have investigated these two polymorphisms for association with both the level of cognitive abilities and their decline with age using a cohort consisting of over 750 elderly nondemented individuals with a follow-up of up to 15 years. We found that volunteers homozygous for the VNTR2 12 allele had a faster rate of decline for all cognitive tests. This reached significance for both tests of fluid intelligence (novel problem solving) (AH1 P=0.002, AH2 P=0.014), the test of semantic memory (P=0.010) and general cognitive ability (P=0.006). No association was observed between the HTTLPR polymorphism and the rate of cognitive decline when analysed either independently or in combination with the VNTR2 polymorphism based on their influence on expression in vitro. No associations were observed between the two polymorphisms and the baseline level of cognitive abilities. This is only the second gene that has been reported to regulate the rate of cognitive decline in nondemented individuals and may be a target for the treatment of cognitive impairment in the elderly.

Aged↗

PubMed2004

The evolution of insight, paranoia and depression during early schizophrenia.

BACKGROUND: How insight, paranoia and depression evolve in relation to each other during and after the first episode of schizophrenia is poorly understood but of clinical importance. METHOD: Serial assessments over 18 months were made using multiple instruments in a consecutive sample of 257 patients with first episode DSM-IV non-affective psychosis. Repeated measures of paranoia, insight, depression and self-esteem were analysed using structural equation modelling, to examine the direction of relationships over time after controlling for confounds. RESULTS: Depression was predicted directly by greater insight, particularly at baseline, and by greater paranoia at every stage of follow-up. Neither relationship was mediated by self-esteem, although there was a weak association of lower self-esteem with greater depression and better insight. Paranoia was not strongly associated with insight. Duration of untreated psychosis and substance use at baseline predicted depression at 18 months. CONCLUSIONS: In first-episode psychosis, good insight predicts depression. Subsequently, paranoia is the strongest predictor. Neither effect is mediated by low self-esteem. Effective treatment of positive symptoms is important in preventing and treating low mood in early schizophrenia.

Adult↗

PubMed2004

Uptake for cervical screening by ethnicity and place-of-birth: a population-based cross-sectional study.

Previous research indicates low screening uptake among South Asian women. We aimed to generate contemporary evidence of uptake by ethnicity using the screening records of eligible women resident in Manchester (n = 72613). Uptake among South Asians was lower than among other women, a difference explained by area- and practice-level confounding. A higher proportion of South Asians were recorded as 'never screened', an effect only partially explained by confounding. In practices with relatively large South Asian populations, uptake was higher among South Asians. Women born in a diverse range of overseas countries had uptake rates below 60 per cent and approximately a third of women born overseas were recorded as 'never screened'. If comprehensive coverage is to be achieved in inner city areas attention should now focus on the needs of a diverse range of ethnic minority groups other than South Asians. The routine collection of ethnicity data in primary care is also indicated.

Adult↗

PubMed2004

A population-based study of primary care predictors of non-attendance for cervical screening.

OBJECTIVE: To identify and estimate the population impact of primary care service delivery factors that independently predict non-attendance for cervical screening. SETTING: Screening records of all eligible women aged 30 years and over and resident in the former Manchester Health Authority area were analysed (n=72,613). METHODS: Practice-level and GP-level explanatory variables, along with area-level covariates, were obtained and merged to the study data set. Logistic regression models were used to identify factors associated with having no recorded history of attending NHS cervical screening services. A multivariate model was created to identify independent predictors of non-attendance with comprehensive adjustment for women's age, area-level socio-demographic factors, and other primary care factors. Attributable fraction estimates were used to assess the population impact of the independent predictors. RESULTS: Large practice size (>4,000 patients), single-handed practice, South Asian male GP, part-time GP employment status, older age and birthplace overseas, and area-level measures of deprivation and transience independently predicted non-attendance. Women born overseas and registered at larger practices were especially unlikely to have ever attended. The combined population attributable fraction estimate for the independent predictors reflecting primary care service delivery was almost 40%, and that for all variables in the final model was over 70%. CONCLUSIONS: Independent predictors of non-attendance reflecting general practice structure, workload and GP characteristics were identified. Although relative risks were modest, the collective population impact of these factors was considerable, which has implications for the implementation of informed targeting and the development of new screening services by Primary Care Trusts.

Adult↗

PubMed2001

Association between idiopathic infantile macrocephaly and autism spectrum disorders.

We conducted a case-controlled, catch-up study of a cohort of boys born with macrocephaly in order to determine whether infantile macrocephaly is a risk marker for the later development of autism spectrum disorders. Our results show that infantile macrocephaly was associated with an increased risk of developing autism spectrum disorders (odds ratio 5.44, 95% CI 1.11-52.15; p=0.03). These findings suggest that neurobiological differences during infancy may predict behavioural manifestations of autism spectrum disorders.

Autistic Disorder↗

PubMed2001

A family genetic study of autism associated with profound mental retardation.

We sought to determine if the family loading for either the broader autism phenotype or for cognitive impairment differed according to whether or not autism was accompanied by severe mental retardation. The sample comprised 47 probands with autism meeting ICD-10 criteria, as assessed by the Autism Diagnostic Interview and the Autism Diagnostic Observation Schedule. Family history interview and findings were compared with those for the higher IQ autism and Down syndrome samples in the Bolton et al. (1994) study. The familial loading for autism and for the broader phenotype was closely comparable to that in the study of higher IQ autism, and different from that for Down syndrome. The family loading for scholastic achievement difficulties was slightly, but significantly, higher when autism was accompanied by severe retardation.

Adolescent↗

PubMed2001

Testing hypotheses on specific environmental causal effects on behavior.

There have been strong critiques of the notion that environmental influences can have an important effect on psychological functioning. The substance of these criticisms is considered in order to infer the methodological challenges that have to be met. Concepts of cause and of the testing of causal effects are discussed with a particular focus on the need to consider sample selection and the value (and limitations) of longitudinal data. The designs that may be used to test hypotheses on specific environmental risk mechanisms for psychopathology are discussed in relation to a range of adoption strategies, twin designs, various types of "natural experiments," migration designs, the study of secular change, and intervention designs. In each case, consideration is given to the need for samples that "pull-apart" variables that ordinarily go together, specific hypotheses on possible causal processes, and the specification and testing of key assumptions. It is concluded that environmental risk hypotheses can be (and have been) put to the test but that it is usually necessary to use a combination of research strategies.

Adult↗

PubMed2001

Multilevel models for censored and latent responses.

Multilevel models were originally developed to allow linear regression or ANOVA models to be applied to observations that are not mutually independent. This lack of independence commonly arises due to clustering of the units of observations into 'higher level units' such as patients in hospitals. In linear mixed models, the within-cluster correlations are modelled by including random effects in a linear model. In this paper, we discuss generalizations of linear mixed models suitable for responses subject to systematic and random measurement error and interval censoring. The first example uses data from two cross-sectional surveys of schoolchildren to investigate risk factors for early first experimentation with cigarettes. Here the recalled times of the children's first cigarette are likely to be subject to both systematic and random measurement errors as well as being interval censored. We describe multilevel models for interval censored survival times as special cases of generalized linear mixed models and discuss methods of estimating systematic recall bias. The second example is a longitudinal study of mental health problems of patients nested in clinics. Here the outcome is measured by multiple questionnaires allowing the measurement errors to be modelled within a linear latent growth curve model. The resulting model is a multilevel structural equation model. We briefly discuss such models both as extensions of linear mixed models and as extensions of structural equation models. Several different model structures are examined. An important goal of the paper is to place a number of methods that readers may have considered as being distinct within a single overall modelling framework.

Adolescent↗

PubMed2001

Child sexual abuse, poor parental care and adult depression: evidence for different mechanisms.

BACKGROUND: Child sexual abuse (CSA) and poor parental care (neglect and institutional care) are associated with depression in adult life. Little is known about possible mechanisms underlying these associations. AIMS: To examine the role of adult intimate-love relationships as differential mediators or moderators of the associations between CSA, poor parental care and adult depression. METHOD: Sampling was carried out in two phases. In the first, questionnaires were sent to women aged 25-36 years in five primary care practices. Second-phase subjects for interview (n=198) were drawn from three strata defined on the basis of childhood adversities. Recalled childhood experiences and recent adult relationships and depression were assessed and rated independently. Frequencies of predictor and response variables, effect estimates and their confidence intervals were weighted back to the general population questionnaire sample. RESULTS: The risk for depression associated with CSA was unaffected by quality of adult relationships, while the risk associated with poor parental care was substantially altered. CONCLUSIONS: There may be different pathways linking CSA and poor parental care to adult depression.

Adult↗

PubMed2001

Child psychiatric symptoms and psychosocial impairment: relationship and prognostic significance.

BACKGROUND: Relatively little is known about the relationships between psychiatric symptoms, diagnosis and psychosocial impairment. AIMS: To examine these contemporaneous relationships and prognostic significance in a large general population sample. METHOD: Symptoms of major depression, conduct and oppositional defiant disorders were assessed by interview in two waves of the Virginia Twin Study of Adolescent behavioural Development (2800 children aged 8-16 years). RESULTS: Many children below the DSM-III-R diagnostic threshold, especially for depression, had symptom-related impairment, whereas many children reaching the symptom threshold for conduct and oppositional defiant disorders were little impaired. Impairment score was linearly related to symptom count, with no evidence of any additional impairment at the diagnostic threshold. For depression, only symptoms predicted later symptoms and diagnosis. For conduct and oppositional defiant disorders, impairment was additionally predictive of later symptoms and diagnosis. CONCLUSIONS: Impairment, in addition to symptoms, is important for both nosology and prognosis.

Activities of Daily Living↗

PubMed2001

Parental concordance and comorbidity for psychiatric disorder and associate risks for current psychiatric symptoms and disorders in a community sample of juvenile twins.

In this report we characterize associations between parental psychiatric disorders and children's psychiatric symptoms and disorders using a population-based sample of 850 twin families. Juvenile twins are aged 8-17 years and are personally interviewed about their current history of DSM-III-R conduct, depression, oppositional-defiant, overanxious, and separation anxiety disorders using the CAPA-C. Mothers and fathers of twins are personally interviewed about their lifetime history of DSM-III-R alcoholism, antisocial personality disorder, generalized anxiety disorder, major depression, panic disorder/agoraphobia, social phobia, and simple phobia using a modified version of the SCID and the DIS. Generalized least squares and logistic regression are used to identify the juvenile symptoms and disorders that are significantly associated with parental psychiatric histories. The specificity of these associations is subsequently explored in a subset of families with maternal plus parental psychiatric histories with a prevalence > 1%. Parental depression that is not comorbid or associated with a different spousal disorder is associated with a significantly elevated level of depression and overanxious disorder symptoms and a significantly increased risk for overanxious disorder. Risks are higher for both symptomatic domains in association with maternal than paternal depression, and highest in association with maternal plus paternal depression. Risks for otherjuvenile symptoms and disorders index the comorbid and spousal histories with which parental depression is commonly associated. Paternal alcoholism that is not comorbid or associated with a maternal disorder is not significantly associated with current psychiatric symptoms or disorders in offspring. Risks for oppositional-defiant or conduct symptoms/disorders in the offspring of alcoholic parents index parental comorbidity and/or other spousal histories.

Adolescent↗

PubMed2001

Do high-threat life events really provoke the onset of psychiatric disorder in children?

Studies on adults have suggested important effects of stressful life events in provoking onset of psychiatric disorder. Only a few comparable studies on children exist, and their results are inconsistent in relation to definite timing effects. Meeting some important methodological challenges overlooked in the past research, this study set out to examine whether the onset of psychiatric disorder in children was more likely to occur shortly after a severe event, as compared with other times. The sample consisted of 99 consecutive, newly referred patients, aged 8-16 years, from a child psychiatry service in London. PACE (Psychosocial Assessment of Childhood Experiences), an investigator-based, standardized interview was used to assess the timing and impact of life events over the preceding 18 months. CAPA (Child and Adolescent Psychiatric Assessment), a standardized diagnostic assessment, was used to establish the presence, timing, and consequential impairment of child and adolescent psychiatric symptoms. In a within-subject, over-time design, conditional logistic regression techniques were employed to examine whether risk of onset was greater in the 9 weeks following a high-threat life event than at other times. There was a small but statistically significant association between child-reported events and child-reported onset; the associations with parent-reported onset were inconsistent. Parent-reported events failed to relate to onset by either source. The study offers only quite limited support to the notion of negative life events provoking onset of psychiatric disorder in children and young people. The possible reasons for this are discussed, together with important conceptual and methodological issues to problems of defining onset, and the choice of appropriate designs for data analysis.

Adolescent↗

PubMed2000

Familial aggregation for conduct disorder symptomatology: the role of genes, marital discord and family adaptability.

BACKGROUND: There is extensive evidence of statistical associations between family discord/ maladaptation and antisocial behaviour in the children, but questions remain on the extent to which the psychopathological risks are genetically or environmentally mediated. METHODS: Twin pairs (N = 1,350), aged 8 to 16 years, in the general population-based Virginia Twin Study of Adolescent Behavioral Development were assessed using the Child and Adolescent Psychiatric Assessment interview administered separately to both twins and both parents. Structured interviews for parental lifetime psychiatric disorders were also administered to the mothers and fathers. Maternal reports on Olsson's Family Adaptability and Cohesiveness questionnaire and the Dyadic Adjustment Scale were used as indices of the family environment. A path analytical model based on an extended twin-family design was used to test hypotheses about parent offspring similarity for conduct disorder symptomatology. RESULTS: Family discord and maladaptation, which intercorrelated at 0.63, were associated with a roughly two-fold increase in risk for conduct disorder symptomatology. When parental conduct disorder was included in the model the environmental mediation effect for family maladaptation remained, but that for family discord was lost. CONCLUSION: It is concluded that there is true environmental mediation from family maladaptation, operating as a shared effect, which accounts for 3.5 % of the phenotypic variance. The assumptions underlying this genetic research strategy are made explicit, together with its strengths and limitations.

Adaptation, Psychological↗

PubMed2000

Personality traits of the relatives of autistic probands.

BACKGROUND: There is substantial evidence that the genetic liability to autism confers a risk for a range of more subtle social and communication impairments, as well as stereotyped and repetitive behaviours. Recent research suggests that increased expression of particular personality traits may be a manifestation of the liability to autism. METHODS: To investigate this we examined the personality traits of the adult relatives of 99 autistic and 36 Down's syndrome probands, using the informant version of the Modified Personality Assessment Schedule. RESULTS: There was significantly increased expression of the traits anxious, impulsive, aloof, shy, over-sensitive, irritable and eccentric among the autism relatives with evidence of different profiles for male and female relatives and for parents and adult children. Factor analysis revealed three broad groups of traits, two of which ('withdrawn' and 'difficult') appeared to reflect impairments in social functioning and a third group of anxiety related traits ('tense'). Each of these factors differed in their pattern of associations with the factor we termed 'withdrawn' showing a similar pattern of association to that found for other autism related conditions. The 'tense' factor appeared in part to be related to the burden of caring for an autistic child. CONCLUSIONS: This study confirms the finding that particular personality traits may aggregate in the family members of autistic individuals and furthermore that some of these traits may be a manifestation of the liability to autism.

Adult↗

PubMed2000

An evaluation of different approaches for behavior genetic analyses with psychiatric symptom scores.

We used a simulation study to evaluate six approaches for behavior genetic analyses of psychiatric symptom scores. For the selection of the correct model, the best results were obtained with approaches using transformed scores in combination with a procedure involving p-values. With normalizing transformations, the chi 2 test statistic gave a reasonable impression of the overall fit of the model but was less accurate when used as a difference test. The asymptotic distribution free estimation methods yielded chi 2s that were much too large. All data analysis techniques yielded substantially biased parameter estimates. The most biased results were obtained with normalizing transformations. The least biased results were obtained with tobit correlations, but because of its large standard errors the most precise estimates were obtained with polychoric correlations and optimal scale scores. An empirical study showed that a recognition of the role of methodological factors was helpful to understand part of the differences between assessment instruments, raters, and data analysis techniques that were found in the real data.

Adolescent↗