Biomedical subjects

Andrew Pickles

Publications and source records attributed to Andrew Pickles.

At least 19 recordsLinked to original sources

PubMed2007

A flexible model for multivariate interval-censored survival times with complex correlation structure.

We focus on the analysis of multivariate survival times with highly structured interdependency and subject to interval censoring. Such data are common in developmental genetics and genetic epidemiology. We propose a flexible mixed probit model that deals naturally with complex but uninformative censoring. The recorded ages of onset are treated as possibly censored ordinal outcomes with the interval censoring mechanism seen as arising from a coarsened measurement of a continuous variable observed as falling between subject-specific thresholds. This bypasses the requirement for the failure times to be observed as falling into non-overlapping intervals. The assumption of a normal age-of-onset distribution of the standard probit model is relaxed by embedding within it a multivariate Box-Cox transformation whose parameters are jointly estimated with the other parameters of the model. Complex decompositions of the underlying multivariate normal covariance matrix of the transformed ages of onset become possible. The new methodology is here applied to a multivariate study of the ages of first use of tobacco and first consumption of alcohol without parental permission in twins. The proposed model allows estimation of the genetic and environmental effects that are shared by both of these risk behaviours as well as those that are specific.

Adolescent↗

PubMed2006

The Autism Diagnostic Observation Schedule: revised algorithms for improved diagnostic validity.

Autism Diagnostic Observation Schedule (ADOS) Modules 1-3 item and domain total distributions were reviewed for 1,630 assessments of children aged 14 months to 16 years with an autism spectrum disorder (ASD) or with heterogeneous non-spectrum disorders. Children were divided by language level and age to yield more homogeneous cells. Items were chosen that best differentiated between diagnoses and were arranged into domains on the basis of multi-factor item-response analysis. Reflecting recent research, the revised algorithm now consists of two new domains, Social Affect and Restricted, Repetitive Behaviors (RRB), combined to one score to which thresholds are applied, resulting in generally improved predictive value.

Adolescent↗

PubMed2006

Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP).

BACKGROUND: Recent reports have suggested that the prevalence of autism and related spectrum disorders (ASDs) is substantially higher than previously recognised. We sought to quantify prevalence of ASDs in children in South Thames, UK. METHODS: Within a total population cohort of 56 946 children aged 9-10 years, we screened all those with a current clinical diagnosis of ASD (n=255) or those judged to be at risk for being an undetected case (n=1515). A stratified subsample (n=255) received a comprehensive diagnostic assessment, including standardised clinical observation, and parent interview assessments of autistic symptoms, language, and intelligence quotient (IQ). Clinical consensus diagnoses of childhood autism and other ASDs were derived. We used a sample weighting procedure to estimate prevalence. FINDINGS: The prevalence of childhood autism was 38.9 per 10,000 (95% CI 29.9-47.8) and that of other ASDs was 77.2 per 10,000 (52.1-102.3), making the total prevalence of all ASDs 116.1 per 10,000 (90.4-141.8). A narrower definition of childhood autism, which combined clinical consensus with instrument criteria for past and current presentation, provided a prevalence of 24.8 per 10,000 (17.6-32.0). The rate of previous local identification was lowest for children of less educated parents. INTERPRETATION: Prevalence of autism and related ASDs is substantially greater than previously recognised. Whether the increase is due to better ascertainment, broadening diagnostic criteria, or increased incidence is unclear. Services in health, education, and social care will need to recognise the needs of children with some form of ASD, who constitute 1% of the child population.

Autistic Disorder↗

PubMed2006

Autism from 2 to 9 years of age.

CONTEXT: Autism represents an unusual pattern of development beginning in the infant and toddler years. OBJECTIVES: To examine the stability of autism spectrum diagnoses made at ages 2 through 9 years and identify features that predicted later diagnosis. DESIGN: Prospective study of diagnostic classifications from standardized instruments including a parent interview (Autism Diagnostic Interview-Revised [ADI-R]), an observational scale (Pre-Linguistic Autism Diagnostic Observation Schedule/Autism Diagnostic Observation Schedule [ADOS]), and independent clinical diagnoses made at ages 2 and 9 years compared with a clinical research team's criterion standard diagnoses. SETTING: Three inception cohorts: consecutive referrals for autism assessment to (1) state-funded community autism centers, (2) a private university autism clinic, and (3) case controls with developmental delay from community clinics. PARTICIPANTS: At 2 years of age, 192 autism referrals and 22 developmentally delayed case controls; 172 children seen at 9 years of age. MAIN OUTCOME MEASURES: Consensus best-estimate diagnoses at 9 years of age. RESULTS: Percentage agreement between best-estimate diagnoses at 2 and 9 years of age was 67, with a weighted kappa of 0.72. Diagnostic change was primarily accounted for by movement from pervasive developmental disorder not otherwise specified to autism. Each measure at age 2 years was strongly prognostic for autism at age 9 years, with odds ratios of 6.6 for parent interview, 6.8 for observation, and 12.8 for clinical judgment. Once verbal IQ (P = .001) was taken into account at age 2 years, the ADI-R repetitive domain (P = .02) and the ADOS social (P = .05) and repetitive domains (P = .005) significantly predicted autism at age 9 years. CONCLUSIONS: Diagnostic stability at age 9 years was very high for autism at age 2 years and less strong for pervasive developmental disorder not otherwise specified. Judgment of experienced clinicians, trained on standard instruments, consistently added to information available from parent interview and standardized observation.

Adult↗

PubMed2006

Estimating familial loading in SLI: a comparison of direct assessment versus parental interview.

PURPOSE: Two approaches commonly used for estimating prevalence of language disorders in families were compared. The 1st involved examining a subset of language items from an investigator-based interview used to record parental information on the language and literacy difficulties in relatives. The 2nd was the direct assessment of ability in immediate family using a battery of standardized verbal ability, language, and literacy assessments. METHOD: Using these 2 methods, the prevalence of language and literacy disorders was investigated in the immediate family (n=271) of 93 children with a history of SLI (mean age 13;11 years). RESULTS: The overall proportion of relatives with reported language or literacy difficulty was similar for both methods (34.5% for reported difficulties compared with 35% on direct assessment). The present study further explored maternal, paternal, and sibling prevalence rates and strength of agreement between parental interview and direct assessment. When a low cutoff score was used, good agreement (of true negatives and true positives) for reading and spelling difficulties and expressive language between the 2 types of case identification method was found. CONCLUSIONS: Parents can be effective identifiers when the impairment is severe (below 2 SDs from the population mean). Poor agreement was observed between report and assessment of receptive language difficulties.

Adolescent↗

PubMed2006

Early adult outcomes of adolescents who deliberately poisoned themselves.

OBJECTIVE: To describe the early adult psychopathological and social outcomes of adolescents who deliberately poisoned themselves. METHOD: Prospective cohort study with a 6-year follow-up of 132 of 158 (84%) adolescents who, between ages 11 and 16 years, had taken part in a randomized trial of a brief family intervention after deliberate self-poisoning. Comparisons were made with a sample of participants matched for age, gender, and childhood social class. Both groups were assessed using standardized measures of psychopathology and social functioning. RESULTS: In most cases (93/132 or 70%) self-harm stopped within 3 years. Psychiatric disorders, particularly depression (74/132 or 56%), were prevalent, and self-harm in adulthood was restricted to this subgroup. There was a strong association between childhood adversity, in particular childhood sexual abuse, and self-harming risk in adulthood. Adulthood adversity also added to the risk, especially for those who had experienced index episode major depression. These associations were not mediated by childhood problem solving and hopelessness. CONCLUSIONS: For some young people, deliberate self-poisoning in adolescence seems to be part of a complex and continuing network of problems, marked by high rates of psychopathology, comorbidity, with other disorders and high psychosocial adversity.

Adolescent↗

PubMed2006

Combining information from multiple sources in the diagnosis of autism spectrum disorders.

BACKGROUND: Standard case criteria are proposed for combined use of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule to diagnose autism and to define the broader category of autism spectrum disorders. METHOD: Single and combined Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule algorithms were compared to best estimate diagnoses in four samples: U.S. (n = 960) and Canadian (n = 232) participants 3 years and older, U.S. participants younger than 36 months (n = 270), and U.S. participants older than 36 months with profound mental retardation (n = 67). RESULTS: Sensitivities and specificities of 80% and higher were obtained when strict criteria for an autism diagnosis using both instruments were applied in the U.S. samples, and 75% or greater in the Canadian sample. Single-instrument criteria resulted in significant loss of specificity. Specificity was poor in the sample with profound mental retardation. Lower sensitivity and specificity were also obtained when proposed criteria for broader spectrum disorders were applied. CONCLUSIONS: The Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule make independent, additive contributions to the judgment of clinicians that result in a more consistent and rigorous application of diagnostic criteria.

Asperger Syndrome↗

PubMed2006

Subjective sleepiness and accident risk avoiding the ecological fallacy.

The present study of sleepiness and accident risk in a HI-FI car simulator aimed to provide subject-level relative risks (RR) with 95% confidence intervals (CI) for different levels of subjective sleepiness measured with the Karolinska Sleepiness Scale (KSS), 1 = very alert, 9 = very sleepy, fighting sleep, an effort to staying awake. Five male and five female shift workers, mean age 37 years, participated with a 2-h drive (08:00-10:00 hours) in a dynamic high-fidelity moving base driving simulator, after a night of work and after a night of sleep. Subjective sleepiness was measured with KSS every 5 min and events of incidents (two wheels outside the right lane), accidents (two wheels off the road or four wheels in opposite lane) and crashes (four wheels off the road) were recorded. The probability of an accident was modelled with a Generalized Linear Mixed Model approach to estimate subject-specific effects, rather than group average effects, to avoid the ecological fallacy. The results showed that sleepiness was strongly related to accident risk. An average subject was estimated at 28.2 times (95% CI RR = 10.7-74.1) increased risk at KSS = 8 and at 185 times (95% CI RR = 42-316) at KSS = 9 compared with KSS = 5. There were large individual differences in event propensity that complicates the prediction of absolute accident risk for individual subjects.

Accidents, Traffic↗

PubMed2006

The Croydon Assessment of Learning Study: prevalence and educational identification of mild mental retardation.

BACKGROUND: Mild mental retardation is an enduring and impairing condition. Its prevalence has varied widely across different studies from .5 to over 8%, with higher rates in completely ascertained samples. The current study estimates the prevalence of low IQ in the mental retardation range (intellectual disability) in a population sample and examines the factors that relate to educational identification. METHOD: A total of 2,730 children in school years 8 and 9 attending local authority schools were assessed in school with the group-administered Cognitive Abilities Test (CAT). A sample of 304 pupils at high, moderate and low risk of mild mental retardation was selected for in-depth study. This included the individually measured full-scale IQ (WISC-III(UK)), the Wechsler Quicktest of attainments, the Strengths and Difficulties Questionnaire from parents and teachers and an abbreviated version of the Social Communication Questionnaire. RESULTS: Of those selected for the in-depth study, 204 (67%) participated, with a greater proportion from the low risk group. A range of prevalence estimates were calculated using different imputation methods and assumptions about individuals not screened. Rates of pupils with WISC IQ < 70 varied from 5.8% to 10.6%. There were no significant gender differences. In contrast to the high prevalence estimates using the WISC, the proportion of pupils scoring in the lowest stanine on the CAT was as expected. Only 15% of those with IQ < 70 had a statement of special educational needs or attended a school for moderate learning difficulties. Behaviour, particularly social communication problems, predicted educational identification. CONCLUSIONS: The current study produced a high estimate of the prevalence of mild intellectual disability based on the WISC but not on the CAT. The findings highlight that the majority of mild intellectual disability in the UK would not be detected using registers. Cases that are detected by registers are more behaviourally disturbed than others.

Adolescent↗

PubMed2005

An association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum disorder.

Autism (OMIM 209850) is a neurodevelopmental disorder with a significant genetic component of a complex nature. Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome critical region (PWACR) on chromosome 15 (q11-13) have been described in several individuals with autism. We have examined five microsatellite markers spread across the 4 Mb PWACR for linkage disequilibrium (LD) in 148 families with autism spectrum disorder (ASD) and a subset of 82 families with autism using the extended transmission disequilibrium test (ETDT). The markers examined were D15S11, D15S128, D15S1506, GABRB3, and D15S1002. In addition we have examined the microsatellite D15S822 for hemizygous deletion status in our sample as it had been previously reported to be increased in autism. We found no significant LD with any of the markers tested either in the ASD or autism families when looking at paternal and maternal meioses combined. However, as there are known imprinted genes in the region, including possibly GABRB3, we also examined for LD in paternal and maternal meioses separately. Examining paternal transmissions only, we found marginal evidence for LD with a protective allele at marker D15S11 in the ASD families (Chi-sq 7 df, P = 0.05) and marginal evidence for risk alleles at markers D15S1506 (Chi-sq 13.7, 6 df, P = 0.06), GABRB3 (Chi-sq 15.9, 8 df, P = 0.11) and D15S1002 (Chi-sq 17.7, 9 df, P = 0.08) in the autism only families. The allele responsible for the association with GABRB3 is the 191 allele which was previously reported to be overtransmitted. Hemizygous deletion of the microsatellite D15S822 was found in 3 out of 340 independent chromosomes in our sample; a rate of 0.8%. This is not significantly different to the frequency in the general population. In conclusion, our results did not rule out the involvement of this chromosomal region, but provided further evidence, albeit very limited, to implicate GABRB3. Further more systematic work in larger samples is required and confirmation that GABRB3 is imprinted is desirable.

Alleles↗

PubMed2005

Challenges in evaluating psychosocial interventions for Autistic Spectrum Disorders.

In 2002, the National Institutes of Health sponsored a meeting concerning methodological challenges of research in psychosocial interventions in Autism Spectrum Disorders. This paper provides a summary of the presentations and the discussions that occurred during this meeting. Recommendations to federal and private agencies included the need for randomized clinical trials of comprehensive interventions for autism as the highest, but not the sole priority. Ongoing working groups were proposed to address psychosocial interventions with a focus on relevant statistics, standardized documentation and methods of diagnosis, development of outcome measures, establishment of standards in research; and the need for innovative treatment designs, including application of designs from other research areas to the study of interventions in ASD.

Autistic Disorder↗

PubMed2005

Pre-linguistic Autism Diagnostic Observation Schedule adapted for older individuals with severe to profound mental retardation: a pilot study.

The Autism Diagnostic Observational Schedule (ADOS) is a semi-structured observational scale developed to assess social interaction, communication and play in individuals who are suspected to have autism. Since the ADOS is not suitable to be used with severely or profoundly mentally retarded adolescents and adults with very limited language skills, materials and some of the tasks of the PL-ADOS and the original ADOS (the former versions of the current ADOS) were adapted. Results indicated that almost all of the overall ratings showed good reliability and discriminative diagnostic validity. Furthermore, the combination of codings into an overall algorithm score on social/communicative behavior resulted in a sensitivity of .82 and a specificity of .85 when using a cut-off score of 15.

Adolescent↗

PubMed2005

Mortality in offspring of parents with psychotic disorders: a critical review and meta-analysis.

OBJECTIVE: Mortality risk in offspring of parents with psychotic disorders is a sensitive and important topic, but evidence on which to base plans for preventive services is limited. The authors synthesized evidence for mortality risk among offspring of parents with psychotic disorders and examined potential modifiers of risk such as offspring age and parental diagnosis. METHOD: Electronic reference and citation databases were searched. Secondary analyses were carried out to generate relative risk estimates and perform post hoc statistical power calculations. A meta-analysis of the association between maternal psychotic disorder and fetal death/stillbirth was conducted. RESULTS: Most of the relevant studies investigated the relationship between exposure to maternal schizophrenia and perinatal or infant mortality outcomes but were not truly population-based and lacked adequate power. Studies published since 1960 generally indicated higher than expected mortality risk in exposed offspring. Meta-analysis indicated an almost twofold higher risk of fetal death/stillbirth among offspring of women with psychoses. Notable gaps in the existing evidence include outcome beyond the first year of life, cause-specific mortality, and effects of exposure to specific parental conditions other than schizophrenia and of exposure to paternal versus maternal disorder. Etiological mechanisms are not fully understood. CONCLUSIONS: Large-scale population-based studies are needed to understand mortality risk in offspring of parents with psychoses. In the absence of etiological evidence, only general preventive measures can be taken. Prevention of offspring mortality at an early age is most likely to be achieved by identification and treatment of maternal disorder and greater provision of support to these vulnerable families.

Adolescent↗

PubMed2004

Juvenile- versus adult-onset depression: multiple differences imply different pathways.

BACKGROUND: Several sources of heterogeneity in major depression have been identified. These include age of onset, presence of co-morbid disorders, and history of childhood sexual abuse. This study examined these factors in the context of the contrast between onset of depression in young women before and after age 16. METHOD: Sampling was carried out in two phases. In the first, questionnaires were sent to women aged 25-36 in five primary care practices. Second-phase subjects for interview (n = 197) were drawn from three strata defined on the basis of childhood adversities. Interviews conducted and rated independently assessed (1) recalled childhood experiences, psychopathology and parental psychiatric disorder, and (2) adult personality functioning and adult lifetime psychopathology. Frequencies of predictor and response variables, effect estimates and their confidence intervals were weighted back to the general population questionnaire sample. RESULTS: Compared with adult-onset depression, juvenile-onset adult depression was associated with co-morbid childhood psychopathology and peer problems, poor parental care, and childhood sexual abuse involving actual or attempted intercourse; in adult life there were higher levels of co-morbid psychiatric disorders, and personality dysfunction. The adult-onset depression group was characterized by a history of contact childhood sexual abuse without actual or attempted intercourse, and to a lesser extent, poor parental care. CONCLUSIONS: The juvenile- versus adult-onset distinction appears to be important to heterogeneity in adult depression, implicating different individual and environmental factors during childhood, and different mechanisms in adult life.

Adolescent↗

PubMed2004

Informant disagreement for separation anxiety disorder.

OBJECTIVE: To characterize informant disagreement for separation anxiety disorder (SAD). METHOD: The sample comprised 2,779 8- to 17-year-old twins from a community-based registry. Children and their parents completed a personal interview about the child's psychiatric history. Parents completed a personal interview about their own psychiatric history and a questionnaire about their marital relationship. RESULTS: Informant agreement for SAD ranged between chance and extremely poor. Most cases of SAD were diagnosed by interview with only one informant. SAD diagnosed only by child interview was associated with an increased odds of father-rated oppositional defiant disorder, and vice versa. SAD diagnosed only by parent interview was predicted by the parental informant's history of antisocial personality disorder. SAD diagnosed only by paternal interview was also predicted by mother-rated marital conflict and dissatisfaction. CONCLUSIONS: Parents and children rarely agree about the presence of any level of child separation anxiety. A symptom "or-rule" mostly indexes diagnoses based on interview with only one informant, but the relative validity of such diagnoses remains unclear.

Adolescent↗

PubMed2004

Course and short-term outcomes of separation anxiety disorder in a community sample of twins.

OBJECTIVE: To assess the course and short-term outcomes associated with separation anxiety disorder (SAD) in a community setting. METHOD: The subjects were 161 of 2,061 8- to 17-year-old twins with SAD from a community-based twin study. Subjects were born between 1974 and 1983. Subjects and parents were personally interviewed about the subject's current psychiatric history between 1990 and 1993. A follow-up interview was conducted, on average, 18 months later. Logistic regression was used to identify predictors and outcomes of persistent SAD. RESULTS: Of the 161 subjects with SAD at time 1, 80% had remitted and 59% were free of any disorder at follow-up. Children with persistent SAD had a significantly higher prevalence of oppositional defiant disorder, significantly more impairment associated with symptoms of attention-deficit/hyperactivity disorder, and mothers who were less satisfied with their marriage at time 1 than children with transient episodes. Children with persistent SAD had a significantly higher prevalence of overanxious disorder or a new minor or major depressive disorder at time 2 than children with transient SAD. After controlling for comorbidity, only an elevated risk of new depressive disorders at time 2 distinguished children with persistent SAD. CONCLUSIONS: Many children with SAD in a community setting are well at follow-up, on average, 18 months later. A minority of children with persistent SAD are at significantly increased risk of a new depressive disorder, especially those with a history of oppositional defiant disorder, impairment associated with symptoms of attention deficit hyperactivity disorder, or parental marital difficulties.

Adolescent↗

PubMed2004

Risks for conduct disorder symptoms associated with parental alcoholism in stepfather families versus intact families from a community sample.

BACKGROUND: It is not known if the prevalence of parental psychiatric disorders is higher in stepfather than intact families, or if parental alcoholism is differentially associated with risk for conduct disorder (CD) symptoms in stepfather families versus intact families. METHOD: The sample comprised 839 girls and 741 boys from 792 intact families and 99 girls and 67 boys from 83 stepfather families from a population-based registry of twins aged between 8 and 17 years. Children's current psychiatric symptoms were assessed at personal interview with the child, mother and father. Parental histories of psychiatric disorder were assessed at personal interview with each residential parent. Associations between CD symptoms and parental alcoholism were characterized using both linear and Poisson regression, and results are presented with and without adjustment for maternal drug use during pregnancy, parental conflict, and estimated socioeconomic status (SES) based on census tract data. RESULTS: Mothers from stepfather families had a higher lifetime prevalence of alcoholism, antisocial personality disorder, depression and social phobia than mothers from intact families. Stepfathers had a higher lifetime prevalence of alcoholism and depression than biological fathers from intact families. Children from stepfather families had more externalizing (CD/ODD) symptoms than children from intact families. Girls who lived with an alcoholic stepfather had significantly more CD symptoms than girls who lived with an alcoholic biological father. Boys who lived with an alcoholic stepfather had significantly fewer CD symptoms than boys who lived with an alcoholic biological father. This sex difference was statistically significant. Adjustment for maternal drug use during pregnancy, parental conflict, and estimated SES based on census tract data did not change these findings. CONCLUSIONS: Children living in stepfather families are exposed to more parental psychiatric risk factors than children from intact families. The increased risk for CD symptoms in girls (but not boys) from stepfather families is partly mediated by or associated with the stepfather's history of alcoholism.

Adolescent↗

PubMed2004

Institutional care: associations between overactivity and lack of selectivity in social relationships.

BACKGROUND: The behaviour of children raised in institutional care in their early years is typified by heightened levels of inattention and overactivity irrespective of the quality of the care. There is some evidence that this behaviour may be specifically associated with forms of attachment disorder behaviours, but to date studies have been restricted to institutions characterised by high levels of malnutrition and lack of active experiences. METHODS: Nineteen primary school age children admitted to good quality residential group care before the age of 1 year were compared with 19 children of the same gender reared in a foster family from the same age. A combination of observational, questionnaire, interview and psychometric measures was employed. RESULTS: A fifth of the institutional children but none of the foster-family children showed a marked lack of selective attachment relationships with their caregivers. The same proportions were found for a lack of selectivity in friendships with their peers but the children showing these features were not identical. A lack of selectivity in relationships was strongly associated with inattention/overactivity, both as observed and reported. The pattern of a marked lack of selectivity and inattention/overactivity was evident only in the boys in the institution-reared group. CONCLUSIONS: It is concluded that the pattern represents a relatively specific response to some feature of an institutional rearing; nevertheless, it occurred in only just over a third of the institutional children, so that it is a far from universal consequence.

Caregivers↗