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M Rutter

Publications and source records attributed to M Rutter.

At least 127 records · Page 7Linked to original sources

A 15-20 year follow-up of adult psychiatric patients. Psychiatric disorder and social functioning.

BACKGROUND: An exploratory study was undertaken of the importance of personality disorder in predicting the long-term outcome for both episodic disorders and social functioning. METHOD: In 1966-67, a representative series of patients with children, free of episodic illness for at least one year, was sampled from the Camberwell Psychiatric Register and systematically assessed over a four-year period, using measures of known reliability and validity. Psychiatric disorder was measured using a PSE-compatible instrument. The follow-up after 15-20 years used the PSE and a systematic assessment of social functioning. RESULTS: Overall outcomes were similar across diagnoses, but an initial categorical diagnosis of personality disorder predicted much poorer outcomes on psychiatric and social measures for patients with unipolar depressive disorders than for those with other diagnoses. CONCLUSIONS: The findings indicate the importance for prognosis of including a systematic assessment of personality disorder in the clinical assessment of patients with depressive disorder.

Adolescent↗

Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism.

The use of the family history method to examine the pattern of recurrence risks for complex disorders such as autism is not straightforward. Problems such as uncertain phenotypic definition, unreliable measurement with increased error rates for more distant relatives, and selection due to reduced fertility all complicate the estimation of risk ratios. Using data from a recent family history study of autism, and a similar study of twins, this paper shows how a latent-class approach can be used to tackle these problems. New findings are presented supporting a multiple-locus model of inheritance, with three loci giving the best fit.

Autistic Disorder↗

Psychiatric genetics: research challenges and pathways forward.

Lessons from past psychiatric genetic research, together with key issues in psychiatry requiring genetic investigation, are reviewed in order to consider the implications for the ways forward. It is argued that traditional quantitative genetics needs to use a combination of twin, adoptee, and family strategies, to examine continuities and discontinuities in psychopathology between childhood and adult life, to compare dimensions and categories, to employ adequate conceptualization and measurement of disorders, to use statistical techniques based on latent constructs, to use biological trait indicators where possible, to examine risk factors as well as diseases, to include good measures of postulated environmental risk variables, to study the interplay between genes and environment, and to study the key assumptions underlying genetic strategies. Molecular cytogenetics needs to consider both the general and specific psychopathological risks associated with chromosome abnormalities and to examine the mechanism involved, to examine the role of submicroscopic chromosomal deletions and of mitochondrial disorders, and to investigate the mechanisms involved in trinucleotide repeat amplifications that take place during intergenerational transmission. Molecular genetics needs to make greater use of smaller pedigrees in view of the concerns over phenotypic definition and genetic heterogeneity in very large extended dense pedigrees, to use sib-pair designs in view of the likelihood that most psychiatric disorder will prove to be multifactorial, to combine association strategies with linkage analyses, to pay careful attention to the definition of phenotypes in probands, to remain in close touch with other branches of biological psychiatry, and to make effective use of collaboration between centers. To date, transgenic models have had a rather limited application in psychiatry but, despite their difficulties, they are likely to provide an underpinning for gene therapy in disorders where that seems feasible.

Genetic Heterogeneity↗

Survival models for developmental genetic data: age of onset of puberty and antisocial behavior in twins.

The use of survival analysis for developmental genetic data is discussed. The main requirements for models based on the decomposition of frailty distributions into shared and unshared components are outlined for the simple case of twins. Extending the earlier work of Clayton, Oakes, and Hougaard, among others, three forms of hazard model are presented, all of which can be applied to pedigree data with flexible baseline hazards without the use of numerical integration. The first two models use an additive decomposition of frailty, with either gamma or positive stable law distributed (PSL) components. The third model previously described by Hougaard involves a multiplicative PSL decomposition. The models are applied to data on the onset of puberty in male twins and illustrate the importance of correct specification of the baseline hazard for correct inference about genetic effects. The difficulty of assessing model specification using information only on the margins is also noted. Overall, the new model with additive PSL components appeared to fit these data best. A second application illustrates the use of a time-varying covariate in examining the impact of puberty on the onset of conduct disorder symptomotology.

Adolescent↗

A simple method for censored age-of-onset data subject to recall bias: mothers' reports of age of puberty in male twins.

Genetic analysis of variation in age of onset of development milestones or psychopathological behaviors has been little researched, owing largely to the computational difficulty of dealing with "censored" observations. Censored observations arise when the only information on individuals is that they have reached a particular age but without onset having occurred. This paper shows how models can be simply fitted to such data using programs that can perform genetic analysis of categorical data by maximum likelihood. The method is illustrated using the program Mx with data on maternal report of the onset of puberty in twin sons from the Virginia Twin Study of Adolescent Behavioral Development. Frequently, data on age of onset is collected by retrospective recall. This can pose a variety of measurement problems. Suggestions are made for models that account for some of these problems or are robust to their presence. Substantial evidence for "telescoping" of onset dates is found for the puberty data. If left unaccounted for, these effects can artifactually inflate estimates of common environment effects.

Adolescent↗

Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders.

Describes the Autism Diagnostic Interview-Revised (ADI-R), a revision of the Autism Diagnostic Interview, a semistructured, investigator-based interview for caregivers of children and adults for whom autism or pervasive developmental disorders is a possible diagnosis. The revised interview has been reorganized, shortened, modified to be appropriate for children with mental ages from about 18 months into adulthood and linked to ICD-10 and DSM-IV criteria. Psychometric data are presented for a sample of preschool children.

Algorithms↗

Beyond longitudinal data: causes, consequences, changes, and continuity.

Longitudinal data have very important advantages for both measurement and the testing of causal hypotheses on the causes or course of psychopathology, but cross-sectional studies should usually be used first. The investigation of causes needs to encompass the several different types of causal question. The study of within-individual change constitutes a most important research strategy to test causal hypotheses, but it is not the only approach. Their testing requires specification of possible mechanisms, together with attention to the differential impact of risk experiences, of the possible role of person-environment interactions and protective mechanisms. This article addresses several strategies needed in using longitudinal data to test cause-and-effect relationships, including natural experiments, testing of competing hypotheses on mechanisms, study of reversal effects, multiple replications in different circumstances, use of designs to dissociate possible mechanisms, testing for dose-response relationships, examination of effect-specificity, considering biological plausibility, and assessing the strength of effects.

Cross-Sectional Studies↗

Autism and known medical conditions: myth and substance.

There is general agreement that autism has an organic basis but there is less agreement on the frequency with which it is associated with known medical conditions. The evidence in the literature on the latter point is reviewed and it is concluded that the rate of known medical conditions in autism is probably about 10%; however the rate appears to be higher in cases of autism associated with profound mental retardation and in cases of atypical autism.

Autistic Disorder↗

Adult outcomes of childhood and adolescent depression. III. Links with suicidal behaviours.

This study followed up into adulthood a group of child psychiatric patients suffering from depressive disorders and a closely matched nondepressed child psychiatric control group. Depression in childhood was a strong predictor of attempted suicide in adulthood. This predictive power was not due to the association between childhood depression and other childhood risk factors such as conduct disorder or suicidality. Rather, it seemed mostly to reside in the association between depression in childhood and major depression in adult life. These findings suggest that the pathways from childhood psychopathology to adult outcomes can be complex, and depend crucially on what happens later.

Adolescent↗

A case-control family history study of autism.

Family history data on 99 autistic and 36 Down's syndrome probands are reported. They confirmed a raised familial loading for both autism and more broadly defined pervasive developmental disorders in siblings (2.9% and 2.9%, respectively, vs 0% in the Down's group) and also evidence for the familial aggregation of a lesser variant of autism, comprising more subtle communication/social impairments or stereotypic behaviours, but not mental retardation alone. Between 12.4 and 20.4% of the autism siblings and 1.6% and 3.2% of the Down's siblings exhibited this lesser variant, depending on the stringency of its definition. Amongst autistic probands with speech, various features of their disorder (increased number of autistic symptoms; reduced verbal and performance ability) as well as a history of obstetric complications, indexed an elevation in familial loading. No such association was seen in the probands without speech, even though familial loading for the lesser variant in this subgroup, was significantly higher than in the Down's controls. The findings suggest that the autism phenotype extends beyond autism as traditionally diagnosed; that aetiology involves several genes; that autism is genetically heterogeneous; and that obstetric abnormalities in autistic subjects may derive from abnormality in the foetus.

Adolescent↗

Influence of temperature on growth rate and competition between two psychrotolerant Antarctic bacteria: low temperature diminishes affinity for substrate uptake.

The growth kinetics of two psychrotolerant Antarctic bacteria, Hydrogenophaga pseudoflava CR3/2/10 (2/10) and Brevibacterium sp. strain CR3/1/15 (1/15), were examined over a range of temperatures in both batch culture and glycerol-limited chemostat cultures. The maximum specific growth rate (mu max) and Ks values for both bacteria were functions of temperature, although the cell yields were relatively constant with respect to temperature. The mu max values of both strains increased up to an optimum temperature, 24 degrees C for 2/10 and 20 degrees C for 1/15. Strain 1/15 might therefore be considered to be more psychrophilic than strain 2/10. For both bacteria, the specific affinity (mu max/Ks) for glycerol uptake was lower at 2 than at 16 degrees C, indicating a greater tendency to substrate limitation at low temperature. As the temperature increased from 2 to 16 degrees C, the specific affinity of 1/15 for glycerol increased more rapidly than it did for 2/10. Thus 1/15, on the basis of this criterion, was less psychrophilic than was 2/10. The steady-state growth kinetics of the two strains at 2 and 16 degrees C imply that 1/15 would be able to outgrow 2/10 only at relatively low substrate concentrations (< 0.32 g of glycerol.liter-1) and high temperatures (> 12 degrees C), which suggests that 1/15 has a less psychrotolerant survival strategy than does 2/10. Our data were compared with other data in the literature for bacteria growing at low temperatures. They also showed an increase of substrate-specific affinity with increasing temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Antarctic Regions↗

Influence of changing temperature on growth rate and competition between two psychrotolerant Antarctic bacteria: competition and survival in non-steady-state temperature environments.

Competition between two psychrotolerant bacteria was examined in glycerol-limited chemostat experiments subjected to non-steady-state conditions of temperature. One bacterium, a Brevibacterium sp. strain designated CR3/1/15, responded rapidly to temperature change, while a second, Hydrogenophaga pseudoflava, designated CR3/2/10, exhibited a lag in growth after a shift-down during a square-wave temperature cycle but not after a shift-up. The effects on competition and survival by these bacteria of both sine-wave and square-wave temperature changes between 2 and 16 degrees C over a 24-h cycle time were examined, as well as square-wave cycles over 12 and 96 h. The changing proportion of each bacterium in the chemostat was determined by plate counting at regular intervals. Under a sine-wave temperature cycle H. psedoflava outcompeted the Brevibacterium sp., but under square-wave temperature cycles the two bacteria coexisted because the lag by H. pseudoflava after the temperature shift-down favored the faster-responding Brevibacterium sp. The two bacteria thus exhibited different survival strategies, with H. pseudoflava adapted to effective competition under steady-state conditions and the Brevibacterium sp. adapted to rapid adaptation and survival in a changing environment. The degree of perturbation of the bacteria, expressed as a temperature challenge index (delta temp/delta time), was greater under a square-wave temperature cycle than under a sine-wave cycle of equivalent amplitude and frequency, and higher-temperature challenge favored the Brevibacterium sp. A computer model was developed to examine competition between the bacteria in transient environments. The frequency of the temperature cycle influenced competition, as with a longer cycle (96 h) the significance of the lag by H. pseudoflava decreased compared with that of a 24-h cycle, and H. pseudoflava predominated in a mixed culture with a 96-h cycle. The shift-down lag by H. pseudoflava, during which it adapted to low temperature, disadvantaged it in a changing temperature environment, but at a short cycle time (12 h) this disadvantage was countered by the incomplete loss of low-temperature adaptation between cycles and thus the carryover of some low-temperature adaptation. Also, it was demonstrated that, as well as consideration of the effect of temperature changes on inducing lags in growth, the loss of adaptation to low temperature between cycles had to be taken into account in the computer model if it was to reproduce the trends in the experimental data.

Antarctic Regions↗

Field trial for autistic disorder in DSM-IV.

OBJECTIVE: This project focused on the development of the definition of autism for DSM-IV. METHOD: Multiple sites were involved in obtaining information regarding 977 patients with the following clinician-assigned diagnoses: autism (N = 454), other pervasive developmental disorders (N = 240), and other disorders (N = 283). A standard coding system was used, and the raters (N = 125) had a range of experience in the diagnosis of autism. Patterns of agreement among existing diagnostic systems were examined, as was the rationale for inclusion of other disorders within the class of pervasive developmental disorders. RESULTS: The DSM-III-R definition of autism was found to be overly broad. The proposed ICD-10 definition most closely approximated the clinicians' diagnoses. Inclusion of other disorders within pervasive developmental disorders appeared justified. Partly on the basis of these data, modifications in the ICD-10 definition were made; this and the DSM-IV definition are conceptually identical. CONCLUSIONS: The resulting convergence of the DSM-IV and ICD-10 systems should facilitate both research and clinical service.

Age of Onset↗

Analyzing twin resemblance in multisymptom data: genetic applications of a latent class model for symptoms of conduct disorder in juvenile boys.

A model based on the latent class model is developed for the effects of genes and environment on multivariate categorical data in twins. The model captures many essential features of dimensional and categorical conceptions of complex behavioral phenotypes and can include, as special cases, a variety of major locus models including those that allow for etiological heterogeneity, differential sensitivity of latent classes to measured covariates, and genotype x environment interaction (G x E). Many features of the model are illustrated by an application to ratings on eight items relating to conduct disorder selected from the Rutter Parent Questionnaire (RPQ). Mothers rated their 8- to 16-year-old male twin offspring [174 monozygotic (MZ) and 164 dizygotic (DZ) pairs]. The impact of age on the frequency of reported symptoms was relatively slight. Preliminary latent class analysis suggests that four classes are required to explain the reported behavioral profiles of the individual twins. A more detailed analysis of the pairwise response profiles reveals a significant association between twins for membership of latent classes and that the association is greater in MZ than DZ twins, suggesting that genetic factors played a significant role in class membership. Further analysis shows that the frequencies of MZ pairs discordant for membership of some latent classes are close to zero, while others are definitely not zero. One possible explanation of this finding is that the items reflect underlying etiological heterogeneity, with some response profiles reflecting genetic categories and others revealing a latent environmental risk factor. We explore two "four-class" models for etiological heterogeneity which make different assumptions about the way in which genes and environment interact to produce complex disease phenotypes. The first model allows for genetic heterogeneity that is expressed only in individuals exposed to a high-risk ("predisposing") environment. The second model allows the environment to differentiate two forms of the disorder in individuals of high genetic risk. The first model fits better than the second, but neither fits as well as the general model for four latent classes associated in twins. The results suggest that a single-locus/two-allele model cannot fit the data on these eight items even when we allow for etiological heterogeneity. The pattern of endorsement probabilities associated with each of the four classes precludes a simple "unidimensional" model for the latent process underlying variation in symptom profile in this population. The extension of the approach to larger pedigrees and to linkage analysis is briefly considered.

Adolescent↗

Cause and course of psychopathology: some lessons from longitudinal data.

Case-control studies of clinic samples constitute the usual research method for the investigation of the causes and course of psychiatric disorder. However, they carry substantial disadvantages and if causal hypotheses are to be tested in rigorous fashion, it is necessary to use longitudinal research strategies applied to epidemiologically based samples. Their advantages are reviewed with respect to the use of 'experiments of nature' for testing causal mechanisms through the study of within-individual change over time in relation to some prospectively measured alteration in the risk variable. Attention is drawn to the value of longitudinal data in studying the processes involved in 'escape' from risk; in examining differential vulnerability to risk experiences; in validating diagnostic categories; in investigating the timing of disorders; and in evaluating the role of variables that cannot be recalled. The data from a range of longitudinal studies are used to note some of the key implications for developmental and psychopathological concepts.

Adolescent↗