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Biomedical subjects

J Silberg

Publications and source records attributed to J Silberg.

At least 19 recordsLinked to original sources
PubMed2001

Genetic moderation of environmental risk for depression and anxiety in adolescent girls.

BACKGROUND: There is huge individual variation in people's response to negative life events. AIMS: To test the hypothesis that genetic factors moderate susceptibility to the environmentally mediated risks associated with negative life events. METHOD: The Virginia Twin Study of Adolescent Behavioral Development (VTSABD) was used to study the effects of independent life events (assessed from maternal interview) on depression/anxiety (assessed from child interview) in 184 same-gender female twin pairs, aged 14--7 years, measured on two occasions. RESULTS: There was no genetic effect on the independent negative life events studied. A significant gene-environment interaction was found using structural equation modelling. There was no effect of independent life events on adolescents' depression in the absence of parental emotional disorder, but a significant effect in its presence. CONCLUSIONS: There is an environmentally mediated effect of life events on depression/anxiety. Genetic factors play a significant role in individual differences in susceptibility to these environmentally mediated risks.

Adolescent↗
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↗
PubMed2000

Childhood sexual abuse and adult psychiatric and substance use disorders in women: an epidemiological and cotwin control analysis.

BACKGROUND: Women who report childhood sexual abuse (CSA) are at increased risk for developing psychiatric disorders in adulthood. What is the diagnostic specificity and cause of this association? METHODS: In a population-based sample of 1411 female adult twins, 3 levels of CSA were assessed by self-report and cotwin report: nongenital, genital, and intercourse. Interviews with twins and parents assessed family background and diagnoses of psychiatric and substance dependence disorders. Odds ratios (ORs) were calculated by logistic regression. RESULTS: By self-report, 30.4% reported any CSA and 8.4% reported intercourse. Self-reported CSA was positively associated with all disorders, the highest ORs being seen with bulimia and alcohol and other drug dependence. The ORs were modest and often nonsignificant with nongenital CSA and increased with genital CSA and especially intercourse, where most ORs exceeded 3.0. A similar pattern of findings was seen with CSA as reported by the cotwin, although many ORs were smaller. Controlling for family background factors and parental psychopathology produced a small to modest reduction in ORs. In twin pairs discordant for CSA, the exposed twin was at consistently higher risk of illness. CONCLUSIONS: Women with CSA have a substantially increased risk for developing a wide range of psychopathology. Most of this association is due to more severe forms of CSA and cannot be explained by background familial factors. Although other biases cannot be ruled out, these results are consistent with the hypothesis that CSA is causally related to an increased risk for psychiatric and substance abuse disorders.

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↗
PubMed1999

The influence of genetic factors and life stress on depression among adolescent girls.

BACKGROUND: The possible causes of greater depression among adolescent girls were investigated by examining variation in the influence of genetic and environmental risk factors among 182 prepubertal female, 237 prepubertal male, 314 pubertal female, and 171 pubertal male twin pairs from the Virginia Twin Study of Adolescent Behavioral Development. OBJECTIVES: To compare the trajectory of depressive symptoms among boys and girls from childhood to adolescence; to analyze the role of genetic, shared, and unique environmental factors in depression among prepubertal and pubertal male and female twins; and to investigate a possible link between liability to depression and one salient index of the child's environment: past-year life events. METHODS: Child-reported depression was assessed using the Child and Adolescent Psychiatric Interview and ratings of past-year life events and pubertal status obtained by maternal questionnaire and interview, respectively. RESULTS: The impact of life events on depression was particularly evident in the adolescent girls. The results from model fitting indicate increased heritability for depression in this group, and its long-term consistency was mediated primarily by latent genetic factors. Model fitting also showed that at least part of the liability to depression and to life events can be linked to a common set of genes in the adolescent girls, and there is a notable developmental increase in the genetic variance for life events. CONCLUSIONS: The greater heritability for depression in pubertal girls, its genetic mediation over time, and the increase in genetic variance for life events may be one possible explanation for the emergence of increased depression among pubertal girls and its persistence through adolescence.

Adolescent↗
PubMed1999

Genetics and child psychiatry: I Advances in quantitative and molecular genetics.

Advances in quantitative psychiatric genetics as a whole are reviewed with respect to conceptual and methodological issues in relation to statistical model fitting, new genetic designs, twin and adoptee studies, definition of the phenotype, pervasiveness of genetic influences, pervasiveness of environmental influences, shared and nonshared environmental effects, and nature-nurture interplay. Advances in molecular genetics are discussed in relation to the shifts in research strategies to investigate multifactorial disorders (affected relative linkage designs, association strategies, and quantitative trait loci studies); new techniques and identified genetic mechanisms (expansion of trinucleotide repeats, genomic imprinting, mitochondrial DNA, fluorescent in-situ hybridisation, behavioural phenotypes, and animal models); and the successful localisation of genes.

Adolescent↗
PubMed1999

Genetics and child psychiatry: II Empirical research findings.

Key substantive findings from quantitative and molecular genetic research are reviewed in relation to affective disorder, schizophrenia, autism, hyperkinetic/attention deficit disorder, oppositional and conduct disorders, drug/alcohol problems, and Tourette's syndrome/chronic tics.

Adolescent↗
PubMed1998

Genetic "clocks" and "soft" events: a twin model for pubertal development and other recalled sequences of developmental milestones, transitions, or ages at onset.

We propose and explore a twin model to examine the basis for synchrony that often characterizes different facets of normal development. In so doing we also present an approach to the analysis of "soft" events; events for which available reports of dates or ages of occurrence are unreliable or inconsistent. Discrepancies among reports are accounted for by a statistical measurement model. This combines current status error reflecting uncertain definition of onset and two mechanisms for the phenomenon of "telescoping," namely, systematic compression of the time scale and heteroscedastic random measurement error. Statistically, the model can be viewed as a mixed generalized linear model with random effects within both mean and variance functions or, alternatively, as involving multiplicative random effects. We apply the model to multiple maternal reports on menarche and onset of breast development in twin daughters. Fitted to data from the Virginia Twin Study Of Adolescent and Behavioral Development by the use of penalized/predictive quasi-likelihood, the model provided much improved estimates of the true age-at-onset distribution as compared to those from a naive analysis. Results suggested that the observed variance was made up almost entirely of genetic variance and measurement error variance due to telescoping and current status errors and that the timing of breast development and menarche are largely under the control of a common set of genes. Results also indicated that maternal recollections of the onset of breast development were both more poorly defined and subject to greater recall errors than maternal recollections of menarche.

Adolescent↗
PubMed1998

Genetic and environmental influences on subtypes of conduct disorder behavior in boys.

Oppositional and conduct disorders are a heterogeneous collection of disruptive behaviors associated with diverse risk factors and varying outcomes. Data from males in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) are used to explore the relative importance of genetic and environmental influences on four previously described disruptive subtypes: property violations, status violations, oppositional behavior, and aggression. Striking differences between results according to mother and child ratings are found, indicating the need to consider carefully the origin of rater differences. Child ratings indicate support for a general genetic liability, with greatest influence on property violations, oppositional behavior and aggression. Maternal ratings suggest that the genetic factors influencing conduct disorder behavior are more specific to the behavioral area, with the stronger genetic influence on property violations and aggression.

Adolescent↗
PubMed1997

Age changes in the causes of individual differences in conservatism.

Age-related changes are analyzed in the correlation of 3416 monozygotic and 3780 dizygotic U.S. twin pairs aged between 9 and 75+ years for conservatism scores derived from a 28-item social attitude inventory. The effects of the shared environment are overwhelming in twins aged 20 years or younger. In older twins, genetic effects appear to play a larger role. A more dynamic conception of the interaction between genes and environment in the development of complex human differences is needed.

Adolescent↗
PubMed1996

Heterogeneity among juvenile antisocial behaviours: findings from the Virginia Twin Study of Adolescent Behavioural Development.

The examination of heterogeneity in antisocial behaviour was accomplished by applying latent class analytic methods to multivariate categorical data on 389 same-sex male twins, aged 11 to 16 from the Virginia Twin Study of Adolescent Behavioural Development (VTSABD). The data included multiple measures of oppositional and conduct disorder, attention deficit disorder, hyperactivity, impulsivity, reading disability and anxiety from mother, teacher, and child report from both questionnaire and interview (child and adult psychiatric assessment; CAPA). A latent four-class model provided a good fit to the data and yielded four phenotypically and aetiologically distinct latent classes: (1) a non-symptomatic class influenced by both additive genetic and shared environmental factors; (2) a hyperactivity-conduct disturbance class accounted for by both additive and non-additive genetic effects; (3) a 'pure' conduct disturbance class with a very strong shared environmental component; and (4) a multisymptomatic class explained entirely by the additive effect of the genes. Further characterization of these four latent classes by age of the child and parental psychiatric history is also shown.

Adolescent↗
PubMed1996

Genetic and environmental influences on the covariation between hyperactivity and conduct disturbance in juvenile twins.

Structural equation models were applied to the maternal ratings of 265 MZ and 163 DZ male-male, 347 MZ and 160 DZ female-female, and 262 male-female twin pairs, aged 8-16 years, who participated in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). Substantial additive genetic influences and contrast effects were found for hyperactivity, and additive genetic and shared environmental effects or positive comparison effects (particularly for the girls) for oppositional/ conduct disturbance. Bivariate model fitting showed that the covariation between hyperactivity and oppositional/conduct problems in both younger and older boys and girls is almost entirely attributable to genetic factors. However, whereas in the younger males and females the same set of genes explain all the variation in hyperactivity and conduct disturbance, in the older cohort at least some of the genetic effects are behavior- and gender-specific.

Adolescent↗
PubMed1995

Differences in the refractory properties of two distinct inhibitory circuitries in field CA1 of the hippocampus.

Extracellular reflections of IPSPs were examined in two distinct circuitries in field CA1 of the hippocampus. Stimulation in the stratum radiatum in the presence of AMPA receptor antagonists elicited positive potentials in the same stratum that were eliminated by picrotoxin, a blocker of GABAA receptors. Laminar profile analysis revealed that the response was maximal in the stratum radiatum at a point well distal to the pyramidal cell body layer and had a negative reflection in the stratum oriens. These field IPSPs presumably mediate the feedforward inhibition normally activated by the Schaffer-commissural projections to field CA1. Stimulation of the alveus produced an antidromic response followed by a much slower positive potential in recordings collected in the pyramidal cell layer. The latter response was suppressed by AMPA receptor antagonists or picrotoxin, as expected for disynaptic, recurrent (feedback) inhibition. The laminar profile for the feedback field IPSPs had its maximum near the pyramidal cell layer and its negative dipole in the stratum radiatum. Feedforward IPSPs were inhibited by about 50% if they were preceded within 200 ms by a priming pulse while feedback IPSPs were reduced by less than 20% under comparable conditions. The refractory effect was minimally dependent on stimulation intensity but was strongly affected by an antagonist of GABAB receptors. Attempts to modify IPSPs in the s. radiatum with long trains of low frequency stimulation or with theta-burst stimulation were not successful, suggesting that GABAergic synapses do not have the plasticities found in their glutamatergic counterparts. These results indicate that interneurons contacted by the extrinsic afferents of hippocampus form GABAergic synapses that differ in terms of spatial location and functional properties from the synapses generated by interneurons innervated by the recurrent collaterals of the pyramidal cells. The findings also suggest that repetitive afferent activity, while reducing the influence of dendritic IPSPs on excitatory input, will leave feedback suppression of cell spiking largely intact.

2-Amino-5-phosphonovalerate↗
PubMed1995

Multiple raters of disruptive child behavior: using a genetic strategy to examine shared views and bias.

Most research on child behavior incorporates information from different individuals. While agreement between informants is generally only modest, there is little understanding of the processes underlying disagreement. In twin studies, differential agreement among raters for MZ and DZ twins is of particular concern. The processes underlying differences among mother, father, and child ratings of oppositional and conduct disorder symptoms are explored. Evidence in favor of a shared parental view of behavior is presented. Parental ratings give higher intrapair correlations, which could be due to either parents rating their twins more similarly or twins contrasting themselves. Rater bias and situational specificity are among the possible explanations of differential ratings. The effects of incorporating multiple raters of behavior on estimates of genetic and environmental effects are explored. These suggest that genetic influences are greater for the shared (multiple-rater) phenotype than for individual ratings; reduction in measurement error is only a partial explanation.

Adolescent↗
PubMed1995

Effect of thiocyanate on AMPA receptor mediated responses in excised patches and hippocampal slices.

The binding affinity of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors for [3H]AMPA is increased 10-30-fold by the chaotropic anion thiocyanate. The present experiments tested if thiocyanate alters AMPA receptor mediated current fluxes and if any such effects are reflected in the waveform of synaptic responses. Currents were measured after a step application of glutamate or AMPA to patches excised from pyramidal cells of hippocampal slice cultures. Application of 1 mM AMPA produced responses with an average peak amplitude of 86 pA at -50 mV and a 10-90% rise time of 1.7 +/- 0.1 ms; the responses desensitized to a steady-state level below 10% of the peak current with a time constant of 11.1 +/- 0.7 ms. Glutamate in presence of D-amino-phosphonopentanoate produced similar responses which were inhibited by 6-cyano-7-nitro-quinoxaline-dione and enhanced by aniracetam or cyclothiazide and thus are characteristic for AMPA receptors. Thiocyanate accelerated the decay of AMPA responses two-fold and reduced the peak current by 30-50% with an EC50 of 3.2 mM which is comparable to its EC50 for enhancing binding. Effects on the desensitization of glutamate induced responses were much smaller and only evident at the highest thiocyanate concentration; no effect was seen on response amplitude. Binding and physiological effects can be adequately explained by assuming that thiocyanate enhances conversion from the sensitive to the desensitized state of the receptor and reduces ligand dissociation from the desensitized state. Synaptic responses were measured in disinhibited hippocampal slices. Perfusion with 20 mM sodium thiocyanate increased the slope of the field excitatory postsynaptic potential by 44.9 +/- 4.2% and reduced its decay time by 10.4 +/- 4.3%. The former effect appears to result at least in part from an increase in transmitter release since it was accompanied by a decrease in paired-pulse facilitation and was reduced in magnitude after enhancing transmitter release. The decrease in the decay time constant points to an effect of thiocyanate on AMPA receptors in situ which is similar to that seen in excised patches. These results demonstrate that an increase in binding affinity may be indicative of reduced rather than enhanced current flow through AMPA receptors. In addition, the results provide further evidence that the kinetics of the AMPA receptor channel contribute significantly to at least the decay phase of fast excitatory synaptic responses.

Animals↗
PubMed1994

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↗