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Florence Levy

Publications and source records attributed to Florence Levy.

15 recordsLinked to original sources
PubMed2006

A twin study of attention-deficit/hyperactivity disorder dimensions rated by the strengths and weaknesses of ADHD-symptoms and normal-behavior (SWAN) scale.

BACKGROUND: When symptom rating scales are used in the general population, there is severe skewness, with many individuals having no symptoms. While this has major implications for genetic designs that require extremely discordant and concordant (EDAC) siblings, little is known of the genetics of scales which seek to differentiate within the "no ADHD symptom" group. METHODS: Parents of Australian twins completed two attention-deficit/hyperactivity disorder (ADHD) questionnaires, the Australian Twin Behaviour Rating Scale (ATBRS), based on conventional DSM-IV symptom scores, and the Strengths and Weaknesses of ADHD-Symptoms and Normal-Behavior (SWAN) scale, which includes above-average performance on attention and activity. The two scales were compared in two age groups of same-sex twins, 528 pairs aged 6 to 9 and 488 pairs aged 12 to 20. RESULTS: Parents reported higher levels of activity and attention in their twins when reporting using the SWAN scale than when using the ATBRS, and while the monozygotic (MZ) correlations were similar on both scales, the dizygotic (DZ) correlations were consistently higher on the SWAN. On DSM-IV based scales, parents exaggerated differences within those sibling pairs in the "with few ADHD symptoms" category. CONCLUSIONS: The SWAN may provide a more realistic description of the ADHD phenotype for the selection of twin and sibling pairs for genetic analysis.

Adolescent↗
PubMed2006

Cortical-subcortical re-entrant circuits and recurrent behaviour.

OBJECTIVE: To explore the application of Parallel Distributed Processing (PDP) models to biological cortical-subcortical re-entrant circuits, and their implications for recurrent psychiatric symptomatology. METHOD: The literature on cortical-cortical and cortical-subcortical re-entrant circuits is reviewed and possible neural network (PDP) analogies are described. Examples from the attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) literature are explored and compared. RESULTS: A common circuit architecture for at least five circuits was found. Recurrent PDP models suggest that subcortical centres can exert significant influences on behaviour, but their effect will depend on gating processes at higher centres, governed by both feedback (phasic arousal/reinforcement) and synaptic activity at higher levels. The latter can vary around a 'Golden Mean' at cortical receptor levels, which degrades when it is either over-aroused or under-aroused. The Continuous Performance Task, which models both working memory and inhibitory processing is a useful task for functional imaging of an attentional network. CONCLUSION: Recurrent symptoms occur as a result of incoordination between phasic subcortical inputs and synaptic gating processes in cortical-subcortical circuits. Obsessive-compulsive disorder and ADHD represent opposite manifestations of recurrent cortical-subcortical processing deficits, with excess arousal in the former and insufficient maintenance of reinforcement and working memory in the latter. These processes may be subject to separate genetic influences at cortical versus subcortical levels.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

Gender differences in ADHD subtype comorbidity.

OBJECTIVE: To examine gender differences in attention-deficit/hyperactivity disorder ("ADHD") symptom comorbidity with "oppositional defiant disorder", "conduct disorder", "separation anxiety disorder", "generalized anxiety disorder", speech therapy, and remedial reading in children. METHOD: From 1994 to 1995, data from a large sample (N = 4,371) of twins and siblings studied in the Australian Twin ADHD Project were obtained by mailed DSM-IV-based questionnaires, investigating patterns of comorbidity in the three subtypes of "ADHD": "inattentive", "hyperactive/impulsive", and "combined". A total of 1,550 questionnaires were returned (87%) over the next 12 to 18 months. RESULTS: Analysis of variance showed significant between-group differences in males and females for inattention and hyperactive/impulsive symptom counts with higher rates of "oppositional defiant disorder" and "conduct disorder" in males, and higher rates of "separation anxiety disorder" in females indicating internalizing disorders are more common in females and externalizing disorders are occurring more often in males. Differences were found between the "ADHD" subtypes and the no ADHD category for all comorbid conditions, for both males and females. Children without ADHD consistently had fewer symptoms, while children with the combined subtype showed consistently more comorbid symptoms indicating a strong relationship between high rates of externalizing symptoms and high rates of internalizing symptoms. Gender differences in speech therapy were significant only for the children without ADHD. The rates of "separation anxiety disorder" were higher in females with the "inattention" subtype and the rate of "generalized anxiety disorder" higher for females with the "combined" subtype, indicating that the subtypes of ADHD were associated with these internalizing disorders in different ways. CONCLUSIONS: Although comorbidity differs among ADHD subtypes, there were no significant gender differences in comorbidity for externalizing disorders. Inattentive girls may present with anxiety. Clinical approaches for both males and females should be sensitive to possible language and reading problems.

Analysis of Variance↗
PubMed2005

Characterizing the ADHD phenotype for genetic studies.

The genetic study of ADHD has made considerable progress. Further developments in the field will be reliant in part on identifying the most appropriate phenotypes for genetic analysis. The use of both categorical and dimensional measures of symptoms related to ADHD has been productive. The use of multiple reporters is a valuable feature of the characterization of psychopathology in children. It is argued that the use of aggregated measures to characterize the ADHD phenotype, particularly to establish its pervasiveness, is desirable. The recognition of the multiple comorbidities of ADHD can help to isolate more specific genetic influences. In relation to both reading disability and conduct disorder there is evidence that genes may be involved in the comorbid condition that are different from pure ADHD. To date, progress with the investigation of endophenotypes for ADHD has been disappointing. It is suggested that extending such studies beyond cognitive underpinnings to include physiological and metabolic markers might facilitate progress.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Synaptic gating and ADHD: a biological theory of comorbidity of ADHD and anxiety.

To derive a biologically based theory of comorbidity in Attention Deficit Hyperactivity Disorder (ADHD). Theoretical concepts and empirical studies were reviewed to determine whether the behavioral inhibition concept provided an understanding of biological processes involved in comorbidity in ADHD. Empirical studies of ADHD have shown comorbidity of ADHD and anxiety, while studies of behavioral inhibition tend to suggest independent disruptive and anxiety traits. This paradox can be resolved by an understanding of the dynamics of mesolimbic dopamine (DA) systems, where reward and delay of reinforcement are determined by tonic/phasic DA relationships, resulting in impulsive 'fearless' responses when impaired. On the other hand, comorbid anxiety is related to impaired synaptic processes, which selectively gate fear (or aggressive) responses from the amygdala at the accumbens. Monosynaptic convergence between prefrontal, hippocampal, and amygdala projection neurons at the accumbens allows the operation of a synaptic gating mechanism between prefrontal cortex (PFC), hippocampus, and amygdala. Impairment of this mechanism by lowered PFC inhibition allows greater amygdala input, and anxiety-related processes more impact, over the accumbens. In conclusion, a dual theory incorporating long-term tonic/phasic mesolimbic DA relationships and secondly impairment of PFC and hippocampal inputs to synaptic gating of anxiety at the accumbens has implications for comorbidity in ADHD, as well as for possible pharmacological interventions, utilizing either stimulant or axiolytic interventions. The use of DA partial agonists may also be of interest.

Anxiety↗
PubMed2004

Should sluggish cognitive tempo symptoms be included in the diagnosis of attention-deficit/hyperactivity disorder?

OBJECTIVE: To determine the impact of including sluggish cognitive tempo items on the factor and latent class structure of attention-deficit/hyperactivity disorder (ADHD) subtypes in boys and girls. METHOD: Parent report of two sluggish cognitive tempo items on a population-based sample of 1430 female twins and 1414 male twins were analyzed along with parent report of the 18 DSM-IV ADHD items using principal components analysis and latent class analysis. RESULTS: The inclusion of the two sluggish cognitive tempo items resulted in distinct factor structures for boys and girls. For boys there were separate inattentive, hyperactive/impulsive, and sluggish factors. For girls there were separate inattentive/sluggish, hyperactive, and impulsive factors. In contrast, sluggish cognitive tempo items had minimal impact on the latent class structure of ADHD for both boys and girls. CONCLUSIONS: The inclusion of sluggish cognitive tempo items markedly changed ADHD symptom associations for boys and girls in a factor analytic framework. In contrast, latent class subtyping of ADHD shows limited impact of the inclusion of sluggish cognitive tempo items, emphasizing the very different assumptions about underlying continua of behavior rather than discrete classes that distinguish the two approaches.

Adolescent↗
PubMed2004

Familial clustering of latent class and DSM-IV defined attention-deficit/hyperactivity disorder (ADHD) subtypes.

BACKGROUND: Findings from family and twin-based studies of Attention Deficit/Hyperactivity Disorder (ADHD) have indicated that inattentive and combined subtypes cluster together among sibling pairs who both express ADHD symptoms. The current report examines the familial clustering of ADHD subtypes, defined according to latent class and DSM-IV criteria, in a general population sample of 2,848 Australian twins, 1,013 of their non-twin siblings and 4,036 female twins from Missouri, USA. Significant clustering of DSM-IV inattentive and combined subtypes, and significant clustering of the same latent classes among siblings was predicted. METHOD: Logistic regression was used to assess 1) the clustering of same and different subtype combinations among twin and twin-sibling pairs and 2) whether genetic influences contribute significantly to the observed patterns of subtype combinations among siblings. RESULTS: With the exception of the DSM-IV hyperactive-impulsive subtype and the severe hyperactive-impulsive latent class, all other sibling DSM-IV and latent class ADHD subtypes consistently exhibited significant same-subtype clustering with MZ probands, DZ probands and their siblings in both samples. Furthermore, a significant genetic influence contributing to subtype concordance was detected for every DSM-IV subtype excluding hyperactive-impulsive, and for all eight latent classes. While some instances of significant different-subtype clustering among siblings was observed across both classification systems and samples, the particular subtype combinations involved were largely inconsistent across samples and no significant genetic influences contributing towards these discordant subtype combinations were detected. CONCLUSIONS: For both DSM-IV and latent class subtypes, the overall pattern of findings in both samples indicated significant familial clustering of same-subtype combinations and significant genetic influences contributing to these patterns of subtype concordance, despite important sample differences. These findings further extend previous work and are most consistent with the presence of multiple independent forms of ADHD.

Adolescent↗
PubMed2003

Special twin environments, genetic influences and their effects on the handedness of twins and their siblings.

It has been suggested that twinning may influence handedness through the effects of birth order, intra-uterine crowding and mirror imaging. The influence of these effects on handedness (for writing and throwing) was examined in 3657 Monozygotic (MZ) and 3762 Dizygotic (DZ) twin pairs (born 1893-1992). Maximum likelihood analyses revealed no effects of birth order on the incidence of left-handedness. Twins were no more likely to be left-handed than their singleton siblings (n = 1757), and there were no differences between the DZ co-twin and sibling-twin covariances, suggesting that neither intra-uterine crowding nor the experience of being a twin affects handedness. There was no evidence of mirror imaging; the co-twin correlations of monochorionic and dichorionic MZ twins did not differ. Univariate genetic analyses revealed common environmental factors to be the most parsimonious explanation of familial aggregation for the writing-hand measure, while additive genetic influences provided a better interpretation of the throwing hand data.

Birth Order↗
PubMed2003

Small for gestational age as a predictor of behavioral and learning problems in twins.

The study examines the effects of being born small for gestational age (SGA) on rates of behavioral problems in twins and siblings, utilising data from the Australian Twin Study of disruptive behavior disorders in twins and their siblings. Participants were 3944 twins and their siblings who were assessed at two intervals three years apart. At the first assessment (1991), they ranged between 4 and 12 years of age. Items assessing Attention Deficit/Hyperactivity Disorder were based on DSM-III-R criteria (Time 1) and DSM-IV criteria (Time 2). Other measures included history of speech and reading therapy, demographic information and obstetric and neonatal history. Results indicated that both male and female twins, who were extremely growth restricted (small for gestational age up to the third percentile-WGA3) showed more inattention, and poorer speech and reading scores. The effects were greater for males. Male twins who were small for gestation age, up to the 10th percentile, were more likely to have a DSM-IV diagnosis of Inattention. Implications of these results included WGA3 male twins being at a "triple disadvantage" for subsequent behavioral and learning problems, in that being male, being a twin and being small for gestational age are all significant factors. Recommendations are made for early intervention for low birthweight male twins. The study is consistent with recent follow-up studies of very-low-birthweight singletons, indicating male disadvantage in cognitive outcome. While there is some genetic component to SGA, it does constitute a potentially major contribution to common environmental effects that must be considered in twin-based genetic analyses.

Child Behavior Disorders↗
PubMed2002

Project for a scientific psychiatry in the 21st century.

OBJECTIVE: To discuss potential advances in neuroscientific knowledge in the 21st century, enabling the realization of Freud's original vision of a basic biological science and an associated metapsychology. RESULTS: The Australian Twin Study of Attention Deficit Hyperactivity Disorder (ADHD) has demonstrated the high heritability of the core symptoms of ADHD, as well as showing important genetic and environmental influences on comorbid conditions. Brain mapping techniques suggest that working memory, as measured by an A-X Continuous Performance Task, is important in ADHD. METHODS: To outline the development of our own clinical research into ADHD, and the potential for future behaviour and molecular genetic approaches. CONCLUSIONS: The 21st century promises new and exciting developments in phenomenology, genetics, and neuroscientific understandings in Child Psychiatry.

Attention Deficit Disorder with Hyperactivity↗
PubMed2002

Replication of the latent class structure of Attention-Deficit/Hyperactivity Disorder (ADHD) subtypes in a sample of Australian twins.

BACKGROUND: Previous efforts to subtype Attention-Deficit/Hyperactivity Disorder (ADHD) using latent class analysis (LCA) applied to DSM-IV symptom profiles of adolescent female twins from Missouri (USA) have identified distinct classes within the domains of inattention, hyperactivity-impulsivity and combined-type problems. The objective of the current report is to determine if the latent class structure of ADHD subtypes can be replicated in a culturally distinct sample of female and male Australian twins. METHOD: LCA was applied to parent-report DSM-IV ADHD symptom profiles of N=2,848 child and adolescent Australian twins and compared to North American findings. Separate models were fitted for females (N= 1,432) and males (N= 1,416). RESULTS: The most congruent latent ADHD classes across samples included a non-symptomatic class, three mild-moderate and two severe classes. Also present within samples was a rare hyperactive-impulsive class and a unique class, the structure of which was idiosyncratic across samples. Mean symptom endorsement and individual symptom endorsement probabilities for each of the stable classes were similar across samples. Consistent with previous findings, there was substantial overlap between the DSM-IV inattentive and combined subtypes with the severe inattentive and severe combined latent classes. However, DSM-IV inattentive and combined subtypes were distributed over several latent classes in each sample, and a substantial proportion of individuals with no DSM-IV diagnosis were also assigned to these severe classes. CONCLUSIONS: Results from LCA using an Australian twin sample replicate six of the eight latent class subtypes previously reported using Missouri female twins and extend the findings to male twins. LCA and DSM-IV systems of ADHD classification identify different phenotypic groups, and the basis of this disparity merits further investigation.

Adolescent↗
PubMed2002

Recruitment and attrition in twin register studies of childhood behavior: the example of the Australian Twin ADHD Project.

There are a growing number of large-scale initiatives for twin registers of children. The Australian Twin ADHD Project (ATAP) is used to illustrate two key limitations which may arise with such studies, namely (1) the importance of including or possibly excluding families in which one or both twins have significant developmental disability, and (2) the selective failure to recruit and/or the selective attrition of families in which parents and children share behavioral difficulties. Initially ATAP excluded 1 in 6 of families whose twins were enrolled in the volunteer-based Australian Twin Registry (ATR), and as more children with significant problems were identified, these families were sequentially excluded. With longitudinal data over ten years, two points about retention were identified: the difficulty of retaining the twins in late adolescence, and the loss of the families whose twins had more ADHD symptoms. We discuss strategies for limiting the loss of families and for ensuring comparability of data across registers with similar interests but different methods of recruitment and exclusion.

Adolescent↗
PubMed1999

Sex differences in genetic and environmental influences on DSM-III-R attention-deficit/hyperactivity disorder.

Approximately 5% of children are affected by attention-deficit/hyperactivity disorder (ADHD), and more boys are affected than girls. This study examined the magnitude of genetic and environmental influences on ADHD and several questions regarding sex differences in its prevalence and liability. The participants were 2,391 twin and sibling pairs from Australia, ages 3-18. ADHD symptoms in the general population were highly heritable (h2 = .85-.90), as were deviant ADHD scores in the selected population. The magnitude of familial influences was similar for boys and girls, although there were shared environmental influences on ADHD in girls but not boys and dominance genetic influences on ADHD in boys but not girls. Specific genetic and environmental influences were highly similar for boys and girls. Evidence supported the polygenic multiple threshold model rather than the constitutional variability model of sex differences in ADHD.

Adolescent↗