Biomedical subjects

David A Hay

Publications and source records attributed to David A Hay.

14 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

Meeting the educational needs of multiple birth children.

There has been a significant increase in the number of twins and higher multiples so that one child in 33 is now a multiple. It is therefore not unusual for schools to have several sets of twins, as well as triplets and even higher multiples. By being the same age and in the same school year if not class, twins and higher multiples are not like brothers and sisters born closely together. Teachers and parents need to be aware of particular issues that may affect the physical, intellectual, personal, social and emotional development of multiple birth children, and to ensure that school policy and practice include this special group of children and parents. These issues include: preterm birth catch-up and implications for starting school; the balance of competition and cooperation among multiples; separation in school and the evidence from recent longitudinal studies; legislative and other initiatives on the development of school policy; the particular needs of higher multiples.

Child↗

PubMed2006

Having a co-twin with attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood disorder which occurs more often in twins than singletons. This article focuses on the psychosocial consequences of having a co-twin with ADHD. Specifically, the level of anxiety (generalized and separation) in non-ADHD children who have a co-twin with ADHD is examined using data from the Australian Twin ADHD Project (ATAP). Parental report data on 501 dizygotic (DZ) twin pairs aged 6 to 15 and their siblings were used to examine (i) anxiety symptoms in twin pairs discordant for ADHD, (ii) how the effects of an ADHD twin on their co-twin and siblings are related to the type of ADHD, and (iii) whether the effects are greater for the nonaffected twin than nontwin siblings. Results show that anxiety was high in co-twins of children with the combined subtype of ADHD, with increased symptoms of both generalized and separation anxiety. Inattentive ADHD had smaller effects, which were confined to generalized anxiety and were specific to the co-twin rather than other siblings. These results have clinical implications in managing the entire multiple birth family where one twin has ADHD, and also has implications for genetic analysis in modeling the relationship of ADHD to internalizing disorders.

Adolescent↗

PubMed2005

Cryptophycins-309, 249 and other cryptophycin analogs: preclinical efficacy studies with mouse and human tumors.

Cryptophycins-1 and 52 (epoxides) were discovered to have in-vitro and in-vivo antitumor activity in the early 1990s. The chlorohydrins of these, Cryptophycins-8 and 55 (also discovered in the early 1990s) were markedly more active, but could not be formulated as stable solutions. With no method to adequately stabilize the chlorohydrins at the time, Cryptophycin-52 (LY 355073) entered clinical trials, producing only marginal antitumor activity. Since that time, glycinate esters of the hydroxyl group of the chlorohydrins have been synthesized and found to provide stability. Three of the most active were compared herein. Cryptophycin-309 (C-309) is a glycinate ester of the chlorohydrin Cryptophycin-296. The glycinate derivative provided both chemical stability and improved aqueous solubility. After the examination of 81 different Cryptophycin analogs in tumor bearing animals, C-309 has emerged as superior to all others. The following %T/C and Log Kill (LK) values were obtained from a single course of IV treatment (Q2d x 5) against early staged SC transplantable tumors of mouse and human origin: Mam 17/Adr [a pgp (+) MDR tumor]: 0%T/C, 3.2 LK; Mam 16/C/Adr [a pgp (-) MDR tumor]: 0%T/C, 3.3 LK; Mam 16/C: 0%T/C, 3.8 LK; Colon 26: 0%T/C, 2.2 LK; Colon 51: 0%T/C, 2.4 LK; Pancreatic Ductal Adenocarcinoma 02 (Panc 02): 0%T/C, 2.4 LK; Human Colon HCT15 [a pgp (+) MDR tumor]: 0%T/C, 3.3 LK; Human Colon HCT116: 0%T/C, 4.1 LK. One additional analog, Cryptophycin-249 (C-249, the glycinate of Cryptophycin-8), also emerged with efficacy rivaling or superior to C-309. However, there was sufficient material for only a single C-249 trial in which a 4.0 LK was obtained against the multidrug resistant breast adenocarcinoma Mam-16/C/Adr. C-309 and C-249 are being considered as second-generation clinical candidates.

Animals↗

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↗

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↗

PubMed2004

Together or apart?

Explore the source record for details and available documents.

Anxiety, Separation↗

PubMed2003

Fine and gross motor ability in males with ADHD.

In the this study, both fine and gross motor ability of males with attention-deficit-hyperactivity disorder (ADHD) were compared with a group of control children. Three groups of males with the following ADHD subtypes: predominantly inattentive (ADHD-PI; n = 50), hyperactive/impulsive (ADHD-HI; n = 16), or combined (ADHD-C; n = 38) were compared with 39 control males. Mean ages for the control group were 10 years 4 months (SD 1 year 4 months, range 7 years 8 months to 12 years 11 months); for the ADHD-PI group, 10 years (SD 1 year 2 months, range 7 years 10 months to 13 years); for the ADHD-HI group, 9 years 11 months (SD 1 year 2 months), range 7 years 11 months to 12 years 6 months); and for the ADHD-C group 10 years 2 months (SD 1 year 4 months, range 8 to 13 years). The Australian Disruptive Behaviours Scale and Connors' Parent Rating Scale-Revised were used to assess ADHD symptomatology. Verbal IQ was estimated using two verbal subtests of the Wechsler Intelligence Scale for Children, and movement ability was assessed using the Movement Assessment Battery for Children (MABC) and the Purdue Pegboard test. Findings demonstrated that the children with ADHD had significantly poorer movement ability than control children. A high percentage of these children displayed movement difficulties consistent with developmental coordination disorder (DCD). In addition, the current study found that the type and degree of movement difficulty differed between subtypes. The Total Impairment score, as derived from the MABC, was less severe for the ADHD-HI group than the other two ADHD groups, but more severe than for the control group. Males with ADHD-PI and ADHD-C had significantly poorer fine motor ability (p < 0.001) than control males, whereas the ADHD-HI group did not differ significantly from any of the other groups. As children with ADHD only and the control group did not differ significantly on fine motor ability but were significantly better than children categorized with both ADHD and DCD, it was argued that poorer fine motor ability found in children with ADHD could not be attributed to deficits in attention and concentration, but rather to factors relating to their motor ability.

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↗

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↗

PubMed2002

How mothers cope with the death of a twin or higher multiple.

Estimates suggest up to 15% of multiples grow up as singleton survivors. Few studies have reported how bereaved multiple birth mothers with a surviving multiple cope with their bereavement. Using the population-based Western Australian Twin Child Health study database and other sources, we interviewed 66 bereaved mothers with at least one surviving multiple. For many, this contact was the first acknowledgement of their status as multiple birth mothers since their loss. The Beck Depression Inventory 2nd Edition (BDI) showed significant reduction in depression between the time of loss and our interview. For mothers as a group there was a high correlation between current and retrospective BDI, and retrospective BDI and all three Perinatal Grief Scales (PGS). There was a significant correlation between the three grief factors on the PGS. When subdivided, this held for mothers who suffered a loss at or before the neonatal period, but not for those whose loss occurred later. Bereaved mothers of multiples scored significantly higher on the PGS than the PGS norm for bereaved mothers of singletons, which we attribute to others not acknowledging their grief, and/or recruitment differences. There were no significant differences in PGS scores related to cause, the time since death, or sibling number or age. Spiritual beliefs and finding meaning in loss were positively related to scores for adjustment and acceptance. Although traumatised, most mothers accommodated their losses meaningfully in their lives. Their own support recommendations are included.

Adult↗

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↗