Neilson Martin

Depressive symptoms in children and adolescents: changing aetiological influences with development

BACKGROUND Evidence suggests that depressive symptoms become increasingly heritable as children grow into adolescence. However, the literature is not entirely consistent in this respect and existing longitudinal twin studies have examined changes within adolescence only. METHOD Parent and self-report questionnaire data were used to examine the genetic and environmental influences on depressive symptoms in a UK sample of 670 twin pairs aged 5-17. Age effects were examined cross-sectionally and longitudinally using data collected over a 3-year period. RESULTS Cross-sectional analyses showed that shared environmental effects had significant influence in younger children but not in adolescence, when depression scores were significantly more heritable. The results of these cross-sectional analyses were supported when two waves of parent-report data collected over three years were analysed. Significant new genetic influences emerged in adolescence but no new shared environmental influences. Some sex differences were found, with girls showing greater genetic influence than boys, but only from parent-report data. CONCLUSIONS These findings support and extend earlier work which has shown increasing genetic influence on depressive symptoms as children grow into adolescence.

Comorbid Problems in ADHD: Degree of Association, Shared Endophenotypes, and Formation of Distinct Subtypes. Implications for a Future DSM

We aimed to assess which comorbid problems (oppositional defiant behaviors, anxiety, autistic traits, motor coordination problems, and reading problems) were most associated with Attention-Deficit/Hyperactivity Disorder (ADHD); to determine whether these comorbid problems shared executive and motor problems on an endophenotype level with ADHD; and to determine whether executive functioning (EF)—and motor-endophenotypes supported the hypothesis that ADHD with comorbid problems is a qualitatively different phenotype than ADHD without comorbid problems. An EF—and a motor-endophenotype were formed based on nine neuropsychological tasks administered to 816 children from ADHD—and control-families. Additional data on comorbid problems were gathered using questionnaires. Results indicated that oppositional defiant behaviors appeared the most important comorbid problems of ADHD, followed by autistic traits, and than followed by motor coordination problems, anxiety, and reading problems. Both the EF—and motor-endophenotype were correlated and cross-correlated in siblings to autistic traits, motor coordination problems and reading problems, suggesting ADHD and these comorbid problems may possibly share familial/genetic EF and motor deficits. No such results were found for oppositional defiant behaviors and anxiety. ADHD in co-occurrence with comorbid problems may not be best seen as a distinct subtype of ADHD, but further research is warranted.

Is disabling fatigue in childhood influenced by genes

BACKGROUND Medically unexplained chronic fatigue in childhood may cause considerable disability and (by definition) its cause remains unclear. A study of fatigue in healthy twins has been undertaken to examine whether or not genetic factors play a part. METHOD A questionnaire survey of the main carers of an epidemiological population-based sample of 670 twin pairs who were asked about periods of unexplained and disabling fatigue in their twins. Out of 1340 individuals a period of disabling fatigue was reported for 92 (6.9%). Thirty-three (2.5%) reported disabling fatigue for more than 1 month. Zygosity could be confidently assigned in 98% of the sample providing 278 monozygotic (MZ) and 378 dizygotic (DZ) pairs. These data were analysed using a structural equation modelling approach. RESULTS The results showed that disabling fatigue in childhood is highly familial with an MZ tetrachoric correlation (rMZ) of 0.81 and a DZ tetrachoric correlation (rDZ) of 0.59, for fatigue lasting at least a week. The most acceptable model using Akaikes information criteria, was one containing additive genetic effects (A) and shared environment (C) plus residual (or non-shared) environment (E). For fatigue lasting at least a month rMZ was 0.75 and rDZ 0.47. The most acceptable model included just A and E. However, the role of shared environment could not be conclusively rejected. CONCLUSIONS Unexplained disabling fatigue in childhood is substantially familial. Both genetic and shared environmental factors are worth further exploration in a search for the causes.

Genetic Overlap Between Measures of Hyperactivity/Inattention and Mood in Children and Adolescents

OBJECTIVE Evidence suggests that there is substantial comorbidity between attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder in childhood and adolescence. This study aims to investigate the degree to which etiological factors are shared between the symptoms of these significantly heritable disorders. METHOD A twin study design was used to determine to what extent the covariation between the traits of ADHD and depression is genetically or environmentally mediated, based on parental reports. A general community sample of 645 twin pairs aged 5 to 17 years from the Cardiff Study of All Wales and North England Twins project took part in the study. Parent-rated measures of hyperactivity/inattention (Abbreviated Conners Hyperactivity subscale) and depression (Short Mood and Feelings Questionnaire). RESULTS Phenotypes derived from the scales were significantly correlated in both boys and girls. Bivariate structural equation modeling revealed a large overlap in underlying genetic factors (boys, rA = 0.77; girls, rA = 0.67) along with a smaller influence of nonshared environment. CONCLUSIONS These findings suggest that there are common genes conferring liability to both hyperactive/inattentive and depressive traits in children and adolescents. This has implications for future molecular genetic research into ADHD and major depressive disorder. Additionally, it indicates that the comorbid clinical presentation of these disorders may reflect a common genetic pathway.

A genetic study of Attention-Deficit Hyperactivity Disorder, Conduct Disorder, Oppositional Defiant Disorder and Reading Disability: Aetiological overlaps and implications

Attention Deficit Hyperactivity Disorder (ADHD) commonly co‐occurs with Oppositional Defiant Disorder, Conduct Disorder and Reading Disability. Twin studies are an important approach to understanding and modelling potential causes of such comorbidity. Univariate and bivariate genetic models were fitted to maternal report data from 2040 families of twins from the Australian Twin ADHD Project. All measures showed a heritability of over 0.8 and little role for the common family environment, except for the combined subtype of ADHD with a heritability of 0.69 and a common environment of 0.19. About one‐third of the genetic variance in ADHD was shared with the other behaviours, the largest overlap being with Oppositional Defiant Disorder. Common environmental effects were shared between the combined ADHD subtype and the other measures. Some implications of these findings for home and school are discussed.

Motor disorder and anxious and depressive symptomatology: A monozygotic co-twin control approach

The aim of this study was to investigate the relationship between poor motor ability and anxious and depressive symptomatology in child and adolescent monozygotic twins. The co-twin control design was used to explore these mental health issues in MZ twins concordant and discordant for a motor disorder, and controls. This methodology offers the unique opportunity to control for genetic effects and shared environmental influences, and permits the investigation of non-shared environmental influences. The Developmental Coordination Disorder Questionnaire was used to identify 23 sets of twins discordant for a motor disorder, 23 sets concordant for a motor disorder, and 773 sets of twins with no motor disorder from a total sample of 2122 Australian sets of twins. The Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour questionnaire was used to exclude participants with high Attention Deficit Hyperactivity Disorder symptomatology. Anxious and depressive symptomatology were assessed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) based questionnaires on Generalised Anxiety Disorder and Sad Affect. Results indicated significantly higher levels of anxious and depressive symptomatology in twins with a motor disorder in discordant pairs compared to their co-twins without a motor disorder, and controls. There were significantly higher levels of anxious symptomatology in twins with a motor disorder in discordant sets than in sets of twins concordant for a motor disorder. There were significantly higher levels of anxious symptomatology in concordant twins than in controls. Implications of these findings are discussed with emphasis on understanding and recognising the relationship between a motor disorder and anxious and depressive symptomatology in clinical practice for children and adolescents with these disorders.

Neuropsychological measures probably facilitate heritability research of ADHD

Previous studies, in which cognitive and motor neuropsychological tasks were administered to 816 children from Attention-Deficit/Hyperactivity Disorder (ADHD)- and control-families, showed that various of these measures appeared useful for genetic research in ADHD by forming candidate endophenotypes: underlying, heritable, vulnerability traits that mark an enhanced liability for developing ADHD. The current study extends these findings by showing that six of these ten measures correlate more strongly between siblings than an ADHD composite, suggesting these measures may have a larger heritability than ADHD itself. Significant sibling cross-correlations also suggested that six of ten neuropsychological measures related to similar familial (and heritable) factors as ADHD, suggesting these measures to be useful for ADHD genetic research. An aggregated neuropsychological composite appeared to be the most powerful, since it correlated more strongly between siblings than most individual task measures. These findings suggest heritability research in ADHD will probably be facilitated by including neuropsychological measures.

Attention deficit hyperactivity disorder: a Rasch analysis of the SWAN Rating Scale.

The prevalence of attention-deficit/hyperactivity disorder (ADHD) has been estimated at 3–7% in the population. Children with this disorder are often characterized by symptoms of inattention and/or impulsivity and hyperactivity, which can significantly impact on many aspects of their behaviour and performance. This study investigated the characteristics of the SWANRatingScale and its discrimination of ADHD subtypes. This instrument was developed by Swanson and his colleagues and measures attentiveness and hyperactivity on a continuum, from attention problems to positive attention skills, using a seven-point scale of behaviour: “far below average” to “far above average”. The Australian Twin Attention-Deficit/Hyperactivity Disorder Study consists of questionnaire data collected from families in 1990/2007. The Rasch model was used to measure the characteristics of items from the SWANRatingScale; how well these items discriminated between those with and without ADHD. The prevalence of each subtype was found to be 5.3% for inattentive ADHD, 4.3% for hyperactive ADHD and 4.6% for combined ADHD. A total of 14.2% of the cohort appeared to have ADHD. While the inattentive items appeared to be consistent with each other in their measurement behaviour and response patterns, the hyperactive items were less consistent. Further, the combined subtype appeared to be an entirely different type, with unique features unlike the other two subtypes. Further work is needed to distinguish the diagnostic features of each subtype of ADHD.

Do aggressive and non-aggressive antisocial behaviors in adolescents result from the same genetic and environmental effects?

Antisocial behavior (ASB) in adolescents can broadly be separated into two forms; aggressive and non‐aggressive. Both are heritable and it has been suggested that aggressive ASB is more heritable. The extent to which genes contribute to the correlation between the two is unknown. Structural equation modeling was applied to a population‐based twin sample of 258 twins pairs aged 11–18 to estimate the heritability of each form of ASB and to estimate the extent to which the phenotypic correlation was the consequence of shared genes and environmental factors. Non‐shared environment and genetic factors substantially influenced both forms of ASB. The heritability of aggressive (but not non‐aggressive) ASB was significantly higher in girls than in boys. Combining both sexes, a model in which the genetic effects on aggressive and non‐aggressive ASB were identical could be rejected. Our results suggest a partial genetic overlap with a specific genetic effect contributing to the variance of aggressive ASB and a stronger genetic effect on aggression in females than in males.

An investigation into etiological pathways of DCD and ADHD using a monozygotic twin design.

We previously described a co-twin control design using questionnaire data on monozygotic twins discordant and concordant for developmental coordination disorder (DCD) and attention deficit hyperactivity disorder (ADHD). Our results suggested that DCD and developmental ADHD had different causal pathways, and that second-born twins were at higher risk for oxygen perfusion problems than first-born twins. In the current study we further explored our findings using DNA confirmed zygosity and assessments of 4 female and 10 male sets of monozygotic twins, aged 8 to 17 years, from the first study. Using the McCarron Assessment of Neuromuscular Development (MAND), twice as many second- as first-born twins met criteria for DCD. Second-born twins attained significantly lower scores on 1-minute Apgar, MAND Gross Motor, Bimanual Dexterity and Neuromuscular Development Index. Seven of the nine twins who met criteria for DCD experienced perinatal oxygen perfusion problems. This supported findings in the first study of an association between perinatal oxygen perfusion problems and DCD, and our hypothesis that DCD and cerebral palsy have similar causal pathways. We found similar numbers of males and females discordant for DCD. On telephone interview using the Diagnostic Interview Schedule for Children Parent Interview, the only first-, and all five second-born twins who met criteria for ADHD had an inattentive component - three Inattentive; three Combined. All twins positive for ADHD were male. This adds support to our hypothesis that ADHD symptoms found in some participants may reflect secondary ADHD associated with environmental factors, rather than developmental ADHD.