Test of Alternative Hypotheses Explaining the Comorbidity Between Attention-Deficit/Hyperactivity Disorder and Conduct Disorder

There is significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD). The conclusions of studies that examined the causes of comorbidity between ADHD and CD conflict, with some researchers finding support for the three independent disorders model and others finding support for the correlated risk factors model. We tested these models and eleven alternative hypotheses using the same analytical approach. The participants were 110 monozygotic twin pairs and 181 dizygotic twin pairs recruited from the Colorado Learning Disabilities Research Center Twin Study. The three independent disorders model did not fit the data, whereas the correlated risk factors model fit the data well. Several other comorbidity models fit the data as well as or better than the correlated risk factors model. The results suggest that correlated risk factors are a better explanation for the comorbidity between ADHD and CD than a third, independent ADHD+CD subtype.     

Current concepts on the neurobiology of Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) is an early onset, clinically heterogeneous disorder of inattention, hyperactivity, and impulsivity. In contrast to the widespread acceptance of ADHD as a childhood diagnosis, Its prevalence In adults and its implications for clinical practice remain a source of controversy. Throughout the lifecycle, a key clinical feature observed in ADHD patients is comorbidity with Conduct Depressive, Bipolar, and Anxiety disorders. Family studies consistently support the assertion that ADHD runs in families. Heritability data from twin studies of ADHD attribute about 80 percent of the etiology of ADHD to genetic factors. Adoption studies of ADHD also implicate genes in its etiology. Molecular genetic data are bolstered by considerations suggesting that DRD4 and DAT genes may be relevant for ADHD. Independently of genes, prenatal exposure to nicotine and psychosocial adversity have also been identified as risk factors for ADHD. Structural and functional imaging studies consistently implicate catecholamine-rich fronto-subcortical systems in the pathophysiology of ADHD. The effectiveness of stimulants, along with animal models of hyperactivity, point to catecholamine disruption as at least one source of ADHD brain dysfunction. Although not entirely sufficient, changes in dopaminergic and noradrenergic function appear necessary for the clinical efficacy of pharmacological treatments for ADHD, providing support for the hypothesis that alteration of monoaminergic transmission in critical brain regions may be the basis for therapeutic action in ADHD.     

Problems in Psychiatric Genetic Research: A Reply to Faraone and Biederman

This article examines evidence cited in favor of the operation of genetic factors in attention-deficit hyperactivity disorder (ADHD). Like other psychiatric conditions, a belief in the genetic basis of ADHD is derived from the results of family, twin, and adoption studies. Because family studies are widely believed to be confounded by environmental factors, primary emphasis is placed on twin and adoption studies. ADHD twin studies depend on the validity of the equal environment assumption (EEA), which holds that the environments of identical (MZ) and fraternal (DZ) twins are the same. Here it is argued that however the EEA is defined, it cannot be accepted. Therefore, the greater similarity or concordance of MZ twins when compared to DZ twins is plausibly explained by environmental factors. Adoption studies constitute a third method for investigating the role of genetic factors in ADHD. It is argued that these studies are greatly flawed by factors including non blinded diagnoses and the failure to study the biological relatives of adoptees. After an examination of the total weight of evidence in favor of a genetic basis or predisposition for ADHD, it is concluded that a role for genetic factors is not supported and that future research should be directed toward psychosocial causes     

Zur Therapie von ADHS bei komorbiden Autismus-Spektrum-Störungen

Until recently, research on the co-occurrence of ADHD with autism spectrum disorder (ASD) has been limited by the fact that current classification systems did not allow a dual diagnosis of these two neurodevelopmental disorders. Since the DSM-5 permits a double diagnosis of ADHD plus ASD, research on their comorbidity has substantially increased. In addition to shared and distinct etiological factors, studies have revealed a high clinical impact of the combined symptomatology on affected individuals. This article provides a selective overview of evidence-based, mainly pharmacological treatment strategies in ADHD/ASD phenotypes.     

ADHD and delinquency--a developmental perspective

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders of childhood and adolescence. Until now, it has been unclear whether ADHD by itself constitutes a risk factor for later delinquency or does so only in combination with other disruptive symptoms. This article seeks to give a comprehensive account of the literature to shed light on the developmental pathway from childhood ADHD to adult criminality. Comorbid ADHD and conduct disorder (CD) are significantly related to a range of biological and environmental risk factors such as neurocognitive impairment, high parental psychopathology, poor social functioning, and other comorbid mental disorders, particularly substance abuse, that are described in this review. In addition, the results of treatment studies are presented, with a special focus on the results of the Multimodal Treatment Study of Children with ADHD (MTA). Although treatment programs, including medication and psychosocial treatment, can be very effective in improving the functioning of children with ADHD in the social and academic domains in the short term, there is no conclusive evidence that such treatments lower the risk for developing delinquency in adulthood.     

Understanding the Covariation Among Childhood Externalizing Symptoms: Genetic and Environmental Influences on Conduct Disorder,Attention Deficit Hyperactivity Disorder,and Oppositional Defiant Disorder Symptoms

Conduct disorder (CD), attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD) are common childhood externalizing disorders that frequently co-occur. However, the causes of their comorbidity are not well understood. To address that question, we analyzed data from > 600 Finnish twin pairs, who completed standardized interviews at age 14. Behavior genetic methods were used to examine how genetic/environmental factors contribute to each disorders symptoms and to their covariation. We found significant genetic effects on each disorder with only modest evidence of shared environmental influences. Our data suggest the comorbidity among CD, ADHD, and ODD is primarily explained by shared genetic influences; however, each disorder was also under unique genetic influence, supporting the distinction of each disorder.     

Youth Appraisals of Inter-parental Conflict and Genetic and Environmental Contributions to Attention-Deficit Hyperactivity Disorder: Examination of GxE Effects in a Twin Sample

Identification of gene x environment interactions (GxE) for attention-deficit hyperactivity disorder (ADHD) is a crucial component to understanding the mechanisms underpinning the disorder, as prior work indicates large genetic influences and numerous environmental risk factors. Building on prior research, children’s appraisals of self-blame were examined as a psychosocial moderator of latent etiological influences on ADHD via biometric twin models, which provide an omnibus test of GxE while managing the potential confound of gene-environment correlation. Participants were 246 twin pairs (total n = 492) ages 6–16 years. ADHD behaviors were assessed via mother report on the Child Behavior Checklist. To assess level of self-blame, each twin completed the Children’s Perception of Inter-parental Conflict scale. Two biometric GxE models were fit to the data. The first model revealed a significant decrease in genetic effects and a significant increase in unique environmental influences on ADHD with increasing levels of self-blame. These results generally persisted even after controlling for confounding effects due to gene-environment correlation in the second model. Results suggest that appraisals of self-blame in relation to inter-parental conflict may act as a key moderator of etiological contributions to ADHD.     

Genetics and educational psychology

Background: Molecular genetics, one of the most energetic and exciting areas of science, is slowly but surely coming to educational psychology. Aims: We review recent molecular genetic research on learning disabilities as a sign of things to come in educational psychology. We also consider some misconceptions about genetics that have slowed the acceptance of genetics in educational psychology. Samples: Diverse samples of children with learning disabilities have been studied, primarily in the UK and the USA. Methods: Linkage analysis can detect genes that have large effects on learning disabilities. Association analysis can detect genes of much smaller effect size, which is important because common disorders such as learning disabilities are likely to be influenced by many genes as well as by many environmental factors. Results: For reading disability, replicated linkages have been identified on chromosomes 6, 15 and 18. A gene responsible for a rare type of language impairment has recently been identified. For common language impairment, linkages on chromosomes 16 and 19 have recently been reported. More than 200 genetic disorders, most extremely rare, include mental retardation among their symptoms, and chromosomal abnormalities are a major cause of mental retardation. Conclusions: Although finding specific genes associated with learning disabilities is unlikely to have much of a direct application for teachers in the classroom, such findings will have far‐reaching implications for diagnosis, treatment and prevention of learning disabilities and for research in educational psychology. Educational psychology has been slower to accept evidence for the importance of genetics than other areas of psychology in part because of misconceptions about what it means to say that genetics is important for common complex disorders such as learning disabilities.     

Is personality disorder inherited? An overview of the evidence

Genetic factors appear to be of considerable importance in determining normal variation in personality. This is suggested by family, twin, and adoption studies as well as by indirect findings based on animal and psychophysiological studies. In contrast, there is consistent evidence that the contribution of shared family environment is minimal. Despite difficulties in defining personality disorder, it appears that many types of personality disorder, in particular schizotypal personality disorder and antisocial personality disorder/criminality, are also influenced genetically. The genetic transmission of normal personality traits and disorder is most easily explained by the contribution of multiple genes of small effect rather than by single-gene inheritance. Recent advances in molecular genetics have led to the localization of genes of minor effect for some traits. This raises the possibility of detecting a molecular basis of traits and disorders such as personality and personality disorder.Anita Thapar is supported by a Research Training Fellowship from the Medical Research Council.     

Developmental cognitive genetics: how psychology can inform genetics and vice versa

Developmental neuropsychology is concerned with uncovering the underlying basis of developmental disorders such as specific language impairment (SLI), developmental dyslexia, and autistic disorder. Twin and family studies indicate that genetic influences play an important part in the aetiology of all of these disorders, yet progress in identifying genes has been slow. One way forward is to cut loose from conventional clinical criteria for diagnosing disorders and to focus instead on measures of underlying cognitive mechanisms. Psychology can inform genetics by clarifying what the key dimensions are for heritable phenotypes. However, it is not a one-way street. By using genetically informative designs, one can gain insights about causal relationships between different cognitive deficits. For instance, it has been suggested that low-level auditory deficits cause phonological problems in SLI. However, a twin study showed that, although both types of deficit occur in SLI, they have quite different origins, with environmental factors more important for auditory deficit, and genes more important for deficient phonological short-term memory. Another study found that morphosyntactic deficits in SLI are also highly heritable, but have different genetic origins from impairments of phonological short-term memory. A genetic perspective shows that a search for the underlying cause of developmental disorders may be misguided, because they are complex and heterogeneous and are associated with multiple risk factors that only cause serious disability when they occur in combination.     

Developmental cognitive genetics: How psychology can inform genetics and vice versa

Developmental neuropsychology is concerned with uncovering the underlying basis of developmental disorders such as specific language impairment (SLI), developmental dyslexia, and autistic disorder. Twin and family studies indicate that genetic influences play an important part in the aetiology of all of these disorders, yet progress in identifying genes has been slow. One way forward is to cut loose from conventional clinical criteria for diagnosing disorders and to focus instead on measures of underlying cognitive mechanisms. Psychology can inform genetics by clarifying what the key dimensions are for heritable phenotypes. However, it is not a one-way street. By using genetically informative designs, one can gain insights about causal relationships between different cognitive deficits. For instance, it has been suggested that low-level auditory deficits cause phonological problems in SLI. However, a twin study showed that, although both types of deficit occur in SLI, they have quite different origins, with environmental factors more important for auditory deficit, and genes more important for deficient phonological short-term memory. Another study found that morphosyntactic deficits in SLI are also highly heritable, but have different genetic origins from impairments of phonological short-term memory. A genetic perspective shows that a search for the underlying cause of developmental disorders may be misguided, because they are complex and heterogeneous and are associated with multiple risk factors that only cause serious disability when they occur in combination.     

Genetic overlap between ADHD symptoms and EEG theta power

Biological markers that are grounded in neuroscience may facilitate understanding of the pathophysiology of complex psychiatric disorders. One of the most consistent and robust neural abnormalities in attention deficit hyperactivity disorder (ADHD) is increased EEG power in the theta band at rest (4–8 Hz). The present study used a twin design to estimate the extent of genetic overlap between increased theta power and risk for ADHD in order to validate theta power as a marker of genetic risk for ADHD. At rest, EEG was measured in 30 monozygotic and dizygotic adolescent twin pairs concordant or discordant for high ADHD symptom scores and 37 monozygotic and dizygotic control twin pairs with low ADHD symptom scores. Structural equation modelling was used to estimate the heritability of theta power and partition the genetic and environmental contributions to the overlap between ADHD and theta power. A significant phenotypic correlation between ADHD symptoms and elevated theta power was found. Theta power demonstrated moderate to high heritability estimates (0.77) and moderate genetic correlations with ADHD (0.35) suggesting shared genetic influences. Increased theta power is a candidate biological marker of genetic risk for ADHD, which warrants further investigation of the neurobiological mechanisms that underlie the genetic relationship.     

Gene-Environment Interactions in ADHD: The Roles of SES and Chaos

Although attention-deficit/hyperactivity disorder (ADHD) is highly heritable, emerging evidence suggests symptoms are associated with interactions between genes and the environment (GxE) during development. This study tested whether heritability of ADHD symptoms is moderated by two environmental factors: socioeconomic status (SES) and chaos (household disorganisation). A population sample of 520 twin pairs (N = 1040, 52.3% female) from 6 to 15 years completed measures of behavior and home environment. Structural equation modelling was then used to test whether environmental factors were associated with a change in the extent to which genes explain variability in ADHD symptoms. Neither chaos nor SES moderated heritability, with consistent contributions from both genes and environment indicated across socioeconomic strata and levels of chaos. This finding contrasts with those of previous research, underlining the need to replicate results in the emerging field of GxE research across different populations and statistical methods. Robust findings may assist in developing targeted interventions for genetically vulnerable individuals.     

Verhaltensgenetik

Behavioural genetics has provided ample evidence for the influence of genes on personality traits and psychological disorders. In this review, the methodological strategies of behavioural genetics are described and study results with special relevance for psychotherapists are highlighted.Moreover, some traditional myths and misunderstandings are discussed. In particular, two findings are underscored: While genetic factors substantially contribute to the development of personality traits, environmental influences shared by the members of a family appear to be virtually absent. In contrast, environmental factor specific to an individual seem to play an important role.Second, genes do not only have a direct impact on the development of psychological disorders, but also act in an indirect way by increasing the probability of exposure to stressful life events which in turn function as risk factors for psychological disorders. It is concluded that research should incorporate both genetic and environmental factors to be able to evaluate their relative impact and elucidate the interaction of nature and nurture.     

Identification of Genes Influencing a Spectrum of Externalizing Psychopathology

ABSTRACT— Alcohol dependence, drug dependence, childhood conduct disorder, and adult antisocial behavior commonly occur in combination. Data from multiple literatures, including twin/family studies and electrophysiological studies, suggest that the overlap of these disorders is largely due to a shared genetic liability that contributes to a spectrum of externalizing psychopathology. These findings suggest that some genes will not be specific to any one externalizing disorder but will predispose individuals broadly to a spectrum of externalizing psychopathology. Here we review evidence for specific, identified genes, GABRA2 and CHRM2 , that follow this pattern and confer risk for a spectrum of externalizing disorders. These findings confirm the etiological structure of psychopathology suggested by psychological research and suggest exciting new roles that psychologists can play in understanding the pathways underlying associations between genes and behavior.     

Sensory-motor deficits in children with developmental coordination disorder, attention deficit hyperactivity disorder and autistic disorder

Children who have been diagnosed with any one developmental disorder are very likely to meet diagnostic criteria for some other developmental disorder. Although comorbidity has long been acknowledged in childhood disorders, little is understood about the mechanisms that are responsible for the high level of comorbidity. In a series of studies, we have investigated the link between sensory-motor deficits and developmental disorders. Poor sensory-motor integration has long been implicated as a cause of motor problems in developmental disorders such as developmental coordination disorder (DCD), and our recent research has also investigated sensory-motor deficits in children with attention deficit hyperactivity disorder (ADHD) and autistic disorder. Based on a critical examination of relevant literature and some of our recent research findings, we argue that the importance of poor sensory-motor functioning in discriminating children with different disorders has been underestimated. Poor sensory-motor coordination appears to be linked to DCD, but not ADHD. Also, sensory-motor deficits in children with DCD and autistic disorder may provide insight into some of the social difficulties found in these groups of children. This research will increase our understanding of why children with one developmental disorder typically also have problems in other areas.     

Sources of covariation among attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder: the importance of shared environment.

Research has documented high levels of covariation among childhood externalizing disorders, but the etiology of this covariation is unclear. To unravel the sources of covariation among attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD), the authors studied 11-year-old twins (N = 1,506) from the Minnesota Twin Family Study. Symptom counts for each of these disorders were obtained from interviews administered to the twins and their mothers. A model was fit that allowed the parsing of genetic, shared environmental (factors that make family members similar to each other), and nonshared environmental (factors that make family members different from each other) contributions to covariation. The results revealed that although each disorder was influenced by genetic and environmental factors, a single shared environmental factor made the largest contribution to the covariation among ADHD, ODD, and CD.     

多动症的遗传学研究概述

多动症多始于儿童期,并能持续至成年期。传统的家庭、双生子和养子女研究表明,多动症是受遗传影响的。双生子研究现在被用来定义多动症表型,分析性别差异,测试基因对持续性和共病的影响,以及研究遗传与环境的互动。多动症的分子遗传学研究集中在功能候选基因的关联分析上。多动症与DRD4和DRD5的关系比较一致。最新的研究也显示COMT的影响。关联分析（linkage analysis）显示这些单个基因的影响都不大。这个领域还有待于大规模的“全基因关联”分析。至今为止的证据显示,研究基因-表型关联以及基因与环境互动对多动症的影响将日趋重要     

Evidence for the Trait-Impulsivity Etiological Model in a Clinical Sample: Bifactor Structure and Its Relation to Impairment and Environmental Risk

The trait-impulsivity etiological model assumes that a general factor (trait-impulsivity) underlies attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and other externalizing disorders. We investigated the plausibility of this assumption by testing the factor structure of ADHD and ODD in a bifactor framework for a clinical sample of 1420 children between 6 and 18 years of age (M = 9.99, SD = 3.34; 85% male). Further, the trait-impulsivity etiological model assumes that ODD emerges only if environmental risk factors are present. Our results support the validity of the trait-impulsivity etiological model, as they confirm that ADHD and ODD share a strong general factor of disruptive behavior (DB) in this clinical sample. Furthermore, unlike the subdimensions of ADHD, we found that the specific ODD factor explained as much true score variance as the general DB factor. This suggests that a common scale of ADHD and ODD may prove to be as important as a separate ODD subscale to assess externalizing problems in school-age children. However, all other subscales of ADHD may not explain sufficient true score variance once the impact of the general DB factor has been taken into consideration. In accordance with the trait-impulsivity model, we also showed that all factors, but predominantly the general factor and specific inattention factor, predicted parent-rated impairment, and that predominantly ODD and impulsivity are predicted by environmental risk factors.     

Comorbid ADHD: Implications for the Treatment of Anxiety Disorders in Children and Adolescents

Despite high comorbidity rates and potential clinical implications, the influence of co-occurring attention-deficit/hyperactivity disorder (ADHD) on outcomes of cognitive-behavioral treatment (CBT) for anxious youth remains poorly understood. In this qualitative review, the current literature on the influence of comorbid ADHD on CBT of youth with diverse anxiety disorders is explored. Peer-reviewed studies examining ADHD, at the diagnostic and symptom level, received highest priority. In addition, inasmuch as some studies did not isolate the effects of ADHD from other disruptive behavior disorders (DBDs: oppositional defiant disorder, conduct disorders), studies with the three DBDs were explored as well. Ten studies met our specified methodological criteria. Findings are discussed in relation to the following two factors: type of anxiety disorder and measurement of ADHD (diagnostic or symptom level) in these studies. There was evidence that youth with a variety of anxiety disorders and with co-occurring ADHD fared worse than their counterparts without ADHD. Additionally, grouping ADHD with other DBDs tended to obscure the negative impact of ADHD on treatment outcomes. Additional research is needed to delineate the influence of comorbid ADHD specifically on treatment outcomes for the various anxiety disorders. Clinical implications of treating anxious youth with comorbid ADHD are explored.