Twin study of the etiology of comorbidity between reading disability and attention-deficit/hyperactivity disorder.

This study utilized a sample of 313 eight- to sixteen-year-old same-sex twin pairs (183 monozygotic, 130 dizygotic) to assess the etiology of comorbidity between reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD). RD was assessed by a discriminant function score based on the Peabody Individual Achievement Test, a standardized measure of academic achievement. The DSM-III version of the Diagnostic Interview for Children and Adolescents was used to assess symptoms of ADHD, and separate factor scores were computed for inattention and hyperactivity/impulsivity (hyp/imp). Individuals with RD were significantly more likely than individuals without RD to exhibit elevations on both symptom dimensions, but the difference was larger for inattention than hyp/imp. Behavior genetic analyses indicated that the bivariate heritability of RD and inattention was significant (h(2)(g(RD/Inatt)) = 0.39), whereas the bivariate heritability of RD and hyp/imp was minimal and nonsignificant (h(2)(g(RD/Hyp)) = 0.05). Approximately 95% of the phenotypic covariance between RD and symptoms of inattention was attributable to common genetic influences, whereas only 21% of the phenotypic overlap between RD and hyp/imp was due to the same genetic factors.

Psychiatric comorbidity associated with DSM-IV ADHD in a nonreferred sample of twins.

OBJECTIVE: To test the external validity of the dimensions and subtypes of DSM-IV attention-deficit/hyperactivity disorder (ADHD) by assessing the prevalence of psychiatric comorbidity. METHOD: Eight- to 18-year-old twins with ADHD (n = 105) and without ADHD (n = 95) were recruited through local school districts. Comorbid disorders were assessed by structured diagnostic interviews with the parent and child and by a behavioral rating scale completed by the child's classroom teacher. RESULTS: Symptoms of inattention were associated with lower intelligence and higher levels of depression, whereas symptoms of hyperactivity-impulsivity were associated more strongly with symptoms of oppositional defiant disorder (ODD) and conduct disorder (CD). All DSM-IV subtypes were associated with higher rates of ODD and CD in comparison with controls, and the combined type was associated with more disruptive behavior disorder symptoms than the other 2 subtypes. The combined type and predominantly inattentive type were associated with more symptoms of depression than controls or the predominantly hyperactive-impulsive type. CONCLUSIONS: These results provide support for the discriminant validity of the dimensions and subtypes of DSM-IV ADHD and suggest that clinicians should carefully screen for comorbid disorders as part of a comprehensive assessment of ADHD.

Experimental cross-validation of DSM-IV types of attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine the discriminant validity of DSM-IV attention-deficit/hyperactivity disorder (ADHD) types by testing the hypothesis that types are associated with specific kinds of functional impairment and to compare overlap of DSM-IV and DSM-III-R ADHD. METHOD: Consecutive referrals (n = 692) to a pediatric subspecialty clinic for ADHD were classified into 1 of each of the 3 DSM-IV types of ADHD using parent and teacher checklist ratings of ADHD symptoms. The resulting types were compared on clinical correlates and on whether the children also met criteria for DSM-III-R ADHD. RESULTS: The validity of DSM-IV types was supported by dimension-specific impairment and other distinct correlates. Academic problems aggregated in the 2 types defined by extreme inattention, and externalizing problems aggregated in the 2 types defined by extreme hyperactivity. CONCLUSION: DSM-IV appeared superior to DSM-III-R in subcategorical homogeneity and in exhaustiveness (ability to classify all apparent cases).

Validity of DSM-IV attention-deficit/hyperactivity disorder for younger children.

OBJECTIVE: Little is known about the validity of the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in young children. Moreover, the results of the DSM-IV field trials raised concerns that inclusion of the new predominantly hyperactive-impulsive type of ADHD in DSM-IV might increase the likelihood of the diagnosis being given to active but unimpaired preschool and primary school children. METHOD: The validity of DSM-IV criteria for each subtype of ADHD was evaluated in 126 children, aged 4 through 6 years, and 126 matched comparison children. Probands and controls were classified by using structured diagnostic interviews of the parent and a DSM-IV checklist completed by the teacher. RESULTS: Children who met DSM-IV criteria for each subtype of ADHD according to parent and teacher reports differed consistently from controls on a wide range of measures of social and academic impairment, even when other types of psychopathology and other potential confounds were controlled. CONCLUSIONS: When diagnosed by means of a structured diagnostic protocol, all three DSM-IV subtypes of ADHD are valid for 4- through 6-year-old children in the sense of identifying children with lower mean scores on measures of adaptive functioning that are independently associated with ADHD.

A comparison of the cognitive deficits in reading disability and attention-deficit/hyperactivity disorder.

This study used a nonreferred sample of twins to contrast the performance of individuals with reading disability (RD; n = 93), attention-deficit/hyperactivity disorder (ADHD; n = 52), RD and ADHD (n = 48), and neither RD nor ADHD (n = 121) on measures of phoneme awareness (PA) and executive functioning (EF). Exploratory factor analysis of the EF measures yielded underlying factors of working memory, inhibition, and set shifting. Results revealed that ADHD was associated with inhibition deficits, whereas RD was associated with significant deficits on measures of PA and verbal working memory. The RD + ADHD group was most impaired on virtually all measures, providing evidence against the phenocopy hypothesis as an explanation for comorbidity between RD and ADHD.

A comparison of the neuropsychological profiles of the DSM-IV subtypes of ADHD.

Recent research on the DSM-IV subtypes of attention-deficit/hyperactivity disorder (ADHD) has demonstrated that the subtypes differ in demographic characteristics, types of functional impairment, and profiles of comorbidity with other childhood disorders. However, little research has tested whether the subtypes differ in underlying neuropsychological deficits. This study compared the neuropsychological profiles of children without ADHD (n = 82) and children who met symptom criteria for DSM-IV Predominantly Inattentive subtype (ADHD-IA; n = 67), Predominantly Hyperactive Impulsive subtype (ADHD-HI; n = 14), and Combined subtype (ADHD-C; n = 33) in the areas of processing speed, vigilance, and inhibition. We hypothesized that children with elevations of inattention symptoms (ADHD-IA and ADHD-C) would be impaired on measures of vigilance and processing speed, whereas children with significant hyperactivity/impulsivity (ADHD-HI and ADHD-C) would be impaired on measures of inhibition. Contrary to prediction, symptoms of inattention best predicted performance on all dependent measures, and ADHD-IA and ADHD-C children had similar profiles of impairment. In contrast, children with ADHD-HI were not significantly impaired on any dependent measures once subclinical symptoms of inattention were controlled. Our results do not support distinct neuropsychological deficits in ADHD-IA and ADHD-C children, and suggest that symptoms of inattention, rather than symptoms of hyperactivity/impulsivity, are associated with neuropsychological impairment.

Etiology of inattention and hyperactivity/impulsivity in a community sample of twins with learning difficulties.

A community sample of 373 8 to 18 year-old twin pairs in which at least one twin in each pair exhibited a history of learning difficulties was utilized to examine the etiology of inattention and hyperactivity/impulsivity (hyp/imp). Symptoms of attention-deficit/hyperactivity disorder (ADHD) were assessed by the DSM-III Diagnostic Interview for Children and Adolescents. Inattention and hyp/imp composite scores were created based on results of a factor analysis. Results indicated that extreme ADHD scores were almost entirely attributable to genetic influences across several increasingly extreme diagnostic cutoff scores. Extreme inattention scores were also highly heritable whether or not the proband exhibited extreme hyp/imp. In contrast, the heritability of extreme hyp/imp increased as a linear function of the number of inattention symptoms exhibited by the proband. This finding suggests that extreme hyp/imp may be attributable to different etiological influences in individuals with and without extreme inattention. If this result can be replicated in other samples, it would provide evidence that the hyp/imp symptoms exhibited by individuals with Combined Type ADHD and Predominantly Hyp/Imp Type ADHD may be attributable to different etiological influences.

Utility of behavior ratings by examiners during assessments of preschool children with attention-deficit/hyperactivity disorder.

This study examines the clinical utility of behavior ratings made by nonclinician examiners during assessments of preschool children with Attention-Deficit/Hyperactivity Disorder (AD/HD). Matched samples of children with (n = 127) and without (n = 125) AD/HD were utilized to test the internal, convergent, concurrent, and incremental validity of ratings completed by examiners on the Hillside Behavior Rating Scale (HBRS). Results indicated that HBRS ratings were internally consistent, possessed sufficient interrater reliability, and were significantly associated with parent and teacher reports of AD/HD when controlling for age, gender, intelligence, and symptoms of other psychopathology. HBRS ratings also were significantly associated with other measures of functioning, and provided a significant increment in the prediction of impairment over parent and teacher report alone. These findings suggest that behavioral ratings during testing provide a unique source of clinical information that may be useful as a supplement to parent and teacher reports.

Comorbidity of reading disability and attention-deficit/hyperactivity disorder: differences by gender and subtype.

This study used a community sample of 494 twins with a reading disability (223 girls, 271 boys) and 373 twins without a reading disability (189 girls, 184 boys) to assess the relation between reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD). Symptoms of DSM-III and DSM-IV ADHD were classified into symptoms of inattention and symptoms of hyperactivity-impulsivity (H/I). Results indicated that individuals with RD were more likely than individuals without RD to meet criteria for ADHD and that the association between RD and ADHD was stronger for symptoms of inattention than for symptoms of H/I. Parents and teachers reported similar rates of ADHD, suggesting that ADHD symptoms were pervasive across settings and were not solely attributable to academic frustration. Analyses of possible gender differences revealed that RD was significantly associated with inattention in both girls and boys but associated with H/I only in boys. This difference may provide a partial explanation for the discrepancy between the gender ratio obtained in referred (approximately 4 boys to 1 girl) and nonreferred (1.2 to 1.5 boys to 1 girl) samples of individuals with RD. Specifically, the hyperactive and impulsive behaviors exhibited by boys with RD may be more disruptive than the inattentive behaviors exhibited by girls and may therefore precipitate more frequent referrals for clinical attention.

Childhood and current ADHD symptom dimensions are associated with more severe cannabis outcomes in college students.

BACKGROUND: Numerous studies have shown that attention deficit/hyperactivity disorder (ADHD) is associated higher risk of cannabis use disorders (CUD). However, these studies are limited in that most did not: (a) differentiate the role of hyperactivity-impulsivity (HI) and inattention (IN); (b) control for associated psychopathology; and (c) consider more fine-grained CUD-related measures. Our aim was to clarify the unique and interactive contributions of inattention and hyperactivity symptoms to age of cannabis initiation and DSM-IV cannabis dependence, craving, and severity of problems related to cannabis use while statistically controlling for symptoms of comorbid psychopathology in a non-clinical sample of young adults. METHODS: Cannabis variables, current use of cigarettes and alcohol, current and childhood ADHD, and comorbid internalizing and externalizing psychopathology were assessed in 376 male and female undergraduates. RESULTS: Results indicate that current and childhood IN were independently associated with more severe cannabis use, craving, and problem use-related outcomes in young adulthood (p's<.01) and that childhood HI symptoms were associated with earlier initiation of cannabis (p<.01). Further, current IN symptoms moderated the relationships between level of use and more severe outcomes (p's<.01), such that higher IN strengthened positive associations among use and problem cannabis use. Associations with ADHD symptom dimensions and current use of alcohol and cigarettes were also present. CONCLUSIONS: Thus, current and childhood inattention symptoms as well as childhood hyperactive-impulsive symptoms emerged as significant factors in cannabis-related outcomes in young adults, even after statistically controlling for important confounding variables.

Inhibitory control of memory retrieval and motor processing associated with the right lateral prefrontal cortex: evidence from deficits in individuals with ADHD.

Studies of inhibitory control have focused on inhibition of motor responses. Individuals with ADHD consistently show reductions in inhibitory control and exhibit reduced activity of rLPFC activity compared to controls when performing such tasks. Recently these same brain regions have been implicated in the inhibition of memory retrieval. The degree to which inhibition of motor responses and inhibition of memory retrieval might involve overlapping systems has been relatively unexplored. The current study examined whether inhibitory difficulties in ADHD extend to inhibitory control over memory retrieval. During fMRI 16 individuals with ADHD and 16 controls performed the Think/No-Think (TNT) task. Behaviorally, the Stop Signal Reaction Time task (SSRT) was used to assess inhibitory control over motor responses. To link both of these measures to behavior, the severity of inattentive and hyperactive symptomatology was also assessed. Behaviorally, ADHD individuals had specific difficulty in inhibiting, but not in elaborating/increasing memory retrieval, which was correlated with symptom severity and longer SSRT. Additionally, ADHD individuals showed reduced activity in rLPFC during the TNT, as compared to control individuals. Moreover, unlike controls, in whom the correlation between activity of the rMFG and hippocampus predicts inhibitory success, no such correlation was observed for ADHD individuals. Moreover, decreased activity in rIFG in individuals with ADHD predicted a decrease in the ability to inhibit motor responses. These results suggest that inhibitory functions of rLPFC include control over both memory and motoric processes. They also suggest that inhibitory deficits in individuals with ADHD extend to the memory domain.

Bivariate linkage scan for reading disability and attention-deficit/hyperactivity disorder localizes pleiotropic loci.

BACKGROUND: There is a growing interest in the study of the genetic origins of comorbidity, a direct consequence of the recent findings of genetic loci that are seemingly linked to more than one disorder. There are several potential causes for these shared regions of linkage, but one possibility is that these loci may harbor genes with manifold effects. The established genetic correlation between reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD) suggests that their comorbidity is due at least in part to genes that have an impact on several phenotypes, a phenomenon known as pleiotropy. METHODS: We employ a bivariate linkage test for selected samples that could help identify these pleiotropic loci. This linkage method was employed to carry out the first bivariate genome-wide analysis for RD and ADHD, in a selected sample of 182 sibling pairs. RESULTS: We found evidence for a novel locus at chromosome 14q32 (multipoint LOD=2.5; singlepoint LOD=3.9) with a pleiotropic effect on RD and ADHD. Another locus at 13q32, which had been implicated in previous univariate scans of RD and ADHD, seems to have a pleiotropic effect on both disorders. 20q11 is also suggested as a pleiotropic locus. Other loci previously implicated in RD or ADHD did not exhibit bivariate linkage. CONCLUSIONS: Some loci are suggested as having pleiotropic effects on RD and ADHD, while others might have unique effects. These results highlight the utility of this bivariate linkage method to study pleiotropy.

Psychiatric comorbidity in children and adolescents with reading disability.

This study investigated the association between reading disability (RD) and internalizing and externalizing psychopathology in a large community sample of twins with (N = 209) and without RD (N = 192). The primary goals were to clarify the relation between RD and comorbid psychopathology, to test for gender differences in the behavioral correlates of RD, and to test if common familial influences contributed to the association between RD and other disorders. Results indicated that individuals with RD exhibited significantly higher rates of all internalizing and externalizing disorders than individuals without RD. However, logistic regression analyses indicated that RD was not significantly associated with symptoms of aggression, delinquency, oppositional defiant disorder, or conduct disorder after controlling for the significant relation between RD and ADHD. In contrast, relations between RD and symptoms of anxiety and depression remained significant even after controlling for comorbid ADHD, suggesting that internalizing difficulties may be specifically associated with RD. Analyses of gender differences indicated that the significant relation between RD and internalizing symptoms was largely restricted to girls, whereas the association between RD and externalizing psychopathology was stronger for boys. Finally, preliminary etiological analyses suggested that common familial factors predispose both probands with RD and their non-RD siblings to exhibit externalizing behaviors, whereas elevations of internalizing symptomatology are restricted to individuals with RD.