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PubMed2026

Shared genetic architecture between ADHD and intelligence varies across ADHD subtypes.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition frequently accompanied by cognitive difficulties. Although previous genetic studies have demonstrated substantial overlap between ADHD and intelligence, most have treated ADHD as a single phenotype. However, whether this shared genetic architecture differs across ADHD subtypes remains unclear. METHODS: We conducted a genome-wide cross-trait analysis integrating large-scale genome-wide association study (GWAS) datasets of overall ADHD, its subtypes-childhood ADHD, persistent ADHD, and late-diagnosed ADHD-and intelligence (total N > 300,000). Genome-wide genetic correlations, polygenic overlap, local genetic correlations, and variant-level associations between ADHD phenotypes and intelligence were evaluated to characterize their shared genetic architecture. Shared variants were identified through cross-trait enrichment analyses and subsequently mapped to genes for functional annotation and gene-set enrichment. Bidirectional associations were evaluated using two-sample Mendelian randomization with sensitivity analyses. Additional GWAS datasets were used to validate the robustness of shared loci by assessing the consistency of effect directions. RESULTS: All ADHD phenotypes showed significant negative genetic correlations with intelligence (rg ranging from -0.3442 to -0.4205). Despite these modest genome-wide correlations, cross-trait analyses revealed substantial genetic overlap, including polygenic overlap, local genetic correlations, and variant-level associations. We identified 184 loci jointly associated with ADHD traits and intelligence, including 64 novel loci, whereas no shared loci were detected for persistent ADHD under the current analysis. Functional annotation revealed biologically distinct enrichment patterns across subtypes: childhood ADHD loci were linked to early neurodevelopmental processes, while late-diagnosed ADHD loci were enriched in synapse-related and neuronal signaling pathways. Mendelian randomization analyses suggested bidirectional associations, with stronger evidence supporting a directional association from intelligence to ADHD risk. Furthermore, these shared loci showed largely consistent effect directions across additional GWAS datasets, providing support for the robustness of the findings. CONCLUSIONS: The shared genetic architecture between ADHD and intelligence varies across ADHD subtypes, highlighting distinct biological pathways underlying cognitive heterogeneity in ADHD. These findings suggest that the relationship between ADHD liability and general cognitive ability is not uniform across ADHD subtypes and may inform future research on risk stratification and early identification in child and adolescent psychiatry.

Humans↗
PubMed1989

Behavioral and cognitive subtypes of ADHD.

Attention-deficit hyperactivity symptoms are observed by teachers in 9.2% of a nonreferred elementary school population. Two subtypes of attention-deficit hyperactivity disorder (ADHD), a cognitive form and a behavioral form, are identified. The behavioral subtype includes about 80% of those identified and is characterized by distinct clinical phenomenology of inattention, impulsivity, and hyperactivity. These children can be described on a continuum of severity, with the most severe showing behavioral features indistinguishable from conduct disorder. Children with behavioral subtypes of ADHD do not exhibit the specific skill deficits on neuropsychological tests that are characteristic of reading disabled children. There is a second, less prevalent type of cognitive attention-deficit hyperactivity disorder constituting approximately 20% of ADHD children that includes severe academic underachievement along with inattention, impulsivity, and overactivity. Children with the cognitive subtype exhibit information processing deficits that involve inadequate encoding and retrieval of linguistic information, characteristic of reading disabilities.

Adolescent↗
PubMed1989

Effect of anxiety on cognition, behavior, and stimulant response in ADHD.

The effect of the comorbidity of overanxious disorder (ANX) in attention deficit hyperactivity disorder (ADHD) on laboratory measures of behavior, cognition, and stimulant response was examined. Seventy-nine children who met DSM-III-R criteria for ADHD were tested further for an oppositional defiant disorder (ODD), conduct disorder (CD), or ANX. Subjects with comorbid ANX showed less impulsiveness on a laboratory measure of behavior and had longer, sluggish reaction times on the Memory Scanning Test than those without ANX. ADHD subjects with comorbid ANX were less frequently diagnosed as CD. Forty-three of the subjects completed a double-blind trial of methylphenidate; subjects with comorbid anxiety had a significantly poorer response to the stimulant than those without anxiety, while the comorbidity of ODD or CD did not affect stimulant response. The results suggest that ADHD with comorbid ANX may represent children with primary anxiety who develop secondary inattentiveness, or they may represent a different subtype of ADHD, perhaps similar to the condition of attention deficit disorder without hyperactivity under DSM-III.

Anxiety Disorders↗
PubMed1990

Inattentive and noninattentive ADHD children: do they constitute a unitary group?

Teacher-rated ADHD and normal control children were administered a continuous performance test (CPT), and were then further subdivided based upon the presence or absence of objectively assessed attentional deficits. In addition, children were assessed using several measures of cognitive and behavioral functioning. Attentional deficits were significantly more prevalent among the ADHD group, but about half of the ADHD children showed no evidence of objectively assessed attentional dysfunction. Further group analyses indicated that ADHD children with objectively assessed attentional dysfunction appeared cognitively impaired, while ADHD children without objective evidence of attentional dysfunction had more conduct problems. CPT inattention was not related to the presence of cognitive impairments or conduct problems in the control group. These data must be considered preliminary because teacher ratings were the only source of diagnosis and a single measure of inattention was used. However, they suggest that two subtypes of ADHD children can be identified, one characterized by inattention and learning problems, and the other by conduct problems.

Achievement↗
PubMed1992

A twin study of the etiology of comorbidity: attention-deficit hyperactivity disorder and dyslexia.

Monozygotic and dizygotic twin pairs, in which at least one member of each pair is reading disabled (RD), were assessed for attention-deficit hyperactivity disorder (ADHD). Within pair cross-concordances of the RD and ADHD qualitative diagnoses for monozygotic twins were larger than for dizygotic twins, although not significantly so (p less than 0.10). Thus, the data suggest that RD and ADHD may be primarily genetically independent. However, trends in the data and subtype analyses suggest that in some cases RD and ADHD may occur together because of a shared genetic etiology and that a genetically mediated comorbid subtype may exist.

Achievement↗
PubMed1991

Stage I and II subdiaphragmatic Hodgkin's disease.

From January 1971 to December 1986, 521 patients with Hodgkin's disease were evaluated and treated at the Yale University School of Medicine or one of its close affiliates. A total of 258 patients had pathologic stage (PS) I or II disease, with 239 patients having Hodgkin's disease above the diaphragm (ADHD) and 19 patients having Hodgkin's disease below the diaphragm (BDHD). A comparison of patients with BDHD versus patients with ADHD showed that patients with BDHD were older (mean age, 42 versus 28 years of age, P = 0.005), were initially seen less often with nodular sclerosis subtype (32% versus 77%, P = 0.00001), and had a higher male: female ratio (2.8 versus 1.2, P = 0.12). Ten patients with BDHD (53%) had positive findings at staging laparotomy (0 of 4 clinical stage [CS] IA patients and 10 of 15 (67%) CS II patients). Radiation therapy alone was the initial treatment of choice for 74% of patients with BDHD versus 94% of the patients with ADHD. There was no statistical difference in the overall survival or relapse-free survival rates for patients with BDHD versus ADHD (10-year survival rates, BDHD = 73% and ADHD = 81%). However, patients with BDHD who initially had intra-abdominal disease had a statistically significant increase in death rate (60%) due to Hodgkin's disease compared with patients with BDHD who initially had only peripheral nodal disease (0%). Treatment recommendations for patients with BDHD should be tailored to the specific clinical presentation of each patient. For most PS IA/IIA patients initially seen with peripheral nodal disease, radiation therapy alone is a successful treatment program. However, combined modality therapy should be the treatment of choice for patients with BDHD initially seen with intra-abdominal disease.

Abdominal Neoplasms↗
PubMed1992

Attention deficit disorder in reading-disabled twins: evidence for a genetic etiology.

In order to assess the genetic etiology of attention deficit hyperactivity disorder (ADHD), the basic regression model for the analysis of selected twin data (DeFries & Fulker, 1985, 1988) was fitted to questionnaire data (DICA: Diagnostic Interview for Children and Adolescents; Herjanic, Campbell, & Reich, 1982) for 37 identical and 37 fraternal twin pairs tested in the Colorado Reading Project. Results of this analysis suggest that ADHD is highly heritable. Moreover, adjusting DICA scores for either IQ or reading performance differences did not substantially change parameter estimates. In future analyses of larger data sets, distinguishing between possible subtypes of attentional problems (e.g., ADD with or without hyperactivity) may facilitate tests of more searching etiological questions.

Achievement↗