Genetic Interplay Between Attention-Deficit/Hyperactivity Disorder and Pain Suggests Neurodevelopmental Pathways and Comorbidity Risk
Background: In this study, we investigated the genetic connections between attention-deficit/hyperactivity disorder (ADHD), migraine (MGN), and multisite chronic pain (MCP). The goal was to identify specific shared biological mechanisms that contribute to the overlap between ADHD and these pain-rela...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Biological Psychiatry Global Open Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667174325000710 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849434408415657984 |
|---|---|
| author | Nicolas P. Ciochetti Victor F. de Oliveira Iago Junger-Santos Cibele E. Bandeira Maria E. Tavares Eduardo S. Vitola Luis A. Rohde Gustavo Melo de Andrade Bruna S. da Silva Eugenio H. Grevet Claiton H. Dotto Bau Diego L. Rovaris |
| author_facet | Nicolas P. Ciochetti Victor F. de Oliveira Iago Junger-Santos Cibele E. Bandeira Maria E. Tavares Eduardo S. Vitola Luis A. Rohde Gustavo Melo de Andrade Bruna S. da Silva Eugenio H. Grevet Claiton H. Dotto Bau Diego L. Rovaris |
| author_sort | Nicolas P. Ciochetti |
| collection | DOAJ |
| description | Background: In this study, we investigated the genetic connections between attention-deficit/hyperactivity disorder (ADHD), migraine (MGN), and multisite chronic pain (MCP). The goal was to identify specific shared biological mechanisms that contribute to the overlap between ADHD and these pain-related conditions. Methods: We utilized various post–genome-wide association study analyses on summary data from samples ranging between 225,534 and 766,345 individuals. In an independent sample of patients with ADHD and control participants (665 cases and 995 controls), we evaluated MGN and MCP polygenic risk scores (PRSs) in relation to comorbid profiles, symptom severity, and neuroimaging brain scores. Results: The findings show a strong biological overlap between ADHD and MCP, with a less pronounced relationship with MGN. Key regions and genes associated with ADHD and MCP were enriched in neurodevelopmental pathways, including those involved in neuron projection morphogenesis and nervous system development. Drug-set enrichment analysis identified that some of these pathways are potentially influenced by paracetamol, a drug that has been implicated as a class I environmental risk factor for ADHD when exposure occurs prenatally. Causal inference analysis using a 5-fold larger ADHD summary dataset demonstrated stronger effects of MCP on ADHD than the reverse. In the independent sample, higher MCP PRSs were linked to structural brain features, increased comorbidity with substance use and bipolar disorder, and heightened severity of ADHD symptoms. Conclusions: These findings underscore the significant genetic relationship between ADHD and MCP, suggesting that shared genetic factors may influence brain development and contribute to diverse clinical outcomes in ADHD. |
| format | Article |
| id | doaj-art-58643d4bee5044aa8cf0728a1ed89480 |
| institution | Kabale University |
| issn | 2667-1743 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biological Psychiatry Global Open Science |
| spelling | doaj-art-58643d4bee5044aa8cf0728a1ed894802025-08-20T03:26:39ZengElsevierBiological Psychiatry Global Open Science2667-17432025-07-015410051710.1016/j.bpsgos.2025.100517Genetic Interplay Between Attention-Deficit/Hyperactivity Disorder and Pain Suggests Neurodevelopmental Pathways and Comorbidity RiskNicolas P. Ciochetti0Victor F. de Oliveira1Iago Junger-Santos2Cibele E. Bandeira3Maria E. Tavares4Eduardo S. Vitola5Luis A. Rohde6Gustavo Melo de Andrade7Bruna S. da Silva8Eugenio H. Grevet9Claiton H. Dotto Bau10Diego L. Rovaris11Laboratory of Physiological Genomics of Mental Health, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, BrazilLaboratory of Physiological Genomics of Mental Health, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, BrazilLaboratory of Physiological Genomics of Mental Health, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, BrazilLaboratory of Physiological Genomics of Mental Health, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, BrazilLaboratory of Physiological Genomics of Mental Health, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil; ADHD Outpatient Program & Developmental Psychiatry Program, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilLaboratory of Physiological Genomics of Mental Health, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil; ADHD Outpatient Program & Developmental Psychiatry Program, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilADHD Outpatient Program & Developmental Psychiatry Program, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Departamento de Psiquiatria, Faculdade de Medicina, Programa de Pós-Graduação em Psiquiatria e Ciências do Comportamento, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Medical Council, UniEduK and Unifaj, Indaiatuba, Brazil; Center for Research and Innovation in Mental Health, National Institute of Developmental Psychiatry, São Paulo, BrazilCenter for Teaching and Research in Brain Aging (NUDEC), Federal University of São Paulo, São Paulo, BrazilLaboratory of Physiological Genomics of Mental Health, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil; ADHD Outpatient Program & Developmental Psychiatry Program, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Department of Basic Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, BrazilADHD Outpatient Program & Developmental Psychiatry Program, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Departamento de Psiquiatria, Faculdade de Medicina, Programa de Pós-Graduação em Psiquiatria e Ciências do Comportamento, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilADHD Outpatient Program & Developmental Psychiatry Program, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Departamento de Psiquiatria, Faculdade de Medicina, Programa de Pós-Graduação em Psiquiatria e Ciências do Comportamento, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Departamento de Genética, Instituto de Biociências, Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilLaboratory of Physiological Genomics of Mental Health, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil; Address correspondence to Diego L. Rovaris, Ph.D.Background: In this study, we investigated the genetic connections between attention-deficit/hyperactivity disorder (ADHD), migraine (MGN), and multisite chronic pain (MCP). The goal was to identify specific shared biological mechanisms that contribute to the overlap between ADHD and these pain-related conditions. Methods: We utilized various post–genome-wide association study analyses on summary data from samples ranging between 225,534 and 766,345 individuals. In an independent sample of patients with ADHD and control participants (665 cases and 995 controls), we evaluated MGN and MCP polygenic risk scores (PRSs) in relation to comorbid profiles, symptom severity, and neuroimaging brain scores. Results: The findings show a strong biological overlap between ADHD and MCP, with a less pronounced relationship with MGN. Key regions and genes associated with ADHD and MCP were enriched in neurodevelopmental pathways, including those involved in neuron projection morphogenesis and nervous system development. Drug-set enrichment analysis identified that some of these pathways are potentially influenced by paracetamol, a drug that has been implicated as a class I environmental risk factor for ADHD when exposure occurs prenatally. Causal inference analysis using a 5-fold larger ADHD summary dataset demonstrated stronger effects of MCP on ADHD than the reverse. In the independent sample, higher MCP PRSs were linked to structural brain features, increased comorbidity with substance use and bipolar disorder, and heightened severity of ADHD symptoms. Conclusions: These findings underscore the significant genetic relationship between ADHD and MCP, suggesting that shared genetic factors may influence brain development and contribute to diverse clinical outcomes in ADHD.http://www.sciencedirect.com/science/article/pii/S2667174325000710Attention-deficit/hyperactivity disorderGenome-wide association studyMigrainePainPleiotropyPolygenic risk score |
| spellingShingle | Nicolas P. Ciochetti Victor F. de Oliveira Iago Junger-Santos Cibele E. Bandeira Maria E. Tavares Eduardo S. Vitola Luis A. Rohde Gustavo Melo de Andrade Bruna S. da Silva Eugenio H. Grevet Claiton H. Dotto Bau Diego L. Rovaris Genetic Interplay Between Attention-Deficit/Hyperactivity Disorder and Pain Suggests Neurodevelopmental Pathways and Comorbidity Risk Biological Psychiatry Global Open Science Attention-deficit/hyperactivity disorder Genome-wide association study Migraine Pain Pleiotropy Polygenic risk score |
| title | Genetic Interplay Between Attention-Deficit/Hyperactivity Disorder and Pain Suggests Neurodevelopmental Pathways and Comorbidity Risk |
| title_full | Genetic Interplay Between Attention-Deficit/Hyperactivity Disorder and Pain Suggests Neurodevelopmental Pathways and Comorbidity Risk |
| title_fullStr | Genetic Interplay Between Attention-Deficit/Hyperactivity Disorder and Pain Suggests Neurodevelopmental Pathways and Comorbidity Risk |
| title_full_unstemmed | Genetic Interplay Between Attention-Deficit/Hyperactivity Disorder and Pain Suggests Neurodevelopmental Pathways and Comorbidity Risk |
| title_short | Genetic Interplay Between Attention-Deficit/Hyperactivity Disorder and Pain Suggests Neurodevelopmental Pathways and Comorbidity Risk |
| title_sort | genetic interplay between attention deficit hyperactivity disorder and pain suggests neurodevelopmental pathways and comorbidity risk |
| topic | Attention-deficit/hyperactivity disorder Genome-wide association study Migraine Pain Pleiotropy Polygenic risk score |
| url | http://www.sciencedirect.com/science/article/pii/S2667174325000710 |
| work_keys_str_mv | AT nicolaspciochetti geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk AT victorfdeoliveira geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk AT iagojungersantos geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk AT cibeleebandeira geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk AT mariaetavares geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk AT eduardosvitola geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk AT luisarohde geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk AT gustavomelodeandrade geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk AT brunasdasilva geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk AT eugeniohgrevet geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk AT claitonhdottobau geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk AT diegolrovaris geneticinterplaybetweenattentiondeficithyperactivitydisorderandpainsuggestsneurodevelopmentalpathwaysandcomorbidityrisk |