{
  "abstract": "Objectives To estimate the risk of incident attention deficit hyperactivity disorder (ADHD) in individuals with phenotypical primary Raynaud’s phenomenon (RP).Design Retrospective cohort study.Setting De-identified electronic health record data from a large, federated network of healthcare organisations, predominantly secondary and tertiary care centres in North America, between March 2005 and March 2025.Participants Individuals with RP were identified using at least two international classification of diseases (ICD)-10 I73.0 codes, excluding systemic autoimmune rheumatic diseases to approximate a primary RP phenotype. Comparator individuals had at least two irritable bowel syndrome ICD-10 K58 codes, excluding inflammatory bowel disease and connective tissue diseases. Cohorts were stratified a priori by age (<45 and ≥45 years).Interventions After propensity score matching, analyses included 32,516 matched pairs aged <45 years and 61,408 matched pairs aged ≥45 years.Main outcome measures The primary outcome was incident ADHD. Time-to-event analyses were conducted using 1:1 propensity score matched Cox proportional hazards models, with matching performed separately within age strata using relevant demographic, comorbidity and medication covariates, including ADHD-related and cardiovascular medications.Results Among 32,516 (<45 years) and 61,408 (≥45 years) matched pairs, RP was associated with a higher incidence of ADHD in individuals aged ≥45 years (HR 1.251, 95% CI 1.097–1.426), whereas evidence in those aged <45 years was weaker and did not reach conventional statistical significance (HR 1.088, 95% CI 0.996–1.189).Conclusions In conclusion, RP was associated with an increased risk of incident ADHD, including accounting for known implicated ADHD-related medications, although estimates under <45 years lack precision. Future research is warranted to confirm and explore these observations, including potentially shared pathobiological mechanisms, including small fibre neuropathy, between primary RP and ADHD.",
  "authors": [
    {
      "affiliations": [
        "Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK",
        "Department of Rheumatology, Salford Care Organisation, Northern Care Alliance NHS Foundation Trust, Salford, UK",
        "NIHR Manchester Biomedical Research Centre, Manchester, UK"
      ],
      "name": "Michael Hughes"
    },
    {
      "affiliations": [
        "Rheumatology, UTHealth, Houston, Texas, USA"
      ],
      "name": "Zsuzsanna Hortobagyi McMahan"
    },
    {
      "affiliations": [
        "Pulmonology Unit, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, University of Trieste, Trieste, Italy"
      ],
      "name": "Barbara Ruaro"
    },
    {
      "affiliations": [
        "Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK",
        "Department of Medicine, University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK"
      ],
      "name": "Uazman Alam"
    },
    {
      "affiliations": [
        "Tameside and Glossop IC NHS FT, Ashton-under-Lyne, UK",
        "The University of Manchester, Manchester, UK",
        "Manchester Metropolitan University, Manchester, UK"
      ],
      "name": "Edward Jude"
    },
    {
      "affiliations": [
        "Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK",
        "NIHR Manchester Biomedical Research Centre, Manchester, UK"
      ],
      "name": "Sizheng Steven Zhao"
    }
  ],
  "title": "Primary Raynaud’s phenomenon is associated with attention deficit hyperactivity disorder: a cohort study harnessing electronic healthcare records",
  "uid": "8c81e86d-dc31-58c4-92a0-ed42ab36f6f0"
}