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. 2025 Jun 2;23(1):62.
doi: 10.1186/s12969-025-01103-5.

Predictive factors of comorbid attention-deficit/hyperactivity disorder in early systemic autoimmune and auto-inflammatory disorders

Briac Daniel  1 , Eric Acquaviva  2 , Brigitte Bader-Meunier  3 , Alexandre Belot  4 , Glory Dingulu  5 , Cecile Dumaine  5 , Albert Faye  5 , Marie-Louise Frémond  3   6 , Laura Lavialle  2 , Ulrich Meinzer  5 , Pierre Quartier  3 , Caroline Vinit  5   7 , Richard Delorme  2 , Isabelle Melki  6   8 , Pierre Ellul  9   10
Affiliations

Predictive factors of comorbid attention-deficit/hyperactivity disorder in early systemic autoimmune and auto-inflammatory disorders

Briac Daniel et al. Pediatr Rheumatol Online J. .

Abstract

Background: The immune system is physiologically involved in brain development and homeostasis. Consequently, early immune-mediated events are known risk factors for neurodevelopmental disorders (NDD). We recently found that early systemic autoimmune and autoinflammatory disorders (ESAID) are associated with an increased risk of neurodevelopmental disorders due to the direct impact of inflammation on brain development. However not all ESAID patient will develop NDD. In this study, we aimed to better characterized the natural history of the NDD comorbidity and investigate the influence of others NDD risk factors in ESAID patients with ADHD (ESAID+/ADHD+; n = 14) compared to patient with ESAID without ADHD (ESAID+/ADHD-; n = 14) and patient with ADHD without ESAID (ESAID-/ADHD + = 35).

Findings: We did a case control study using a cohort of ESAID patients (ARTEMIS) and an ADHD cohort (Robert Debre) and found that the onset of ADHD in patients with ESAID is associated with global cognitive brain impairment that does not appear to be due to shared genetic risk factors, reinforcing the hypothesis of an immune-mediated mechanism. Regarding the etiopathogenesis of this comorbidity, we found that low birth weight, a known risk factor for NDD, contributes to the development of ADHD in ESAID patients.

Conclusions: Pediatricians, and in particular pediatric rheumatologists, need to be aware of the frequency of ADHD-related comorbidities in ESAID patients. They should therefore systematically look for NDD in ESAID patients, particularly in cases of low birth weight. Early detection and management of NDD is the only way to limit its impact on morbidity and life trajectory.

Keywords: Child and adolescent psychiatry; Neurodevelopment; Neuroimmunology.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was accepted by the committee for the French «Comité de Protection des Personnes» (2020-A02841-38). Consents for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart. (A) We first recruited 35 ADHD patients matched on sex and age in a 1/2.5 ratio with 14 patients ADHD+/ESAID + from the ARTEMIS cohort. 1 As previously published, in ARTEMIS, we considered that patient have ADHD if the ADHD-RS > 2SD. (B) We matched on sex and age in a 1/1 ratio the preselected ADHD+/ESAID + patients from the ARTEMIS cohort with14 patient ADHD-/ESAID + from the ARTEMIS cohort
Fig. 2
Fig. 2
Predicting factors of comorbid ADHD in patients with ESAID. A-B Classification tree of ADHD risk and classification performance. C) Multiple component analysis with D) graph of variables used and importance in the MCA. BRIEF Behavior rating inventory of executive function, ADHD: Attention deficit hyperactivity disorder, AID: Autoimmune disease, NDD: Neurodevelopment disorder, ESAID: Early systemic autoimmune and auto-inflammatory disorders
See this image and copyright information in PMC

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