Attention-Deficit/Hyperactivity Disorder (ADHD), a prevalent childhood neurodevelopmental disorder with complex etiology involving genetic and environmental factors, causes impairments across various life domains and substantial social and economic burden. Identifying correlates to prevent its onset and decrease its incidence is crucial. To our knowledge, our study represents the first case–control investigation of Lebanese ADHD patients to explore potential correlations between familial, maternal, and child health variables and ADHD to enhance understanding of its etiology and aid in prevention efforts. We recruited 61 Lebanese ADHD patients and 58 matched controls aged 6–24 years from all districts of Lebanon. The data to analyze were collected using a questionnaire. We employed statistical tests, including the independent samples t-test and the Chi-square test or Fisher’s exact test. We conducted a multivariate logistic regression analysis to identify the statistically significant factors explaining ADHD likelihood. We observed male predominance (68.9%) among patients. Maternal anemia during pregnancy (OR = 3.654; 95% CI [1.158–11.529]), maternal self-reported stress during pregnancy (OR = 3.268; 95% CI [1.263–8.456]), neonatal jaundice (OR = 5.020; 95% CI [1.438–17.532]), and familial history of ADHD (OR = 12.033; 95% CI [2.950–49.072]) were significantly associated with increased odds of the disorder. On the other hand, breastfeeding (OR = 0.263; 95% CI [0.092–0.757]) was identified as a protective factor against ADHD. This pilot study shed light on risk and protective factors associated with ADHD in the Lebanese population. The results are relevant, as some identified correlates could be avoidable. Further rigorous investigation is required to expand upon the observed correlations and to assist in early detection, prevention, and intervention strategies targeting ADHD.

Introduction: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by hyperactivity, inattention, and impulsivity that often persist until adulthood. Frequent comorbid disorders accompany ADHD and two thirds of children diagnosed with ADHD also suffer from behavioural disorders and from alteration of sensory processing. We recently characterized the comorbidity between ADHD-like symptoms and pain sensitisation in a pharmacological mouse model of ADHD, and we demonstrated the implication of the anterior cingulate cortex and posterior insula. However, few studies have explored the causal mechanisms underlying the interactions between ADHD and pain. The implication of inflammatory mechanisms has been suggested but the signalling pathways involved have not been explored.Methods: We investigated the roles of purinergic signalling, at the crossroad of pain and neuroinflammatory pathways, by using a transgenic mouse line that carries a total deletion of the P2X4 receptor.Results: We demonstrated that P2X4 deletion prevents hyperactivity in the mouse model of ADHD. In contrast, the absence of P2X4 lowered thermal pain thresholds in sham conditions and did not affect pain sensitization in ADHD-like conditions. We further analysed microglia reactivity and the expression of inflammatory markers in wild type and P2X4KO mice. Our results revealed that P2X4 deletion limits microglia reactivity but at the same time exerts proinflammatory effects in the anterior cingulate cortex and posterior insula.Conclusion: This dual role of P2X4 could be responsible for the differential effects noted on ADHD-like symptoms and pain sensitization and calls for further studies to investigate the therapeutic benefit of targeting the P2X4 receptor in ADHD patients.

Various factors—motivation, interest, fatigue, and external stimuli—influence creative mental processes and attention control (AC). Creative thinking (CT) relies on AC and involves coordinated neural networks and pathways. The cognitive function of AC requires the capacity to direct attention toward distinct features of the environment or internal thoughts. Such selectivity is a key to limiting distractions, preserving focus, and assimilating the essential information needed for CT. Despite progress in creativity research, characterization of underlying neural mechanisms remains limited. To address this gap, we identify the obstacles slowing progress in this area and suggest strategies to overcome them. Moving forward, establishing a collaborative research agenda across multiple disciplines is central to continuing the progress made to date. By fostering such an interdisciplinary research agenda can open new therapeutic avenues for attention-deficit/hyperactivity disorder.

Mécanismes corticaux des interactions entre sensibilisation douloureuse et trouble de l'attention avec ou sans hyperactivité (TDAH) dans un modèle murin: Le trouble du déficit de l'attention avec ou sans hyperactivité (TDAH) et la douleur chronique sont deux syndromes complexes d’origine multifactorielle. Des études confirment une comorbidité entre ces deux pathologies. Cependant, les mécanismes ne sont toujours pas élucidés. Une hyperactivité des neurones de l’ACC et une dérégulation de la voie ACC-insula postérieure (PI) ont été démontrées dans un modèle de souris TDAH. La neuroinflammation serait impliquée dans cette concomitance. Notre hypothèse suggère que la neuroinflammation déclencherait une amplification de l’activité neuronale dans l’ACC, sensibilisant ainsi les voies impliquées dans les symptômes du TDAH et la perception douloureuse. Ce travail de thèse vise donc à identifier les mécanismes inflammatoires à l’origine du TDAH et de la sensibilisation douloureuse qui lui est associée, avec un intérêt porté sur le rôle du récepteur purinergique P2X4 dans cette comorbidité.Afin de répondre à cette question, nous avons généré un modèle de souris TDAH par injection unilatérale et intracérébroventriculaire de 6-hydroxydopamine (6-OHDA), à P5. D’une part, des souris sauvages mâles et femelles âgées de deux mois ont été sacrifiées, leurs cerveaux ont été extraits et leurs ACC et PI ont été disséqués. Des tissus fixés ont été utilisés pour des études morphologiques tandis que des tissus frais ont été utilisés pour des études transcriptomique, protéomique et phosphoprotéomique. D’autre part, des souris avec un knock-out total du récepteur P2X4 ont été soumises à des tests de sensibilisation à la douleur (thermique et mécanique) et d'hyperactivité. Les tissus provenant d’ACC fixés ont été utilisés afin d’étudier les changements morphologiques microgliaux tandis que des tissus provenant d’ACC et de PI fraîchement extraits ont été utilisés pour des analyses transcriptomiques.En ce qui concerne les marqueurs identifiés chez les souris modèles de TDAH, nos résultats démontrent (i) des changements dans la morphologie des cellules microgliale et astrocytaire, associés à une réactivité cellulaire, dans l'ACC des souris 6-OHDA, (ii) la présence d’un environnement pro-inflammatoire dans l'ACC et la PI des souris 6-OHDA, (iii) des modifications dans l'expression de multiples protéines et l’activité de plusieurs kinases (sérine-thréonine et tyrosine) dans l'ACC et la PI des souris 6-OHDA, associées à des altérations du guidage axonal, de l’apoptose, de la dynamique du cytosquelette, de cascades de signalisation, de neurotrophines et de neurotransmetteurs, et (iv) des variations des interactions neurones-glie, et en particulier de la communication entre les neurones et les astrocytes dans l'ACC des souris 6-OHDA. L'intégration des données a permis d'identifier quatre processus altérés dans l'ACC et la PI des souris mâles et femelles 6-OHDA : l'apoptose, le guidage axonal, la plasticité synaptique (potentialisation à long terme) et la croissance des prolongements neuronaux ; des processus précédemment associés au TDAH et aux douleurs chroniques. De plus, nos résultats suggèrent un effet délétère du récepteur P2X4 sur l’activité locomotrice des souris et la réactivité microgliale. Il exercerait néanmoins un effet protecteur en limitant l'expression de molécules pro-inflammatoires, probablement sécrétées par des cellules non-microgliales.En conclusion, nos travaux fournissent des pistes sur les mécanismes inflammatoires qui sous-tendent la comorbidité entre le TDAH et la sensibilisation à la douleur. Ces pistes devront ultérieurement être validées individuellement. Le maintien d’un environnement pro-inflammatoire dans l'ACC et la PI entraîne des changements dans certains processus synaptiques (potentialisation à long-terme, guidage axonal, croissance des composants neuronaux) et apoptotiques. Ces altérations modifieraient la connectivité cellulaire et l'activité neuronale, participant ainsi à la pathogenèse du TDAH et de la douleur chronique.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most widespread neurodevelopmental disorders globally, marked by chronic symptoms of inattention and/or hyperactivity-impulsivity. Its multifactorial origin and phenotypic heterogeneity make it a complex condition, and despite substantial research, the precise causes of ADHD remain poorly understood. A significant challenge in advancing ADHD research is the lack of a unified resource that consolidates animal models across different species and considers the diversity of ADHD subtypes and associated coexisting conditions. This lack of standardization of the models delays progress in developing a deeper understanding of the neuronal and molecular mechanisms behind the disorder, which is essential to advance its treatment. This review aims to bridge this gap by offering a comprehensive compilation of available animal models used in ADHD research, accompanied by an evaluation of their validity. It is essential for researchers to have access to a range of models, each selected based on the specific scientific objectives and hypotheses of their studies. The review highlights that an extensive approach to studying ADHD, including its various dimensions and associated conditions, requires the use of multiple animal models. Moreover, it emphasizes the importance of assessing the mechanisms and broader effects of current pharmacological treatments while also exploring novel therapeutic possibilities. By providing a clearer and more structured resource, this work pursues to assist researchers in selecting the most appropriate models for their investigations. Additionally, it aims to contribute to the broader understanding of ADHD neurobiology, offering new perspectives for new models and the potential for more targeted therapeutic strategies. SIGNIFICANT STATEMENT: Attention-deficit/hyperactivity disorder (ADHD), one of the most prevalent neurodevelopmental disorders globally, is marked by inattention and/or hyperactivity-impulsivity. This review evaluates animal models for ADHD and its coexisting conditions, emphasizing the need for diverse models to reflect its complexity. It underscores the importance of selecting appropriate models to address specific research goals and investigates current and potential pharmacological treatments, providing a vital resource for advancing ADHD research and improving therapeutic approaches.