Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous condition that imposes a significant public health and socioeconomic burden. Beyond its core symptoms, the disorder is associated with elevated healthcare costs, reduced productivity, and increased risks of psychiatric comorbidities, including depression, anxiety, and substance use disorders (SUD) [1-3]. Despite decades of research, challenges persist in achieving timely and accurate diagnosis, partly due to cross-national differences in diagnostic practices, under-recognition in girls, and symptom overlap with other neurodevelopmental and psychiatric disorders [4]. Delayed or missed diagnosis can lead to chronic functional impairment and long-term disability. Against this backdrop, a comprehensive synthesis of contemporary evidence—spanning epidemiology, neurobiology, diagnostics, and therapeutic strategies—is essential to guide clinicians and inform future research. This review therefore provides an updated overview of ADHD, emphasizing comorbidity profiles, emerging treatment modalities, and directions for precision medicine.

Globally, childhood ADHD is estimated to affect 5%-7% of the population, with prevalence varying according to diagnostic criteria and cultural context [5]. In the United States, parent surveys indicate an increase in diagnoses from approximately 6%-8% in the early 2000s to around 9%-10% by 2018, and more than 75% of affected children present with at least one psychiatric comorbidity [6]. Epidemiological surveys in Korea have reported ADHD prevalence rates of about 13% in primary school children and nearly 7% in adolescents [7]. Although early childhood diagnosis remains challenging due to developmental variability, the incidence of preschool ADHD diagnoses more than doubled between 2007 and 2016, reflecting heightened awareness and improved detection strategies [6]. ADHD frequently persists beyond childhood. Longitudinal studies indicate that 65% to 75% of children with ADHD continue to exhibit clinically significant symptoms into adolescence and adulthood [6]. The estimated adult prevalence ranges from 2% to 4%, with substantial functional impairments across occupational, academic, and interpersonal domains [8]. Despite its chronic nature, adult ADHD remains underdiagnosed, in part because of diagnostic overshadowing by comorbidities and the challenges of retrospective symptom reporting. Sex differences are also notable, with boys more commonly diagnosed in childhood. However, this discrepancy may reflect referral bias, as girls—particularly those with predominantly inattentive presentations—tend to exhibit less overtly disruptive symptoms and are therefore often underdiagnosed [9]. These epidemiological trends underscore the public health burden of ADHD and highlight the need for age- and gender-sensitive screening, early intervention strategies, and longitudinal care systems to improve outcomes across the lifespan.

ADHD is increasingly recognized as a complex neurodevelopmental condition arising from disruptions in interconnected neural circuits and neurotransmitter systems (Fig. 1). Foundational neurobiological models implicate frontostriatal networks—including the prefrontal cortex, striatum, and cerebellum—which play central roles in regulating executive processes, sustaining attention, and coordinating movement [10]. Structural magnetic resonance imaging meta-analyses have demonstrated reductions in cortical thickness and subcortical volumes, particularly in the caudate, pallidum, and thalamus, as well as altered fronto-striato-cerebellar connectivity that correlates with symptom severity [11,12]. A central feature of ADHD pathophysiology is aberrant dopaminergic and noradrenergic signaling. Altered dopamine transporter density and receptor gene variants (e.g., dopamine receptor D4 [DRD4], DRD5) disrupt mesocorticolimbic and nigrostriatal pathways, impairing reward processing and executive function [13-15]. Although dopamine-related gene variants such as dopamine transporter 1 (DAT1) may contribute to ADHD vulnerability, their effect sizes are small and inconsistent across studies. ADHD is now understood as a polygenic disorder in which multiple common variants (e.g., DAT1, DRD4, DRD5, synaptosome associated protein 25 [SNAP25]) interact with environmental factors, rather than any single gene determining the phenotype [16,17]. A 2024 systematic review underscored that dysregulation of catecholamine tone within prefronto-striatal circuits serves as a core mechanism in ADHD. Noradrenergic deficits emerging from locus coeruleus-prefrontal projections further contribute to attentional instability and arousal dysregulation [18].

Recent work using resting-state functional magnetic resonance imaging shows that individuals with ADHD exhibit increased temporal variability in the default mode, cingulo-parietal, and frontoparietal networks—patterns associated with attention deficits and executive dysfunction [11,19]. Complementary network neuroscience approaches highlight atypical subcortico-cortical connectivity, including rightward asymmetry in the superior longitudinal fasciculus, which is associated with hyperactivity and attentional control deficits in adults [11]. These findings underscore ADHD as a disorder of dynamic network organization, not one limited to neurotransmitter imbalances. Building on this network-based perspective, recent studies emphasize the neurobiological convergence between ADHD and epilepsy. Children with epilepsy exhibit significantly higher rates of ADHD than the general pediatric population, suggesting shared neurobiological mechanisms [20]. Neuroimaging and neurophysiological evidence implicate dysfunction in fronto-thalamo-striatal and fronto-cerebellar circuits, contributing to overlapping impairments in executive function, attention, and impulse control [11]. Specific epilepsy syndromes, such as juvenile myoclonic epilepsy and frontal lobe epilepsy, frequently exhibit abnormalities in frontal and thalamocortical networks, mirroring patterns observed in ADHD [21]. Moreover, glutamatergic hyperexcitability has been proposed as a shared pathophysiologic substrate that increases susceptibility to both conditions [22]. These findings support a network-level dysregulation model of ADHD that extends beyond traditional monoaminergic theories [23]. Emerging evidence has also associated hypofrontality—decreased resting cerebral blood flow in the prefrontal cortex—with cognitive control deficits in ADHD, alongside signs of neuroinflammation and gut-brain axis dysbiosis, suggesting an integrative biological framework [24,25]. This multifactorial pathophysiology indicates a shift toward precision medicine, targeting specific neural circuit dysfunctions and molecular mechanisms for personalized treatment strategies.

The diagnosis of ADHD is clinical and is guided by standardized criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The DSM-5 categorizes ADHD into three presentations: predominantly inattentive, predominantly hyperactive-impulsive, and combined type. Diagnosis requires at least six symptoms of inattention and/or hyperactivity-impulsivity for children up to age 16, or five for individuals aged 17 and older, that are present for a minimum of 6 months, are inappropriate for developmental level, and impair functioning in two or more settings (e.g., home, school, work) [26,27]. Comprehensive clinical evaluation involves structured interviews, behavioral observations, and standardized rating scales. Commonly used tools include the SNAP-IV rating scale, Conners Rating Scales, and the Child Behavior Checklist [28]. These scales collect input from multiple informants—typically parents and teachers—to capture symptom presence and severity across settings. Differential diagnosis is critical, as symptoms of ADHD may overlap with other conditions such as anxiety, depression, learning disorders, autism spectrum disorder (ASD), and normal developmental variations. In addition, a high rate of psychiatric comorbidities—including oppositional defiant disorder (ODD), conduct disorder, mood disorders, and SUD—often complicates the clinical picture and necessitates thorough assessment [28]. Underdiagnosis remains a concern, particularly in girls and minority populations, where inattentive symptoms may be misinterpreted or overlooked. Delayed diagnosis is associated with increased functional impairment, academic failure, and social difficulties [29]. Early identification and intervention are therefore critical to optimizing outcomes for individuals with ADHD.

Comorbidities are present in over 60% of individuals with ADHD and vary with developmental stage. Notably, many children with ADHD have a history of early language delay beginning around 2 to 3 years of age, a finding commonly noted in developmental assessments and associated with later attentional and executive function challenges. In preschoolers, ODD, communication disorders, and anxiety are common. During the school-age years, learning disabilities, tic disorders, and anxiety predominate, while adolescents often present with mood disorders, conduct disorder, and SUD [30]. Accurate diagnosis requires a developmental lens and comprehensive, multi-informant assessment using structured interviews and validated scales (Table 1). The differential diagnosis must consider overlapping symptoms with ASD, anxiety, and early-onset bipolar disorder. ADHD symptoms may also mimic or be masked by seizure-related cognitive slowing in epilepsy [31]. Particular attention should be given to distinguishing ADHD from epileptic syndromes, especially absence seizures, which may present with frequent, brief lapses in attention that mimic inattentive symptoms. A failure to identify comorbidities risks misdiagnosis and suboptimal treatment planning.

The treatment of ADHD is most effective when combining modalities tailored to patient age, symptom severity, functional impairment, and comorbidities. ADHD should be managed as a chronic neurodevelopmental disorder within a multimodal framework that integrates pharmacologic therapy, behavioral interventions, and educational support, with ongoing collaboration among families, schools, and healthcare providers [32,33].

Emerging research increasingly recognizes ADHD as a heterogeneous neurodevelopmental disorder with wide variability in symptoms, comorbidities, and treatment responses. This underscores the growing importance of precision medicine.

Genetic studies have identified dopamine-related gene variants (e.g., DAT1, DRD4) that influence individual responses to stimulant medications such as methylphenidate [52]. Neuroimaging findings, including reduced prefrontal cortical thickness and altered frontostriatal connectivity, have been associated with symptom persistence and treatment resistance [53,54]. These biomarkers may help predict the clinical course and guide medication selection. Translational research has expanded therapeutic targets beyond the dopamine and norepinephrine systems. Novel agents that modulate glutamatergic signaling and cholinergic tone are under investigation, while studies of the gut-brain axis suggest that probiotics or dietary interventions may benefit specific ADHD subtypes [51,55]. Digital technologies, such as wearable sensors and smartphone apps, provide tools for real-time behavioral monitoring, enabling dynamic and adaptive care models. Additionally, machine learning algorithms trained on multimodal datasets are being explored to classify ADHD subtypes and predict outcomes, although this work remains in the early stages of clinical application. Collaborative efforts through large-scale consortia (e.g., Enhancing NeuroImaging Genetics through Meta-Analysis [ENIGMA] ADHD) are essential to validate biomarkers across populations and translate neuroscience discoveries into practice. Collectively, these innovations aim to replace the traditional one-size-fits-all paradigm with individualized, data-driven care.

Despite advances in understanding and treatment, ADHD remains a subject of debate in both clinical and public domains. One major controversy involves the potential overdiagnosis of ADHD, particularly among younger children within a given academic year, who may be developmentally less mature [56]. This has led to concerns that normal behavioral variation is being pathologized. Another controversial area is the long-term safety and efficacy of stimulant medications, which, while effective, raise questions about cardiovascular effects, growth suppression, and potential for misuse [44,57]. Discussion is also focused on the role of social and cultural factors in diagnosis, with underdiagnosis more prevalent among girls and ethnic minority groups [58]. The rising popularity of non-pharmacologic interventions, such as digital therapeutics and dietary modifications, has generated both hope and skepticism given the limited high-quality evidence. Continued dialogue and research are essential for refining diagnostic criteria, reducing disparities, and optimizing treatment strategies based on individual needs.

ADHD is a complex neurodevelopmental disorder with significant implications across the lifespan. A combination of pharmacological and behavioral therapies remains the mainstay of treatment, with newer modalities such as digital therapeutics and microbiome-targeted strategies gaining interest. Accurate diagnosis, timely intervention, and individualized care plans are essential for optimizing outcomes. Continued research into neurobiological mechanisms, comorbidities, and treatment innovations will enhance our ability to deliver effective, evidence-based care for individuals with ADHD.