Attention-Deficit/Hyperactivity Disorder (ADHD): A Comprehensive Review Integrating Neurobiology, Gender Differences, Cognitive Profiles, Psychosocial Dimensions, and Emerging Therapeutic Approaches

Nora Manseur*

Author and independent researcher, Annaba, Algeria

*Correspondence: Nora Manseur, author & independent researcher, Annaba, Algeria.

Tel: +213551853311.

E-mail: nora.mans.official@gmail.com

Received: 01 Dec, 2025; Accepted: 09 Dec, 2025; Published: 12 Dec, 2025.

Copyright: © 2025 Nora Manseur. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribu tion, and reproduction in any medium, provided the original author and source are credited

Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a chronic neurodevelopmental condition characterized by pervasive patterns of inattention, hyperactivity, and impulsivity that impair functioning across academic, occupational, emotional, and social domains. Although traditionally conceptualized as a childhood disorder, longitudinal evidence suggests that symptoms persist into adulthood in approximately 50–65% of cases. Classical research has thoroughly examined ADHD epidemiology, genetics, and neurobiology, but emerging literature reveals additional dimensions that expand the disorder’s conceptual framework. These include sex-specific neurobiological patterns, hormonal influences across the female lifespan, emotional dysregulation, rejection sensitivity, sensory processing differences, sleep–wake disturbances, hyper focus, creativity-linked cognitive traits, and the phenomenon of social masking—particularly among females and late-diagnosed adults.

Recent decades have also introduced innovative therapeutic approaches that complement established pharmacological and psychosocial treatments, including neurostimulation, digital therapeutics, microbiome-based hypotheses, and cognitive enhancement technologies. This integrative review synthesizes classical evidence and recent advances in ADHD research, highlighting the disorder’s multifaceted nature and emphasizing the need for individualized, developmentally sensitive, and gender-responsive care

Keywords

ADHD, neurodevelopmental disorder, executive dysfunction, emotional dysregulation, sex differences, hyper focus, sensory processing, neurostimulation, digital therapeutics, microbiome, neuroimaging, multimodal, circadian rhythms, DSM-5, ICD-11.

Introduction

Attention-Deficit/Hyperactivity Disorder (ADHD) is among the most extensively studied neurodevelopmental dis orders, affecting approximately 5–7% of children and 2.5–4% of adults worldwide [1,2]. Once considered a childhood-restricted condition, ADHD is now recognized as a lifespan disorder associated with academic under achievement, occupational instability, impaired emotional regulation, interpersonal challenges, and elevated psychi atric comorbidity. Global diagnostic rates have increased in recent years—not due to a true rise in incidence, but rather improved awareness, reduced stigma, and expand ed access to diagnostic services [3]. Nevertheless, ADHD remains underdiagnosed among females, individuals from lower socioeconomic backgrounds, and older adults, un

derscoring persisting inequities in clinical recognition. While traditional conceptualizations emphasized behavior al manifestations of inattention and hyperactivity, contem porary research demonstrates that ADHD encompasses a far more complex interplay of neurobiological, psycho logical, hormonal, and environmental factors. The purpose of this review is to integrate classical ADHD knowledge with emerging evidence, including dimensions not tra ditionally included in standard reviews: neurobiological subtypes, sensory dysregulation, hyper focus, emotional sensitivity, gender-specific presentations, circadian rhythm disturbances, digital therapeutics, neurostimulation, and microbiome research. This integrated perspective offers a broader and more nuanced understanding of ADHD’s het erogeneity across the lifespan.

Diagnostic Frameworks and Classification

ADHD is classified in the DSM-5 and DSM-5-TR as a neu rodevelopmental disorder marked by persistent symptoms of inattention and/or hyperactivity-impulsivity that interfere with functioning across two or more settings [4]. The DSM 5 introduced onset before age 12 as a criterion, replacing the earlier threshold of seven years. The ICD-11 aligns conceptually with DSM-5, describing ADHD as a persistent pattern of impaired attention and/or hyperactive-impulsive

behavior inconsistent with developmental level [5]. Although DSM-5 identifies three presentations—predom inantly inattentive, predominantly hyperactive-impulsive, and combined—these categories capture only part of the underlying heterogeneity. Neurobiological research in creasingly supports functional subtypes based on patterns of network dysregulation rather than observable behaviors. This conceptual shift highlights limitations in current diag nostic systems and a growing need for precision-based classifications.

Epidemiology and Global Trends

Large meta-analyses demonstrate consistent ADHD prev alence across cultures when standardized diagnostic criteria are applied [1,2]. However, diagnostic rates vary due to cultural stigma, medical access, and differences in healthcare practices. Underdiagnosis remains pervasive in populations where internalizing symptoms predominate, particularly among girls and adult women who may mask or compensate for impairments.

Socioeconomic disparities also affect diagnosis: children from lower-income families face structural barriers such as reduced access to evaluation, fewer educational sup ports, and greater exposure to adversity, which may ex acerbate symptoms. Conversely, overdiagnosis concerns

have been raised in certain clinical settings, highlighting the importance of comprehensive assessment.

Etiology and Pathophysiology

Genetic Contributions

Twin and family studies estimate ADHD heritability at 70–80%, placing it among the most heritable psychiatric conditions [6]. Genome-wide association studies support a polygenic risk architecture comprising numerous small-ef

fect variants [7]. Shared genetic vulnerability is well-doc umented between ADHD and autism spectrum disorder, major depressive disorder, bipolar disorder, and substance use disorders, reflecting overlapping neurodevelopmental pathways.

Neurobiological Mechanisms

Neuroimaging findings consistently indicate structural and functional alterations in the prefrontal cortex, cerebellum, and basal ganglia among individuals with ADHD [8,9]. Functional imaging reveals atypical activation of networks responsible for attention, executive functioning, and emo

tional regulation. Central to ADHD pathophysiology is dys regulation in dopaminergic and noradrenergic neurotrans mission, explaining stimulant medication efficacy.

Environmental Factors

Environmental contributors interact with genetic predispo sitions throughout development. These include prenatal nicotine or alcohol exposure, low birth weight, prematuri ty, and early adversity [10]. Although these factors do not independently cause ADHD, they may modulate severity and expression of symptoms.

Beyond Traditional Models: Emerging Neurobiological Subtypes

Traditional diagnostic presentation categories fail to cap ture underlying neural variability. Emerging neuroscience proposes subtypes reflecting dysfunction in specific brain networks:

Executive Network Dysfunction

Characterized by deficits in planning, organization, work ing memory, and cognitive flexibility, reflecting impaired fronto-striatal activation.

Default Mode Network (DMN) Intrusion

Abnormal persistence of DMN activity during tasks results in internal distractions and task disengagement.

Reward Deficiency Subtype

Linked to hypoactivation of mesolimbic reward circuits, re sulting in low motivation, novelty-seeking, and preference for immediate rewards.

Sluggish Cognitive Tempo (SCT)

A distinct cluster involving daydreaming, mental fogginess, and slowed information processing. Though not included in DSM-5, SCT is increasingly recognized in research.

Gender-Specific Manifestations and Hormonal Influ ences

Females with ADHD frequently present with inattentive symptoms, internalizing difficulties, and emotional sen sitivity, contributing to underdiagnosis [3]. Neuroimaging studies suggest sex-linked differences in brain develop ment, including enhanced limbic-prefrontal reactivity in fe males and more pronounced hyperactivity-related motor circuitry alterations in males.

Across the female lifespan, hormonal fluctuations signifi cantly influence ADHD symptomatology:

• Menstrual cycle: symptoms worsen during low-estro gen phases.

• Postpartum period: estrogen drops may intensify ADHD symptoms.

• Perimenopause/menopause: increased attentional and emotional difficulties.

These patterns highlight the importance of hormone-in formed assessment and treatment.

Clinical Presentation Across the Lifespan

Childhood

Symptoms include hyperactivity, impulsivity, poor sus tained attention, and academic difficulties. Disruptive be havior may dominate clinical attention, overshadowing cognitive impairments.

Adolescence

Hyperactivity may diminish, but executive dysfunction and emotional reactivity often intensify. Risk-taking behaviors and academic overwhelm are common.

Adulthood

Symptoms manifest primarily as disorganization, inconsis tent productivity, emotional impulsivity, time-management deficits, and occupational instability. Adults may describe chronic internal restlessness and difficulty regulating at tention.

Emotional Dysregulation, Hyper focus, and Cognitive Profiles

Emotional Dysregulation

Although not a DSM-5 criterion, emotional lability is highly prevalent. Individuals may experience rapid mood shifts, frustration intolerance, and heightened stress reactivity.

Rejection Sensitivity Dysphoria (RSD)

Many report intense emotional pain in response to per ceived criticism, leading to avoidance, social withdrawal, or conflict.

Hyper focus

Despite distractibility, individuals often experience ep isodes of deep, prolonged concentration on stimulat ing tasks. Hyper focus can facilitate creativity but impair task-shifting and daily functioning.

Working Memory Impairment

Reduced working memory capacity significantly contrib utes to academic and functional challenges.

Sensory Processing Differences

Individuals may exhibit hypersensitivity or hyposensitivity to sounds, lights, textures, or movement.

Comorbidity

ADHD frequently co-occurs with:

• Anxiety disorders

• Major depressive disorder

• Substance use disorders

• Sleep disorders

• Learning disabilities

Comorbidity complicates diagnosis and may worsen func tional outcomes.

Sleep and Circadian Rhythm Disturbances ADHD is strongly associated with sleep-wake disruptions,

including delayed circadian phase, insomnia, and poor sleep quality. Sleep deficits exacerbate attentional, emo tional, and executive impairments. Treatment of sleep dis orders can significantly improve overall functioning.

ADHD in Relationships, Family Dynamics, and Occupational Life

ADHD impacts communication, emotional expression, and household management in romantic relationships. Adults with ADHD are overrepresented among divorced individu als, particularly when untreated. Occupationally, individu als may experience inconsistent performance, time-blind ness, and difficulty with routine tasks, yet often excel in dynamic, creative, and fast-paced environments. ADHD traits are disproportionately present in entrepreneurial populations.

Microbiome, Nutrition, and Physiological Factors

Emerging research explores links between gut microbiota and ADHD through immune, metabolic, and neurochem ical pathways. Nutritional factors such as omega-3 defi ciency may influence symptom severity, and elimination of

artificial food dyes may benefit a subgroup of children. Digital Therapeutics and Technology-Based Interventions Digital therapeutics, such as the FDA-approved vid eo-game–based treatment EndeavorRx, offer novel cog nitive training platforms. Wearable devices enable moni toring and executive-function training. These technologies complement, rather than replace, pharmacotherapy and behavioral interventions.

Neurostimulation Approaches

Non-invasive neurostimulation techniques show promise: • Transcranial Direct Current Stimulation (tDCS) im proves working memory.

• Repetitive Transcranial Magnetic Stimulation (rTMS) modulates prefrontal networks.

• Trigeminal nerve stimulation devices are emerging as pediatric options.

Further research is required to establish efficacy.

Evidence-Based Treatment

Psychostimulant medications remain first-line, with strong

efficacy across age groups [11]. Non-stimulant medica tions—including atomoxetine, guanfacine, clonidine, and viloxazine—provide alternatives for patients who cannot tolerate stimulants [12,13]. Psychosocial treatments such as cognitive-behavioral therapy [14], behavioral parent training, and academic accommodations significantly en hance outcomes. Multimodal treatment consistently out performs single-modality approaches [15-17].

Prognosis and Public Health Implications Early diagnosis and continuous support improve academ ic, occupational, and relational outcomes [18-20]. Untreat ed ADHD increases risks for substance misuse, accidents, unemployment, economic hardship, and mental-health disorders [21]. Public health systems must address diag nostic inequities and expand access to evidence-based treatments.

Future Directions

Emerging research emphasizes:

• Precision psychiatry

• Biomarker identification

• Artificial-intelligence-assisted diagnostics • Digital phenotyping

• Hormone-sensitive treatment approaches • Personalized neuromodulation therapies These innovations aim to reduce reliance on symp tom-based diagnosis and improve individualized care.

Conclusion

ADHD is a multifaceted neurodevelopmental disorder shaped by genetic vulnerabilities, neurobiological alter ations, hormonal influences, and environmental factors. Its impact extends far beyond inattention and hyperactivity, encompassing emotional, sensory, cognitive, and social dimensions across the lifespan. Incorporating emerging evidence into clinical practice offers a more comprehen sive and humane understanding of ADHD. Multimodal, personalized, and gender-responsive approaches repre sent the future of effective diagnosis and treatment.

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