Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition that typically emerges in childhood, with most patients exhibiting noticeable symptoms prior to the age of 12. The prevalence of ADHD in childhood is approximately 5-7% (1). Epidemiological evidence suggests that approximately 50–70% of childhood-onset cases persist into adulthood, whereas the prevalence in adults is estimated at 2–3%, based on population studies (2). Furthermore, many adults with ADHD lack a recorded history of the illness in their youth. Therefore, it is not always possible to conclusively indicate the presence of childhood ADHD (3–5). A systematic review and meta-analysis by Song et al. (2021) classified adult ADHD into persistent (childhood-onset) and symptomatic (regardless of childhood-onset) subtypes, with global prevalence estimates of 2.58% and 6.76%, respectively. Prevalence rates for both subtypes exhibited age-dependent declines, while the persistent subtype demonstrated higher prevalence in low- and middle-income countries (LMICs) (6).

Adults with ADHD typically exhibit more heterogeneous clinical manifestations compared to children and adolescents. These manifestations extend beyond the classic symptoms of hyperactivity and include broader emotional dysregulation and functional impairments (7). Common symptoms in adults with ADHD include difficulty paying attention to details, issues in organizing tasks and activities, inappropriate verbalization, restlessness, difficulty relaxing, chronic fatigue, forgetfulness, and inattention (8, 9). Neuropsychological issues, such as deficiencies in inhibition, memory, executive functioning, decision-making, and emotional control, are also prevalent (10). These functional impairments can profoundly impact various aspects of life, including work, academics, social interactions, and daily functioning, placing a significant burden on patients, their families, and society as a whole (11). Compared to males, female patients often present with more inattentive and internalizing symptoms, which may allow them more time to develop coping strategies to mask core symptoms (12).

About 70% of adults with ADHD also suffer from another mental health issue, such as bipolar disorder, anxiety disorder, substance use disorder, or a personality disorder (7). Among these, anxiety and depressive disorders are the most common. Studies suggest that up to 50% of ADHD patients experience anxiety disorders, which is a higher risk than the general population for individuals with ADHD. Similarly, the prevalence of depression among ADHD patients ranges from 18.6% (13) to 53.3% (14). The types of comorbidities also vary by gender. A study of 40,103 adults with ADHD found that anxiety, depression, bipolar disorder, and personality disorders are more common in females, while schizophrenia and substance use disorders are more prevalent in males (15). These comorbidities pose significant clinical challenges, as their coexistence with ADHD results in a greater disease burden and more severe clinical outcomes compared to either condition in isolation (16).

Anxiety disorders are among the most prevalent comorbidities, estimated to affect 25–50% of ADHD patients (17). Epidemiological and clinical investigations have shown a significant prevalence of comorbid phobias in children, adolescents (18), and adults (19) with ADHD. One epidemiological study found that approximately 47% of adults with ADHD have comorbid anxiety disorders (13). A study by Andréanne et al. involving 353 adults with ADHD revealed that 56% of participants had at least one anxiety disorder (20). An additional investigation that involved 473 college students discovered that those diagnosed with ADHD exhibited increased levels of anxiety in comparison to controls (21). In contrast to those with ADHD who do not have anxiety disorders, those with concurrent anxiety disorders usually have more severe symptoms (22), a higher number of psychiatric comorbidities, and an earlier age of onset (17). The presence of combined anxiety disorders correlates with more childhood ADHD symptoms, higher scores on adult ADHD rating scales, and greater emotional dysregulation.

In patients with comorbid conditions, symptoms interact bidirectionally. Comorbid anxiety can significantly alter the manifestation of ADHD symptoms. For instance, inattention may arise secondary to anxiety (23), and the presence of anxiety symptoms may exacerbate difficulties with attention (24). On the basis of Weiss et al., cognitive deficits resulting from ADHD symptoms could contribute to the development of anxiety, which subsequently worsens inattention, creating a vicious cycle. For individuals with ADHD and co-occurring anxiety disorders, working memory deficiencies may be a significant area of impairment (25). Working memory deficiencies can lead to attention problems and anxiety disorders, which in turn make working memory problems worse. As a result, these three symptoms are intricately intertwined. Furthermore, comorbid anxiety disorders may correlate with a higher risk of suicidal behaviors as well as a non-significant trend toward heightened aggression toward others. Research indicates that anxiety disorders increase feelings of anger and tension within individuals. ADHD, a condition that involves inadequate impulse control and emotional dysregulation, complicates the difficulty in managing impulses and regulating negative emotions in response to frustration. Consequently, individuals with comorbid anxiety disorders often exhibit heightened aggression (26). Among patients with both conditions, the likelihood of hospitalization (27) and the occurrence of psychotic symptoms (28) are also higher. In academic settings, high levels of anxiety are associated with reduced learning efficiency and academic performance. Additionally, anxiety can increase daily stress levels, potentially disrupting sleep and reducing coping abilities. Studies have shown that sleep disturbances, such as delayed sleep onset and sleeping fewer than six hours per night, are common among adults with ADHD and concomitant anxiety disorders (29). These issues might negatively impact self-esteem, weaken perception of familial/social support, and diminish frustration tolerance (20), ultimately impairing social functioning across multiple domains.

Another common comorbidity is depressive disorders, with studies reporting a prevalence rates of ranging from 18.6% (13) to 53.3% (14) among individuals with ADHD. Those with both conditions experience higher disease burden, longer illness duration, and reduced quality of life compared to those with either disorder alone. A Swedish (2018–2021) study on adults with ADHD identified depression and anxiety are common psychiatric comorbidities, with a higher prevalence in females (30). Overlapping symptoms between mood disorders and ADHD complicate diagnosis and treatment. For instance, adults with depressive disorders may exhibit symptoms of inattention (e.g., an inability to concentrate due to repetitive, intrusive thoughts), psychomotor agitation, and restlessness, which overlap with symptoms of ADHD, but they also experience reduced interest, anhedonia (loss of pleasure), and fatigue. Research suggests that stress, depression, and anxiety may result from undiagnosed and untreated ADHD (31). Patients with ADHD and comorbid conditions exhibit greater disease burden (32) and experience reduced treatment effectiveness (33). Therefore, further research is needed to explore the underlying mechanisms contributing to the high comorbidity rates in individuals with ADHD.

A systematic search was conducted across three major databases: PubMed, Google Scholar and Web of Science. The search combined Medical Subject Headings (MeSH) terms and free-text keywords (see examples below) using Boolean operators (AND/OR):

Attention Deficit Hyperactivity Disorder:(“Attention Deficit Hyperactivity Disorder”OR “ADHD”)

Adult: (“Adult”OR “adults”)

Comorbidity: (“Comorbidity”)

Time Frame: Studies published in English from inception up to December 2024.

Twin studies estimate ADHD heritability at 0.76 (34). Twin and family studies suggest that the association between ADHD and comorbid conditions can be partially explained by genetic factors (35). For example, in a study by Ebba Du Rietz et al., a powerful polygenic approach was employed using polygenic risk scores (PRSs) derived from a large-scale ADHD genome-wide association study(GWAS) to investigate if genetic variants associated with adult ADHD influence its comorbidities. The results demonstrated that the PRS for ADHD significantly predicts both depressive disorders and anxiety disorders (36). Recently, GWAS and PRS analyses have robustly established a genetic correlation between ADHD and major depressive disorder (MDD) (37). Current research suggests that the NTAD gene cluster (comprising NCAM1, TTC12, ANKK1, and DRD2, located at 11q22-23) is associated with the clinical heterogeneity of adult ADHD. Specifically, the ANKK1-DRD2 genes are linked to comorbid MDD and Generalized anxiety disorder (GAD) in adults with ADHD, whereas the NCAM1 and DRD2 genes independently contribute to the susceptibility to MDD in these patients (38). Additionally, several studies have shown that the NOS1 gene, which encodes nitric oxide synthase 1 and produces the gaseous neurotransmitter NO, is also associated with adult ADHD. A polymorphic promoter repeat (NOS1 ex1f-VNTR), particularly the short allele variants (e.g., the 21-repeat allele), is associated with severe depressive illness and anxiety (39).Furthermore, genetic influences vary between male and female patients. A study of 564 adults with ADHD found that the HTR1B polymorphism (rs11568817 G allele) affects the occurrence of different complications in females with ADHD. The HTR1B allele, rs11568817, is linked to GAD in females with ADHD, while the rs6296C allele may act as a protective factor against GAD. Additionally, the rs11568817 allele is associated with MDD in females (40). Furthermore, research by Mekli et al. suggests that the rs6296 C allele may increase the risk of anxiety in adults when exposed to stressful life events (41).

Proteomic studies further support the associations between ADHD and depression as well as anxiety. ADHD shares 8–34% of effector proteins with each comorbid condition, with anxiety disorders showing the highest degree of overlap. Based on protein-protein interaction network analysis, 52% of ADHD-related effector proteins are either shared or directly linked with 54% of MDD-associated proteins, indicating robust molecular convergence (42). This indicates the existence of shared genetic pathways that may underlie the high comorbidity rates between ADHD and depressive as well as anxiety disorders.

A key neurobiological link between ADHD and GAD (43) is reduced dopamine transporter (DAT) availability in the striatum, observed in both conditions. For patients with comorbid depression, the pathogenesis of ADHD is strongly tied to dopamine (DA) and norepinephrine (NE) deficiencies, particularly within the striatum. The limbic-cortical-striatal-pallidal-thalamic(LCSPT) circuit, which regulates emtion and affect, is modulated by neurotransmitters such as glutamate, GABA, and monoamines. Dysfunction in this circuit and its associated monoaminergic systems is implicated in MDD (44). Altered monoamine signaling contributes to reward processing deficits, including reduced hedonic tone (loss of pleasure), a hallmark shared by MDD and ADHD (45). These deficits arise partly from LCSPT circuit dysregulation and manifest behaviorally as preference for immediate rewards and insensitivity to delayed incentives, a pattern well-documented in children with ADHD (46). The abnormal alterations in reward-motivation circuits (e.g., ventral striatum) (47) are similar to those observed in depression, suggesting overlapping neurobiological pathways. Critically, both disorders exhibit disrupted DA and NE transmission, particularly in the ventral striatum, underscoring shared mechanisms in monoaminergic dysfunction (45).

Patients with depression and ADHD share common neurocognitive impairments, particularly in “cold” cognitive functions (executive and non-executive functions that occur in predominantly abstract, unemotional contexts), including inattention and difficulties in decision-making. A meta-analysis incorporating 18 systematic reviews revealed that the shared neurocognitive impairments in ADHD patients and those with comorbid depression are most likely due to executive function deficits—particularly in verbal fluency, selective attention, working memory, and long-term memory—rather than general cognitive deficits related to lower IQ (48). Executive function deficits in ADHD patients may increase their risk of comorbid depression. This risk arises because “cold” executive functions may be linked to emotional processing, which is crucial in the etiology and incidence of depression (49). Additionally, this may impair emotional regulation, and particularly poor self-regulation could increase susceptibility to depression in individuals with ADHD (48). For instance, executive impairment is related to common depressive symptoms including cognitive rigidity and excessive rumination (50).

Furthermore, a hallmark of ADHD is delayed brain maturation, spanning childhood and adolescence, with pronounced delays in the prefrontal cortex (51). Evidence indicates that this delayed cerebral development and its impact on related neurocognitive skills are not merely characteristic of ADHD but may also increase susceptibility to depression during the highly sensitive adolescent-to-adult transition (51). Current research indicates that delayed maturation of the prefrontal cortex and its impact on executive functions—particularly selective attention, verbal fluency, and working memory—serve as pre-existing risk markers for the onset of depression. These factors may make adolescents and young adults with ADHD more susceptible to comorbid depression (48). In terms of reward processing, numerous studies have shown that disturbances in the prefrontal-striatal circuit are strongly associated with ADHD. This circuit is particularly critical for reward processing, as it is involved in dopaminergic neurotransmission, which is central to both emotional and motivational processes (52). A study conducted on 24 patients diagnosed with MDD discovered a correlation between depressive symptoms and activity of the ventral striatum during reward anticipation (53). Additionally, an experiment by Pulcu et al. observed increased delay discounting (DD task) results in patients with depression, which may be explained by their potentially more pessimistic outlook on the future, thereby reducing the perceived value of future rewards. The delay discounting rate is also increased in ADHD patients, although the underlying mechanisms differ from those in depression. Future research is needed to directly compare individuals with and without comorbidities to determine whether the mechanisms driving these increases are fundamentally distinct (54).

In terms of brain function and structure, patients with ADHD and those with comorbid GAD, the most prevalent type of anxiety disorder in ADHD, exhibit overlapping neurodevelopmental abnormalities. Neuroimaging research indicates that adults with ADHD exhibit reduced gray matter volume in the visual cortex and reduced thickness in the medial occipital cortex (55). They also demonstrate hyperactivation of the occipital lobe during tasks requiring inhibition, working memory, and attention (56). Similarly, abnormalities in the occipital cortex have been observed in individuals with depression. A resting-state functional magnetic resonance imaging (fMRI) study revealed that MDD is associated with decreased functional connectivity between the ventral attention network(VAN) and regions that extend from the precuneus to the occipital lobe and posterior cingulate cortex, which are active in visual attention (57). This implies that both individuals with ADHD and those with depression exhibit attentional processing deficits, particularly in visual attention and working memory. Additionally, a study revealed that adults with ADHD exhibit reduced hippocampal volume, which is associated with higher hyperactivity scores (58), while those with comorbid depression show even smaller hippocampal volumes (59). The cited studies focus on structural abnormalities associated with ADHD and MDD but do not explicitly differentiate between acute and remitted MDD stages. However, the overlapping hippocampal and occipital cortical deficits identified across ADHD and MDD may provide indirect clues. Structural and functional abnormalities in the hippocampus and occipital attention networks are evident in both ADHD and MDD, suggesting that neurodevelopmental disruptions in these circuits may underlie shared vulnerabilities. However, longitudinal studies are required to confirm whether these abnormalities precede symptom onset and determine their causal role in comorbidity.

Current guidelines recommend prioritizing treatment for the most severe, functionally impairing, and unstable condition in patients with ADHD comorbid with depressive or anxiety disorders. After stabilization or improvement, comorbidities should be addressed sequentially (9). For comorbid ADHD and mood disorders, pharmacological stabilization of the mood disorder (e.g., depression) is typically prioritized, followed by reassessment of residual ADHD symptoms once mood symptoms are controlled (60).

For example, if depression causes significant functional impairment, effective antidepressant treatment may alleviate depressive symptoms (e.g., anhedonia, irritability, inattention), indirectly improving ADHD-related challenges. If a patient has mild depression but ADHD is the main contributor to functional impairment, long-acting stimulants may alleviate core ADHD symptoms (e.g., inattention, impulsivity), thereby indirectly improving mood dysregulation linked to ADHD-related stressors. For example, stimulant-induced improvements in executive functioning (e.g., task completion, time management) can reduce daily frustrations and failures—common precursors to secondary depressive symptoms. When both conditions contribute equally to impairment, concurrent treatment may be considered. However, initiating therapies sequentially—rather than simultaneously—is advised to clarify source-specific side effects or inefficacy (61).

ADHD symptoms cannot be effectively treated with selective serotonin reuptake inhibitors (SSRIs), which are used to treat anxiety and depression. However, the management of ADHD can mitigate the progression of comorbid conditions. Numerous studies report that when ADHD is effectively treated, symptoms of comorbid mental health conditions can also improve. In patients with comorbidities, for instance, atomoxetine(ATX) has demonstrated dual benefits for ADHD and comorbid anxiety/depression. Additionally, early intervention for ADHD patients may alter the developmental trajectory of comorbid conditions during the adult lifespan (62). It is hypothesized that improvements in ADHD symptoms post-treatment can reduce functional impairments and enhance quality of life, thereby attenuating the onset or progression of comorbid anxiety or depression symptoms (63).