Increasing Health Literacy on ADHD: A Cross-Disciplinary Integrative Review Examining the Impact of ADHD on Brain Maturation, Composition and Function and Cognitive Processes Across the Life Course

Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental condition (American Psychiatric Association, [1]) that remains relatively misunderstood by health care practitioners, teachers, parents, and individuals with the condition [2]. Characterised by persistent inattentive and/or hyperactive-impulsive symptoms that are inconsistent with a person’s developmental level (American Psychiatric Association, [1]), ADHD affects the ability to exert age-appropriate self-control [3]. Across the life course, this highly genetic condition [4, 6] significantly impacts a person’s neuropsychological development, everyday functioning, mental and physical health, quality of life, and life expectancy [7, 9].

Evidence-based clinical practice guideline for ADHD, such as the Australian and UK guidelines [10], National Institute for Health and Care Excellence [NICE], [11]), recommend the provision of ADHD-related education and training to healthcare providers and teachers, and psychoeducation to people with ADHD and their families. These recommendations are echoed by people with lived experience of ADHD and their families who report low rates of ADHD-related literacy and an unmet need for ADHD education [2]. Providing evidence-based education on ADHD, however, is challenging. Not only are research findings difficult to access, consensus on the pathophysiology and neuropsychology underlying ADHD has not been achieved. Scientists are continuing to learn about the brain’s functional architecture [12], and what is ‘known’, is not necessarily absolute. It reflects (1) converging evidence from diffusion tensor imaging (DTI), structural and functional magnetic resonance imaging (MRI; fMRI, respectively), positron emission tomography (PET), single-photon emission computed tomography (SPECT), neurophysiology (electroencephalography, EEG), post-stroke lesion studies, and post-mortem anatomic dissection, and (2) scientists’ interpretations of how brain structure and connectivity translates into cognitive, behavioural, social and emotional outcomes [12]. Furthermore, the interpretation of study findings is complicated by factors such as the brain’s structural and functional complexity, and clinical (participant age, comorbidity) and study (specialty, methodological, data interpretation) heterogeneity [12, 13]. Other factors that have likely impeded the advancement towards consensus include the assumption that ADHD-associated cognitive challenges underpin ADHD symptoms rather than coexist and make independent contributions to ADHD presentation, and ADHD-related heterogeneity [14]. People with ADHD can present with a range of situationally variable symptoms that tend to change across the life course, as well as different neurocognitive profiles and developmental trajectories [15].

Regardless of these challenges, the need for education that improves healthcare practitioner, teacher, parent and consumer ADHD-related health literacy remains [2]. The aim of this cross-disciplinary integrative review is to synthesise the evidence on the impact ADHD has on brain maturation, composition and function as well as cognitive processes, across the life course to develop a single source of empirical evidence on the biologically-based, innate person characteristics that may influence a child or adult with ADHD’s developmental trajectory and functional capacity, as well as their mental wellbeing and other socio-emotional outcomes. As per Bronfenbrenner’s [16] Bioecological model of human development, an individual’s biologically-based person characteristics interact with the broader environment, and along with the subjective experiences they elicit in them, influence their actualisation of potential and their socio-emotional outcomes across the life course. This information is therefore needed to provide insights into the possible neurobiological and cognitive mechanisms underlying ADHD-related functional, mental health and socio-emotional outcomes and to support self-awareness, acceptance, recovery and personal empowerment of persons with ADHD.

By making this scientific knowledge more accessible we hope that it will be used to inform the content of evidence-based ADHD education programs. We acknowledge that the way in which the information is presented, however, will need to be adjusted to ensure that it is comprehensible and meaningful to recipients. We will be using the findings of the review to develop a ‘framework/checklist” that parents, adults and clinicians can use to identify the possible mechanisms that may be contributing to an individual with ADHD’s challenges. In line with the complexity associated with ADHD (including the heterogeneity and impact of situational variability), this framework/checklist will serve as a tool for identifying possible ADHD-related factors that ‘may’ impact on the achievement of a desired end state, and to identify the scaffolding that may be required to facilitate recovery and personal empowerment.

This integrative review was conducted according to the stages outlined by Whittemore & Knafl [17]: problem identification, literature search, data evaluation, data analysis, and presentation of synthesised findings. Integrative methodology was chosen as it enables researchers to examine a phenomenon more broadly; systematically assimilate data from a diverse range of research specialities, methodologies and perspectives in order to advance understanding of complex concepts and phenomena; and draw evidence-based, holistic conclusions and new perspectives that promote better understanding of a topic and can be used to inform clinical practice [17‐19].

A strategy for searching ‘Medline’, ‘American Psychology Association (APA) PsycArticles’ and ‘Cumulated Index to Nursing and Allied Health Literature (CINAHL)’ databases was developed with the assistance of a Curtin University Librarian. Broad search terms were chosen that would enable us to capture the breadth of international papers on the topic. For the ‘Medline’ search, the following MESH heading was used: ‘Attention Deficit Disorder with Hyperactivity/’. For the APA PsycArticles’ and ‘CINAHL’ searches, as well as a ‘Medline’ search that was limited to 2023, the following keywords were used: ‘Attention Deficit Disorder with Hyperactivity/’, ‘Attention Deficit Hyperactivity Disorder’, ‘Attention Deficit-Hyperactivity Disorder’, ‘Deficit-Hyperactivity Disorder, Attention or Disorder’, ‘Attention Deficit-Hyperactivity or Hyperkinetic Syndrome’, ‘Hyperkinetic or Attention Deficit Disorder’, ‘Attention or Brain Dysfunction, Minimal Brain’, ‘Minimal Brain Dysfunction’, ‘Minimal cerebral dysfunction’ or ‘ADHD’. All searches were limited to review studies that synthesised findings from primary empirical studies (i.e., meta-analysis; systematic, structured, integrative and scoping reviews), that were written in English and published between January 1998 and July 2023. This timeline was chosen because the first review papers examining the findings of magnetic resonance imaging (MRI) studies assessing the brain structure of children with ADHD were published in 1998. The search strategy ensured that a manageable number of studies would be captured from a wide range of specialties (i.e., neuroscience, medical, psychology and nursing) employing different methodologies (experimental and non-experimental/observational) and ontological (i.e., biomedical, social constructivist, and critical realist) and epistemological paradigms (i.e., positivism, interpretivism, critical theory and pragmatism).

LEB conducted a search of all databases using this strategy on 4th December 2023. The reference lists of studies that met the study inclusion/exclusion criteria were also searched by LEB to identify any relevant reviews not captured by the database searches. Because none of the six pertinent longitudinal case–control neuroimaging studies captured during these searches, which were deemed important to include as they provide insight into the age-related and brain-related differences associated with ADHD, were included in any reviews that met the inclusion/exclusion criteria, or in the case of Shaw (2013; 2012) and Proal (2011) included in their entirety, the decision was made to include these studies in this review. An additional purposeful search was then carried out on the 20th December 2023 to identify any other relevant but not captured studies. During this search, two large cross-sectional ENIGMA neuroimaging studies examining anatomical brain structure with greater than 2,000 participants, were identified [20, 21]. After confirming these papers were not included in any of the reviews, the decision was made to also include these papers.

The search yielded 4869 papers, of which 153 were duplicates and removed. Following title and abstract screening, 4578 papers were excluded as they did not meet the study inclusion criteria. The six longitudinal case–control and two large cross-sectional neuroimaging studies identified by LEB were then added to the papers requiring full text screening bringing the total to 146; 114 papers were found to met the study inclusion critera (see Fig. 1). Supplementary information, Appendix C contains a list of excluded studies.

Table 1 contains a list of the review papers included in this integrative review, along with a summary of their findings and quality scores. Where available, reported magnitude of effect sizes are also reported in this table. Given the vast heterogeneity (i.e., speciality, inclusion/exclusion criteria, measures and constructs assessed; participant comorbidity), we do not report overall effect sizes in the narrative synthesis below. Instead, we use terms such as (1) tend to, and (2) possibly, potentially, may, etc., to reflect the number of review papers and their quality scores that were converged to contribute to an identified theme or the components of a theme, and the reported sample size, magnitude of effect sizes, heterogeneity, risk of bias, etc. Doings so aligns with integrative review methodology and our goal of creating a framework/checklist that is reflective of ADHD-related individuality and the limitations of study findings, which can be used to consider the factors that may be contributing to the challenges a person with ADHD may be experiencing. A composite summary of the allocated quality scores can be found in Supplementary information, Appendix D. Thirty-two review papers were ranked as high quality, 46 as moderate, 31 as low and five as very low. The main criteria that affected quality scores was lack of quality assessment (n = 89). Risk of publication bias was only assessed in 42 papers. As the impact of comorbidity on review study findings can only be determined via meta-analysis, systematic, scoping, and structured reviews were automatically marked ‘No’ for this criteria. Although a wide range of comorbid conditions could impact findings, if participants with at least one comorbid condition were excluded from studies employing meta-analysis, the need to statistically determine the impact of comorbidity was deemed ‘Not applicable’.

Sixty-two reviews included psychophysiological and brain-imaging studies, 48 neuropsychological studies, and four, a combination of both. The most common brain imaging methods employed were fMRI, closely followed by magnetic resonance imaging (MRI) (See Supplementary information, Appendix E). A wide variety of neuropsychology tests were employed to examine various aspects of cognition, such as working memory, response inhibition, attention regulation, cognitive flexibility, cognitive fluency, reaction time, etc., which made it difficult to consolidate results.

This integrative review synthesised evidence on the impact of ADHD on the brain and cognitive function in order to gain greater insight into the biologically-based, innate person characteristics that influence a child and adult with ADHD’s functional capacity.

The findings of the review suggest ADHD is possibly associated with a significant delay in cortical maturation. As brain maturation generally follows a predictable developmental trajectory that aligns with chronological age and results in (1) the differentiation of neural structures, (2) the emergence of cognitive processes, and (3) improvements in processing speed, the amount of information that can be mentally manipulated in working memory, and the complexity of such mental manipulations [139, 142], this delay in cortical maturation likely postpones cognitive maturation. It may also result in children with ADHD having cognitive and self-regulation skills that significantly lag behind their typically developing peers. This implies children with ADHD likely require supporting scaffolding that bridges the gap between their innate capacity and age-related expectations placed on them and to be successful.

The findings also indicate ADHD is also associated with anatomical, functional and cognitive differences, many of which tend to remain in adulthood. Individuals with ADHD may display atypical connectivity within and between various regions of the brain that likely contribute to differences in cognitive processing [44]. Both commissural fibres and association fibres appear to be implicated, along with many large-scale brain networks. They may also display heterogeneous differences in executive and non-executive abilities that can impact higher order cognitive processing. These include working memory, inhibitory control, cognitive flexibility, alerting attention, reward processing, and long-term memory. The cognitive processes related to reaction time, time perception and estimation, planning and complex decision-making/problem-solving also appear to be heterogeneously impacted. Furthermore, in-the-moment cognitive performance in individuals with ADHD may improve in response to scaffolding in the form of reinforcement [74], while reward delay may impose a demotivational influence [99].

The anatomical, functional and cognitive differences associated with ADHD likely influence an individual’s ability to maintain alertness (arousal), attentional vigilance and focus; stop (inhibit a habitual/instinctual response), evaluate choice alternatives and make informed decisions before responding with words or actions; develop self and social awareness; listen and learn; perceive time; plan, prioritise, stay organised and take action over time; successfully achieve their goals; and navigate social expectations. Of note is that these challenges are neuropsychological in nature. They are not a choice, and outside of an individual with ADHD’s ability to control [7]. The cognitive differences associated with ADHD also have no diagnostic utility due to the heterogeneous nature of the study findings [14], and because intelligence has been shown to significantly mediate cognitive tests results in the presence of ADHD [143].

Together, the findings of this paper highlight the need for clinicians to ensure healthcare interventions provided to children and adults with ADHD align with their neurocognitive profile. One way this can be accomplished is by including this information in education interventions in a way that is neuro-affirming; supports the development of self-understanding, self-acceptance, self-compassion; and facilitates positive adaption and personal empowerment via the use of supporting scaffolding. This information is vital for ensuring parents and teachers are able to (1) sensitively understand and interpret a child’s ADHD-related symptoms and behavioural tendencies, (2) appreciate what they are likely to be able to do or not do at a particular age, (3) proactively ensure there is a good fit to their inherited vulnerabilities, and either the demands placed upon them or the scaffolding and support provided, and (4) commence the process of collaboratively fostering in them protective and recovery-oriented traits so that they reach adulthood with their self-esteem intact and have the knowledge and skills required to navigate life successfully in adulthood. For adults with ADHD this information can help combat the shame they have often internalised due to life-long negative messages and experiences of failure, as well as provide insight into the type of scaffolding they can put in place to support their ADHD-related cognitive differences so that they can set themselves up for success and protect themselves from disappointment and harm. We aim to use these findings to develop a ‘framework/checklist” that parents, adults and clinicians can use to identify the possible mechanisms that may be contributing to an individual with ADHD’s challenges and the scaffolding that may help to facilitate hope, success, safety and personal empowerment. We also wanted to ensure this information is easily accessible so it can be used to develop education interventions that support ADHD literacy and the identification of appropriate healthcare interventions. We acknowledge that the findings, however, will need to be tailored to meet the needs of different recipient groups in order for them to be comprehensible and meaningful.

More specifically, understanding the underlying reasons why individuals with ADHD display difficulties with response inhibition for example, provides healthcare providers, educators and individuals with ADHD and their parents insight into why it can be almost impossible for individuals with ADHD to ‘stop and think before speaking or acting’ without medication that increases synaptic dopamine availability and scaffolding that assists an individual to delay (i.e., access barriers) or prevents a response (i.e., removal of temptations from sight). Acknowledging individuals with ADHD can lack self-awareness due to problems with interference control [58, 72], which impacts self-monitoring and self-exploration [144], explains the individuals with ADHD require support that gently facilitates introspective attention and the development of self-awareness. Understanding ADHD-related visual working memory clarifies why it is important for individuals with ADHD to make things visible, while problems with prospective memory illustrates why setting alarms and using visual prompts is very helpful. While understanding (1) how rewards can induce phasic dopamine release and in doing so support cognitive function depending upon their perceived valence, and (2) reward delay can have a demotivating influence on individuals with ADHD due to delay discounting, provides insight into the need for positive reinforcement to be in-the-moment and commensurate with the values of an individual with ADHD. However, as reinforcement is unable to change an underlying developmental delay [7], expectations of what reinforcement can achieve also needs to align with an individual’s cognitive capacity, otherwise a reward can easily become a form of punishment.

Clinicians, teachers and parents should also consider the impact ADHD likely has on all forms of learning as well as all aspects of the emotional regulation process when providing guidance on support interventions to ensure they align with the neurocognitive profile associated with ADHD. For example, ADHD-related attention regulation difficulties likely disrupt observational learning and classical conditioning, as well as the ability to employ distractions techniques (attentional deployment) as a means of regulating emotions. ADHD-inhibition and reward processing differences likely impact learning via operant conditioning as well as the ability to stop, think and practice situation selection and situation modification in order to avoid being emotionally triggered.

Several limitations should be taken into account when considering the findings of this integrative review. Firstly, significant levels of heterogeneity were found in many of the included review papers. This heterogeneity likely reflects differences in the examined hypotheses, assessed clinical populations, inclusion and exclusion criteria including whether medication usage or co-morbidity was taken into consideration, experimental design (we did not examine the impact different brain imaging techniques had on findings), meta-analytic methods, calibration across scanners, applied statistical thresholds, data-analysis approaches, and reporting practices [24, 59, 72, 116]. Furthermore, the findings of many included studies may be influenced by the presence of comorbidity as some captured studies included primary studies that (1) didn’t report on comorbidity or (2) included participants with comorbidity, while others did not address the potential influence identified comorbidity had on study findings via meta-regression. A dual diagnosis of autism and ADHD was also not permitted until the release of the Diagnostic Statistical Manual of Mental Disorders (DSM), 5th edition, published in 2013. Whether this is an issue remains unclear. While some researchers argue that comorbid disorders “should always be statistically controlled to ensure that the neuropsychologic impairments associated with ADHD cannot be explained more parsimoniously” (Lahey et al., 1998, as cited in [83], p. 1342), others researchers argue that as the majority of individuals with ADHD have a comorbid disorder, restricting a sample to those without comorbidities would severely reduce the generalisability of study findings [58].

Although recently reported effect sizes have become more reliable and reported heterogeneity rates have reduced with increased study rigor [77, 81], it is likely ADHD research findings will always remain somewhat heterogeneous due to both the equifinality (different originating risks leading to the same clinical outcome) and the multi-finality (the same pattern of risk leading to a different outcome) associated with ADHD [145]. That is, ADHD heterogeneity will continue to reflect the development of divergent, individual ontological phenotypes due to interactions between an ADHD individual’s genetic predisposition and social environmental exposure [14, 15], and their ability to adapt or use compensatory strategies (Frazier et al., 2007 cited in [77]).

Secondly, the number of studies included in captured reviews focusing on a particular phenomenon likely impacted findings. Gao et al. [55] reported that the number of studies examining differences in the individual large-scale brain networks of people with ADHD was relatively small, which made integrating the results for the VAN, DAN, SSN and visual network difficult via meta-analysis. Viera de Melo et al. (2018) reported studies providing aggregated results of fMRI reviews often included trials with functional tasks that were not fully described. This made it impossible for them to identify the different methods, variations and individual contribution each task made to the final effect sizes [24].

Thirdly, although the neurocognitive differences associated with ADHD also contribute to the strengths that individuals with the condition display, no captured studies interpreted findings in a positive light or provided insight into the positive traits that can accompany ADHD. For example, while research has identified that ADHD is associated with difficulties such as set-shifting and task-switching, these difficulties also likely contribute to ADHD-related hyperfocus, which is often viewed as being a strength-based trait by individuals with the condition as it supports high productivity and flow [146], even though hyperfocus can also be problematic. Individuals with ADHD also report that although ADHD-related impulsivity can lead to poor outcomes, it also likely contributes to their adventurous, spontaneous nature and makes life fun [146]. Additionally, ADHD-related mind wandering which interrupts the focus and concentration, may underlie ADHD-related traits such as high creativity [147], divergent thinking, uninhibited imagination [148], and ability to think outside of the box [146]. As narratives and discourse around ADHD influences how people with the condition view and understand themselves, identifying ADHD-related strengths that individuals with the condition can recruit in order to function at a high level [149], is vital for reducing the stigma surrounding ADHD. It could assist individuals with the condition to identify scaffolding they could put in place to support their cognitive differences as well as facilitate hope, perception of competence, resilience, adaption to disability and psychological well-being [150].

ADHD tends to affect a person across the life course. This review found ADHD is associated with (1) a significant delay in cortical maturation along with differences in neuro anatomy that do not appear to fully resolve in adulthood, (2) atypical brain and (3) atypical cognitive processes. The cognitive functions heterogeneously implicated by the presence of ADHD include working memory, inhibitory control, cognitive flexibility, alerting attention, reward processing, and long-term memory, along with reaction time, time perception and estimation, planning and complex decision making/problem-solving.