9 minute read
The neuroscience of ADHD
The neuroscience of ADHD
A 2020 review found that the prevalence of attention-deficit/hyperactivity disorder (ADHD) is higher (7.47%) in children and adolescents in Africa compared to the global average (5.3%).1,2
Advertisement
This was the first review and metaanalysis of ADHD prevalence in children and adolescents in Africa, according to the authors. Similar to international trends, they found that the prevalence was greater in boys (10.60%) than in girls (5.28%).1
Definition and types of ADHD
ADHD is the most common neurodevelopmental disorder in children and adolescents. According to the Diagnostic Statistical Manual fifth revision (DSM-5), ADHD is characterised by impaired levels of inattention, disorganisation, and/or hyperactivity-impulsivity.1
Inattention and disorganisation involve failure to stay on task, seeming not to listen, and losing things at levels that are not consistent with age or developmental level.1
Hyperactivity-impulsivity entails overactivity, fidgeting, inability to stay seated, intruding into other people’s activities, and inability to wait. Symptoms are excessive for age or developmental level.1
Types of ADHD
The DSM-5 differentiates between the following types of ADHD:1
» ADHD-I (predominantly inattentive): Characterised by maladaptive levels of inattention, but not hyperactivity–impulsivity
» ADHD-HI (predominantly hyperactive–impulsive type): Characterised by maladaptive levels of hyperactivity–impulsivity, but not inattention
» ADHD-C: Characterised by significant symptoms of both inattention and hyperactivity–impulsivity.
Whilst international studies show a predominance of ADHD-I, followed by ADHD-C and ADHD-HI, the authors of the African systemic review found that ADHD-I was most common subtype of ADHD in Africa, followed by ADHD-HI and ADHD-C. ADHD-I subtype is the most prevalent subtype in both males and females, while evidence suggest that all three subtypes are prevalent among males.1
Table 1: Prevalence of ADHD subtypes according to gender1
Subtype: ADHD-I Boys: 4.05% Girls: 2.21%
Subtype: ADHD-C Boys: 3.62% Girls: 1.5%
Subtype: ADHD-HI Boys: 3.61% Girls: 1.52%
Not ‘only’ a behaviour disorder
Numerous studies have shown that ADHD is not ‘only’ a behavioural disorder, write Boshomane et al. In essence, ADHD is a complex cognitive disorder, which involves impairment of executive functions (EFs), also called executive or cognitive control.2,4
One definition of EFs is: ‘A product of the co-ordinated operation of various processes to accomplish a particular goal in a flexible manner’. EFs are vital to manage intellectual resources. Together with metacognition, they play a key role in how we consciously regulate our thoughts and behaviours. They are also associated with academic performance.3,7
There are three core EFs:4
1. Inhibition (interference self-control)
2. Working memory (holding information in mind and mentally working with it or said differently, working with information no longer perceptually present)
3. Cognitive flexibility (also called setshifting, mental flexibility or mental setshifting are closely linked to creativity).
Neuropsychological studies found that children and adolescents with ADHD exhibited significant deficits in EF domains compared to those without ADHD. Boshomane et al explain that these deficits influence response inhibition, working memory, set-shifting and planning.2
A recent study shows that 93% of children with ADHD struggled with self-restraint, 73% with emotion regulation, 60% with selfmotivation (especially boys), 57% with time management and 41% with problem-solving.5
Another recent study reports a link between lower scores of conscientiousness and agreeableness in adolescents (12- to 16-years) with ADHD, and higher scores on neuroticism. The researchers point out that their study included more cases of ADHD-I, which may explain these results since inattentive symptoms appear to be more specifically related to conscientiousness and neuroticism.6
They also observed links between ADHD and some of the personality traits closely related to self-regulation abilities that are impacted in ADHD. For example, high impulsivity and disrupted goal-directed behaviour may be related to lower conscientiousness and agreeableness, and higher neuroticism, which would probably explain some of the breakdowns in the self-regulation abilities of children and adolescents with ADHD.6
What causes executive dysfunction?
Neuroimaging studies show that the prefrontal cortex (PFC) is a key determinant of executive functioning. The PFC consists of the orbitomedial and the dorsolateral prefrontal regions and is connected to many other parts of the brain, notably the limbic and cortical regions of the parietal and temporal lobes.11
The orbitomedial cortex is involved in sensory processing (taste and olfaction), regulation of the internal environment, control of drives, and emotional behaviour. The dorsolateral cortex is involved in cognitive functions.11
To function properly, the PFC requires optimal levels of two catecholamine neurotransmitters – norepinephrine (NE) and dopamine (DA). Too little (as when we are drowsy or fatigued) or too much (as when we are stressed) markedly impairs PFC regulation of behaviour and thought.8
When functioning is not impaired, the PFC allows us to concentrate and sustain our attention, especially under ‘boring conditions’ such as long delays between stimuli (eg a teacher who talks slowly).8
It helps us to focus on material that is important but not inherently salient (eg studying for a test, reading homework) and to inhibit internal and external distractions, to divide and shift our attention as appropriate with task demands (so-called multi-tasking), to plan and organise for the future as well as to regulate our behaviour and inhibit inappropriate responses.8
Genetic and imaging studies suggest that many patients with ADHD have inadequate transmission of NE or DA or both, as well as a smaller PFC and reduced functional activity. Other studies report more disorganised white matter tracks emanating from the PFC in patients with ADHD, which have been associated with weaker prefrontal connectivity.8
Other brain regions connected to the PFC such as the caudate and cerebellum, have also been reported to be smaller in some studies of children with ADHD. There is also evidence of slower prefrontal maturation in some patients with ADHD.8
Are stimulants effective in improving executive functioning?
The efficacy of psychostimulants in reducing ADHD symptoms has been shown in numerous clinical trials of both children and adults with ADHD. As mentioned already, the PFC requires optimal levels of norepinephrine (NE) and dopamine (DA). ADHD treatments work by enhancing NE and DA functions, thus improving PFC functioning and activity.8
NE stimulation of alpha-2A receptors enhances PFC function by strengthening appropriate network connections (increasing signals), and DA stimulation of D1 receptors, which exerts its beneficial effects by weakening inappropriate connections (decreasing noise).8
Psychostimulants are currently the firstline treatment for ADHD in both children and adults. Methylphenidate (MPH) is the most widely prescribed and exerts its therapeutic effect by blocking the function of the NE and DA transporters. As a result, the bioavailability of NE and DA is improved, correcting deficits.9
Numerous studies have shown that MPH improves reaction time, task-switching, focused attention, word-matching, and go/no-go tasks in children with ADHD. Low-dose MPH has also been shown to improve sustained attention, signal detection, and attentional setshifting. In addition, it has been shown that MPH improves working memory capacity.9,10
Considerations when prescribing ADHD medication
According to the authors of the 2019 the NationalInstitute for Health and Care Excellence guideline, the following must be taken into consideration when prescribing ADHD medication:12
• When prescribing stimulants for ADHD, think about modified-release once-daily preparations for the following reasons:
» Convenience
» Improving adherence
» Reducing stigma (because there is no need to take medication at school or in the workplace)
» Reducing problems of storing and administering controlled drugs at school
» The risk of stimulant misuse and diversion with immediate-release preparations
» Their pharmacokinetic profiles.
• Immediate-release preparations may be suitable if more flexible dosing regimens are needed, or during initial titration to determine correct dosing levels
• When prescribing stimulants for ADHD, be aware that effect size, duration of effect and adverse effects vary from person to person
• Think about using immediate- and modifiedrelease preparations of stimulants to optimise effect Í Be cautious about prescribing stimulants for ADHD if there is a risk of diversion for cognitive enhancement or appetite suppression
• Do not offer immediate-release stimulants or modified-release stimulants that can be easily injected or insufflate if there is a risk of stimulant misuse or diversion
• Prescribers should be familiar with the requirements of controlled drug legislation governing the prescription and supply of stimulants.
Guideline recommendations
The 2019 American Paediatric Association (APA) guidelines recommend:13
Recommendations Children aged 4- to 6-years
MPH may be considered if behavioural interventions do not provide significant improvement and there is moderate-tosevere continued disturbance in the child’s functioning. In areas in which evidence-based behavioural treatments are not available, the clinician needs to weigh the risks of starting medication before the age of six-years against the harm of delaying treatment.
Children aged 6- to 12-years
Prescribe approved medications for ADHD, along with parent training in behaviour management (PTBM) and/or behavioural classroom intervention (preferably both PTBM and behavioural classroom interventions).
Children aged 12- to 18-years
Prescribed approved medications for ADHD with the adolescent’s assent. The clinician is encouraged to prescribe evidence-based training interventions and/or behavioural interventions as treatment of ADHD, if available.
Conclusion
High prevalence of ADHD in children and adolescents is seen in Africa, indicating that ADHD is a serious public health that should be focusedon. Early pharmacologic intervention with comprehensive, holistic psychosocial approach in addressing psychological, behavioural, and occupational or educational needs will be the mainstay of ADHD management.
References
1. Ayano G, Yohannes K and Abraha M. Epidemiology of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents in Africa: A systematic review and meta-analysis. Ann Gen Psychiatry, 2020.
2. Boshomane TT, Pillay BJ, Meyer A et al. Attentiondeficit/hyperactivity disorder and behavioural planning deficiencies in South African primary school children. South African Journal of Psychiatry, 2020.
3. Viana-Saenz L, Sastre-Riba S, Urracca-Martinez M et al. Measurement of Executive Functioning and High Intellectual Ability in Childhood: A Comparative Meta-Analysis. Sustainability, 2020.
4. Diamond A. Executive Functions. Annu Rev Psychol, 2014.
5. El Wafa HEA, Ghobashy SAEL and Hamza AM. A comparative study of executive functions among children with attention deficit and hyperactivity disorder and those with learning disabilities. Middle East Current Psychiatry, 2020.
6. Kriegel V, Amador-Campos JA and Guardia-Olmos J. Executive functions, Personality traits and ADHD symptoms in adolescents: A mediation analysis. PLoS One, 2020.
7. Elliot R. Executive functions and their disorders: Imaging in clinical neuroscience . British Medical Bulletin, 2003.
8. Arnsten AFT. The Emerging Neurobiology of Attention Deficit Hyperactivity Disorder: The Key Role of the Prefrontal Association Cortex. J Pediatr, 2009.
9. Urban KR and Gao W-J. Psychostimulants As Cognitive Enhancers in Adolescents: More Risk than Reward? Front Public Health, 2017.
10. Metha MA, Owen AM, Sahakian BJ et al. Methylphenidate Enhances Working Memory by Modulating Discrete Frontal and Parietal Lobe Regions in the Human Brain. The Journal of Neuroscience, 2000.
11. Fuster JM. Prefrontal Cortex. International Encyclopedia of the Social & Behavioral Sciences, 2001.
12. NICE. Attention deficit hyperactivity disorder: diagnosis and management, 2019. https://www. guidelines.co.uk/mental-health/nice-adhdguideline/454106.article.
13. Wolraich ML, Hagan JF, Allan C et al. AAP subcommittee on children and adolescents with attention-deficit/hyperactive disorder. Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics, 2019. SF
