Lecture 6 - ADHD

ADHD

-historically classified as mental health disorder

-conceptualised as a neurodevelopmental condition/neurodiversity

-but is treatable with drugs unlike other neurodevelopmental conditions

-behaviours may not always cause clinical impact

characteristics of ADHD

-triumvirate of symptoms → hyperactivity, impulsivity, attentional problems

-diagnosed typically based on childhood presentations:

• difficulty sustaining attention in tasks

• fidgets or squirms

• or both

DSM 5-TR (characteristics of ADHD)

-persistent pattern of inattention and/or hyperactivity-impulsivity interfering with functioning, with symptoms present before age 12 in two or more settings

-frontline treatment is lisdexamfetamine or methylphenidate

ICD-11 (characteristics of ADHD)

-persistent pattern of inattention and/or hyperactivity that has a direct negative impact on academic, occupational or social functioning

-needed both inattention and hyperactivity in ICD-10

inattention (symptom presentations)

-lack of attention in academic, occupational or social situations

-careless mistakes

-difficulty maintaining sustained attention

-failing to take in or respond to instructions

-shifting from one task to another without completing any of them

-being easily distracted by irrelevant stimuli or events

hyperactivity (symptom presentations)

-excessive fidgetiness

-not remaining seated

-excessive running or climbing when inappropriate

-talking excessively

-difficulty participating in sedentary activities

impulsivity (symptom presentations)

-impatience

-difficulty in delaying responses

-constantly interrupting others

-drive for immediate rewards over delayed rewards

-proneness to accidents

-indulging in dangerous activities

diagnosis and persistence

-5% children and 2-3% adults diagnosed

-male:female diagnosis of 3:1 -> referral bias and issues with criteria

-trend is narrowing in adults → men and women equally likely to think they had ADHD

-underdiagnosis costs UK £17B per year

-symptoms continue into adulthood

1902 (history of ADHD)

-G.F Still first formally recorded definition of ADHD

-identified children with core traits of modern ADHD

-described as a defect of moral control

prehistory (history of ADHD)

-may have been adaptive for migration hunter-gather societies

-genes associated with ADHD have high prevalence in some modern nomadic tribes

ancient greece (history of ADHD)

-hippocrates described children who had quickened responses to sensory experience, but less tenaciousness because the soul moves quickly to the next impression

-recommend they eat fish instead of meat → some recent evidence suggests omega 3 fish oils can help ADHD

1600s (history of ADHD)

-shakespeare character with malady of attention

-plays showing ADHD-like behaviours

1800s (history of ADHD)

-faust character described as having pattern motor activity, constantly coupled with impulsive actions, without any attention to parents’ warnings or adverse consequences

1920 (history of ADHD)

-encephalitis lethargica link between ADHD-like behaviours and neural changes

-symptoms comatose like sleepiness and headaches → post encephalitic behaviour was distractible, irritable and antisocial

-also presented parkinsonian symptoms → common factor of dopamine

1937 (history of ADHD)

-benzedrine first evidence of stimulant efficacy in the treatment of ADHD-like behaviours

-noticed children became calm and easier to work with

-first evidence of stimulant efficacy in neurodiversity

1960s (history of ADHD)

-introduction of minimal brain dysfunction

-shift between thinking of ADHD as acquired (brain damage/dysfunction) to developmental/behavioural

-first DSM criteria → hyperkinetic reaction of childhood in DSM 2

1980s (history of ADHD)

-refinement of criteria

-ADHD diagnostic label:

• 1980 → ADD with or without hyperactivity

• 1987 → ADHD label officially used

• 1994 → DSM 4 introduce ADHD subtypes, required before age of 7

2000s to present (history of ADHD)

-introduction of ADHD sub-types in DSM

-lowered symptoms needed for adult diagnosis

-move towards neurodiversity in research and societal understanding

current research focus

-understand shorter life expectancies

-how symptoms fluctuate over time

-genetic basis and shared basis with other conditions

-neural changes underpinning ADHD and how to target these

-improving treatment efficacy

-more effective diagnosis

educational attainment

-ADHD students 6.5x more likely to leave school with sub-GCSE qualifications

-higher risk in girls (8.46x)

-significantly increased likelihood of exclusion

occupational outcomes

-mean age 41 with childhood ADHD diagnosis

-lower employment rates

-lower occupational status and lower average salaries compared to controls

peer relations

-ADHD significantly more likely to be ‘rejected’ by peers

-social challenges may begin as early as 7-10

-UG students watched video of woman showing symptoms of ADHD, depression or no psychopathology → rejection significantly higher for those with ADHD or depression

physical health and accidents

-at increased risk of accidents and injuries

-risk and type of injuries changes over the lifespan

-ADHD medication decreases the risk of accidents and injuries in all ages

-1.6x more likely to require medical treatment for accidents in 12 month period

mental health

-anxiety and depression very common

-substance use disorders much more common in adults with childhood ADHD

-but untreated ADHD is the risk and treatment is protective

issues with outcome studies

• small samples or prescription based identification

• methodological issues → lab or classroom settings and rejection may be a response to stigma rather than behaviours

• problems with controls → comorbidity effects, SES, parental factors, different symptom clusters displayed by participants

• problems with the constructs → little evidence of general intelligence deficits in ADHD, may reflect ability to complete standardised tests

frontal issues

-executive control

-evidence from:

• neuropsychological tests

• structural imaging

• functional imaging

dopamine issues

-reward processing

-mechanisms of drugs

-differences in reward processing

-some relevant genetic evidence → 76% twin studies

-gene-environment interactions

• mDAT1 gene + exposure to prenatal smoking

iowa gambling task (frontal cortex)

-neuropsychological test of cognitive impulsivity

-4 decks of cards with advantageous decks and disadvantageous decks

-ADHD groups typically seduced by big immediate gains despite long-term loss

• represents delay aversion

-associated with strong preference for smaller soon rather than larger late rewards

-characteristics of behavioural disinhibition and linked to dopamine dysfunction

behavioural inhibition model

-failure to inhibit behaviour:

• attention problems → distractibility

• kinetic symptoms → movement

-neural basis is frontal cortex

frontal cortex insult

-Phineas Gage

-neurocognitive disorders, schizophrenia, lesion studies in animals

structural evidence (ADHD and frontal cortex)

-consistent reductions in frontal lobe compared to age matched controls → associated with control and EFs

-effect size is small changes in cortical thickness rather than large changes

-but evidence may be a delay rather than chronic underdevelopment

-correlational

function evidence (ADHD and frontal cortex)

-broad evidence of frontal hypoactivity during cognitive tasks of attention

-reviews show areas where ADHD patients have greater level of activation

-limited research on adults → delayed maturation

-may represent task performance deficits rather than real world deficits

-continuous performance task measures sustained attention

overview of ADHD and frontal cortex

-deficits in neuropsychological tests of frontal functions

-insult to frontal regions

-frontal regions are underdeveloped relative to age-matched controls

-frontal regions show hypoactivation during cognitive tasks of attention

ADHD and dopamine

-associated with increased dopamine clearance → dopamine vacuuming where it isn’t around long enough to have an effect

-drugs used to treat ADHD increase dopamine levels in murine forebrain

-microdialysis → invasive technique that enables sampling of neurotransmitters, allows us to monitor drug-induced changes

effects of stimulants on dopamine levels

-both d-amphetamine and methylphenidate significantly increase DA levels in PFC or other regions with dopaminergic neurons:

• d-amphetamine more potent

• methylphenidate longer lasting

stimulant mechanisms (ADHD and dopamine)

-both drugs interfere with dopamine transport

• amphetamine → enters pre-synaptic neuron and reverses transporters DA out of cells

• methylphenidate → antagonises transports, blocks reuptake

DAT and dopamine vacuum (ADHD and dopamine)

-drug-naive ADHD children have more transporters

-so dopamine is cleared too quickly, creating a low dopamine state

-PET evidence that methylphenidate occupies DAT, decrease dopamine transporter binding preventing reuptake too quickly → suggests therapeutic benefits are achieved through impeding DA reuptake

reward and reinforcement (ADHD and dopamine)

-robust evidence that dopamine is released during reward and that this is disrupted in ADHD

-may be due to tonic vs phasic activity → researchers could be recording phasic rather than tonic activity

tonic activity (ADHD and dopamine)

-cells constantly fire at low rate

-dopamine signal maintains things in a state where ready to respond to reward

-motivation and on-task concentration

phasic activity (ADHD and dopamine)

-sharp burst of activity in dopaminergic neurons in response to reward

tonic vs phasic dopamine

-dopamine activity in the striatum key to efficient reward processing

-PET scan for DA receptors in striatum during reward in ADHD vs non-ADHD

-higher binding means reduced DA activity

• found higher binding at rest → lower tonic DA activity

• lower binding during rewards → enhanced phasic DA