VP - ADHD Flashcards
What is ADHD?
Attention-Deficit/Hyperactivity Disorder
A neurodevelopmental disorder characterized by impairing levels of inattention, impulsiveness, and hyperactivity.
What are the two main domains and three presentations of ADHD?
Domains:
1. Inattention
1. Hyperactivity/impulsivity
Presentations:
1. Inattentive
1. Hyperactive/Impulsive
1. Combined
What are the inattentive symptoms of ADHD? (9)
- Often fails to pay attention to details or makes careless mistakes.
- Often has difficulty concentrating
- Often does not seem to listen when spoken to directly.
- Often does not follow through on instructions and fails to finish tasks.
- Often has difficulty organizing daily activities.
- Tends to procrastinate, especially tasks that require mental effort.
- Often loses things.
- Is often easily distracted by external stimuli.
- Is often forgetful in daily activities.
At least 6/9 symptoms in childhood; 5/9 in adulthood
What are the impulsivity-hyperactivity symptoms of ADHD? (9)
- Often fidgets.
- Cannot stay seated for long.
- Feels restless.
- Tends to be loud.
- Talks excessively.
- Has more energy than others.
- Often has difficulty awaiting turn.
- Often says things without thinking.
- Often interrupts others.
At least 6/9 symptoms in childhood; 5/9 in adulthood
What is the prevalence and demographic differences of ADHD? (4)
- Affects 4-6% of children and 2-3% of adults.
- Higher prevalence in males (2.5:1 male-to-female ratio in children and young people).
- No significant differences between low- and high-income countries
- ADHD often persists into adolescence (50-80%) and adulthood (30-50%). (tends to get better with age)
How does ADHD impact everyday life? (4)
Negative effects on:
- Academic performance and employment: Poor grades, failure, low self-esteem.
- Health: Obesity, vision disorders, allergies, asthma, diabetes, somatic issues.
- Risk behaviors: Addictions, unhealthy eating/drinking habits, higher risk of accidents.
- Social and emotional issues: Bullying, criminal behaviors, emotional problems.
What are the key diagnostic criteria for ADHD? (3)
- Age-inappropriate levels of hyperactive-impulsive and/or inattentive symptoms for at least 6 months
- Symptoms appear in multiple settings (e.g., home, school) and impact daily life.
- Some symptoms present in early to mid-childhood.
How is ADHD diagnosis conducted? (4)
- Psychiatric interviews.
- Rating scales (e.g., Conner’s Rating Scales).
- Collateral information (e.g., from school).
- neuropsychological tests (e.g., QB-Test)
NO objective markers
What are the factors that contribute to the development of ADHD? (3)
Liability threshold model: Genetic and environmental factors accumulate until a threshold is crossed.
Genetic factors: Polygenic risk, familial patterns, and broader psychiatric vulnerabilities.
Environmental factors: Toxins, maternal substance use during pregnancy, nutrient deficiencies, stress, infections, poverty, and trauma.
What brain networks are associated with ADHD (3) and how do they contribute to ADHD?
Fronto-striatal networks
Crucial for:
- executive functions
- attention
- reward processing.
Parietal connections
Involved in:
- spatial awareness
- attention
- sensory integration.
Cerebellar connections
Related to:
- motor control
- balance
- cognitive functions.
Abnormalities/disruptions in these networks are implicated in ADHD.
What modulates the activity within these networks?
Dopaminergic and noradrenergic pathways
What is dopamine’s role in the brain’s catecholaminergic pathways? (3)
- Dopamine (DA) is synthesized in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA).
- DA regulates movement via the nigrostriatal pathway
- Mesocortical and mesolimbic pathways influence executive functions and affect regulation.
What is norepinephrine’s role in the brain? (2)
- Originates in the locus coeruleus (LC) and connects with cortical regions like the prefrontal cortex (PFC).
- Modulates attention and arousal state.
What are cortico-striatal loops? (2)
- GABA-glutamatergic circuits, regulated by dopamine,
- Link the cortex, basal ganglia, and thalamus
What are the three main loops and how do they contribute to ADHD?
- Motor loop: Sensorimotor cortex-striatum-thalamus for motor planning.
- Cognitive loop: Prefrontal cortex-striatum-thalamus for planning and learning.
-
Limbic loop: Anterior cingulate cortex/ orbitofrontal cortex (ACC/OFC)-n.accumbens (ventral striatum)-thal-Cortex
Emotion-related movements (e.g., smiling). - These circuits contribute to executive functions and affect regulation, which can be impaired in ADHD.
How do dopamine and norepinephrine optimize PFC function?
Dopamine (D1 receptors): Reduces ‘noise’ in glutamatergic circuits by increasing cAMP (helps suppress irrelevant neural activity).
Norepinephrine (α2A receptors): Enhances ‘signal’ by reducing cAMP production (strengthening specific synaptic connections).
What are the roles of the direct (3) and indirect (3) pathways in motor control?
Direct pathway:
- Facilitates movement via D1 receptor stimulation,
- Involves the striatum, internal globus pallidus, and thalamus
- thalamus disinhibited and subsequent motor cortex activation
Indirect pathway:
- Inhibits unwanted movements via D2 receptor stimulation
- Involves the striatum, external globus pallidus, subthalamic nucleus, and internal globus pallidus
- Thalamic inhibition, supressing unwanted movements
What is the inverted U curve in ADHD pathophysiology?
Both excessive and insufficient catecholamine release negatively affect PFC functions, leading to suboptimal brain activity.
What evidence supports catecholaminergic dysfunction in ADHD? (4)
- Candidate gene studies
- Animal models.
- Efficacy of stimulants.
- PET/SPECT studies showing greater striatal DAT binding in ADHD.
Note: DAT removes dopamine from the synapse
What challenges exist in DAT binding studies for ADHD?
Inconsistent findings may stem from:
- Effects of previous stimulant treatment.
- Adaptive responses to chronic treatment causing persistent DAT blockade.
What are medications for moderate/severe ADHD? (2)
- Stimulants e.g. methylphenidate (Ritalin, Concerta) are first-line treatments.
- Other options include lisdexamfetamine, atomoxetine, and guanfacine.
What are the common side effects and precautions for stimulant medications in ADHD? (5)
- Increased blood pressure
- Increased heart rate.
- Decreased appetite.
- Sleep disturbances.
Precautions:
- Monitor blood pressure, heart rate, height, and weight before and during treatment.
How is ADHD managed for different age groups (NICE guidelines)?
Preschoolers (< 5 years)
- ADHD-focused group parent training.
- Specialist advice and medication if severe.
Children and adolescents (≥5 years):
- Group-based ADHD-focused support.
- Medication progression: Methylphenidate (first line) Lisdexamfetamine/ dexamphetamine (second line), Atomoxetine/Guanfacine (non stimulants)
- CBT if symptoms persist.
Adults:
- Medications in order: Methylphenidate, Lisdexamfetamine/dexamphetamine, Atomoxetine.
- Supportive psychological interventions if requested or medications ineffective.
What is the difference between Ritalin and Concerta?
- Ritalin: Short-acting; ideal for children.
- Concerta: Long-acting; better suited for adolescents and adults.
How does methylphenidate (MPH) work in ADHD treatment? (3)
- Exists as enantiomers: d-threo-MPH and l-threo-MPH. The d-enantiomer is primarily responsible for the therapeutic effects.
- Blocks dopamine (DA) and norepinephrine (NE) transporters, increasing DA and NE levels in the synaptic cleft.
- Involves allosteric binding to transporters.
How does Amphetamine work in ADHD treatment? (3)
- Also exists as Enantiomers: d-isomer more potent for DAT but equally potent for norepinephrine transporters (NET) binding
- Competitive inhibitor of DAT and NET
- Reverses the direction of these transporters at higher doses, releasing stored neurotransmitters
What is lisdexamfetamine, and how does it differ from other stimulants? (2)
- A long-acting d-amphetamine prodrug hydrolyzed in the blood to active form.
- Provides therapeutic effects for up to 13–14 hours.
How do acute stimulant doses affect brain activity/functional connectivity? (3)
- Shift activity in ADHD brains towards patterns seen in neurotypical peers.
- Enhance connectivity in task-related networks (fronto-striatal/parietal).
- Suppress activity in the default mode network (DMN).
Note: Prolonged stimulant treatment might not translate into long-lasting changes of brain anatomy/activity, although this may require further investigation.
What are the roles of non-stimulants like atomoxetine and guanfacine in ADHD treatment? (4)
Atomoxetine:
- Selective norepinephrine reuptake inhibitor.
- Acts on the prefrontal cortex (PFC)
- Safer use in addiction (Lower levels of NET in the n. accumbens - reduces the risk of abuse).
Guanfacine (children only):
- Selective α2A receptor agonist, mediating NE effects in PFC.
- Weaker sedative and hypotensive effects than clonidine.
What are some predictors of ADHD treatment response?
- Individuals with a smaller left superior longitudinal fasciculus (SLF I) may respond less to methylphenidate (MPH).
- Combined biological and clinical characteristics increase prediction accuracy for treatment response.
What did MRI studies reveal about brain alterations in ADHD non-responders? (2)
- ADHD non-responders show more brain alterations than responders.
- Cortical differences are enriched for biologically plausible genes, such as those involved in noradrenaline transport, a target of methylphenidate
