ADHD

Question 1

Diagnosing ADHD

Answer 1

-Symptoms must be present before the age of 12; cannot diagnose before age 3.
-Impairment present in at least 2 different settings
-Evidence of functional interference: Socially, Academically, or in Extracurricular activities
-Subtypes = Inattentive, Hyperactive/Impulsive, and Combined

Question 2

ADHD “causes”

Answer 2

-Genetic (75%)
-Delayed maturation of prefrontal cortex circuitry
-Ineffective “tonic” NE and DA neurotransmission/hypoactivity of dopamine and norepinephrine pathways in brain regions such as the prefrontal cortex (PFC)

Question 3

ADHD Comorbidities

Answer 3

Comorbidities result from inadequate tuning in the VMPFC
Conditions: Learning disability, anxiety disorder, mood disorder, conduct disorder, oppositional defiant disorder, substance use disorder

Question 4

Nicotine use in ADHD

Answer 4

Nicotine enhances DA release and enhances arousal –> subjective improvement of ADHD symptoms.
ADHD smoke 2x more compared to non-ADHD population.

Question 5

ADHD medications primarily target _____ symptoms.

Answer 5

hyperactivity and impulsivity

Question 6

Dopamine reward system

Answer 6

Bursts of firing by DA = phasic DA stimulation is thought to reinforce learning and reward conditioning
Known to fire when: education, recognition, career development, enriching social/family connections, other enriching experiences

Question 7

ADHD Inattentive subtype

Answer 7

capacity for executive function is impaired, selective attention, difficulty with sustained attention and problem solving

Question 8

Hyperactive/impulsive subtype

Answer 8

get into more trouble

Question 9

ADHD Tx

Answer 9

1. Assess/manage substance abuse problems
2. Treat mood and anxiety
3. Evaluate for other common ADHD comorbidities
4. Stimulants or non-stimulants

Question 10

ADHD Stimulants

Answer 10

Methylphenidate (Ritalin, Concerta): increases synaptic levels of DA and NE through selective inhibition of presynaptic transporters
Dextroamphetamine/Amphetamine Salts (Adderall, Vyvanse): cause release of DA, NE, and 5-HT into the synapse

Question 11

ADHD Non-stimulants

Answer 11

Guanfacine (Intuniv)
Clonidine (Catapres)
Viloxazine (Qelbree)
Atomoxetine (Strattera)
Wellbutrin (Bupropion)

Question 12

Contraindications to Stimulant Use

Answer 12

-Known cardiac abnormalities
-Moderate to severe hypertension
-Hyperthyroidism
-Motor tics & Tourette’s Syndrome
-Glaucoma
-Agitation
-Anxiety
-History of drug abuse
-Concurrent MAOI within 14 days
*Strattera contraindicated in hypertension and glaucoma

Question 13

Pediatric ADHD Tx

Answer 13

1. Behavioral therapy for children 5 years and younger
2. Dextroamphetamine & amphetamine salts for 3 years and older
3. Methylphenidate for 6 years and older

Question 14

Tx monitoring ADHD

Answer 14

-Physical exam (height, weight, BP, pulse); height & weight 1-2x per year for kids
-Monitor for adverse effects and adjust medication dose/timing
-Monitor for therapeutic response initially every 1-2 weeks and then every 1-3 months
-Assess both behaviors and academic achievements
-Meds no longer needed if: No symptoms for 1 year, No need for medication adjustment, Lack of deterioration after missed dose
-Consider timed trial off meds during low stress time

Question 15

Neurobiology of Inattention

Answer 15

Executive dysfunction and linked to inefficient information processing in the dorsolateral prefrontal cortex (DLPFC)

Sustained attention is hypothetically modulated by a cortico-striato-thalamo-cortical loop that involves the dorsolateral prefrontal cortex (DLPFC) projecting to the striatal complex. Inefficient activation of the DLPFC can lead to difficulty following through or finishing tasks, disorganization, and trouble sustaining mental effort

Question 16

Neurobiology of Selective attention

Answer 16

Inefficient information processing in the dorsal anterior cingulate cortex (dACC).

Selective attention is hypothetically modulated by a cortico-striato-thalamo-cortical loop arising from the dorsal anterior cingulate cortex (dACC) and projecting to the striatal complex, then the thalamus, and back to the dACC. Inefficient activation of dACC can result in symptoms such as paying little attention to detail, making careless mistakes, not listening, losing things, being distracted, and forgetting things

Question 17

Neurobiology of Impulsivity

Answer 17

Impulsivity is associated with a cortico-striato-thalamo-cortical loop that involves the orbital frontal cortex (OFC), the striatal complex, and the thalamus. Examples of impulsive symptoms in ADHD include talking excessively, blurting things out, not waiting one’s turn, and interrupting

Question 18

Neurobiology of hyperactivity

Answer 18

Motor activity, such as hyperactivity and psychomotor agitation or retardation, can be modulated by a cortico-striato-thalamo-cortical loop from the prefrontal motor cortex to the putamen (lateral striatum) to the thalamus and back to the prefrontal motor cortex. Common symptoms of hyperactivity in children with ADHD include fidgeting, leaving one’s seat, running/climbing, being constantly on the go, and having trouble playing quietly.

Question 19

ADHD: DA and NE

Answer 19

Excessive noradrenergic neurotransmission can lead to impaired working memory due to stimulation of α1 (and β1) receptors. Excessive dopaminergic neurotransmission can lead to overstimulation of D1 receptors in the prefrontal cortex

Question 20

Prefrontal motor cortex is linked to ___________ symptoms

Answer 20

hyperactive

Question 21

Orbitofrontal cortex is linked to _________________symptoms

Answer 21

impulsive

Question 22

DLPFC is linked to ___________ symptoms

Answer 22

sustained attention and problem solving

Question 23

dACC is linked to ___________ symptoms

Answer 23

selective attention

Question 24

Mesocortical Dopamine Pathway

Answer 24

Projects to the prefrontal cortex and is responsible for modulating attention and executive function

Question 25

Stimulant mechanism of action

Answer 25

Block the reuptake of dopamine and norepinephrine in the synapse, increasing their availability and improving attention and focus.
They can also promote increased release of dopamine and norepinephrine from presynaptic neurons

Question 26

Amphetamines mechanism of action

Answer 26

Competitive inhibitor and pseudosubstrate for NETs and DATs, binding at the same site that the monoamines bind to the transporters, thus inhibiting NE and DA reuptake

Question 27

Stimulant therapeutic effects

Answer 27

Effective at reducing core symptoms of ADHD, such as inattention, hyperactivity, and impulsivity.
They enhance cognitive control, task persistence, and working memory.

Question 28

Stimulant side effects

Answer 28

Insomnia, reduced appetite, weight loss, irritability, and potential for increased anxiety. Cardiovascular side effects such as increased heart rate and blood pressure.

Question 29

Stimulant risk for abuse

Answer 29

due to their ability to increase dopamine levels in reward pathways (e.g., mesolimbic dopamine system)

Question 30

Atomoxetine (Strattera)

Answer 30

Non-stimulant. A norepinephrine reuptake inhibitor (NRI) that selectively blocks the norepinephrine transporter, increasing norepinephrine levels in the PFC.
Does not have dopaminergic effects in the striatum or nucleus accumbens, thus it has low abuse potential compared to stimulants.

Question 31

Guanfacine (Intuniv) and Clonidine (Kapvay)

Answer 31

Non-stimulant. Alpha-2A adrenergic agonists that enhance prefrontal cortical function by strengthening working memory, impulse control, and attention through increased norepinephrine signaling. Clonidine is approved to treat hypertension and ONLY controlled-release Clonidine is approved for ADHD
Often used as adjunctive therapy with stimulants or as a second-line treatment.

Question 32

Viloxazine ER

Answer 32

Non-stimulant. Inhibitor of the norepinephrine transporter (NET) and also has actions at serotonin 2B (5HT2B) and 5HT2C receptors