ADHD Pahtophysiology

Question 1

ADHD Defined

Answer 1

Inattention (distractibility from sustained tasks)
Hyperactivity (excessive physical restlessness and activity)
AND/OR
Impuslsivity (impaired impulse control)

Question 2

ADHD Cause

Answer 2

Exact cause is unknown but it involves hypoactivity of key dopaminergic and/or adrenergic pathways in the basal ganglia and frontal cortex

Question 3

Combined Type ADHD

Answer 3

If both inattention and hyperactivity/impusivity criterion are met for 6 months

Question 4

Predominatly Inattentive Type ADHD

Answer 4

if inattention criterion is met but hyperactivity/impulsivity criterion is not met for the past 6 months

Question 5

Predominantly Hyperactive-Impulsive ADHD

Answer 5

If hyperactivity/impulsivity criterion is met but inattention criterion is not met for the past six months

Question 6

Comorbidities seen in untreated ADHD

Answer 6

MDD or anxiety disorder (25%)
Oppositional Defiant Disorders (60%)
Substance abuse, academic failure, work/family problems and emotional distress

Question 7

**Genes in ADHD

Answer 7

Dopamine (MAJOR)
Serotonin
NE (alpha 2A)

Question 8

**Environmental Causes of ADHD

Answer 8

Smoking
Lead exposure
Alcohol
Viral infections
Food and food additive (less than 5% of cases)
Lack of essential fatty acids or thyroid hormones

Question 9

Age of Onset for ADHD

Answer 9

Around 6 or 7
Symptoms of inattention become noticeable
Synapses begin to be eliminated here and continue through early adolescence

Question 10

What symptoms increase with age?

Answer 10

Inattention

Question 11

What symptoms decrease with age?

Answer 11

Impulsivity and hyperactivity (you learn what is and isn’t okay)

Question 12

Hypotheses of ADHD Malfunction

Answer 12

Response inhibitoin of executive brain function is deficient in the PFC
Dysregulation of arousal (treatments modulate DA and NE to improve executive function and regulate arousal)

Question 13

PFC in Humans

Answer 13

It makes us human
It exerts executive control over decision making and behavior
It helps anticipate reward, punishment, for empathy and complex emotions

Question 14

Dorsal Anterior Cingulate Cortex =

Answer 14

SELECTIVE ATTENTION

Question 15

Dorsolateral PFC =

Answer 15

SUSTAINED ATTENTION, PROBLEM SOLVING AND EXECUTIVE FUNCTION

Question 16

PFC =

Answer 16

HYPERACTIVE SYMPTOMS

Question 17

Orbitofrontal Cortex =

Answer 17

IMPULSIVE SYMPTOMS

Question 18

Deficient Arousal

Answer 18

State of hypoarousal during the day may experience inattentiveness, cognitive dysfunction and sleepiness with impulsivity all caused by HYPOACTIVITY in the OFC

Question 19

Enhancing Arousal in PFC

Answer 19

Increase teh drive of the arousal netwrok by enhancing arousal NT DA and NE

Question 20

Excessive Arousal

Answer 20

All due to PFC being out of tune
Associated with phasic firing of DA and NE neurons
Stress activates NE and DA circuits leading to phasic firing!!

Question 21

Stimulant MOA

Answer 21

Slow-dose stimulants amplify tonic NE and DA signals (Block NET in PFC and DAT in NA)

Question 22

Methyphenidate MOA and dose

Answer 22

Daytrana patch, concerta, ritalin
Blocks NET adn DAT
Low dose given slowly

Question 23

Ampehtamine MOA

Answer 23

Adderall, adderall XR, vyvanse

Competitive inhibitor and psuedosubstrate for NET and DAT

Question 24

Stimulant Effects

Answer 24

Improvement depends on how fast, how much and how long
Want: slow onset, robust drug levels and long duration
Don’t Want: pulsatile stimulants bc they cause rapid increase in NE and DA leading to euphoria and abuse

Question 25

Stimulants QD

Answer 25

Provide 8-12 hours of control | Methylphenidate (concerta and daytrana patch)

Question 26

Stimulant side effects

Answer 26

Rare: height deficit Reduced appetite and weight loss Insomnia and headache

Question 27

Non-Adrenergic Agents MOA

Answer 27

PFC lacks high concentrations of DAT so DA uses NET sometimes Inhibiting NET increases both DA and NE in the PFC (not much happens in NA so no abuse potential)

Question 28

Atomoxetine Brand, MOA, time to work

Answer 28

Strattera Selective NE Reuptake Inhibitor Takes 2-4 weeks to start working Initially worsens the situation but then will normalize firing

Question 29

Atomoxetine (Strattera) SE

Answer 29

``` Nausea Anorexia Fatigue Sedation Insomnia Suicidal thoughts ```

Question 30

Alpha 2 Adrenergic Receptors

Answer 30

High presence in PFC but not NA | Adjuncts to reduce disruptive behavior and aggression and to improve sleep

Question 31

Clonidine MOA & SE

Answer 31

Alpha 2 Non-Selective Receptor Agonists | Binds also to imidazoline receptors causes sedation and hypotensive effects

Question 32

Guafacine brand, MOA

Answer 32

Intuniv Selective Alpha 2A Receptor Agonists Reduced side effect profile