ADHD Flashcards
Learn the basics of ADHD
Describe the symptoms of ADHD?
Developmentally inappropriate levels of
- Inattentiveness
- Impulsivity
- Hyperactiviy
What factors must exist to be diagnosed?
Diagnosed in childhood:
- Persistent for six months
- Be present before age 7
- Functional impairment: executive function deficit most characteristic.
What is hyperactivity?
Excessive fidgetiness or talking
- Peak at age 8 and then decline.
What is impulsivity?
Difficulty taking turns; blurt out answers
- Peaks at age 8, but does not decline.
What is inattention?
Forgetfulness, distractibility
- Does not appear until age 8 or 9.
Describe the prevalence.
Estimates range from 2-18%
- Most estimates are 5-10% in school age children.
- Roughly 4x more common in boys (may reflect referral bias)
- 30-70% of individuals continue to show symptoms into adulthood
- Adult prevalence ~4%
Explain ADHD with other disorders.
Often comorbid with other disorders
- ODD, CD, Anxiety, Depression, Learning disabilities
- Primary deficit appears to be dysregulation of NE and DA in prefrontal cortex.
- ~70% of children successfully treated with pharmacotherapy.
Describe the relevance of environmental factors.
Diet: food additives, refined sugars, food sensitivity, deficiency in fatty acids, Fe/Zn deficiency.
- premature birth/low birth weight
- prenatal alcohol exposure
- head trauma
Describe Adult ADHD.
Disinhibition characteristic - Poor self-regulation - Poor goal-directed behavior - Appear disorganized and hectic. Some people have late-onset - Suggestion to remove diagnostic creteria of beofre age 7.
Explain the genetic significance of ADHD.
Monozygotic concordance: 92% Dizygotic convergence: 33% Implicate genes: DRD1, Drd2, DRD4, DRD5 - 5-TH transporter gene - 5-HT 1B receptor - SNAP 25 - Metabotropic glutamate receptor (GRM5), - Increased number of CNA's (15 vs 7%)
What are the differences in noradernergic system?
Modulates cortical functipns:- attention, alertness, vigilance, executiee
- Imbalance between NE and DA results in pathology.
- Small changes can have large impact on PFC function.
The effects of Norepinephrine.
Increases the signal strengthens connectivity of input to cells.
- acts on alpha2A receptors on dendritic spines.
- antagonize alpha2A receptors to miimic ADHD.
- Agonize alpha 2A rectors to improve function.
- High levels impair PFC function.
The effects of Dopamine.
- Acts on D1 receptors
- Weaken irrelevant inputs to cells.
- Transporter density increased in patients
- High levels weaken too many connections and inhibit firing.
Describe the effects of too little NA and DA.
The PFC abilities drops (distracted, disorganized, forgetful, and impulsive) and the levels of catecholamine release involved in the arousal state is low (fatigued).
- LOW pfc abilities and FATIGUED
Describe the effects of NA alpha1, beta1, and excessive D1.
Person is: STRESSED and has LOW PFC abilities.
Describe the effects of NA alpha2A and moderate D1.
Person is: ALERT and has HIGH PFC abilities (Focused, Organized, and Responsible)
Children who are ambidextrous were:
Twice as likely to have some form of ADHD.
Tie in socioeconomic status into ADHD prevalence.
Children that had parents with LOWER education and welfare had higher chances of having ADHD.
- Divorce rates also increase.
What is SNAP-25?
Protein: Synaptosomal associated protein
Gene: gene of interest encodes a protein component that interacts with syntaxin and VAMP to form SNARE complex.
Why is SNAP-25 important?
SNARE complex holds vesicles at the presynaptic membrane to regulate neurotransmitter exocytosis.
- SNAP-25 promotes axonal growth, dendritic spine formation and synaptic plasticity.
EG. reduction of SNAP-25 expression => morphologically immature dendritic spines
Describe SNAP-25 gene application.
The Model for ADHD: Coloboma mouse w/ a deletion in SNAP-25
What is observed:
- increased norepinephrine in striatum and nucleus accumbens
- Increasing copies of risk haplotype reduces SNAP-25 expression
Explain the trends in ADHD brain morphology.
Overall decreased brain volume - Caudate nucleus - Prefrontal cortex (white matter) - Corpus callosum - Cerebellar vermis By late adolescence these differences tend to disappear
SNAP-25 gene study.
The Study:
- Dense SNP mapping across SNAP-25 gene in families with and without ADHD
- PCR of SNAP-25 transcripts in inferior frontal gyrus
What they found:
- increased AAC (risk haplotype) => decreased expression of SNAP-25 in IFG tissue
- increased GTC (protective haplotype) => increased expression of SNAP-25 in IFG tissues
What is involved in the Dopaminergic systems?
VTA, striatum, PFC
DAT1, dopamine receptors (esp. D2, D3, D4)
What is involved in the Noradrenergic system?
DLPFC, locus coeruleus
- Some evidence for serotoninergic and cholinergic systems.
What are some other observed abnormalities?
Cortical thinning Alterations in structural connectivity Parietal/temporal lobes PFC and striatum Alterations in functional connectivity Asymmetry in caudate Decreased blood flow to putamen Aberrant and/or delayed cortical development Hypoactivation of networks related to executive function, cognition, emotion, sensorimotor functions.
Explain the Dopamine-Transfer Deficit (DTD) Theory.
Plasticity in DA cells during learning suggest that behavioral reinforcers can gradually be transferred to previously neutral cues that predict eventual reward
- In normal children, positive reinforcement is gradually transferred to predictors of reward
Leads to continuous anticipatory DA signaling
- In ADHD children this transfer is disrupted
In absence of continuous behavior reinforcement, the DA anticipatory signaling is weak or absent
What is sustained attention?
The ability to maintain goal-directed focus in the absence of exogenous or external cues.
- reciprocal interaction between cortical and subcortical areas
- triggers locus coeruleus to release norepinephrine in the cortex
- right hemisphere dominant
What is the temporal explanation?
ADHD symptoms result of impaired timing functions
- inferior and orsolateral PFC, cerebellum, and parietal lobe implicated
What is the default mode network (DMN) explanation?
ADHD symptoms result from intrusion of DMN activity during cognitive tasks.
- Ventromedial PFC, posterior cingulate gyrus, and lateral parietal cortex implicated
How has the DSM V changed?
Examples added to show symptoms are various ages/developmental periods.
- Comorbid diagnosis with autism is allowed
- Cross situational requirement increased
- Onset criteria change
What is TOVA?
Test of Variables of Attention
- Can be used in combination with other interviews and psychological evaluations to diagnose ADHD.
- Could identify non-hyperactive ADHD 84% of the time and hyperactive ADHD 90% of the time.
What is NEBA?
The NEBA system is a brain can test approved by FDA to diagnose ADHD.
- Involves non-invasive EEG recording
- Measures the ratio between theta and beta waves.
- Significantly higher ratio in those with ADHD.
What are some behavioral therapies?
Limiting distractions
Sports
Positive reinforcement
What are the stimulants of Pharmacotherapy?
Methylphenidate (Ritalin) Amphetamines - Adderall - Dextroamphetamine - Vyvanse
What are non-stimulants of Pharmacotherapy?
Norepinephrine
- Reuptake inhibitors
- Alpha-2-adrenergic agonists
- Antidepressants
What do amphetamines do?
First used as a therapy for child behavior disorders in 1937.
- Increase synaptic dopamine levels
- Very similar structure to DA
- May cross plasma membrane
