ADHD Flashcards

1
Q

DSM diagnosis

A

more than 6 of the listed symptoms of inattention or hyperactivity/impulsivity for more than 6 months before the age of 12.

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2
Q

Genetic causes

A

Highly heritable
70-90% heritability in twins. 5x increase risk in first degree relatives.

There is no one gene that causes ADHD, but there are multiple gene variants that are slightly associated - maybe each gene plays a part in the different phenotypic traits of ADHD, multifactorial.

D4 mutation may result in reduced cAMP response.

DAT1 mutation may affect DAT expression in striatum.

Cytokine polymorphism in ADHD may lead to heightened neuroinflammation.

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3
Q

Environmental causes

A

Neonatal hypoxia
maternal smoking and drinking
premature birth

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4
Q

Neurobiology

A

DA hyperactivity

smaller and less active fronto-striatal complex
reduced striatal metabolism
hyperactivity of the sensory cortex

Smaller brain (4%) particularly right lobe (8%). smaller basal ganglia and cerebellum.

High co-morbidity with other disease, particularly anxiety and oppositiaonal defiant disorder.

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5
Q

Glutamate receptor mutations and ADHD, and effect of the hyperactivity of DA

A

High interaction between glutamate and DA. Lots of overlap where they both innervate.

Glutamine produced in Glial cells from glutamate (from Krebs and reuptake by EEAT), and transported to the presynaptic neurone, where it is converted into glutamate by glutaminase.

Mutations in NMDARs: GluN2A and GluN2B have been associated with ADHD.
mutation in kianate receptor GluK2 also associated with hyperactivity syndromes.

mutations in mGluR5 and mGluR7 are also associated with hyperactive-impulsive symptoms.

Striatal glutamate release facilitates DA release by acting on the NMDARs.

hyperactivity of DA signalling is expected to increase NMDARs and AMPARs, subsequently increasing glutamate output.

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6
Q

Pharmacological management

A

Methylphenidate - DAT and NAT inhibitors
amphetamines: DAT inhibitor (TAAR1 mediated) and VMAT2 inhibitor
Atomoxetine and TCAs - NAT inhibitors
clonidine - a2 agonist
memantine
fasoracetam - mGluR activator

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