psychop 4

What is the pathophysiology of ADHD?

ADHD is associated with dysfunction in brain circuits, particularly involving the anterior cingulate cortex, dorsolateral prefrontal cortex, orbital frontal cortex, prefrontal motor cortex, and ventral striatum.

What medications are used for ADHD treatment?

• Amphetamine

• Atomoxetine

• Clonidine

• Guanfacine

• Lisdexamfetamine

• Methylphenidate

What brain areas are involved in ADHD and their function?

• Anterior Cingulate Cortex: Involved in error detection and emotional regulation

• Dorsolateral Prefrontal Cortex: Executive function, working memory, decision-making

• Orbital Frontal Cortex: Decision making, emotional regulation

• Prefrontal Motor Cortex: Motor control and planning

• Ventral Striatum: Reward processing and motivation

What neurotransmitters are involved in ADHD?

• Norepinephrine (NE): Increases incoming signals and connections between prefrontal networks via stimulation of alpha 2A receptors

• Dopamine (DA): Decreases noise and prevents inappropriate connections via stimulation of D1 receptors

What is the FDA regulation and legal ramifications for prescribing stimulants for ADHD?

Stimulants are tightly regulated, requiring careful assessment and documentation, and are subject to legal restrictions due to their potential for abuse.

What neurobiological models are associated with ADHD?

ADHD models focus on dysregulation of dopamine and norepinephrine in brain circuits involved in attention and executive function.

What brain circuit is associated with ADHD?

The cortico-striatal-thalamo-cortical (CSTC) circuit, particularly the prefrontal cortex and its connections to subcortical structures like the ventral striatum.

What is the mechanism of action of amphetamines?

Increase synaptic NE and DA by promoting release and blocking reuptake.

What is the mechanism of action of methylphenidate?

Blocks reuptake of NE and DA, increasing their levels in the synaptic cleft.

How does lisdexamfetamine work?

Prodrug converted to dextroamphetamine, which increases NE and DA release.

What is atomoxetine's mechanism of action?

Selective norepinephrine reuptake inhibitor (NRI); increases NE in the prefrontal cortex.

What is the MOA of clonidine and guanfacine?

Alpha-2A adrenergic receptor agonists; reduce sympathetic outflow and improve prefrontal regulation.

Which ADHD med’s absorption is increased with high-fat meals?

Guanfacine.

Which meds act on alpha-2A receptors?

Clonidine and guanfacine

Which medications have pregnancy risks?

Stimulants (e.g., amphetamines, methylphenidate) are generally Category C; caution advised.

What are the legal ramifications of prescribing stimulants?

Stimulants are Schedule II controlled substances; require careful documentation, compliance with state laws, and risk assessment for abuse/misuse.

What are the core neurobiological theories of ADHD?

Dysregulation of NE and DA neurotransmission in prefrontal cortex and impaired CSTC circuits.

What test is used for sustained attention?

N-back test.

What tests are used for selective attention?

Stroop test and evaluation of cingulate cortex function

What are appropriate questions to ask when evaluating ADHD?

Inquire about inattention, hyperactivity, impulsivity, symptom onset, duration, impact on functioning, school/work performance, and comorbid symptoms.

What neurotransmitter is most commonly affected in Alzheimer's disease?

Acetylcholine (deficiency leads to cognitive decline).

What are beta-amyloid plaques and neurofibrillary tangles associated with?

Alzheimer’s disease; they disrupt neuronal communication and cause cell death.

Name the brain circuit involved in dementia.

Cortical-hippocampal circuit (critical for memory and cognition).

What are the 3 stages of Alzheimer’s disease?

Mild (early), Moderate (middle), Severe (late).

Donepezil - mechanism of action?

Acetylcholinesterase inhibitor – increases acetylcholine in synapses

Donepezil - key side effects?

Nausea, diarrhea, insomnia, muscle cramps, bradycardia.

Galantamine - mechanism of action?

Acetylcholinesterase inhibitor and allosteric modulator of nicotinic receptors.

Rivastigmine - formulation option that improves compliance?

Transdermal patch.

Memantine - mechanism of action?

NMDA receptor antagonist – regulates glutamate to prevent excitotoxicity.

Which dementia medications are typically used in moderate to severe stages?

Memantine and Donepezil.

Alzheimer’s vs. Lewy Body Dementia - key distinguishing feature?

Lewy Body Dementia often includes visual hallucinations and Parkinsonism.

Frontotemporal dementia - major symptom presentation?

Early changes in personality, behavior, and language.

Huntington’s Disease - inheritance pattern and main symptoms?

Autosomal dominant; chorea, psychiatric symptoms, and cognitive decline.

What labs should be monitored with acetylcholinesterase inhibitors?

Heart rate (bradycardia risk), weight (GI side effects), liver enzymes (if indicated).

How are behavioral and psychiatric symptoms of dementia managed?

Non-pharmacologic strategies first (environmental adjustments), then cautious use of psychotropics if needed

What part of the brain is crucial for evaluating the relative appeal of a reward?

The orbitofrontal cortex (part of the prefrontal cortex).

What is the central structure of the brain's reward system?

The mesolimbic dopamine system, including the ventral tegmental area (VTA) and nucleus accumbens (NAc).

Which neurotransmitter primarily modulates the reward system?

Dopamine (DA).

What is the role of dopamine in pleasure?

Dopamine is associated with wanting (motivation and craving), not necessarily liking (pleasure).

Which neurotransmitter system is most responsible for the sensation of pleasure or "liking"?

The opioid system, particularly μ-opioid receptors.

What is the term for decreased responsiveness to repeated pleasurable stimuli?

Habituation.

What brain area is essential for remembering emotional associations and conditioning?

The amygdala.

How do dominant monkeys differ from subordinates in dopamine D2 receptor levels?

Dominant monkeys have higher D2 receptor levels and self-administer less cocaine.

What causes anhedonia in depression according to the chapter?

A deficit in motivation and energy, not a lack of capacity to experience pleasure.

What are the three major causes of relapse in addiction?

1) Drug re-exposure, 2) Cues associated with use, and 3) Stress.

What transcription factor is associated with tolerance and withdrawal in addiction?

CREB (cyclic AMP response element-binding protein).

What long-lasting transcription factor may explain persistent relapse risk?

Δ-FosB.

How does adolescence affect risk-taking behavior in the brain?

Increased NAc activation (approach) and decreased amygdala inhibition (restraint).

What are two categories of pharmacologic treatments for addiction?

1) Blocking reinforcement (e.g., naltrexone) and 2) Substitution (e.g., methadone).

What is a concern about long-term stimulant use (e.g., methylphenidate) in ADHD?

Potential neurotoxicity and changes in dendritic structure or brain development, especially in youth.

What does attention involve in the brain?

Selecting and focusing on relevant stimuli while ignoring others due to limited cognitive capacity.

What is measured by Continuous Performance Tests (CPTs)?

Attention and impulsivity.

Which brain region is central to working memory?

The prefrontal cortex (PFC).

What is the delayed-response task used to assess in monkeys?

Working memory retention during a delay period.

Which neurotransmitters modulate working memory?

Dopamine (DA) and norepinephrine (NE).

What effect does stimulating the vagus nerve have?

It increases NE release and can enhance learning and attention.

What is the goal of neurofeedback in ADHD treatment?

Increase beta waves and reduce theta/alpha waves to improve focus.

What area of the brain is associated with impulse control and delay of gratification?

The nucleus accumbens (NAc).

What is a major finding from the Stanford marshmallow study?

Children who delayed gratification had better adolescent outcomes and SAT scores.

What happens to dopamine transporter density with age?

It decreases, which correlates with improved impulse control.

What brain changes are commonly seen in ADHD?

Smaller brain volume, thinner PFC gray matter, and smaller cerebellum.

What compensatory brain change is seen in ADHD children who improve over time?

Normalization of gray matter thickness in the right parietal cortex.

What is neglect syndrome and which brain area is involved?

It is ignoring one side of space/body, often due to right parietal cortex damage.

What role does the cerebellum play in ADHD?

It is involved in timing and motor coordination; smaller volume is linked to ADHD.

What are potential long-term concerns with stimulant use?

Possible effects on cortical thinning and future Parkinson's risk; more studies needed

What are the three hallmark findings of Alzheimer’s disease observed by Alois Alzheimer?

Cortical atrophy, extracellular amyloid plaques, and intracellular neurofibrillary tangles.

What is the primary component of amyloid plaques in Alzheimer’s disease?

Amyloid-beta (Aβ), particularly Aβ-42.

What protein is cleaved to form amyloid-beta?

Amyloid-beta precursor protein (APP).

What enzymes are involved in generating amyloid-beta?

β-secretase and γ-secretase.

What is the proposed role of α-secretase in Alzheimer’s prevention?

It cleaves APP in a way that prevents amyloid-beta formation.

What causes neurofibrillary tangles?

Hyperphosphorylation of tau proteins, leading to their detachment and aggregation.

Where does Alzheimer’s pathology begin in the brain?

The entorhinal cortex of the hippocampus.

What imaging agent is FDA-approved to detect amyloid in the brain?

Florbetapir F18 (Amyvid) for PET scans.

What does increased tau protein in cerebrospinal fluid (CSF) indicate?

Neuronal damage associated with Alzheimer’s disease.

What is the amyloid hypothesis of Alzheimer’s disease?

The accumulation of toxic amyloid-beta is the primary cause of neurodegeneration.

What monoclonal antibody showed promising results in clearing amyloid and slowing cognitive decline?

Aducanumab.

What complication may arise from high doses of aducanumab?

Amyloid-related imaging abnormalities (ARIA) such as cerebral edema or microhemorrhages.

What experimental treatment involves inserting NGF-expressing fibroblasts into the brain?

Nerve growth factor (NGF) gene therapy.

What is the significance of the Nun Study in Alzheimer’s research?

It showed early-life linguistic ability predicted later-life cognitive resilience despite AD pathology.

How does caloric restriction affect Alzheimer’s pathology in animal studies?

It increases α-secretase activity and reduces amyloid-beta accumulation.

What are the 9 modifiable dementia risk factors identified by the Lancet Commission?

Less education, hypertension, obesity, hearing loss, smoking, depression, physical inactivity, social isolation, and diabetes.

What was the result of giving red wine (Cabernet Sauvignon) to Alzheimer’s mice?

Reduced cortical amyloid-beta and improved memory.