Dysfunction

Question 1

All psychotic disorders are characterized by at least one of the follow symptoms

Answer 1

1. Delusions
2. Hallucinations
3. Disorganized thinking
4. Negative symptoms

Question 2

Schizophrenia symptoms

Answer 2

1. Positive symptoms: delusions and hallucinations
2. Negative symptoms: anhedonia, asociality, lack of motivation
3. Cognitive impairments: problems with memory, processing speed, and attention

Question 3

The course of schizophrenia

Answer 3

Schizophrenia symptoms don’t appear until adolescence. At the onset, these symptoms are attenuated. Typically, at 25, the disorder begins to progress towards full-blown schizophrenia. The chronic/residual stage tends to occur after 35.

Question 4

Dopamine hypothesis

Answer 4

The positive symptoms of schizophrenia are caused by excessive activity in dopaminergic brain regions

Question 5

Which part of the brain is implicated in schizophrenia?

Answer 5

the VTA

Question 6

Anti-psychotic drugs for schizophrenia

Answer 6

Haloperidol: dopamine antagonist
Risperidone: dopamine antagonist that also blocks seretonin receptors to prevent Parkinsonian symptoms
Clozapine: the most effective anti-psychotic

Question 7

Medication for OCD

Answer 7

SSRIs or clomipramine

Question 8

Autism spectrum disorders

Answer 8

A group of neurodevelopmental disabilities that cause social, behavioral, and communicational impairments

Question 9

Medications to treat ASD

Answer 9

rizperidone and aripiprazole

Question 10

Which brain regions are implicated in the social impairments associated with ASD?

Answer 10

amygdala, frontotemporal, and frontoparietal regions

Question 11

Which brain regions are implicated in the behavioral impairments associated with ASD?

Answer 11

basal ganglia and thalamus

Question 12

Which brain regions are implicated in the communicaion impairments associated with ASD?

Answer 12

basal ganglia, thalamus, cerebellum, and motor area

Question 13

Compare the developing brains of children with ASD and controls

Answer 13

The brains of children with ASD have larger volume compared to controls, suggesting a divergent developmental trajectory

Question 14

Describe dendritic spine pathology in ASD

Answer 14

The brains of people with ASD contain excessive dendritic spines suggesting overgrowth or lack of pruning

Question 15

FMRP role

Answer 15

Binds to RNA, shuttles between nucleus and cytoplasam. Involved in the transport of mRNA to synapses and its translation to proteins. Involved in RNA interference, helps with non-coding certain RNA.

Question 16

What happens in the absence of FMRP?

Answer 16

FMRP regulates proteins that stablize and mature developing synapses

Question 17

Hyperexcitability in FXS

Answer 17

FXS is associated with hyper-excitability and an imblance of excitation and inhibition. In the absence of FMRP, ion channels are dysregulated. This can alter the duration and peak of action potentials which affects the duration and amplitude of calcium influx through voltage gated calcium channels. As a result, more or less neurotransmitters are released

Question 18

Non-neuronal effects of neurodevelopmental disorders

Answer 18

1. Altered NSC proliferation, fate specification, and maintenance
2. Altered astrocyte-neuron interactions
3. Impaired white matter development and myelination
4. stunted dendritic morphogenesis and axon targetting -> reduced synaptogenesis and altered circuit integration

Question 19

How are neurodegenerative disorders differentiated

Answer 19

Where the degeneration starts in the brain

Question 20

What are catastrophic cliffs

Answer 20

Our ability to handle deviations from the norm decreases as we age, and this leads to the progressive loss of neurons

Question 21

Common pathological hallmarks of neurodegenerative disorders

Answer 21

Protein misfold -> aggregation -> cell death

Question 22

Common pathways altered in neurodegenerative disorders

Answer 22

1. Protein quality control
2. Autophagy-lysosome pathway
3. Mitochondria homeostasis
4. Protein seeding
5. Stress granules protect aggregates from being degraded

Question 23

Parkinson’s disease

Answer 23

Degeneration of dopaminergic neurons in the substantia nigra and their projections to the striatum

Question 24

Pathophysiology of α-synuclein in Parkinson’s Disease

Answer 24

Monomers form unstable dimers. These dimers then form oligomers of varying morphologies. These oligomers can penetrate the membrane, making it more “leaky”. This facilitates a seeding effect. Oligomers can also form reactive fibrels that aggregate into lewy bodies.

Question 25

Levodopa therapeutic window

Answer 25

There’s a short window before levodopa dosage is high enough to be effective and low enough to not cause diskinesia.

Question 26

Alzheimer’s Disease Progression (Healthy)

Answer 26

Signs of AD entorhinal cortex -> hippocampus. Memory loss is the first symptom. Progression begins 10-20 years before onset of symptoms. Cortical shrinkage as nerve cells die.

Question 27

Alzheimer’s Disease Progression (Mild)

Answer 27

Cortical shrinkage as disease spreads through the brain. motor abilities remain, but judgement is dampened which leads to dangerous situaitons

Question 28

Alzheimer’s Disease Progression (Advanced)

Answer 28

Extreme cortical shrinkage. patients become totally dependent. Die from aspiration neumonia

Question 29

Role of APP and β-amyloid

Answer 29

mutations in APP cause prefrential cleavage by beta-secretase. This results in soluble beta amyloid protein which can accrete with like proteins to form insoluble oligomers. Mutations in presenilin-1 and presenilin-2 cause prefrential cleavage by y-secratase.

Question 30

β-amyloid Mechanisms of Action

Answer 30

beta amyloid proteins can form oligomers. Oligomers can accrete to form fibrels which can form plaques. Beta-amyloid fibrils can cause a local inflammatory response. By some unknown mechanism, beta-amyloiid proteins cause an increase of hyperphosphorylized tau.

Question 31

Phosphorylated Tau and Neurofibrillary Tangles

Answer 31

Hyperphosphorylated tau proteins and MAPs which destabilizes existing microtubules and blocks the formation of new ones This prevents axonal transport, causing synaptic death.