Introduction to the Neuroscience of Mental Illness

Question 1

Three Main Types of Neurotransmitters:

Answer 1

Acetylcholine (ACh):
Monoamines:
Amino Acids:

Question 2

Acetylcholine (ACh):

Answer 2

• Found in CNS and PNS; important for memory, attention, and motor control.
• Deficient in conditions like Alzheimer’s and Huntington’s.

Question 3

Monoamines:

Answer 3

• Includes dopamine, serotonin, noradrenaline, and adrenaline.
• Regulate mood, arousal, cognition, motor control, and reward.
• Imbalances linked to depression, schizophrenia, anxiety.

Question 4

Amino Acids:

Answer 4

• Glutamate (excitatory): involved in learning and memory; excess causes excitotoxicity.
• GABA and glycine (inhibitory): regulate neuronal excitability.

Question 5

Cholinergic and Monoamine Synapses:

Answer 5

Neurotransmitters are synthesised, released, bind to receptors, and are then inactivated.
Inactivation mechanisms:
- Reuptake (e.g., serotonin via SSRIs)
- Enzymatic degradation (e.g., ACh by acetylcholinesterase; monoamines by MAO)
- Diffusion away from the synapse

Question 6

Pharmacological Targets in Synapses:

Answer 6

• Agonists
• Antagonists
• Reuptake inhibitors
• Enzyme inhibitors
• Allosteric modulators

Question 7

Agonists:

Answer 7

mimic neurotransmitters (e.g., dopamine agonists)

Question 8

Antagonists:

Answer 8

block receptors (e.g., antipsychotics blocking D2)

Question 9

Reuptake inhibitors:

Answer 9

increase neurotransmitter levels (e.g., SSRIs)

Question 10

Enzyme inhibitors:

Answer 10

prevent breakdown (e.g., MAOIs, anticholinesterases)

Question 11

Allosteric modulators:

Answer 11

enhance or inhibit receptor sensitivity

Question 12

Normal Ageing Changes:

Answer 12

• Minimal neuronal loss; instead, shrinkage of neurons, reduced dendritic branching, and slower synaptic transmission.
• Primarily affects hippocampus and prefrontal cortex.
• Functional effects: slower processing, naming difficulties, and mild memory decline.

Question 13

Age-Associated Cognitive Decline (AACD)

Answer 13

Mild impairments in memory or attention; awareness of deficit; preserved function.

Question 14

Dementia:

Answer 14

• Global cognitive decline (memory, language, judgement), progressive, impairs daily function.
• Not a part of normal ageing

Question 15

Types of Dementia:

Answer 15

1. Alzheimer’s disease (AD) – most common
2. Vascular dementia
3. Lewy body dementia
4. Frontotemporal dementia
5. Alcohol-related (Korsakoff’s syndrome)
6. Dementia with Parkinson’s disease

Question 16

Neuropathology of Alzheimer’s Disease:

Answer 16

• β-Amyloid plaques: extracellular deposits from faulty cleavage of APP.
• Neurofibrillary tangles: intracellular twisted Tau protein disrupting microtubules.
• Affects hippocampus, entorhinal cortex, amygdala, then frontal/parietal cortices.

Question 17

Memory and Cognitive Changes in AD:

Answer 17

• Early: short-term memory loss, reduced learning
• Middle: working memory and language issues, disorientation, mood changes
• Late: long-term memory loss, global cognitive failure
• Sundowning, restlessness, hallucinations common in advanced stages

Question 18

Cognitive Testing:

Answer 18

• Direct (explicit) tests: recall tasks (e.g., word lists, story recall)
• Indirect (implicit) tests: learning assessed through performance improvement (e.g., maze tracing)
• Mini-Mental State Exam (MMSE) and similar tools used clinically

Question 19

Treatment Approaches:

Answer 19

Pharmacological:
- Cholinesterase inhibitors (e.g., donepezil): improve
- ACh availability
NMDA receptor antagonists: prevent excitotoxicity

Non-Pharmacological:
- Cognitive stimulation and routine repetition
- Exercise programs: improve ADL function and cognition

Question 20

Emerging Theories & Risk Factors:

Answer 20

• Porphyromonas gingivalis (gum disease bacteria) and Helicobacter pylori may trigger inflammation and Tau pathology.
• Genetic: ApoE4 allele increases AD risk; rare familial AD involves mutations in presenilin 1, 2, and APP genes