Neurodevelopmental models

Question 1

Define a neurodevelopmental model of psychiatric disorder.

Answer 1

A neurodevelopmental model proposes that: • Abnormal brain development occurs early in life • Neural circuits form atypically • Symptoms emerge later when those circuits mature or are stressed Key phrase for exam: “Abnormal developmental trajectory of neural circuits.”

Question 2

What does “”abnormal developmental trajectory”” mean?

Answer 2

Brain development is dynamic and staged. If early deviation occurs: Later maturation stages amplify the abnormality. Symptoms emerge when: • Cognitive demands increase • Circuits fail under stress

Question 3

What are the 6 stages of normal brain development?

Answer 3

1️⃣ Neurogenesis 2️⃣ Neuronal migration 3️⃣ Differentiation 4️⃣ Synaptogenesis 5️⃣ Synaptic pruning 6️⃣ Myelination Memory chain: Make → Move → Specialise → Connect → Refine → Insulate

Question 4

Neurogenesis — what, where, when?

Answer 4

Definition: Production of neurons from neural progenitor cells. Occurs: • Mainly 2nd trimester • Ventricular zone Adult neurogenesis: • Limited to hippocampus Disruption → reduced neuronal numbers.

Question 5

Neuronal Migration — mechanism & relevance

Answer 5

Neurons move from ventricular zone to cortex. Mechanism
* Radial glial scaffolding Timing:
Prenatal If abnormal:
* Cortical disorganisation
* Subtle microstructural abnormalities Linked to schizophrenia vulnerability.

Question 6

Synaptogenesis — key features

Answer 6

Mass formation of synapses. Peaks: • Infancy • Early childhood Brain initially overproduces synapses. This creates temporary hyperconnectivity.

Question 7

Synaptic Pruning — mechanism & importance

Answer 7

Removal of weaker synapses. Mechanism: • Microglia • Complement proteins (C4) Occurs: • Childhood • Major wave in adolescence • Especially prefrontal cortex Too much pruning → reduced connectivity (schizophrenia theory) Too little pruning → excess connectivity (autism theory)

Question 8

Myelination — timeline & psychiatric relevance

Answer 8

Myelin insulates axons → increases conduction speed. Timeline: • Begins prenatally • Continues to mid-20s Prefrontal cortex last to mature. Explains: • Adolescent impulsivity • Late psychosis onset

Question 9

What is a critical period?

Answer 9

A developmental window when brain circuits are especially sensitive to environmental input. Insults during these windows have lasting effects.

Question 10

Prenatal vulnerability — what can go wrong?

Answer 10

Processes active: • Neurogenesis • Migration Risks: • Maternal infection • Hypoxia • Malnutrition • Stress Outcome: Subtle structural abnormalities.

Question 11

Why is adolescence a second major vulnerability window?

Answer 11

Adolescence involves: • Massive synaptic pruning • Dopamine system reorganisation • Prefrontal cortex maturation • Increased stress reactivity Latent abnormalities become clinically visible. Peak onset: • Schizophrenia • Bipolar disorder • Depression

Question 12

What does G × E mean?

Answer 12

The effect of environment depends on genotype. Genetic vulnerability + environmental exposure → amplified risk. Not additive — interactive.

Question 13

What is epigenetics?

Answer 13

Change in gene expression without altering DNA sequence. Mechanisms: • DNA methylation • Histone modification Early stress alters stress-response genes.

Question 14

What is heritability (exam trap)?

Answer 14

Proportion of population variance due to genetics. NOT: • Individual destiny • Percentage genetic cause Schizophrenia heritability ≈ 70–80%.

Question 15

What is the two-hit model?

Answer 15

First hit: Early developmental abnormality. Second hit: Later stressor (e.g. cannabis, trauma). Symptoms emerge when compensatory capacity fails.

Question 16

What is the multiple-hit model?

Answer 16

Accumulation of risk across life: • Polygenic risk • Prenatal insult • Childhood adversity • Adolescent stress • Substance exposure Illness results from cumulative burden.

Question 17

What are microglia?

Answer 17

Resident immune cells of the brain. Functions: • Remove debris • Remove synapses during pruning Overactive microglia → excessive pruning.

Question 18

What is the complement C4 hypothesis?

Answer 18

C4 gene overexpression → increased synapse tagging. Microglia remove more synapses. Result: Reduced cortical connectivity in schizophrenia.

Question 19

What are parvalbumin interneurons?

Answer 19

Fast-spiking GABA inhibitory neurons. Located in: • Prefrontal cortex • Hippocampus Function: • Synchronise pyramidal neurons • Generate gamma oscillations • Support working memory Reduced function in schizophrenia.

Question 20

What happens to dopamine in adolescence?

Answer 20

• Dopamine receptor density peaks • Mesolimbic pathway becomes highly reactive • Mesocortical pathway still maturing Creates vulnerability window.

Question 21

Mesolimbic vs Mesocortical dysfunction?

Answer 21

Mesolimbic hyperactivity → positive symptoms Mesocortical hypoactivity → negative & cognitive symptoms

Question 22

What is abnormal salience?

Answer 22

Dysregulated dopamine assigns importance to neutral stimuli. Leads to delusions.

Question 23

What is the HPA axis?

Answer 23

Hypothalamic–pituitary–adrenal stress system. Produces cortisol.

Question 24

How does stress increase psychosis risk?

Answer 24

Cortisol sensitises mesolimbic dopamine. Repeated stress → dopamine hyperreactivity.

Question 25

**Why is schizophrenia neurodevelopmental?**

Answer 25

• Obstetric risk • Early structural abnormalities • Excessive pruning • Dopamine maturation • Late adolescent onset

Question 26

**Autism — developmental abnormality?**

Answer 26

• Early brain overgrowth • Abnormal connectivity • Early onset

Question 27

**ADHD — developmental abnormality?**

Answer 27

• Delayed cortical maturation • Fronto-striatal dysfunction

Question 28

**Neurodevelopmental vs Neurodegenerative**

Answer 28

Neurodevelopmental: Abnormal early wiring. Neurodegenerative: Progressive neuronal loss. Schizophrenia = primarily developmental.

Question 29

**Q: Define a **neurodevelopmental model** of **psychiatric disorder**.**

Answer 29

**A:** * Abnormal brain development occurs early in life * Neural circuits form atypically * Symptoms emerge later when those circuits mature or are stressed * Key phrase for exam: “Abnormal developmental trajectory of neural circuits.”

Question 30

**Q: What does “”abnormal developmental trajectory”” mean?**

Answer 30

**A:** * Brain development is dynamic and staged. * If early deviation occurs: Later maturation stages amplify the abnormality. * Symptoms emerge when: * Cognitive demands increase * Circuits fail under stress

Question 31

**Q: What are the 6 stages of normal brain development?**

Answer 31

**A:** * 1️⃣ **Neurogenesis** * 2️⃣ **Neuronal migration** * 3️⃣ **Differentiation** * 4️⃣ **Synaptogenesis** * 5️⃣ **Synaptic pruning** * 6️⃣ **Myelination** * Memory chain: Make → Move → Specialise → Connect → Refine → Insulate

Question 32

**Q: Neurogenesis — what, where, when?**

Answer 32

**A:** * Definition: Production of neurons from neural progenitor cells. * Occurs: * Mainly 2nd trimester * Ventricular zone * Adult neurogenesis: * Limited to hippocampus * Disruption → reduced neuronal numbers.

Question 33

**Q: Neuronal Migration — mechanism & relevance**

Answer 33

**A:** * Neurons move from ventricular zone to cortex. * Mechanism: * Radial glial scaffolding * Timing: * Prenatal * If abnormal: * Cortical disorganisation * Subtle microstructural abnormalities * Linked to schizophrenia vulnerability.

Question 34

**Q: Synaptogenesis — key features**

Answer 34

**A:** * Mass formation of synapses. * Peaks: * Infancy * Early childhood * Brain initially overproduces synapses. * This creates temporary hyperconnectivity.

Question 35

**Q: Synaptic Pruning — mechanism & importance**

Answer 35

**A:** * Removal of weaker synapses. * Mechanism: * Microglia * Complement proteins (**C4**) * Occurs: * Childhood * Major wave in adolescence * Especially prefrontal cortex * Too much pruning → reduced connectivity (schizophrenia theory) * Too little pruning → excess connectivity (autism theory)

Question 36

**Q: Myelination — timeline & psychiatric relevance**

Answer 36

**A:** * Myelin insulates axons → increases conduction speed. * Timeline: * Begins prenatally * Continues to mid-20s * Prefrontal cortex last to mature. * Explains: * Adolescent impulsivity * Late psychosis onset

Question 37

**Q: What is a critical period?**

Answer 37

**A:** * A developmental window when brain circuits are especially sensitive to environmental input. * Insults during these windows have lasting effects.

Question 38

**Q: Prenatal vulnerability — what can go wrong?**

Answer 38

**A:** * Processes active: * **Neurogenesis** * **Migration** * Risks: * Maternal infection * Hypoxia * Malnutrition * Stress * Outcome: Subtle structural abnormalities.

Question 39

**Q: Why is adolescence a second major vulnerability window?**

Answer 39

**A:** * Adolescence involves: * Massive synaptic pruning * Dopamine system reorganisation * Prefrontal cortex maturation * Increased stress reactivity * Latent abnormalities become clinically visible. * Peak onset: * Schizophrenia * Bipolar disorder * Depression

Question 40

**Q: What does G × E mean?**

Answer 40

"**A:** * The effect of environment depends on genotype. * Genetic vulnerabilit