Brain and Behaviour (10): Schizophrenia

Schizophrenia (SZ)

A syndrome involving losing touch from reality, affects ~1% of the population.

What are positive symptoms of schizophrenia?

Symptoms that add behaviors:

• Delusions

• Hallucinations

• Thought disorders

What are hallucinations?

Sensory experiences without actual stimuli, commonly auditory or olfactory.

What are negative symptoms of schizophrenia?

Symptoms that reduce normal behaviours:

• Flattened emotion

• poverty of speech (alogia)

• anhedonia

• social withdrawal

• lack of initiative.

What are cognitive symptoms of schizophrenia?

• Poor attention

• memory deficits

• poor problem-solving

• low psychomotor speed

• abstract thinking.

Associated with the Dorsolateral Prefrontal cortex

Which symptoms appear first and last?

Negative symptoms appear first, followed by cognitive, then positive symptoms.

What structural brain differences are found in schizophrenia?

• Enlarged ventricles

• Reduced grey matter in frontal and temporal lobes

• Hippocampal abnormalities.

Is Schizophrenia Genetic?

Yes, highly heritable but polygenic.

What is DISC1?

A gene linked to neuronal development; once thought to be a major risk factor for SZ but now disputed.

How does paternal age affect risk?

Having older fathers increase risk of SZ due to sperm mutations. (Brown et al., 2002)

What does twin research show about heritability of SZ?

Monozygotic twins show higher concordance, especially if monochorionic (shared placenta).

What is the "two-hit" model of schizophrenia?

Early brain disruption + Adolescent synaptic pruning abnormalities = schizophrenia.

What does the dopamine hypothesis propose?

• Overactive mesolimbic dopamine (DA) pathway = positive symptoms

• Underactive mesocortical dopamine (DA) pathway = negative/cognitive symptoms.

What drugs supports the dopamine hypothesis? (treatment)

• Dopamine agonists (e.g., amphetamines) induce psychosis

• Dopamine antagonists (e.g., chlorpromazine) treat symptoms.

What are typical antipsychotics?

D2 antagonists (e.g. chlorpromazine) reduce positive symptoms but cause Parkinson-like side effects and tardive dyskinesia.

What are atypical antipsychotics?

Drugs (e.g. clozapine) that treat both positive and negative symptoms with fewer motor side effects.

What is the Glutamate Hypothesis?

Schizophrenia is due to decreased NMDA receptor functioning (where glutamate binds)

Evidence for Glutamate Hypothesis

• NMDA antagonists (PCP, ketamine) mimic all schizophrenia symptoms

• Glutamate agonists help treat them.

How does NMDA dysfunction explain symptoms?

↓NMDA =

• ↑Mesolimbic Dopamine (→ positive symptoms)

• ↓Prefrontal Dopamine (→ negative/cognitive symptoms).

What role do microglia play in schizophrenia?

Overactive microglia may cause:

• Neuroinflammation

• Pruning deficits

• Altered synaptic circuitry

What environmental factors contribute to SZ?

• Prenatal infections

• Early-life inflammation

• Immune gene variants (e.g., MHC on chromosome 6).

How might estrogen protect against schizophrenia?

It has neuroprotective effects:

• Women have later onset

• Milder symptoms

• Better treatment response.

What causes schizophrenia?

A combination of:

• Genetic vulnerability

• Neurodevelopmental disruptions

• Neurotransmitter dysfunctions

• Immune involvement.