Schizophrenia and Sex Hormones

Question 1

Define psychosis

Answer 1

Impaired relationship with reality

Question 2

Difference between schizophrenia features in M and F

Answer 2

Men:

• earlier onset
• worse symptoms
• more negative symptoms
• poorer prognosis

Question 3

Pathology of schizophrenia brain on MRI

Answer 3

• decreased brain volume

- decreased hippocampus, amygdala, parahippocampal gyrus size

Question 4

Pathology of schizophrenia on PET?

Answer 4

Decreased activation of frontal lobe

Increased activation of temporal lobe

Question 5

Overview of molecular hypotheses implicated in schizophrenia?

Answer 5

• DA hypothesis
• serotonin hypothesis
• excitatory amino acid hypothesis
• phospholipid membrane hypothesis

Question 6

Overview of DA hypothesis w/ experimental evidence?

Answer 6

Increased DA -> +ve symptoms; Decreased DA in mesocort-> negative symptoms

(E) Amphetamine + Levopa -> increased DA -> +ve symptoms in non-schizos

(E) D2-R antag are effective antipsychotics

Question 7

Overview of serotonin hypothesis w/ experimental evidence

Answer 7

increased serotonin -> increased psychotic symptoms

(E) 5HT-R agonists (psilocybin) -> +ve symptoms in non-schizos

(E) 5HT-R antagonists -> decreased psychotic symptoms

Question 8

Overview of excitatory amino acid hypothesis w/ experimental evidence

Answer 8

decreased EAAs/receptors -> schizophrenia

(E) Schizos have decreased CSF glutamate & decreased glutamate-receptors in temporal lobe

(E) NMDA-R antagonist -> +ve and -ve symptoms in non-schizos

Question 9

Overview of phospholipid membrane hypothesis

Answer 9

Abnormalities in phospholipid metabolism -> schizophrenia

Question 10

Prognosis of schizophrenia?

Answer 10

1/3 rule:

1/3 good outcomes
1/3 longer & repeated episodes
1/3 chronic treatment resistance

Question 11

List potential mechanisms behind sex differences in schizophrenia?

Answer 11

• higher incidence of birth injuries in boys
• buffer of early marriage in females (early marriage in F makes it more likely to have strong social relationships)
• sexually dimorphic brain anatomy (testosterone differenitates male characteristics)
• differential effects of androgens and oestrogens

Question 12

Potential relationships between oestrogen and schizophrenia

Answer 12

ACTIVATIONAL EFFECT (reversible)

• oestrogen may be protective against psychosis (increased evidence after menopause, decreased during pregnancy, inreased post partum)
• oestrogen antagonises DA-R (decreased positive symptoms (short term)
• oestrogen’s biphasic effect
• oest maybe up/downreg DA-R
• oestrogen KO in male mice -> apoptosis of hypothal DA neurons
• variants of oest-R alpha genes and mRNA (ESR1 variant -> increased psychosis)

Question 13

Describe the role of testosterone in organisation

Answer 13

ORGANISATIONAL EFFECT

In males, increased testosterone to masculinise hypothalamus (not in F)

Testosterone modulates pre-frontal cortex and amygdala -> organisational effects

Question 14

Role of pre-pulse interval (PPI) in schizophrenia?

Answer 14

Schizos have disrupted PPI response so same startle response to both afforementioned stimuli

Testosterone promotes disruption of PPI

Oestrogen protects against PPI disruption

Question 15

Brief overview of organisational vs activational effects upon schizophrenia

Answer 15

[activational is reversible]

Oestrogen exerts activational effects

Testosterone exerts organisational effects

Oest and test have activational effects on pre-pulse inhibition (PPI)