Sex Hormones and Schizophrenia

Question 1

Define schizophrenia

Answer 1

A severe psychotic mental illness characterised by delusions, auditory hallucinations, thought disorder, odd behaviour, and progressive deterioration in personal, domestic, social, and occupational competence, all occurring in clear consciousness

Question 2

Define hallucination

Answer 2

A perception in the absence of a stimulus

Question 3

Define delusion

Answer 3

A fixed belief held firmly by an individual despite no rational evidence or evidence to the contrary, and which may not be in keeping with socio-cultural background

Question 4

What is the lifetime prevalence of schizophrenia?

Answer 4

1%

Question 5

In which social groups is schizophrenia prevalence higher?

Answer 5

Urban areas, lower socio-economic classes, recent immigrants, prison populations

Question 6

Describe the differences in schizophrenia in males and females

Answer 6

In males, onset is typically earlier (peak age of onset 10-25), with negative symptom impairment more likely and general outcome worse. In females, onset is typically later (25-35 then middle age, bimodal distribution) with negative symptom impairment less likely and general outcome better

Question 7

In which population group is a paranoid presentation more common?

Answer 7

Young males

Question 8

In which population group is a hebephrenic presentation more common?

Answer 8

Young people aged 16-25

Question 9

Describe the ‘rule of thirds’ with schizophrenia

Answer 9

1/3 of patients suffer acute episodes but can lead a normal life in between without medication, 1/3 do not fully recover but their disease can be controlled with medication, and 1/3 are treatment resistant

Question 10

Describe the pathology of schizophrenia

Answer 10

Decreased brain weight and volume, atrophy of the hippocampus, amygdala, and parahippocampal gyrus, enlaregd lateral and 3rd ventricles, reduced cortical grey matter

Question 11

Describe the differences between schizophrenic and healthy brains on PET scans

Answer 11

Schizophrenics have decreased frontal lobe activation and increased temporal lobe activation

Question 12

Describe the dopamine hypothesis of schizophrenia

Answer 12

The positive symptoms of schizophrenia are due to excess dopaminergic activity

Question 13

Give some evidence for the dopamine hypothesis of schizophrenia

Answer 13

1) Amphetamines and levodopa cause positive symptoms in non-schizophrenics
2) All effective antipsychotics are D2 receptor antagonists

Question 14

Describe the serotonin hypothesis of schizophrenia

Answer 14

Schizophrenia is due to excess serotoninergic activity

Question 15

Give some evidence for the serotonin hypothesis of schizophrenia

Answer 15

1) LSD and psilocybin (5-HT receptor agonists) cause positive symptoms in non-schizophrenics
2) Newer antipsychotics are potent 5HT receptor antagonists

Question 16

Describe the excitatory amino acid hypothesis of schizophrenia

Answer 16

Schizophrenia is caused by insufficient excitatory amino acids or their receptors

Question 17

Give some evidence for the excitatory amino acid hypothesis of schizophrenia

Answer 17

1) Schizophrenic patients have low CSF glutamate and decreased glutamate receptors in their temporal lobes
2) A single dose of PDP (NMDA receptor antagonist) causes both positive and negative symptoms in non-schizophrenics

Question 18

State some possible explanations for the sex differences in schizophrenia

Answer 18

Sexually dimorphic brain anatomy, disproportionately high incidence of birth injury in males, differential effects of androgens and oestrogens

Question 19

State some evidence for oestrogen being protective against psychosis

Answer 19

Psychosis is less common in women, psychosis incidence is reduced during pregnancy then increased post-partum, risk is increased after menopause

Question 20

How might oestrogen protect against psychosis? (Lindemar)

Answer 20

It may have a neuroleptic-like effect on the dopaminergic system and antagonise dopamine receptors. (Lindemar found this was beneficial in the short-term but potentially increased symptom incidence long-term)

Question 21

Describe the effect of aromatase deficiency on mice

Answer 21

They develop apoptosis of their hypothalamic dopaminergic neurons

Question 22

Define pre-pulse inhibition

Answer 22

A neurological phenomen where a weak stimulus received before a stronger stimulus reduces the intensity of the second response

Question 23

Name 2 diseases with disrupted pre-pulse inhibition

Answer 23

Schizophrenia, Alzheimer’s disease

Question 24

How does pre-pulse inhibition help explain the gender difference in schizophrenia?

Answer 24

Males have a naturally higher pre-pulse inhibition so may be more vulnerable to its disruption

Question 25

Describe the sexual dimorphism in midbrain dopaminergic circuitry (Crow, 1985)

Answer 25

In females, the hypothalamus must release oestrogen and progesterone in a cyclical manner - in males, hormone release can be constant

Question 26

What starts the differentiation of the male brain in utero?

Answer 26

Testosterone surge at around 6 weeks

Question 27

Describe the difference between activational and organisational sex differences

Answer 27

Organisational effects occur early (e.g. in utero), are irreversible, and are due to testosterone, whereas activational effects occur later, are due to oestrogen or oestradiol, and are thought to be reversible