Psychosis

Front 1

What is the age range of schizophrenia (SZ)? Is there any impact on mortality?

Back 1

Age range: 15 – 44 years old. Life reduction by 10 years.

Front 2

What are the risk factors for schizophrenia (SZ)?

Back 2

o Genetic – family history
o Urban life
o Immigrant status
o Chronic cannabis use
o Stress
o Maternal infection during pregnancy
o Obstetric complications

Front 3

What are the 3 biological theories of SZ?

Back 3

3 current biological theories of SZ:
o Hypo and hyper activity of some regions of the brain
o Hypo functionality
o Changed NT function

Front 4

There are evidences that show SZ people have reduced brain volume, both grey and white matter, and the ventricles are noticeably larger. What specific areas of the gray matter are mostly affected? White matter?

Back 4

Areas of the gray matter mostly affected:
o Prefrontal cortex
o Caudate nuclei (striatum)
o Part of limbic cortex (anterior cingulate cortex)
o Hippocampal region

Areas of white matter:
o Corpus callosum
o Anterior internal capsule
o Superior longitudinal fasciculus

Front 5

Name 5 susceptibility genes for SZ? (3 for CRS; 5 for HLP)

Back 5

Susceptibility genes for SZ:
o DISC1
o NRG1 – neuroglin 1 (must get this)
o DTNBP (dysbindin)
o COMT
o DAOA

Front 6

Describe how NRG1 gene hypothesised to be linked to SZ?

Back 6

NRG1:
o Its receptor, erbB2-4, modulates neuronal migration, GABAergic interneurons and NMDA receptor neurotransmission. Neuron migration might be interrupted during obstetric complications.
o Brains of SZ have increased NRG1 – erbB2-4 interaction -> decreased NMDA phosphorylation  NMDA receptor hypofunction

Front 7

Hypofunctionality. What brain function is disrupted in the SZ brain?

Back 7

SZ brain activates the same cortical-subcortical network when carrying out executive function as normal BUT with reduced activation.
• Results are consistent with disrupted frontal-based circuitry.

Front 8

What are the NTs implicated in SZ? (4)

Back 8

o Dopamine - too much
o Glutamate, particularly NMDA receptor. - too little
o GABA
o Serotonin - link to glutamate expression

Front 9

What is the theory of DA causing SZ?

Back 9

o Nisogastrial system is hyper active
o substantia nigra -> dorsal striatum, linked to motor areas
o Mesolimbic system is under active
o Ventral tegmental area -> ventral striatum, linked to limbic cortex, hippocampus and amygdala -> motivation, memory, emotion

Front 10

Hypotheses for glutamate in SZ? 5-HT? GABA?

Back 10

Glutamate:
NMDA receptor hypofunction in SZ

5HT:
Drugs that affect 5 HT may induce psychosis

GABA:
There are reduced level of GABA synthesising enzyme in SZ

Front 11

What are the positive and negative symptoms of pyschosis?

Back 11

Positive symptoms:
- delusions
- auditory hallucinations
- disorganised speech
- grossly disorganised / catatonic behaviour

Negative symptoms:
- Reduced expression of emotion
- Poverty of speech
- difficulty in initiating goal - directed behaviour
- lack of insight

Front 12

What NTs are associated with depression? What are the class of drugs that can be used to treat

Back 12

Monoamines (serotonin, histamine, noradrenaline)

Antidepressants:
- Monoamine oxidase (MOA) inhibitor
- Selective Serotonin Reuptake inhibitor (SSRI)
- Tricyclics
- Noradrenaline reuptake inhibitor
- Stimulators of noradrenergic & serotonergic neurotransmission

==> All boost synaptic concentrations of monoamines.

Front 13

Name a drug used to treat bipolar disorder. Describe its mode of action.

Back 13

Lithium.
Site of action: second messenger system affecting the gene expression. Lithium effects the activity of protein kinase C (2nd messenger) in animal studies.

Front 14

Name a few examples of anti epileptic drugs. How do they work in general?

Back 14

Examples: valproate, carbamazepine, lamotrigine.

MOA:
reduce cell depolarisation by:
- Increasing [GABA]
- Reducing [glutamate]
- Interfering with depolarising ion channels (mainly sodium channels)

Front 15

What is the general mechanism of typical anti-psychotic? Name some examples.

Back 15

Dopamine D2 antagonist (also inhibit D1 R)

Examples:
haloperidol, chlorpromazine, zuclopenthixol, trifluoperazine, flupenthixol.

Front 16

What are the side effects of typical antipsychotic?

Back 16

Bad SE: extrapyramidal symptoms, worse negative symptoms, ?weight gain.

Front 17

How is atypical antipsychotic better than typical?

Back 17

- More effective in treating negative symptoms
- Less prone to side effects (esp. extrapyramidal symptoms: tardive dyskinesia, akinesia)

Front 18

Why is atypical antipsychotic better than typical?

Back 18

It acts as both dopamin D2 and serotonin antagonist (5HT 2).

Normally serotonin reduces dopamine release at the baseline level. With inhibition to serotonin, baseline level of dopamine is still achieved (-> ?better for negative symptoms)

Front 19

Name the NT link with these diseases:
- Depression
- Bipolar disorder
- Schizophrenia

Back 19

Depression - serotonin and noradrenaline unceractivity
Bipolar disorder - kindling and second messenger dysfunction
Schizophrenia - dopaminergic overactivity

Front 20

What are the enzymes responsible for monoamine breakdown in the periphery?

Back 20

- Monoamine Oxidase (MAO)
- Cathecol-O-Methyltransferese (COMT)

Front 21

What region of the brain is mostly affected in depression?

Back 21

Hypothalamus - homeostasis through hormone.
Others:

Front 22

Name some nuclei of the hypothalamus implicated in depression.

Back 22

- Paraventricular nucleus
- Suprachiasmatic nucleus

Front 23

What hormones are related to depression?

Back 23

- Sex hormones
- ACTH
- Vasopressin
- Oxytocin - affect love, trust others
- Melatonin - sleep/wakefulness

Front 24

What hormones link chronic stress with depression?

Back 24

HPA: glucocorticoids, vasopressin and oxytocin.