Schizophrenia

Question 1

what is the definition of schizophrenia

Answer 1

• Schizophrenia is a chronic mental disorder characterised by a triad of core symptoms
• These are positive, negative and cognitive

Question 2

What is the onset of schizophrenia

Answer 2

• Tends to emerge between ages of 16 and 30, women tend to have a later onset
• Persists throughout a patient’s lifetime

Question 3

what are the three types of symptoms in schizophrenia

Answer 3

• positive
• negative
• cognitive

Question 4

describe examples of the three types of symptoms in schizophrenia

Answer 4

Positive symptoms
- Hallucinations, delusions, agitations, disorganised thinking = gain of function
Negative symptoms
- Introversion, apathy, low self-esteem, personal neglect = loss of function
Cognitive symptoms
- Poor memory (working memory is particularly affected – e.g. remembering a sequence of instructions), attention deficit, executive dysfunction

Question 5

How do you diagnose schizophrenia

Answer 5

• At least two of the following (per DSM-5):
o Delusions.
o Hallucinations.
o Disorganized Speech.
o Disorganized/catatonic behavior.
 Catatonic = a variety of abnormal motor postures.
o Negative symptoms (flat effect = inappropriate response, avolition = decreased motivation).
• At least one must be delusions, hallucinations or disorganized speech.

• Continuous signs of disturbance must persist for 6 months, where the patients must experience at least 1 months of active symptoms with deterioration problems occurring over a significant time.
• must be without substance misuse or mood disorder

Question 6

define catatonic behaviour

Answer 6

= a variety of abnormal motor postures.

Question 7

describe genetics and schizophrenia

Answer 7

• not entire determined by genes
• concordance rates occur higher in MZ twins
• the more closely related you are to a patient with schizophrenia the more likely you are to have it

Question 8

What is the biggest risk factor to do with schizophrenia

Answer 8

genetics

- having a close relativee with it

Question 9

name some examples of genes that are associated with schizophrenia

Answer 9

• Dysbindin: may affect D2 receptors levels/glutamate and GABA transmission
• Neuregulin: neuroplasticity.
• DISC 1: neurodevelopment and signalling in Corticolimbic areas.
• DAOA: glutamatergic transmission
• COMT: dopaminergic transmission.
• BDNF: neurotrophic factor

Question 10

there is a genetic continuum between….

Answer 10

There is a genetic continuum between protypical schizophrenia and protypical mood disorders.
- there is considerable overlap between typical schizophrenia and psychological mood disorder

Question 11

what is the most important predictor of prognosis of someone with schizophrenia

Answer 11

cognitive dysfunction

Question 12

How can you test for frontal cortical dysfunction

Answer 12

Wisconsin card sorting test

– patient won’t be able to adapt as they cannot focus, cant concentrate and cannot make decision in the change of rules

Question 13

describe the structural changes that occur in schizophrenia

Answer 13

• increased rate of grey matter loss this leads to larger ventricles and smaller medial temporal lobes
• hypofrotnality - decreased frontal lobe activation during cognitive task
• overal brain volume loss
• when measuring event related potentials in schizophrenic patients the reaction to stimulation is increased

Question 14

what happens to schizophrenic patients in terms of event related potentials

Answer 14

• there reaction to stimulation is increased

- they have increased salience

Question 15

what is the krapelinian definition of poor outcome for patients with schizophrenia

Answer 15

• this is when the disease follows a progressive deteriorating course and is associated with poor outcome
• this type of schizophrenia is a form of neurodegeneration

Question 16

when does schizophrenia start

Answer 16

• Associated with decreased synaptic spines/decreased dendritic complexity in the cortex.
o This creates abnormalities in formation/maturation of brain circuits.

Question 17

Name and describe some explanations for the psychotic symptoms of schizophrenia

Answer 17

Corticolimbic Circuits and Dopaminergic Systems
• Hypofrontality leads to excessive striatal dopamine release.

Altered brain Connectivity
• Mainly of the default brain network.
o Increased synchrony of DBN when subjects rest/allow mind to wander in SD.
 Possible explanation for psychotic symptoms.

Question 18

name some environmental reasons as to why schizophrenia can start

Answer 18

• viral infections
• cannabis use
• drug abuse
• increased maternal age
• urban environment which is associated more with stress
• winter birth

Question 19

when does schizophrenia start in the males versus in the females

Answer 19

starts mid 20s in males and later in females

Question 20

describe the link between synaptic maturation and the onset of schizophrenia

Answer 20

• there is a critical time around the onset of schizophrenia where there is an change in the transcription of genes in the brain
• this is called the transcriptome trajectory turning point
• these genes that change at this time are associated with synapses and gives an indication that schizophrenia is linked to a deficit in the maturation of synapse

Question 21

describe how the dopaminergic pathway is associated with schizophrenia

Answer 21

• hyperactivity in the mesolimbic pathway

- hypo activity int he mesocortical pathway

Question 22

what are the target of the main pharmacological drugs used to treat schizophrenia

Answer 22

dopamine D2 receptors

- drugs that act on dopamine D2 receptors are antagonists

Question 23

name some typical antipsychotics

Answer 23

• Chlorpromazine – first neuroleptic
• Thioridazine
• Fluphenzine
• Haloperidol
• Flupenthizol

Question 24

How do typical antipsychotics work

Answer 24

• Block dopamine receptors as well as acting as antagonists at other receptors (e.g. muscarinic cholinergic, histamine H1 and alpha2-adrenergic receptors).
• Lack of selectivity of action

Question 25

what factor of typical antipsychotics can help schizophrenia in the community

Answer 25

• Some drugs can be given as depot slow release preparation (makes chronic SD manageable in community). o Also, useful in non-compliance.

Question 26

name the adverse effects of typical antipsychotics

Answer 26

``` • More extrapyramidal effects vs atypical (normally reversible) * o Tardive dyskinesia o Dystonia o Parkinsonism o Bradykinesia o Tremor ``` * Weight gain * Postural hypotension * Blurred vision * Dry mouth (muscarinic) * Hypothermia * QT interval prolongation * Sudden death * Hyperprolactinaemia

Question 27

why does hyperprolactinaemia occur

Answer 27

this is because dopamine usually inhibits the release of prolactin from the pituitary gland but cannot do this if it is inhibited

Question 28

Define and describe the symptoms of extrapyramidal side effects

Answer 28

* Dystonia: continuous spasms and muscle contractions * Akathisia (restlessness) * Parkinsonism (rigidity) * Bradykinesia

Question 29

name some examples of atypical antipsychotics

Answer 29

* Risperidone * Olanzapine * Clozapine * Quetiapine * Paliperidone * Aripiprazole

Question 30

describe the mechanism of action of atypical antipsychotics

Answer 30

• Acts as antagonists at D2 receptors as well as antagonists 5-HT2 receptors

Question 31

what Is the atypical antipsychotics clozapine used for

Answer 31

• Clozapine is used in patients that are drug resistant (30% of SD patients do not respond to treatment).

Question 32

describe the adverse effects of atypical antipsychotics

Answer 32

* Less prone to give extrapyramidal effects. * Improve negative effects/cognitive dysfunction * Significant weight gain * Dyslipidaemia * T2D (insulin resistance)

Question 33

describe what is meant by tardive dyskinesia

Answer 33

involuntary movements of the lips, jaw, face; grimacing, constant chewing, tongue thrusting) - Associated mainly with typical antipsychotics, taken for longer than a few months/years - Often difficult to return to normal

Question 34

what is neuroleptic malignant syndrome

Answer 34

``` • Rare but potentially lethal complication. • It is a medical emergency • Characterized by: o Hyperpyrexia (high fever) o Tremor ```

Question 35

what antipsychotics can be used for slow release

Answer 35

- fluphenazine and haloperidol can be offered in intramuscular infections for slow release

Question 36

what side effect can come with clozapine

Answer 36

- There is a risk of agranulocytosis – therefore blood monitoring is essential

Question 37

what are the non pharmacological approaches to schizophrenia

Answer 37

- CBT - Family therapy - These do not replace the pharmacological treatment

Question 38

what are the aims of treatment for schizophrenia

Answer 38

full symptom control, return to pre-morbid functioning, patient safety

Question 39

what is a new alternative treatment for schizophrenia

Answer 39

NMDA glutmate receptor - schizophrenia is associated with decreased glutmatergic transmission - therefore it may be possible to potentiate the activity of the NMDA glutmate receptor - Modulation of glutamatergic transmission based on metabotropic mGluR may have the potential to alleviate positive and negative symptoms - The reported effectiveness in the first trial was comparable to olanzapine, but with no weight gain, increased prolactin or extrapyramidal effects

Question 40

describe how schizophrenia is linked to inflammation

Answer 40

- increased levels of cytokines during pregnancy can increase the risk of schizophrenia in the offspring - proinflammaotry cytokines are elevated in the pre-frontal cortex of SCH patients - increased loss of cortical grey matter in SCH patients with high levels of cytokines - • SCH patients with high levels of cytokines display signs of greater immune cell migration into the brain • Activated microglia are present in the brains of SCH patients within a few years of the disease onset • Might have an inflammatory status, cytokines in the blood are higher for inflammatory cytokines and in the post mortem there is activation of microglia, this is the state of neuroinflammation

Question 41

describe how schizophrenia is linked to white matter and myelination

Answer 41

* Reduced oligodendrocyte density in SCH * Key molecules regulating myelination are differentially expressed in SCH (e.g. neuregulin 1) * Inflammation and immune activation may lead to oligodendrocyte damage