Schizophrenia Flashcards
Schizophrenia is a chronic mental disorder characterised by a triad of core symptoms. What are they?
Positive - hallucinations, delusions, agitation, disorganised thinking
Negative - introversion, apathy, low self-esteem leading to personal neglect
Cognitive - poor memory, attention deficit, executive dysfunction
What does alogia mean?
The inability to speak because of mental defect, mental confusion, or aphasia.
What does avolition mean?
A severe lack of initiative or motivation. A lack of interest to become engaged in goal-oriented behaviour.
According to the DSM-IV criteria, how long do symptoms have to be present for to make a diagnosis of schizophrenia? How many symptoms are needed?
Two or more of the symptoms, present for a significant portion of time during a 1-month period.
What symptoms are on the DSM-IV criteria? (5)
Delusions
Hallucinations
Disorganised speech
Grossly disorganised or catatonic behaviour
Negative symptoms (e.g. affective flattening, alogia, or avolition)
Identical twins – if one has schizophrenia, what is the lifetime risk of the other developing it? What about with fraternal twins?
48%
17%
What genes are associated with schizophrenia? Which has the most evidence and which has the least?
- Dysbindin (may affect dopamine D2 receptor levels and glutamate and GABA transmission) – strongest evidence in schizophrenia
- Neuregulin 1 (neuroplasticity)
- DISC 1 (neurodevelopment and signalling in corticolimbic areas)
- DAOA (glutamatergic transmission)
- and 6. COMT (dopaminergic transmission) and BDNF (neurotrophic factor) – weakest evidence in schizophrenia
There is a spectrum - prototypical schizophrenia, prototypical mood disorder, and schizoaffective disorder. Which susceptibility genes correlate to which one?
Dysbindin – prototypical schizophrenia
DAOA, BDNF – prototypical mood disorder
DISC 1, NRG1 – schizoaffective disorder
What is the classification of schizophrenia according to DSM-IV? (5)
Paranoid Disorganised Catatonic Undifferentiated Residual
Cognitive dysfunction - why is it important in schizophrenia? How can it be tested?
It is an important predictor of outcome
Wisconsin Card Sorting Test
Is schizophrenia associated with structural changes in the brain?
Larger ventricles
Smaller mesial temporal lobe structures
What can be seen in PET scan imaging in schizophrenia?
Differences in regional blood flow - decrease
in pre-frontal cortex and increase in thalamus and cerebellum
A subset of patients with schizophrenia have brain loss. When is it more significant? What is it correlated with?
Frontal grey matter/brain loss is more significant in the first period of the disease. It is correlated with cognitive performance.
What is the Kraepelinian definition of poor outcome? What is this form of schizophrenia closer to?
Progressive deteriorating course
A form of neurodegeneration
What can be seen in Kraepelinian schizophrenia?
Prominent temporal sulcal markings and enlarged left temporal horn (temporal lobe volume loss and lateral ventricular enlargement).
When does schizophrenia start and why?
Schizophrenia is associated with decreased synaptic spines and decreased dendritic complexity in the cortex. At least some forms of schizophrenia are likely to be due to abnormalities in the formation and maturation of brain circuits.
Corticolimbic circuits - where are there excitatory connections?
Between…
- Prefrontal cortex and temporal/parietal association cortices
- Prefrontal cortex and anterior cingulate cortex
- Prefrontal cortex and hippocampus and parahippocampal cortices
- Prefrontal cortex and thalamus
- Thalamus and anterior cingulate cortex
From…
- Prefrontal cortex to caudate/putamen
Corticolimbic circuits - where are there inhibitory connections?
From GP to thalamus and from caudate/putamen to GP
Corticolimbic circuits - where are there dopamine connections?
Ventral mesencephalon to…
- Hippocampus and parahippocampus
- Caudate/putamen
- Prefrontal cortex
- Anterior cingulate cortex
What is the default mode network?
A network of brain regions that show synchronised activity when subjects rest and allow their minds to wander.
How is brain connectivity altered in schizophrenia patients?
Altered brain connectivity of default brain network - the synchrony, which reflects the strength of functional connections between the different areas, is increased .
Schizophrenia is associated with hyperactivity in which pathway? What about hypoactivity?
Mesolimbic pathway
Hypoactivity in the mesocortical pathway
What are the major pharmacological target of drugs used to treat schizophrenia? What do these drugs act as?
Dopamine D2 receptors
Antagonists
What are the two main families of dopamine receptors?
What sub-types belong to each family?
D1 type: D1, D5
D2 type: D2, D3, D4
What is a neuroleptic drug also known as?
Antipsychotic
What was the first antipsychotic drug?
Chlorpromazine (Largactil)
Name some typical antipsychotics.
Chlorpromazine Thioridazine Fluphenazine Haloperidol Flupenthixol
Name some atypical antipsychotics.
Risperidone Olanzapine Clozapine (blocks D4 receptors) Quetiapine Paliperidone Aripiprazole (partial agonist)
Is fluphenazine atypical or typical?
Typical
Is clozapine atypical or typical?
Atypical
Is paliperidone atypical or typical?
Atypical
According to NICE guidelines, which type of antipsychotic is first choice? Which receptor do these all have antagonist activity at?
Atypical
5-HT2 receptors
What is a major advantage of atypicals compared to typical antipsychotics?
They may improve cognition
What explains the adverse effects of antipsychotics?
They have affinity for various receptors: D2, alpha 1 noradrenergic, 5-HT2, D1, histamine H1, muscarinic…
Antipsychotics are associated extra-pyramidal effects - what do these include?
Is this more associated with typical or atypical?
How many % of D2 receptors have to be blocked for this to happen?
Acute dystonias, parkinsonism, tardive dyskinesia
Typical
80% (60% –> antipsychotic efficacy)
List some side effects of typical antipsychotics.
Rise in prolactin Weight gain EPS (e.g. tardive dyskinesia) Cardiac toxicity (QT interval prolongation) Sudden death
List some side effects of atypical antipsychotics.
Weight gain
Dyslipidemia
Type 2 diabetes
Cardiovascular disease
Which antidepressants are associated with anticholinergic effects?
Clozapine, haloperidol
What is tardive dyskinesia?
Involuntary movements of the lips, jaw, face
Grimacing
Constant chewing
Tongue thrusting
What is neuroleptic malignant syndrome?
A potentially lethal complication of antipsychotics. Symptoms/signs are:
Hyperpyrexia, muscle rigidity, tremor, confusion, autonomic instability.
Some antipsychotics can be offered as depot intramuscular injections for slow-release - name two.
Fluphenazine and haloperidol
How many % of schizophrenic patients do not respond to treatment
30%
What is the drug of choice in drug resistant schizophrenia? Why must blood be monitered?
Clozapine
Risk of agranulocytosis
What are the non-pharmacological treatments?
CBT and family Therapy
Schizophrenia is associated with decreased glutamatergic transmission (hypoglutamatergic state in the cortex) - how could this be targeted for treatment?
Why is this beneficial over current antipsychotics?
It may be possible to potentiate the activity of the NMDA receptor in order to modulate glutamatergic transmission, to alleviate both positive and negative symptoms e.g. activate mGlu2/3 receptors.
No weight gain, increased prolactin or extra-pyramidal effects.
