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60 Cards in this Set

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Schizophrenia has a distinct set of signs and symptoms and is characteristic in patients - T/F?
False

it is a heterogenous psychiatric condition characterized by characterized by perturbations of language, perception, thinking, social activity, affect, and volition
What is the typical onset of schizophrenia ?
Typically late adolescence and has an insidious onset progressing from social withdrawal and perceptual distortions to recurrent delusions and hallucinations
What are some positive symptoms of schizophrenia?
conceptual disorganization, delusions, or hallucinations
What are some negative symptoms of schizophrenia?
loss of function, anhedonia, decreased emotional expression, impaired concentration, and diminished social engagement
What is the rate of suicide death in schizophrenics?
10%
World wide prevelance of schizophrenia?
0.85%
Dx for schizophrenia is via MRI . - T/f?
False - it is a
Dx of exclusion - rule out mood disorders, underlying medical condition or substance abuse and also the side effect of other medications.
What is the concordance rate for schizophrenia in monozygotic twins?
50% (10% dizygotic)
What structural and fuctional abnormalities are associated with schizophrenia?
(1) cortical atrophy and ventricular enlargement;
(2) specific volume - amygdala, hippocampus, right prefrontal cortex, fusiform gyrus, and thalamus;
(3) progressive reduction in cortical volume over time;
(4) reduced metabolism in the thalamus and prefrontal cortex;
(5) abnormalities of the planum temporale; and
(6) changes in the size, orientation, and density of cells in the hippocampus and prefrontal cortex, and decreased numbers of cortical interneurons
What is the dopamine hypothesis of schizophrenia?
increase in the activity of nigrostriatal and mesolimbic systems and a decrease in mesocortical tracts innervating the prefrontal cortex

This has been indicated by drugs that inhibit dopamine - reduce the positive symptoms such as agitation, anxiety, and hallucinations
What is the main treatment of schizophrenia?
Antipsychotics - for acute and maintenance therapy.

Used for treatment of hallucinations, delusions and thought disorders
What is the MOA of antipsychotics?
They bind D2/3 receptors in the ventral striatum - as well as other effects?
Chlorpromazine, Thioridazine and Clozapine are what kind of drugs?
1st generation antipsychotics - with low potency.
What is clozapine?
1st generation antipsychotics - with low potency.
What is haloperidol?
1st generation antipsychotics - with high potency.
Risperidone, Olanzapine and Quetiapine are what kind of drugs?
Second generation antipsychotics.
T/F - moderate - high potency 1st gen antipsychotics are associated with extra pyramidal effects.
True - these are reduced in 2nd gen and low potency antipsychotics.
Clozapine - is a 1st gen antipsychotic but is used to treat resistant cases. Why?
Because of its side effect profile - although it is used because it is better at preventing suicide - perhaps via its different MOA - reformed 5-HT and D4
What are the main factors affecting medication choice for patients?
Side effect profile
Cost
Past personal or family responses to drugs
What is the relapse rate following complete medication withdrawal in schizophrenic Pts?
60% within 6 months -

Medication dose reduction can help improve social functioning for patients on high doses - although complete withdrawal is not recommended.
What are Bleuler's 4 A's of schizophrenia?

And the associated positive symptoms?
- disturbances of Association
‑ Affective disturbances
‑ Ambivalence
‑ Autism


- Delusions (grandeur, paranoia)
‑ Hallucinations
What is the general time course for schizophrenia?
1) prodromal phase (negative symptoms)

2) Psychotic phase (postive symptoms)

3) residual phase -(negative symptoms)

Lengths of time can be years or months
What structural changes have been reported in schizophrenics?
Decreased brain volume
• Increased ventricular size
• Hippocampal asymmetry
• Loss of normal asymmetry (planum temporale)
• Loss of gray matter (cortex)
• Changes in basal ganglia, even cerebellum and many more..
What structural changes have been accompanied by the cognitive changes - regarding schizophrenia?
Presence of cavum septum pellucidum (90%, but often present in healthy controls)
• Changes in the size of lateral ventricles (80%)
• Decreased size of hippocampus (75%)
• Increased size of the third ventricle (70%)
• Structure of adhesio interthalamica
What is the prefrontal cortex associated with ?
• human personality traits
• human-type social interactions
• planning for the future
• cognition

Negative symptoms of schizophrenia
How is synaptic dopamine removed in the PFC?
Metabolism by COMT - not by reuptake like most areas in the brain.
What is COMT?
CatecholOmethyl transferase

Enzyme that deactivates dopamine in the PFC

NOTE: COMT is less active in humans so there is increased activity of dopamine in this location (PFC)
What is the relevance of COMT in the PFC ?
Is it less active in humans and therefore results increased effects of dopamine in the PFC than in other areas of the brain.
What are the normal connections of the PFC with respect to dopamine?

what pathology can be associated with these pathways?
The VTA (ventral tegmental area) send dopaminergic neurons to the PFC and the limbic system.

The PFC then sends inhibitory neurons back to the VTA to inhibit the dopamine signals to PFC and LS.

----- PATHOLOGY in PFC --- mutation in COMT - more stable enzyme and therefore reduced Dopamine
Loss of dopamine effect in PFC --> reduced inhibition of VTA --> increased dopamine effect on PFC and LS (also the PFC also usually inhibits the LS but this is lost in this pathology)

--- INCREASED ACTIVATION OF LIMBIC SYSTEM
What other changes in the PFC could cause the changes seen with a COMT mutations which reduces dopamine in the PFC?
Reduced grey matter
Normal grey matter but reduced glutamergic transmission
Deficient white matter.
What is the evidence for COMT involvement in schizophrenia?
Tansgenic mice with reduced function COMT --> super rat - better functioning
What NTs and their metabolic pathways could be involved in pathology of schizophrenia?
Dopamine metabolism - COMT

glutamate transmission - reuptake or receptors

GABA
Fom where is the major input to the cortex?
Thalamus
Which cells are output cells from the cortex?
Pyramidal cells (large)
Which GABAergic interneuron cells are believed to be involved in the devopment of schizophrenia?
Parvalbumin positive Chandelier cells
What is parvalbumin ?
Calcium binding protein
How are chandelier cells implicated in schizophrenia?
The discrete on/off function of these cells is lacking -- which effects working memory

(via TrkB signalling, DNA methylation and GAD67 deficiency)
What mechanisms have been implicated in the pathogenesis of schizophrenia?
DA inactivation (COMT..?), NMDA receptors (deficient expression), glutamate transport (overexpression of GLT) or decrease expression of GAD67, caused by genetic abnormalities or peculiarities in “epigenetic” (increased DNA methylation) mechanisms.
What is prevention of psychiatric illness?
Interventions that occur before the initial onset of a disorder to prevent the development of disorder

Aim - to reduce prevalence and burden of disease
What is an individual approach to prevention?
To selectively target pele at high risk and help them reduce this risk - ie those with abusive back group - therapy
What is a population approach to mental health prevention?
Targets the whole population, regardless of each individual’s level of risk.

- ie screening questionnaires by GPs
What is primary prevention?
• Approaches to reduce the incidence of problems (i.e. to prevent problems from developing)
What is secondary prevention?
Early detection and management to reduce prevalence
What is tertiary prevention?
Minimize disability once a problem develops
What is universal prevention?
The whole population
What is selected prevention?
Only persons at higher risk than average
What is indicated prevention?
High-risk individuals with minimal but detectable features of a disorder
---- who do not fully meet diagnostic criteria
Who does early intevention target?
– displaying the early signs and symptoms of a mental disorder;
or
– experiencing a first episode of a mental disorder
Universal prevention > selective prevention > indicated prevention and early intervention - in terms of broadness of the strategy, - T/ F?
True
What are some risk factors for mental disease?
• Parental mental illness
• Affectionless parenting
• Parental discord
• Adverse life events
• Perinatal problems
• Low intelligence
What are some protective factors against mental disease?
• Belief in own effectiveness
• Success/Achievement

“Easy” temperament
• Sense of humour and optimism
• Positive school life
• Good peer relations
• High intelligence
• Positive relation with a caregiver
What is the positive parenting program (triple P)?
Program aimed at identifying individuals which may develop mental problems - different levels aim at primary, secondary, and tertiary prevention and intervention
Risk factors for schizophrenia ?
Family history
Pregnancy & birth complications
Season of birth (winter/spring)
Place of birth (urban)
Prenatal viral infections
Poor prenatal nutrition

1st few have better evidence
Which environmental factors are believed to be apart of development of schizophrenia?
 Prenatal/perinatal factors (maternal stress, maternal malnutrition, maternal infection, obstetric complications)
 Early-life stress (maternal separation, childhood trauma)
 Drugs (cannabis, amphetamines)
 Stressful life events
Dx of schizophrenia needs the symptoms to last how long?
6 months
What are are the indications of antipsychotic drugs?
Schizophrenia
Psychosis
MOA of antipsychotics?
All have antagonistic effects are dopamine D2 receptors
What is the dopamine theory of schizophrenia ?
Excess levels of dopamine lead to neurological over activity - and the signs of schizophrenia

Also schizophrenics have raised number or sensitivity of dopamine receptors

Also
Hypodompaminergia in PFC causes the negative symptoms of schizophrenia.
Hyperdopaminergia in subcortical regions (striatum) which causes positive symptoms (Davis et al., 1991)
Which NTs have been implicated in the pathogenesis of schizophrenia?
Dopamine
Glutamate
GABA
T/F
D1 Receptors are inhibitory?
D2 receptors are inhibitory?
D1 are excitatory

D2 are inhibitory