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1

Name the 4 schizophrenic symptoms that are considered "Positive" (enhancement of function). Where are these symptoms originating? Why?

Nucleus Accumbens (Mesolimbic)= too much DAergic activity

  1. Hallucinations
  2. Delusions
  3. Behavioral disorganization
  4. Positive formal thought disorder

 

2

Name the 6 schizophrenic symptoms that are considered "Negative" (deficit of function). Where are these symptoms originating? Why?

+

Name the one schizophrenic symptoms that fits into neither positive or negative as a category. Where is this symptom originating? Why?

Frontal cortex (Mesocortical)= too little DAergic activity​

  1. Alogia
  2. Affective blunting
  3. Avolution
  4. Asociality
  5. Anhedonia
  6. Attentional Impairment

____________

Frontal cortex (Mesocortical)= too little DAergic activity​

Also, COGNITIVE (own category)

3

Schizophrenic symptom: Positive or negative? Location? DA activity level?

Hallucinations

Positive

Nucleus Accumbens (Mesolimbic)= too much DAergic activity

4

Schizophrenic symptom: Positive or negative? Location? DA activity level?

Delusions

Positive

Nucleus Accumbens (Mesolimbic)= too much DAergic activity

5

Schizophrenic symptom: Positive or negative? Location? DA activity level?

Behavioral disorganization

Positive

Nucleus Accumbens (Mesolimbic)= too much DAergic activity

6

Schizophrenic symptom: Positive or negative? Location? DA activity level?

Positive formal thought disorder

Positive

Nucleus Accumbens (Mesolimbic)= too much DAergic activity

7

Schizophrenic symptom: Positive or negative? Location? DA activity level?

Alogia

Negative

Frontal cortex (Mesocortical)= too little DAergic activity​

8

Schizophrenic symptom: Positive or negative? Location? DA activity level?

Affective blunting

Negative

Frontal cortex (Mesocortical)= too little DAergic activity​

9

Schizophrenic symptom: Positive or negative? Location? DA activity level?

Avolution

Negative

Frontal cortex (Mesocortical)= too little DAergic activity​

10

Schizophrenic symptom: Positive or negative? Location? DA activity level?

Asociality

Negative

Frontal cortex (Mesocortical)= too little DAergic activity​

11

Schizophrenic symptom: Positive or negative? Location? DA activity level?

Anhedonia

Negative

Frontal cortex (Mesocortical)= too little DAergic activity​

12

Schizophrenic symptom: Positive or negative? Location? DA activity level?

Attentional impairment

Negative

Frontal cortex (Mesocortical)= too little DAergic activity​

13

What receptor do ALL antipsychotic drugs block?

Dopamine (DA)

D2 receptor

14

Which dopamine pathway in the brain has too little DAergic activity? What types of symptoms is it responsible for?

Frontal cortex (Mesocortical)= too little DAergic activity

NEGATIVE AND COGNITIVE SYMPTOMS

  1. Alogia
  2. Affective blunting
  3. Avolution
  4. Asociality
  5. Anhedonia
  6. Attentional impairment
  7. Cognitive (neither negative nor positive, own category)

15

Which dopamine pathway in the brain has too much DAergic activity? What types of symptoms is it responsible for?

Nucleus Accumbens (Mesolimbic)= too much DAergic activity

POSITIVE SYMPTOMS

  1. Hallucinations
  2. Delusions
  3. Behavioral disorganization
  4. Positive formal thought disorder

16

Identify the APS:

  • First Generation/typical
  • Category: Phenothiazines
  • Tricyclic

Pros

  • Generic
  • Inexpensive
  • Slight extrapyramidal syndrome

Cons

  • Many adverse effects, especially autonomic
  • Neuroleptic (Potentiated anesthesia)
  • 800 mg/day limit
  • Cardiotoxicity
  • Increased risk of tardive dyskinesia
  • No paraenteral form

Chlorpromazine (thorazine)

17

Identify the APS:

  • First generation/typical
  • Category: Butyrophenones

Pros

  • Major advantages over phenothiazines include lower sedation and less alpha-block

  • Generic

  • Cheap

Cons

  • Severe extrapyramidal syndrome

Haloperidol

18

Identify the APS:

  • 2nd generation/atypical
  • Category: Dibenzodiazepine

Pros

  • No EPS: Somehow was selective for causing DPI ONLY in mesolimbic pathway
  • Benefit to treatment resistant patients
  • Higher potency at 5HT2
  • Better against negative symptoms

Cons

  • Agranulocytosis risk requires weekly WBCs
  • Diabetes
  • Weight gain

 

Clozapine

19

Identify the APS:

  • 2nd generation/atypical
  • Category: Benzisoxazole

Pros

  • Broad spectrum w/ few or no EPS at low dose
  • No evidence of agranulocytosis risk
  • Long acting injectable available

Cons

  • high dose EPS
  • high dose hypotension

Risperidone

20

Identify the APS:

  • 2nd generation/atypical
  • Category: Thienobenzodiazepine

Pros

  • Benefit in negative symptoms
  • Little or no EPS
  • No risk of agranlocytosis

Cons

  • Diabetes
  • Hypotension
  • Serious Weight gain
  • Smaller increase in serum PRL than haloperidol

Olanzapine

21

Identify the APS:

  • 2nd generation/atypical
  • Category: Dihydroindolone

Pros

  • similar to other atypicals
  • perhaps less weight gain/diabetes risk

Cons

  • QT prolongation

 

Ziprasidone

22

Identify the APS:

  • 2nd generation/atypical
  • Category: quinolinone

Pros

  • Different mechanism (partial agonist at D2 receptors)
  • Modest affinity at 5-HT2 receptors (antagonist)
  • Partial agonist at 5-HT1a receptors
  • Less effect on prolactin levels
  • No apparent risk of diabetes

Cons

  • No long term studies

Aripiprazole

23

Drugs that increase synaptic DA produce ______

(ex. Amphetamine toxicity; overdoses of L-DOPA)

psychosis

24

Successful treatment with Anti-psychotics (increases or decreases) DA metabolites

Increases DA metabolites

25

True or false: DA receptor density changes in schizophrenia

true

26

How does Amphetamine enhance DA release?

Amphetamine enhances DA release via reversal of the transporter

27

How does L-DOPA produce psychosis?

By increasing DA synthesis by providing more precursor, it may produce psychosis

28

Other than dopamine, what two other neurotransmitter may play a role in Schizophrenia?

 

  1. Serotonin (5-HT2 receptors)
  2. Glutamate (NMDA receptors)

29

In the treatment of psychosis, is there proven clinical efficacy for treating with a 5-HT2 block (serotonin receptor block)?

No; correlation of clinical efficacy with 5-HT2 block is poor

30

Approximately how long does it take for anti-psychotic treatment to become effective? Successful management corresponds to what?

  • 4-6 weeks
  • Corresponds to the development of "depolarization inactivation"=DPI