Psychotic

Question 1

What are the 2 main types of symptoms in psychosis?

Answer 1

• positive symptoms:
  Reflect an ecess of normal function ( e.g, Delusions, hallucinations, distortions or exaggerations in language and communication, disorganized speech, disorganized behaviour, catatonic behaviour, agitation)
• negative symptoms: lack of normal functioning (5 A’s: Alogia, Affective blunting, asociality, anhedonia, avolitions)

Question 2

What is alogia

Answer 2

unable to produce normal speech

Question 3

avolitions

Answer 3

lack of goal directed beahviour

Question 4

the schizephrenia medications available are more benficial for which types of symptoms?

Answer 4

effective for positive symptoms, less effective for negative

Question 5

What are some additional symptoms in schizophrenia (other tha positive and negative)

Answer 5

1. Cognitive symptoms
2. Aggressive symptoms
3. Affective symptoms

Question 6

Which brain circuits are hypothesized to be related to positive symptoms?

Answer 6

mesolimbic circuits

Question 7

Which brain circuits are hypothesized to be related to negative symptoms?

Answer 7

mesocortical/prefrontal cortex

nucleus accumbens reward cicuits

Question 8

Which brain circuits are hypothesized to be related to affective symptoms?

Answer 8

ventromedial prefrontal cortex

Question 9

Which brain circuits are hypothesized to be related to aggressive symptoms?

Answer 9

orbitofrontal cortex and amygdala

Question 10

Which brain circuits are hypothesized to be related to cognitive symptoms?

Answer 10

dorsolateral prefontal cortex

Question 11

What is the stress diathesis model of schizophrenia?

Answer 11

gene x environment interaction:

• genetic vulnerability
• stress from the environment combined with this vulnerability leads to symptoms

Question 12

What is the Dopamine hypothesis of schizophrenia ?

evidence?

Answer 12

Abnormal levels of DA in different areas of the brain drive symptoms

There is too much dopamine in SOME neurocircuits (particularly mesolimbic) which results in psychosis and positive symptoms

• Drugs that increase DA in those ciruits can cause positive symptoms (e.g., delusions, hallucinations)
• Drugs that decrease DA reduce positive symptoms

There is a lack of DA in OTHER neurocircuits that cause frontal lobe hypoactivity
- results in poor attention and concentration, executive control etc.

Low DA results in negative symptoms

Question 13

What are the different types of dopamine receptors?

Which type is hypothesized to be related to schizephrenia?

Answer 13

D1-5

D2 (blocking D2 reduces positive symptoms)

also role of D1 and D3

Question 14

Which pathway is really important in movement?

Answer 14

substantia nigra to striatum

Question 15

What are other hypothesizes causes of schizophrenia?

Answer 15

Glutamate may control DA activity

Abnormal glutamate activity therefore may cause problem in DA functioning and psychosis

Could explain the high vs low DA in different circuits

Question 16

Describe the glutamate-glutamine cycle

Answer 16

EAATs brings glutamate into glial cell

• Glutamine synthetase converts glutamate to glutamine
• Glutamine is transported from the glial cell into the presynaptic neuron
• glutamine is converted into glutamate and packaged into
  Vesicular glutamate transporters (VGLUT)
• releases into synapse
• Terminated by excitatory amino acid transporters (EAATs) in to glial cells

starts over

Question 17

What are the subtypes of glutamate

where can they all be located?

Answer 17

NMDA (ion gated)
AMPA/kainate (ion gated)
mGluR (metabotropic)

All be located on post synaptic neuron

Question 18

Which type of glutamate receptors are responsible for the most rapid Excitatory postsynaptic potentials?

Answer 18

AMPA/kainate receptors

Question 19

What makes NMDA receptors unique?

Answer 19

even though they are ionotropic, it allows the entry of calcium (as well as sodium or potassium)

-> calcium can act as a second messenger

In order to fire:
in addition to glutamate
require the presence of of a co-transmitter (serine or glycine)

must also have SOME level of depolarization

Question 20

Too much glutamate in brain can lead to?

Answer 20

neurotoxicity/cell death

Question 21

NMDA Receptor Insufficiency Theory of Schizophrenia

Answer 21

Glutamate NMDA receptors are located on the post synaptic neuron of 
GABAneric Neurons (release GABA)

• these receptors are defective
• causes GABA neurons to lose tone/activity (not doing their inhibitory job)
• results in excessive glutamate activity
• this excessive glutamate results in exesssive DA activity in the mesolimbic system
• DA activity results in psychosis

in mesocortical system there isa different configuration (there is an additional interneuron) which results in inaquequate DA in the mesocortical

Question 22

Drugs that are good at controlling positive symptoms do what?

Answer 22

Antagonist to D2 receptor (block D2 receptors)

Question 23

What happens if you agonize 5- HT2A receptors?

Answer 23

psychedelic effect

Question 24

Extrapyramidal Symptoms (EPS) caused by conventional antipsychotics

Answer 24

related to blockage of DA in nigrostriatal pathway

Movement issues
– Dystonia: muscle spasms/cramping, esp. neck/shoulders
– Akathesia: restless agitation
– Parkinsonian symptoms: jerky movements,
shuffling
– Tardive dyskinesia: involuntary facial movements (develops later – months to years)

Question 25

What are other negative side effects of conventional antipsychotics? (in addition to EPS)

Answer 25

• Hyperprolactinemia
• Metabolic syndrome
• QTc interval prolongation

Question 26

What do Atypical or Second Generation Antipsychotics do?

Answer 26

anticholinergic

• Greater affinity for 5HT in general, and 5- HT2A specifically (acts as an antagonist)
• Blocking cortical 5-HT2A receptors increases dopamine release
• Greater anticholinergic action coupled with transient D2 action may have the best support to explain improved EPS