L13

Question 1

Psychotic disorders

Answer 1

Range of mental disorders that involve symptoms of psychosis

Question 2

Psychosis

Answer 2

Loss of contact with reality

Question 3

Effect of psychosis

Answer 3

Affects ability to think, feel, act

Question 4

How is Schizophrenia diagnosed

Answer 4

Severe psychotic disorder

If person has 2+ symptoms for 6 months from core clusters: positive, negative, cognitive symptoms

Question 5

Positive symptoms

Answer 5

mental phenomena that are absent in healthy individuals

e.g. hallucinations and delusions

Question 6

Negative symptoms

Answer 6

loss or impairment of normal psychological function

e.g. loss of motivation and social withdrawal

Question 7

Cognitive symptoms

Answer 7

poor concentration, disorganized thinking, poor memory,

Question 8

the risk of schizophrenia is highly

influenced by

Answer 8

genes

Question 9

_____ interact
with a wide range of ____ that can trigger
____ and ____ leading to schizophrenia

Answer 9

predisposing genetic factors interact
with a wide range of environmental
factors that can trigger
neurochemical and structural
changes leading to schizophrenia

Question 10

Schizophrenia is a _____ brain disease

Answer 10

Schizophrenia is a biochemical brain disease

Question 11

Biochemicals =

Answer 11

Neurotransmitters

Question 12

Biochemical Theories of

Schizophrenia

Answer 12

1. Dopamine Hypothesis
2. Glutamate Hypothesis
3. Serotonin (5-HT) Hypothesis

Question 13

Dopamine Hypothesis

Answer 13

Symptoms of schizophrenia are due to the

hyperactivity of the dopamine system

Question 14

what drugs increase synaptic dopamine and what’s the effects

Answer 14

(amphetamine,
cocaine, cannabis)

delusions and hallucinations
at high doses

Question 15

drugs that block dopamine receptors are

Answer 15

effective

antipsychotics (First Generation Antipsychotics)

Question 16

Dopamine neurons are located in

Answer 16

few

discrete brain regions.

Question 17

The largest population

of dopamine neurons are located in

Answer 17

the midbrain (ventral segmental area and substantial nigra).

Question 18

Mesocortical/mesolimbic system:

Answer 18

dopamine
neurons located in the ventral tegmental area
project to the striatum and the prefrontal
cortex

Question 19

Mesocortical/mesolimbic system mediates

Answer 19

mediate memory, learning, affect and

thought organization

Question 20

hyperactivity in Mesocortical/mesolimbic system

Answer 20

psychotic symptoms

Question 21

blocking dopamine transmission

Answer 21

effective at treating the positive symptoms

of schizophrenia

Question 22

what type of protein receptors are dopamine receptors

Answer 22

gpcr

Question 23

two

classes of dopamine receptors:

Answer 23

d1, d2

Question 24

D1 receptors stimulate adenylate

cyclase via

Answer 24

Gs protein

subsequently activate cAMP-

Question 25

relationship between D1 and antipsychotic drugs

Answer 25

a target for antipsychotic drugs unlikely to contribute to the therapeutic action of many anti-psychotics

Question 26

what type of gpcr is D2; mechanism of action

Answer 26

Gi, inhibit the activity of adenylate cyclase

Question 27

D2 and antipsychotic potency relationship

Answer 27

blocking D2 receptors is directly | related to clinical anti-psychotic potency

Question 28

Nigrostriatal system

Answer 28

dopamine neurons in the substantia nigra that project to the striatum.

Question 29

Nigrostriatal system initiates

Answer 29

movement

Question 30

Nigrostriatal system inhibition

Answer 30

inhibiting this pathway is involved in the production of tardive dyskinesias body) after long-term use of some antipsychotics

Question 31

tardive dyskinesias

Answer 31

(involuntary movements of the face and | body)

Question 32

Tuberoinfundibular System

Answer 32

dopamine neurons in the arcuate nucleus that control hormone release in the pituitary

Question 33

how does dopamine release affect Tuberoinfundibular System

Answer 33

Dopamine released here inhibits the | secretion of prolactin and growth hormone

Question 34

long-term use of some anti-psychotics is | associated with

Answer 34

hyperprolactinemia | increased prolactin release

Question 35

Tuberoinfundibular System associated with (3)

Answer 35

amenorrhea, decreased | libido, and infertility

Question 36

Glutamate Hypothesis

Answer 36

Symptoms of schizophrenia linked to deficiencies in glutamate signaling, particularly in the cortex

Question 37

Glutamate Hypothesis support

Answer 37

effects of phencyclidine (PCP/Angel dust) and ketamine which are NMDA antagonists that produce hallucinations and paranoid delusions

Question 38

current theory is that schizophrenia associated with ___ ___ ___ on ___ ___ in the ___ ___. (glutamate theory)

Answer 38

current theory is that schizophrenia associated with hypofunctional NMDA receptors on GABA interneurons in the cerebral cortex.

Question 39

hypofunctional NMDA | receptors leads to

Answer 39

overactivation of downstream glutamate | signaling to the ventral tegmental area

Question 40

Serotonin Hypothesis

Answer 40

Hypothesis: Symptoms of schizophrenia | due to increased serotonin signaling

Question 41

Serotonin Hypothesis inferential evidence

Answer 41

some 5HT agonists are hallucinogenic (e.g. LSD) 5HT antagonist improves positive symptoms of schizophrenia

Question 42

activation of 5HT-2A receptors in the ____ ____ cause ___ by ___ excitation of ____ _____ (activating the ____ _____ system)

Answer 42

activation of 5HT-2A receptors in the prefrontal cortex cause hallucinations by enhancing excitation of glutamate neurons (activating the mesolimbic dopamine system)

Question 43

5HT-2A antagonists block __ release in the ___, thus reducing hallucinations and other ___ symptoms

Answer 43

5HT-2A antagonists block glutamate release in the cortex, thus reducing hallucinations and other positive symptoms

Question 44

First generation antipsychotics, aka

Answer 44

Typical Antipsychotics

Question 45

First generation antipsychotics target and efficacy

Answer 45

targets both classes of dopamine receptors (D1 and D2) efficacy particularly relates to D2 receptor antagonism

Question 46

example of first gen drugs

Answer 46

Haloperidol, chlorpromazine

Question 47

Second Generation Antipsychotics aka

Answer 47

Atypical Antipsychotics

Question 48

second gen targets

Answer 48

antagonists at both 5HT receptors and D2 receptors

Question 49

second gen affinity and result of affinity

Answer 49

``` bind looser (lower affinity) to dopamine receptors produce less dopamine related side effects ```

Question 50

second gen drugs

Answer 50

clozapine, risperidone

Question 51

Between ___-___% occupation of D2 receptors is required to produce an antipsychotic effect for both typical and atypical antipsychotics

Answer 51

60-80%

Question 52

what % of d2 r occupancy results in side effects and what are they

Answer 52

80% Parkinson-like side effects (extra pyramidal symptoms), elevated prolactin (hyperprolactinemia), tardive dyskinesia

Question 53

kinetic hypothesis for mesolimbic/nigrostriatal pathway ___ is released into the synaptic cleft, where it binds to receptors on the ___ ____ membrane

Answer 53

dopamine is released into the synaptic cleft, where it binds to receptors on the post synaptic membrane

Question 54

binding efficiency of mesolimbic/nigrostriatal pathway and why

Answer 54

tight squeeze! | high degree of receptor rebinding

Question 55

kinetic hypothesis for Tuberoinfundibular pathway

Answer 55

dopamine secreted into the blood stream and carried across the blood brain barrier via the hypophysial portal system to the pituitary gland

Question 56

binding efficiency of Tuberoinfundibular pathway and why

Answer 56

high degree of clearance, less receptor | rebinding

Question 57

Fast on, slow off compounds example

Answer 57

haloperidol

Question 58

fast on/slow off rate for compounds like haloperidol and side effects

Answer 58

high receptor binding potential at D2 in the striatum and pituitary high extrapyramidal side effects and increased prolactin release (hyperprolactinemia)

Question 59

Fast on, fast off compounds eg

Answer 59

chlopromazine

Question 60

fast on/FAST OFF rate for compounds like chlopromazine and side effects

Answer 60

The fast on rate leads to high extrapyramidal symptoms fast off rates results in prolactin release staying normal

Question 61

Slow on, fast off compounds e.g.

Answer 61

clozapine

Question 62

slow on rates for compounds like clozapine

Answer 62

lower re- binding potential and low extrapyramidal symptoms fast off rates result in prolactin release staying normal

Question 63

clozapine has unique affinity for ___ receptors side effect?

Answer 63

D4 agranulocytosis (loss of white blood cells)

Question 64

Antipsychotic medications start to work within ___ or ___ (i.e. dopamine receptor blockade reaches 65% quickly) but can take ____ to reach their full effect

Answer 64

hours, days | 4-6 weeks

Question 65

% of people resistant to schizophrenia treatment

Answer 65

30%

Question 66

% of people resistant to antipsychotic medication

Answer 66

50%

Question 67

effects of first gen antipsychotic meds

Answer 67

extrapyramidal symptoms, dyskinesias, prolactin release

Question 68

effects of second gen antipsychotic meds

Answer 68

cardiovascular effects, metabolic syndrome, diabetes, | weight gain