Exam 4 Lecture 1

Question 1

What are the changes made during the May 2013 DSM? Changes made during March 2022 DSM?

Answer 1

May 2013- Publication of the DSM with many changes made. Including moving from roman numerals to express edition to arabic numbers

March 2022- publication of the DSM-5, TR, added further SDOH and cultrual factors in diagnosis

Question 2

How was the DSM 5 changed with regard to mental health providers?

Answer 2

It was reorganized to reflect disorders across a continuum based on developmental and lifespan considerations.

Question 3

What are the neurodevelopmental disorders

Answer 3

1. Intellectual disabilities and delays
2. Autism spectrum disorders
3. ADHD

Question 4

Where are schizophrenia, Depressive disorders and bipolar located on DSM 5?

Answer 4

Bipolar related disorders and depressive disorders have separate chapters. Bipolar is found between schizophrenia spectrum and depressive disorders- reflecting the overlapping nature of bipolar disorders.

Question 5

What do anxiety disorder incorporate in the DSM 5? How does this differ from previous DSM editions

Answer 5

Anxiety disorder includes generalized anxiety disorder, social anxiety, panic disorder

New separate chapters for OCD and related disoders and trauma and stressor related disorders

Question 6

How are substance related disorders expressed in DSM 5

Answer 6

No more abuse and dependence

Set criteria for all substances that only vary with symptom presentation based on type of substance used

(includes gambling disorder- other behavioral excess have been studied but not yet included)

Question 7

How are neurocognitive disorders expressed in DSM 5

Answer 7

• categorized into major and minor neurocognitive disorders
• specifiers include type (alzheimers)

Question 8

Which rating scales assess Depression? Are they patient rated or clinician rated? Other important facts?

Answer 8

-Hamilton depression (HAM D)- clinician rated, gold standard

• Montgomery-Asberg depression rating scale (MADRS)- Clinical trials, gold standard

Question 9

Which rating scales assess Bipolar disorder and Anxiety disorders

Answer 9

Young mania rating scale (YMRS)- clinician rated by patient report

Hamilton anxiety rating scale- (HAM-A)

Question 10

Which rating scales assess Schizophrenia

Answer 10

Positive and negative syndrome scale (PANSS)- gold standard, clinician rated

Brief psychiatric rating scale (BPRS)- gold standard, clinician rated

Question 11

Rating scale for movement side effects of antipsychotics

Answer 11

Simpson Angus (SAS)- drug induced parkinsonian symptoms (clinician rated)

Barnes Akathisia scale (BARS)- Clinician rated, observation of akathisia

Question 12

Rating scale for tardive dyskinesia/ overall movement side effects

Answer 12

Abnormal involuntary movement scale (AIMS)- tardive dyskinesia, clinician rated

Extrapyrimidal symptoms rating scale (ESRS)- clinician rated, parkinsonian symptoms, akathisia, dystonia, and tardive dyskinesia

Question 13

rating scale for overall psychiatric functioning assessment

Answer 13

CLinician global impression (CGI)
CGI-S -severity
CGI- I- improvement
Observer rated
Used to assess change overtime

Global assessment of functioning (GAF)
clinician rated
variable results based on clinician evaluation and experience

Question 14

WHich drug for schizophrenia led to emptying of mental hospitals due to outpatient treatment

Answer 14

Chlorpromazine (phenothiazine)

Question 15

What are the general considerations of schizophrenia

Answer 15

Antipsychotic=neuroleptic=antischizophrenic
most severe and debilitating psychotic disorder
affects 1% of population
Onset- 15-20 y/o
Not split personality

Question 16

symptoms of schizophrenia

Answer 16

Positive symptoms- Hallucinations, delusions, bizarre behavior, thought disorders (respond well to drug treatment)

Negative symptoms- Blunted emotion, poor self care, social withdrawal, poverty in speech (do not respond well to drug treatment)

cognitive symptoms- decrease in cognitive functions. Involves D1 receptors and glutamate receptors

Question 17

describe the etiology of schizophrenia

Answer 17

Neurodevelopmental/anatomical-

in utero/adolescence- increase ventricle size an changes in gray and white matter

genetics- growth migration of neurons (twin studies, families-multiple genes)

Environmental- Birth complications, infections

Gene- environmental interaction- COMT-marijuana

Question 18

Neurotransmitter hypothesis of schizophrenia tx

Answer 18

Dopamine- 1st to be developed, but incomplete
Serotonin- Based on LSD mechanism and mescaline
Glutamate- Based on phencyclidine and ketamine

Question 19

In the serotonin hypothesis of schizophrenia, which two drugs are identified as 5-HT agonists

Answer 19

LSD and mescaline

Question 20

Studies identified _____ as mediator of hallucinogen in serotonin hypothesis

Answer 20

5 HT 2A

Question 21

Antagonism and inverse agonism of 5HT2A leads to

Answer 21

antipsychotic behavior

Question 22

Where do 5HT 2A receptors modulate dopamine release

Answer 22

Cortex, limbic region, striatum

Question 23

what else do 5HT2A receptors modulate the release of

Answer 23

Glutamate and NMDA receptors

Question 24

_______ agonist may be useful in schizophrenia

Answer 24

5HT2C

Question 25

what are phencycladine and ketamine? What do they lead to?

Answer 25

non competitive inhibitors of NMDA receptor.
exacerbate psychosis and cognitive deficits

Question 26

How do dopaminergic agents like L DOPA affect schizophrenia

Answer 26

Exacerbate symptoms of schizophrenia

Question 27

What is seen in D2 receptor density in treated and untreated schizophrenia pts? What do imagine studies show?

Answer 27

Increased density of D2 receptor.
Imaging studies show increased DA release and receptor occupancy in pts

Question 28

How do D2 receptor antagonists affect metabolites in CNS

Answer 28

D2 receptor antagonists initially increase metabolites in CNS and later decrease metabolites in CNS

Question 29

Define binding affinity and Kd/Ki.

Answer 29

Binding affinity- intermolecular force between ligand and receptor.
Kd/Ki is the concentration at which 1/2 of receptors are occupied.
(low number is tight)

Question 30

MAJOR receptors antagonized by antipsychotics

Answer 30

Dopamine receptors
D1 like receptors (D1 and D5)
D2 like receptors (D2, D3, D4)

Question 31

What are some newer agents used to antagonize serotonin receptors for antipsychotic treatment

Answer 31

5 HT 2A antagonists- clozapine, olanzapine, risperidone

Question 32

What are some minor receptors that are antagonized by antipsychotics

Answer 32

NE (norepinephrine)
a1 receptor blockade- causes hypotension and sedation
a2 blockade- may be useful in therapy

Ach
Muscarinic receptors

histamine
H1 receptor antagonist (sedation and weight gain)

Question 33

Which receptor is key for therapeutic
effectiveness for chlorpromazine, haloperidol, clozapine, olanzapine, aripiprazole, quetiapine? Is there a clear pattern?

Answer 33

Chlorpromazine a1 = 5HT 2A > D 2 > D 1
Haloperidol D 2 > a1 > D 4 > 5HT 2A > D 1 > H 1
Clozapine D 4 = a1 > 5HT 2A > D 2 = D 1
Olanzapine 5HT 2A > H 1 > D 4 > D 2 > a1 > D 1
Aripiprazole D 2 = 5HT 2A > D 4 > a1 = H 1&raquo_space; D 1
Quetiapine H 1 > a1 > M 1,3 > D 2 > 5HT 2A

No clear pattern. multiple receptors, individualize therapy based on response

Question 34

What makes D2 receptors more effective drug targets

Answer 34

There is a correlation between binding potency and clinical effectiveness for D2 receptors

Question 35

Most antipsychotics are ____

Answer 35

Antagonists

Question 36

How are presynaptic receptors involved in synthesis and release of neurotransmitters? what effect will blocking these presynaptic receptors have on synthesis and release of neurotransmitter

Answer 36

presynaptic receptors have a safety switch if too much is being produced.
If pre synaptic receptors are blocked, there is an increase in synthesis and relapse.

Question 37

How do D2 receptor antagonists antagonize actions at synapse even though more neurotransmitters are being released

Answer 37

They block both pre and post synaptic signalling, so even though there is more dopamine being released, no exacerbations because post synaptic is also blocked.

Question 38

How do dopamine metabolities in CSF (HVA) react when antipsychotics are given

Answer 38

CSF levels of HVA increase when antipsychotic is given. There is an increase in synthesis and release of dopamine (therefore an increase in dopamine metabolite) overtime. That increase dissipates overtime as adaptive response occurs.

Question 39

Is there an tehrapeutic correlation between change in HVA levels and therapeutic efficacy in antipsychotics

Answer 39

Yes

Question 40

What are the 5 areas of the brain where D2 antagonists exert their action?

Answer 40

Basal ganglia
Mesolimbic
Mesocortical
Hypothalamus and endocrine systems
Medulla

Question 41

What effect do D2 antagonists have on the different areas of the brain?

Answer 41

Basal ganglia (nigrostriatal pathway)- Motor effects, EPS
Mesolimbic- Primary therapeutic effects
Mesocortical- Hypofunction in schizophrenia, antagonists may exacerbate cognitive deficits
Hypothalamus and endocrine systems- D2 receptor blockade in endocrine system
Medulla- chemoreceptor triggerzone, D2 antagonists are antiemetics