Exam 4 Lecture 1 Flashcards
What are the changes made during the May 2013 DSM? Changes made during March 2022 DSM?
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
How was the DSM 5 changed with regard to mental health providers?
It was reorganized to reflect disorders across a continuum based on developmental and lifespan considerations.
What are the neurodevelopmental disorders
- Intellectual disabilities and delays
- Autism spectrum disorders
- ADHD
Where are schizophrenia, Depressive disorders and bipolar located on DSM 5?
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.
What do anxiety disorder incorporate in the DSM 5? How does this differ from previous DSM editions
Anxiety disorder includes generalized anxiety disorder, social anxiety, panic disorder
New separate chapters for OCD and related disoders and trauma and stressor related disorders
How are substance related disorders expressed in DSM 5
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)
How are neurocognitive disorders expressed in DSM 5
- categorized into major and minor neurocognitive disorders
- specifiers include type (alzheimers)
Which rating scales assess Depression? Are they patient rated or clinician rated? Other important facts?
-Hamilton depression (HAM D)- clinician rated, gold standard
- Montgomery-Asberg depression rating scale (MADRS)- Clinical trials, gold standard
Which rating scales assess Bipolar disorder and Anxiety disorders
Young mania rating scale (YMRS)- clinician rated by patient report
Hamilton anxiety rating scale- (HAM-A)
Which rating scales assess Schizophrenia
Positive and negative syndrome scale (PANSS)- gold standard, clinician rated
Brief psychiatric rating scale (BPRS)- gold standard, clinician rated
Rating scale for movement side effects of antipsychotics
Simpson Angus (SAS)- drug induced parkinsonian symptoms (clinician rated)
Barnes Akathisia scale (BARS)- Clinician rated, observation of akathisia
Rating scale for tardive dyskinesia/ overall movement side effects
Abnormal involuntary movement scale (AIMS)- tardive dyskinesia, clinician rated
Extrapyrimidal symptoms rating scale (ESRS)- clinician rated, parkinsonian symptoms, akathisia, dystonia, and tardive dyskinesia
rating scale for overall psychiatric functioning assessment
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
WHich drug for schizophrenia led to emptying of mental hospitals due to outpatient treatment
Chlorpromazine (phenothiazine)
What are the general considerations of schizophrenia
Antipsychotic=neuroleptic=antischizophrenic
most severe and debilitating psychotic disorder
affects 1% of population
Onset- 15-20 y/o
Not split personality
symptoms of schizophrenia
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
describe the etiology of schizophrenia
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
Neurotransmitter hypothesis of schizophrenia tx
Dopamine- 1st to be developed, but incomplete
Serotonin- Based on LSD mechanism and mescaline
Glutamate- Based on phencyclidine and ketamine
In the serotonin hypothesis of schizophrenia, which two drugs are identified as 5-HT agonists
LSD and mescaline
Studies identified _____ as mediator of hallucinogen in serotonin hypothesis
5 HT 2A
Antagonism and inverse agonism of 5HT2A leads to
antipsychotic behavior
Where do 5HT 2A receptors modulate dopamine release
Cortex, limbic region, striatum
what else do 5HT2A receptors modulate the release of
Glutamate and NMDA receptors
_______ agonist may be useful in schizophrenia
5HT2C
what are phencycladine and ketamine? What do they lead to?
non competitive inhibitors of NMDA receptor.
exacerbate psychosis and cognitive deficits
How do dopaminergic agents like L DOPA affect schizophrenia
Exacerbate symptoms of schizophrenia
What is seen in D2 receptor density in treated and untreated schizophrenia pts? What do imagine studies show?
Increased density of D2 receptor.
Imaging studies show increased DA release and receptor occupancy in pts
How do D2 receptor antagonists affect metabolites in CNS
D2 receptor antagonists initially increase metabolites in CNS and later decrease metabolites in CNS
Define binding affinity and Kd/Ki.
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)
MAJOR receptors antagonized by antipsychotics
Dopamine receptors
D1 like receptors (D1 and D5)
D2 like receptors (D2, D3, D4)
What are some newer agents used to antagonize serotonin receptors for antipsychotic treatment
5 HT 2A antagonists- clozapine, olanzapine, risperidone
What are some minor receptors that are antagonized by antipsychotics
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)
Which receptor is key for therapeutic
effectiveness for chlorpromazine, haloperidol, clozapine, olanzapine, aripiprazole, quetiapine? Is there a clear pattern?
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»_space; D 1
Quetiapine H 1 > a1 > M 1,3 > D 2 > 5HT 2A
No clear pattern. multiple receptors, individualize therapy based on response
What makes D2 receptors more effective drug targets
There is a correlation between binding potency and clinical effectiveness for D2 receptors
Most antipsychotics are ____
Antagonists
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
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.
How do D2 receptor antagonists antagonize actions at synapse even though more neurotransmitters are being released
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.
How do dopamine metabolities in CSF (HVA) react when antipsychotics are given
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.
Is there an tehrapeutic correlation between change in HVA levels and therapeutic efficacy in antipsychotics
Yes
What are the 5 areas of the brain where D2 antagonists exert their action?
Basal ganglia
Mesolimbic
Mesocortical
Hypothalamus and endocrine systems
Medulla
What effect do D2 antagonists have on the different areas of the brain?
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
