Psychosis and Antipsychotics Flashcards by Emily Boevers

22q11 deletions

alter expression of genes via decrease of DGCR8 protein expression

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Which of these illnessess does not have psychosis??

Brain tumors
Dementias
Endocrine disorders
Depression
Seizures
Infections
Substance intoxication/withdrawal
Delirium

Depression

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Region hyperactivated in hallucinations

secondary auditory association cortex

located in superior temporal gyrus

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Hallucinations result from increased activity from _______ and decreased activity from ________

Increased from emotional regulation/attention,

Decreased from monitoring/volitional functions

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Structures involved in delusions

fronto-striatal circuits, parietal cortices, amygdala, cerebellum

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Symptoms include: 
Delusions
Hallucinations
Disorganized speech
Disorganized/catatonic behavior
Negative symptoms (flat, alogia, avolition)

Schizophrenia
(at least two symptoms,
at least 1 from the first three
for most of at least 1 month)

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Genetics involved in schizophrenia

KCNH2
DTNBP1
NRG1
DISC1
RGS4

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Structural abnormalities in schizophrenia include:
Enlarged ventricles
Reduced total brain volume
Enlarged occipital lobes
Smaller frontal/temp/par lobes

All but enlarged occipital lobe

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Which of these cells are altered in schizophrenia pathology?
Pyramidal
Chandelier
Neurons
Oligodendrocytes
Astrocytes

All but astrocytes

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Which neurotransmitters have dysfunction in schizophrenia?

DA, glut, GABA, 5-HT, ACh

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What is the increased risk if a sibling has schizophrenia?

9% if sibling only,

16% if one parent + sibling

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What is the heritability estimate of schizophrenia?

80%

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What is the increased risk of schizophrenia in offspring?

13% if one parent,

46% if both parents

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What are examples of common variants in schizophrenia?

SNPs
Tandem repeats

Account for ~30% of risk variance
8300+ variants
100 different genes

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What are examples of rare varients in schizophrenia?

mutations
Unique CNVs (100+ w/ schiz ass’n)
- 22q11 via DGCR8 decrease
- DISC1 translocation (1/11)

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Target of antipsychotic drugs

D2 receptor

D2 side effects:
• Extrapyramidal symptoms: Nigrostriatal pathway, parkinsonism, dystonia, akathisia, tardive dyskinesia after chronic use
• Worse negative/cognitive symptoms: mesocortical pathway
• Hyperprolactinemia, galactorrhea, amenorrhea, gynecomastia (esp risperidone)

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Increases catecholamine via receptor blockade in the presence of MAO inhibition

Chlopromazine

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Classifications of antipsychotics

Chemical
First/Second generation
High/low potency

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Included in chemical class of phenothiazines

Aliphatic: chlorpromazine
Piperidine: thioridazine
Piperazine: fluphenazine, perphenazine

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First generation antipsychotics

chlorpromazine, haloperidol, fluphenazine, perphenazine, thioridazine, trifluoperazine

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Additional effects of second-generation antipsychotics

5-HT2a antagonism, D2 receptor affinity

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Low potency antipsychotics have ______ side effects related to D2 blockage, _______ side effects related to non-DA receptors

Decreased

Increased

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Non-DA side effects of antipsychotics

Anticholinergic
Antihistamine
Alpha-1 adrenergic
QTc prolongation
Increased BP, lipids, blood sugar
Neuroleptic malignant syndrome

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Side effects include agranulocytosis, seizure (high dose), constipation, sialorrhea, myocarditis, orthostatic hypotension + tachycardia

Clozapine

Shown to be more efficacious than other antipsychotics

Clozapine

Longest time to d/c in CATIE study

olanzapine

FDA approved uses of antipsychotics

``` schizophrenia schizoaffective disorder bipolar disorder major depressive disorder Tourette's syndrome ```

Moderate potency antipsychotics

perphenazine, loxapine

High potency antipsychotics

haloperidol, fluphenazine

Low potency antipsychotics

chlorpromazine

Catatonia

decreased reactivity to environment (negativism, rigid posturing, mutism, stupor)

Which major NT systems involved in psychosis?

DA, glut, GABA, 5-HT

Basal magnocellular corticopedal pathway involves...

GABA and ACh pathways

Acute fluctuating disturbance in attention, awareness, cognition

Delirium

Monitoring/volitional structures decreased during auditory hallucinations:

dlPFC, Cerebellum, DACingulate cortex

Emotional regulation and attention structures upregulated during auditory hallucinations:

OFC, VACingulate cortex, subcortical structures

Hyperactive in auditory hallucinations

Secondary auditory association cortex

Delusion of passivity means

someone/somthing external is controlling you

Thought broadcasting means

Others can hear your thoughts

Misinterpreting messages from the external world

Reference

Thought withdrawal means

Thoughts are being taken from your mind

Circuits involved in delusions

Salience/reference Agency/others Fear/paranoia

Abberrations in how brain circuits specify hierarchia predictions, how they compute and response

Delusions

the state or quality by which it stands out relative to its neighbors

Saliance

Symptom domains in Schizophrenia include

``` Delusions Hallucinations Disorganized speech Disorganized or catatonic behavior Negative symptoms (affect, alogia, avolition) ``` + Common cognitive deficits

Structures commonly involved in all delusions

prefrontal cortex, midbrain Other structures: fronto-striatal circuits, parietal cortices, amygdala, cerebellum, anterior cingulate, medial PFC

Alterations in glut affect GABA signalling, increase in glut in PFC, overinhibition of DA.

True --> too little DA results in negative symptoms

Alterations in glut affect GABA signalling, hyperactivity in NAcc and increase in DA.

True --> positive symptoms in schizophrenia

Hereditibility in schizophrenia

up to 80%. Some environmental involvement.

22q11 deletion

alters expression of multiple genes of DGCR8 (microRNA processing complex --> impact other areas of the genome)

DISC1 (disruption of schizophrenia 1)

translocation between 1/11 gene, disrupts gene, produces altered protein, interaction with many pathways (Wint, Dynein, Endopeptidate, Inflammatory, Immune) --> neurodevelopment Found in Family in Scotland, produces other mental disorders

Schiz with shorter time period

schizophreniform disorder

Schiz with low mood

schizoaffective disorder

Schizophrenia is a chronic illness

True

Potency is inverse to efficacy.

False - potency has NO relationship to efficacy.

Likely to cause hyperprolactinemia, galactorrhea, amenorrhea, gynecomastia

Risperidone | + other D2 blockades

Antihistamine effects:

Weight gain | EPS clonazapine, olanzapine

Clozapine scary SE

agranulocytosis (+ seizures, constipation, myocarditis, orthostatic hypotension, tachycardia) Use only for treatment resistant schizophrenia