Flashcards in Psychosis and Antipsychotics Deck (58):
alter expression of genes via decrease of DGCR8 protein expression
Which of these illnessess does not have psychosis??
Region hyperactivated in hallucinations
secondary auditory association cortex
(located in superior temporal gyrus)
Hallucinations result from increased activity from _______ and decreased activity from ________
Increased from emotional regulation/attention,
Decreased from monitoring/volitional functions
Structures involved in delusions
fronto-striatal circuits, parietal cortices, amygdala, cerebellum
Negative symptoms (flat, alogia, avolition)
(at least two symptoms,
at least 1 from the first three
for most of at least 1 month)
Genetics involved in schizophrenia
Structural abnormalities in schizophrenia include:
Reduced total brain volume
Enlarged occipital lobes
Smaller frontal/temp/par lobes
All but enlarged occipital lobe
Which of these cells are altered in schizophrenia pathology?
All but astrocytes
Which neurotransmitters have dysfunction in schizophrenia?
DA, glut, GABA, 5-HT, ACh
What is the increased risk if a sibling has schizophrenia?
9% if sibling only,
16% if one parent + sibling
What is the heritability estimate of schizophrenia?
What is the increased risk of schizophrenia in offspring?
13% if one parent,
46% if both parents
What are examples of common variants in schizophrenia?
Account for ~30% of risk variance
100 different genes
What are examples of rare varients in schizophrenia?
Unique CNVs (100+ w/ schiz ass'n)
- 22q11 via DGCR8 decrease
- DISC1 translocation (1/11)
Target of antipsychotic drugs
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)
Increases catecholamine via receptor blockade in the presence of MAO inhibition
Classifications of antipsychotics
Included in chemical class of phenothiazines
• Aliphatic: chlorpromazine
• Piperidine: thioridazine
• Piperazine: fluphenazine, perphenazine
First generation antipsychotics
chlorpromazine, haloperidol, fluphenazine, perphenazine, thioridazine, trifluoperazine
Additional effects of second-generation antipsychotics
5-HT2a antagonism, D2 receptor affinity
Low potency antipsychotics have ______ side effects related to D2 blockage, _______ side effects related to non-DA receptors
Non-DA side effects of antipsychotics
Increased BP, lipids, blood sugar
Neuroleptic malignant syndrome
Side effects include agranulocytosis, seizure (high dose), constipation, sialorrhea, myocarditis, orthostatic hypotension + tachycardia
Shown to be more efficacious than other antipsychotics
Longest time to d/c in CATIE study
FDA approved uses of antipsychotics
major depressive disorder
Moderate potency antipsychotics
High potency antipsychotics
Low potency antipsychotics
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
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
Thought withdrawal means
Thoughts are being taken from your mind
Circuits involved in delusions
Abberrations in how brain circuits specify hierarchia predictions, how they compute and response
the state or quality by which it stands out relative to its neighbors
Symptom domains in Schizophrenia include
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.
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
Schiz with low mood
Schizophrenia is a chronic illness
Potency is inverse to efficacy.
False - potency has NO relationship to efficacy.
Likely to cause hyperprolactinemia, galactorrhea, amenorrhea, gynecomastia
(+ other D2 blockades)
EPS clonazapine, olanzapine