Schizophrenia & Antipsychotics Flashcards
Shcizophrenia age of onset:
- Men 20-28 Yrs
- Women 26-32 Yrs.
Age on onset = either diagnosis or first psychiatric episode
Schizophrenia biological basis in brain:
Large ventricle spaces in brain - bigger in people with schizophrenia potentially due to brain shrinkage.
Schizophrenia genetic risk factors:
It appears that multiple genes are involved in creating a predisposition to developing the disorder.
“Susceptibility genes”
KCNH2, DTNBP1, NRG1, DISC1, RGS4.
Schizophrenia environmental risk factors
Prenatal problems, obstetric complications, urban/city birth, stressful life events, drug abuse
Examples of positive symptoms:
something added to the persons personality
- Delusions
- Hallucinations
- Disorganized Speech
Examples of negative symptoms:
Depression like symptoms, things taken away from personality
- Emotion
- Decreased motivation
- Interests
- Thought and Speech
- Pleasure
Example of cognitive deficits in schizophrenia:
- Attention
- Working + Verbal Memory
- Executive Function
Mood symptoms of schizophrenia:
- Depression/Anxiety
- Hostility/Aggression
- Suicide
Positive symptoms hypothetically malfunctioning brain circuit.
Mesolimbic and striatal
Negative symptoms hypothetically malfunctioning brain circuit.
Mesocortical/prefrontal cortex
Nucleus accumbent reward circuits
Affective symptoms hypothetically malfunctioning brain circuit. :
Ventromedial prefrontal cortex
Aggressive symptoms hypothetically malfunctioning brain circuit:
Orbitofrontal cortex
Amygldala
Cognitive symptoms hypothetically malfunctioning brain circuit:
Dorsolateral prefrontal cortex
What is DSM-V?
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V)
Psychiatric Diagnoses are categorized by the DSM-V
Covers all mental health disorders for both children and adults
Dopamine theory/treatment:
- Increased dopamine in subcortical pathways
- Psychotic Symptoms
- Agonists of Dopamine neurotransmission induce psychotic symptoms e.g. amphetamine
Antipsychotics are ANTAGONISTS at dopamine D2 receptors. Works by getting into the brain and compete with dopamine for the d2 receptor .
Glutamate theory:
NMDA hypofunction
- NMDA receptor hypofunctional state induced by genetic and non-genetic factors instilled into the brain early in development triggers psychosis in adulthood
- Clinical Observations (Phencyclidine)
People who take PCP and render their NMDA receptors hypofunctional not only experience positive symptoms such as delusions and hallucinations but also affective symptoms, such as blunted affect, negative symptoms, such as social withdrawal, and cognitive symptoms, such as executive dysfunction.
Current treatments: Typical Antipsychotics (neuroleptics) examples and mode of action:
e. g. Haloperidol, Chlorpromazine
- High affinity for dopamine D2 receptors
- Effective against the +ve symptoms
- Ineffective against the -ve symptoms
Typicals (>Atypicals)
- cause motor control impairments, due to their increased blockade of Dopamine D2 receptors. Parkinsonian symptoms, Undesriable SE’s
Atypical Antipsychotics examples:
e. g. Clozapine, Olanzapine, Resperidone
- Higher affinity for serotonin (5-HT2) than dopamine D2 receptors
- “Rich” pharmacology – dirty drugs
- Effective against the +ve symptoms
- Improved efficacy against -ve symptoms ??
Less motor impairments, Significant side-effects, e.g. Weight gain, Metabolic syndrome, Agranulocytosis
4 major pathways of dopamine neurones:
1) Nigrostriatal pathway
2) Mesolimbic pathway
3) Mesocortical pathway
4) Tuberoinfundibular pathway
Side effects of atypical antipsychotics:
Weight gain, dyslipidemia, CVD, diabetes, hyper glycemia, insulin resistance , EPS
What is the window of occupancy:
- Window of occupancy between efficacy & Side effect
- Doses to reach these thresholds vary across antipsychotics
Need to block certain % of receptor to see efficacy. If you increase dose, you increase blockade of receptor – side effects i.e. 70-80% gives parkinsonian side effects
Haloperidol SE’s:
High risk of extrapyramidal side effects however no weight gain
Mechanisms of antipsychotic induced weight gain?
Not fully understood
Theories include antagonism of
- Histamine H1 receptors
- Serotonin 5HT2c receptors
- D2 receptors
- Affecting hormonally controlled systems e.g. leptin
- Marked individual variation implies importance of genetic factors
- Future genetic tests to identify individual susceptibility
Managing weight gain in schizophrenia:
- Warn patients before starting high risk drugs
- Early hunger, snacking and early weight gain all predict long term weight gain
- Weight management - eat less move more
Non-pharmacological weight-management interventions should be a priority (particularly in the early stages of antipsychotic treatment).
Other psychotic drugs for weight gain:
Greater risk of weight gain:
- TCA’s
- Mirtazapine
- Lithium
- Valproate
- Carbamazepine
Lower risk of weight gain:
- SSRI’s
- Duloxetine
- Agomelatine
- Lamotrigine
