Psychology 2310A/B Lecture Notes - Risperidone, Olanzapine, Clozapine

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Schizophrenia (cont’d)
Biological Aspects of Schizophrenia
Genetics
Monozygotic concordance rate = 48%
Polygenic
oNot one, but many different genes
oProduces varying degree of vulnerability across individuals
“Schizophrenic spectrum” concept may be a number of different disorders related to
schizophrenia ranging from least serious to severe
Diathesis-stress models the development of schizophrenia may have a lot to do with
the environment in which a person grew up
Biochemistry – Dopamine Hypothesis
Dopamine is involved in: movement, cognition (memory, attention, problem
solving), motivation and pleasure, sociability
3 Dopamine subsystems
oNigrostriatal – substantia nigra, basal ganglia (Parkinson’s disease)
oMesolimbic – limbic system – reward
oMesocortical –frontal lobes, motor areas
D2 receptors – positive symptoms (delusions, hallucinations) benefit from
antipsychotics (too much dopamine reception happening)
D1 receptors – negative symptoms – inadequate receptor binding antipsychotics can
make these worse (not enough dopamine reception happening)
Evidence for dopamine hypothesis:
oEffects of antipsychotic drugs
oEffects of drugs that increase dopamine (amphetamines, cocaine, L-Dopa)
Excess dopamine production? Receptors? – unclear
Other neurotransmitters: Norepinephrine, glutamate, serotonin, and GABA
Neurophysiology
Structural and functional abnormalities
oDifferent patterns in different patients
oNo integrated model of neural pathology people with schizophrenia have
different abnormalities in the brain
Enlarged lateral ventricles
Cortical atrophy (shrunken cortex) – esp. frontal lobes, also temporal lobes, basal
ganglia
Frontal lobe (hypofrontality): executive functions, avolition, personality change,
working memory
Left temporal lobe: thought disorder, bizarre language, memory, selective attention
Right temporal lobe: flat affect, aprosodia (difficulty picking up the meaning from
your tone of voice sarcasm etc), poor discrimination of facial emotion
Basal ganglia: abnormal motor behavior – rocking, pacing, stereotyped movements,
catatonia
Antipsychotic (Neuroleptic) Medications
Traditional Antipsychotics – 1950s & 60s
oE.g., Chlorpromazine (first tried in London, ON), Haloperidol
oBlock postsynaptic dopamine receptors
oReduce positive symptoms (but not negative)
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Atypical” antipsychotics – 1990s
oE.g., Clozapine, Risperidone, Olanzapine
oTarget serotonin as well as dopamine
oMore effective, fewer side effects
oBut still do not cure the disorder – high relapse rates
oLong-term maintenance doses needed
Side effects of antipsychotic medications
oWeight gain, anxiety, insomnia, dry mouth, constipation, low blood pressure,
sexual dysfunction
oBlurred vision, dizziness, drowsiness
oParkinson-like symptoms (tremors, rigidity)
oDiabetes
oTardive dyskinesia irreversible
oClozapine: immune suppression, risk of death
Weekly blood checks needed to look at white blood cell count
Personality Disorders (Axis II)
From Personality Traits to Personality Disorders
What is a personality trait?
A stable characteristic that make us unique
Personality Disorders (DSM-5):
Enduring (stable) pattern of inner experience (thoughts and feelings) and behaviour
(observable) that deviates markedly from cultural norms
Manifested in 2 or more areas: cognition, affectivity, interpersonal functioning,
impulse control
Inflexible, pervasive across situations
Clinically significant distress or impairment
Stable, long duration – since adolescence or early adulthood
Not a manifestation of another mental disorder, or due to effects of drugs, or general
medical condition
Continuum of Personality Traits
Example: Perfectionism
oAdaptive: “I take pride in what I do”
oSub-clinical: “I feel I have to work on things until I get them right”
oProblematic: “I can’t stop working on something until its perfect, even if it
already satisfies what I need it for”
oDysfunctional: “Because nothing is ever good enough, I never finish
anything”
Common Features of Personality Disorders
Disrupted interpersonal relationships
Repetitive, self-defeating behaviour patterns
Externalizing of blame
Lack of responsibility, empathy toward others
Limited subjective distress (ego-syntonic, meaning they see their personality as
good, rather than ego-dystonic)
Highly resistant to change – limited treatment effectiveness
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