What is the definition of schizophrenia by ICD-10?
a severe and enduring disorder, with fundamental and characteristic distortions of thinking and perception, and affects that are inappropriate or blunted. clear consciousness and intellectual capacity are usually maintained, although cognitive deficits may evolve in the course of time
+ accompanied by high levels of social dysfunction, inability to maintain employment, depression and suicide
What are the different symptoms in schizophrenia?
- -> positive symptoms (psychosis)
- delusions
- hallucinations
- thought disorder
- -> negative symptoms (deficit)
- flat or blunted affect and emotion
- poverty of speech (logia)
- anhedonia (inability to experience pleasure)
- associability (lack of desire to form relationships)
- avolition (lack of motivation)
- -> cognitive impairements
- particularly memory and executive function
What is the difference between hallucination and delusion?
- delusion: fixed, false belief, unshakeable by superior evidence to the contrary, and out of keeping with a person’s cultural norms
- hallucination: a perception, internally generated, in the absence of an external stimulus
What types of delusions do you see in schizophrenia?
- reference: believe things are directed at yourself when they are not
- persecution: people are out to get you
- control: people are controlling you
- bizarre and impossible
What types of hallucinations are typically seen in schizophrenia?
auditory
+ telling them to do things/ negative things about themselves, are very distressing
What is the prevalence of schizophrenia in a population?
- 10-20 per 100000 adult population per year
- UK prevalence: 0.4%
What is the modal age of onset?
Median age?
modal: 20
median: 26 (male, 29 (females)
What is the male:female ratio for schizophrenia?
1.4:4
What is the genetic risk in schizophrenia?
-7% risk in 1st degree relative
-2.3% in second degree relative
-10% dizygotic co-twins
-45% monozygotic co-twins
(SZ inherited not learned)
What is the genes involved in Sz?
- over 200
- connected to glutamate, dopamine and GABA neurotransmitter function, neuronal structures, plasticity, general synaptic function, or to inflame/immune response
What are the environmental risk involved in Sz?
- child abuse, taken into care
- cannabis or other substances misuse
- second generation of UK ethnic minority
- migration
- peri-natal oxygen deprivation, maternal starvation while in utero
- urban living, overcrowded parental separation, general deprivation as a child
How is the onset and presentation of Sz?
- preceded by subtle social and cognitive impairment, even in infant
- (prodromal/at risk state): often progresses over years from vague symptoms of depression, anxiety, insomnia or negative symptoms to vague but psychotic symptoms and then full psychosis
–> you can manage to not develop psychosis (early development or prodromal stages)
What are the diagnosis criteria under ICD-10?
- -> at least 1 first rank symptom for at least 1 month:
1. thought echo, thought insertion, thought withdrawal, thought broadcasting
2. delusions of control, influence or passivity, clearly referred to body or limb movements or specific thoughts, actions and sensations
3. auditory hallucinations giving a running commentary or discussing the patient between themselves, hallucinatory voices from parts of the body
4. persistent delusions that are completely impossible - -> OR at least 2 second rank symptoms (for a mouth)
1. other persistent hallucinations in any modality
2. thought disorder (neologisms, loosening or breaks in he train of though resulting in incoherent or irregular speech)
3. catatonic behaviour
4. negative symptoms, not due to depression or medications
What are the four major projections of the dopamine system?
- nigrostriatal pathway
2 mesolimbic pathway - mesocortical pathway
- tuberoinfundibulnar pathway
What are the components of the nigrostriatal pathway projection in Sz?
substantia nigra (SNc;A9) to striatum
- -> SNc to sensiromotor (dorsal) striatum: motor (involuntary) control
- -> SNc to associative (mid) striatum: cognition, volition, emotion
What are the components of the mesolimbic pathway projection in Sz?
- ventral tegmental area (VTA, A10) in midbrain to limbic regions associated with reward, motivation, affect and memory
- includes ventral striatum (nucleus accubens), amygdala, hippocampus and medial prefrontal cortex
What are the components of the mesocortical pathway projection in Sz?
VTA to frontal cortex, including dorsolateral prefrontal cortex (DLPFC)
–> cognitive function, motivation and emotional response
What are the components of the tuberoinfundibular pathway projection in Sz?
puberal region (hypothalamus) to median eminence (infundibular region at top of pituitary stalk) --> DA acts to inhibit prolactin release from pituitary
What are the different types of dopamine receptors and where do you find them?
- -> D1 receptor family
- D1 (motor, associative, ventral striatum + cerebral cortex)
- D5 (hippocampus and hypothalamus)
- -> D2 receptor family
- D2 (L+S) (motor, associative, ventral striatum)
- D3 (ventral and associative striatum, hippocampus and amygdala)
- D4 (frontal cortex, medulla, midbrain and amygdala)
auto receptors on terminals (SNc and VTA):
D2S: DA synthesis, metabolism and release
D3: DA release
Which are the receptors that are heterogeneously dispersed in the brain?
D1 and D2: seen in all functional subdivisions of the striatum
D4: seen most in frontal cortex
What are the DA abnormalities in Sz and how does it relate to symptoms?
- excessive DA release in the striatum (associative): positively correlates with positive symptoms and with good treatment response to antipsychotic drugs
- inadequate release of dopamine in the frontal cortex: associated with deficits in cognitive function (DLPFC)
(3. normal to decrease DA in ventral striatum (limbic))
What is the primary abnormality in Sz?
GABA or glutamate systems:
NMDA receptor is hypofunctional
by what mechanisms of dysfunction does decrease NMDAr function cause Sz?
- excessive glutamate release: causing excitotoxicity (impaired neuronal development, makes disease progression worse): neg symptoms
- DA dysregulation via glu-DA interactions: postive symptoms
What is the GLU-DA interaction hypothesis?
- neurodevelopmentally hypofunctional NMDA receptor mediated synapse on parvalbumin-containing GABA neurones (cortex)
- GABA release is low and doesn’t adequately suppress portico-brainstem glutamate outflow
- excessive direct glutamate stimulation of SNc DA interneuron cell bodies leads to increase DA in associative striatum and sensorimotor striatum
- excessive indirect glutamate stimulation of mesocortical/mesolimbic DA neurones cell bodies in VTA (increase GABA interneurone)
- decrease DA release in cortex
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pharmacology66
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EBM39
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neuroembryology/case 151
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laws and ethics19
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BSS30
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histology65
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pain/ case 278
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addiction22
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Vision141
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sensation/perception/attention21
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the ear45
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stroke/case 539
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memory33
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General Anxiety Disorder20
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MS19
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major depressive disorder32
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case 7/ Parkinson's disease35
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schizophrenia37
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neuromuscular/case 969
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case 1024
