SZ- Risk Factors, Symptoms, Theories & Neuropathology Flashcards
List 3 positive symptoms of SZ
- Delusions
- Hallucinations
- Disorganised speech
List 4 negative symptoms of SZ
- Decrease in emotions (Blunt affection)
- Decreased motivation (Avolition)
- Poverty of speech
- Decrease pleasure (Anhedonia)
List 3 mood symptoms
- Depression/ Anxiety
- Hostility/ Aggression
- Suicide
List 3 cognitive deficits
- Attention
- Working & Verbal Memory
- Executive Function
Using diagnosis according to DSM-5
- The patient must have experienced at least 2 of the following:
– Delusions
– Hallucinations
– Disorganized speech
– Disorganized or catatonic behaviour
– Negative symptoms - At least 1 of the symptoms must be the presence of delusions, hallucinations, or disorganised speech
- Continuous signs of the disturbance must persist for at least 6 months, during which the patient must experience at least 1 month of active symptoms (or less if successfully treated), with social or occupational deterioration problems occurring over a significant amount of time
- Schizophrenia subtypes were removed from the DSM-5 because they did not appear to be helpful for providing better-targeted treatment or predicting treatment response
Diagnosis according to ICD-10
Symptoms to be present most of the time for 1 month or more, including:
* One or more of the following features if they are clear-cut:
– Hallucinatory voices
– Thought echo, thought insertion or withdrawal, and thought broadcasting.
– Delusions of control, influence, or passivity
– Persistent delusions of other kinds that are culturally inappropriate and completely impossible, such as religious or
political identity, or superhuman powers and abilities (for example being able to control the weather, or being in
communication with aliens from another world).
* Or any two of the following criteria:
– Persistent hallucinations in any form, when accompanied by fleeting or half-formed delusions without clear affective
content, or by persistent over-valued ideas (similar to preoccupations), or when occurring every day for weeks or
months on end.
– Breaks or interpolations in the train of thought, resulting in incoherence or irrelevant speech, or neologisms (invented
words).
– Catatonic behaviour, such as, excitement, posturing, or waxy flexibility; negativism; mutism; and stupor.
– Negative symptoms, such as marked apathy, reduced speech, and blunting or incongruity of emotional responses,
usually resulting in social withdrawal and lowering of social performance; it must be clear that these are not due to
depression or to antipsychotic medication.
– A significant and consistent change in the overall quality of some aspects of personal behaviour, manifest as loss of
interest, aimlessness, idleness, a self-absorbed attitude, and social withdrawal.
Schizophrenia risk factors
- Strong genetic component
- “Susceptibility genes”
– Common variants with small cumulative effect
– Rare variants with large effect - Environmental risk factors
Susceptibility genes
- Catechol-O-methyl-transferase (COMT) point mutation at position 158 Val Met
- Many affected genes are around the glutamatergic synapse
List of susceptibility genes:
1. Dysbindin
2. Neuroegluin
3. DISC-1
4. DAOA
5. DAAO
6. RGS4
7. CHRNA7
8. GAD1
9. AKT1
10.FEZ1
11. MUTED
12. MAO-!
13. Nur77
14. BDNF
15. Dopamine 2 & 3 receptors
Genetic risk factors - CNVs
- Copy number variations (CNVs) are when a segment of a chromosome is deleted or duplicated
- Many CNVs are present in healthy individuals
- CNVs associated with psychiatric and neurodevelopmental disorders
- Implicated in schizophrenia, bipolar disorder, and autism
- “All CNVs that have been implicated in SCZ are rare in the population, but confer significant risk (odds ratios 2–60)”
Environmental and other risk factors
Foetal history of obstetric complications:
- Viral infection in pregnancy e.g. influenza in 2nd trimester
- Hypoxia at birth
- Winter/autumnal birth
- Maternal malnutrition
* Dutch Hunger Winter 1944-45
* Chinese famine 1959-61
- Urbanisation
- Traumatic emotional event during childhood:
- Death of a parent
- Migration to a foreign country
- Increased paternal age
- Recreational drug use e.g. Cannabis
Structural brain changes
- Cerebral atrophy
- Enlarged ventricles
- Reduced volume of:
– Basal ganglia
– Limbic regions e.g. hippocampus
– Temporal lobe
Dopamine (DA) theory
- Agonists of dopamine neurotransmission induce psychotic symptoms
- 1st generation anti-psychotics are antagonists at
D2 receptors
Increased dopamine in the mesolimbic pathway ->
Psychotic symptoms
Dopamine pathways
Four major dopamine pathways in the brain:
- Mesolimbic pathway: an excess of dopamine in this pathway has been linked to psychosis and the positive symptoms of schizophrenia
- Mesocortical pathway: problems with neurotransmitter function in this pathway may be responsible for the negative symptoms
- Nigrostriatal pathway: motor control and Parkinson’s Disease
- Tubero-infundibular pathway: hormone secretion
Glutamate (Glu) theory
- NMDA receptor hypofunctional state induced by genetic and non-genetic factors instilled into brain early in development triggers psychosis in adulthood
- Induces complex disinhibition syndrome – this may explain the post-mortem changes observed in some
patients - May be modelled in animals by NMDA receptor antagonism
GABAergic deficits
- Post-mortem studies provide evidence for specific deficits in parvalbumin (PV) immunoreactive GABAergic
interneurons in the PFC in schizophrenia. - Cortical and hippocampal inhibitory GABA neurons are a central element in the pathology of schizophrenia.
