Schizophrenia Flashcards
1- who and where did the term come from?
2- afflicts how much of the worlds population?
3- what do ancient writings indicate?
4- what are the major symptoms of schizophrenia (cultures)
5- what cost?
6- what is schizophrenia?
1- Eugen Bleuler (1908) – term “schizophrenia” to refer to a break from reality
2- Afflicts 1% of the world’s population
3- Ancient writings indicate that the disorder has been around for thousands of years
4- The major symptoms of schizophrenia are universal, similar across cultures
5- Monetary cost - exceeds the cost of all cancers and is associated with much higher (13x) suicide rate compared to the general population
6- Schizophrenia is a syndrome – ‘a collection of signs and symptoms of unknown aetiology’ (Insel, 2010, Nature)
Symptoms of Schizophrenia:
- categories?
- symptom onset?
- when do they appear?
- what symptoms are the first to emerge?
- Three categories of symptoms: positive, negative, and cognitive
- Symptom onset is usually in early adulthood but can happen earlier or later
- Appear gradually, over a period of 3-5 years.
- Negative symptoms are the first to emerge, followed by cognitive symptoms. The positive symptoms emerge last.
Positive Symptoms:
- how do they make themselves known?
- what do they include?
- explain one in depth
- Make themselves known by their presence (excess).
- They include thought disorders, delusions and hallucinations
- Thought disorders:
– disorganized, irrational thinking - probably the most important symptom of schizophrenia
– great difficulty arranging thoughts logically, and sorting out plausible conclusions from absurd ones.
– during conversation they jump from one topic to another as new associations come up.
– sometimes utter meaningless words or choose words for rhyme rather than for meaning.
What are delusions and what are the types?
Delusions are beliefs that are contrary to fact. There are many types:
- persecution - false beliefs that others are plotting and conspiring against oneself.
- grandeur - false beliefs about one’s power and importance (godlike powers, special knowledge that no one else possesses)
- control related to persecution i.e the person believes that he or she is being controlled by others through radar or a tiny radio receiver implanted in his or her brain.
What are hallucinations and what are the types?
Hallucinations are perceptions of stimuli that are not actually present.
- Most common are auditory, but they can involve any of the other senses.
- Typically, voices talk to the person, order them to do something, scold the person for his or her unworthiness or utter meaningless phrases.
- Olfactory hallucinations are also fairly common and they often contribute to the delusion that others are trying to kill them (smelling things which are not there)
Negative Symptoms
Known by the absence or diminution of normal behaviours:
- flattened emotional response
- poverty of speech
- lack of initiative
- persistence
- anhedonia
- social withdrawal
What do cognitive symptoms include?
- difficulty in sustaining attention
- low psychomotor speed (the ability to rapidly and fluently perform movements of the fingers, hands, and legs)
- deficits in learning and memory
- poor abstract thinking
- poor problem solving
Cognitive Symptoms:
- what are neurocognitive deficits associated with?
- what did Weinberger (1988) suggest?
- All neurocognitive deficits are associated with frontal lobe hypofunction
- Weinberger (1988) suggested that the negative symptoms of schizophrenia are caused primarily by hypofrontality, decreased activity of the frontal lobes, the dlPFC in particular
– Lower performance in IQ tests
– Planning and information processing deficits
– Attentional deficits (e.g. Stroop test)
– Working memory deficits (e.g. Wisconsin Card Sorting Test)
– Sensory-motor gating deficits (P50 and PPI tasks)
– Anti-saccade task
– Oculomotor function (eye tracking)
dlPFC in controls vs schizophrenia
less activation in frontal lobes and dlPFC compared to controls
The Stroop task
- The instructions are to name the colour of the ink in two conditions: congruent (word and ink colour are in agreement) and incongruent (colour of ink and word are not in agreement)
- Schizophrenia patients are slower and less accurate
- Involves inhibiting the tendency to read the words
Wisconsin Card Sort Test
Stack cards in different piles- change strategies until you do what they expect you to do. People with sz are unable to change their strategy and organise their cards in a different way.
Normally, during the task, there is an increase in regional blood flow to the dlPFC as measured by fMRI
What are sensory-motor gating deficits?
Difficulties screening out irrelevant stimuli and focusing on salient ones
Sensory-Motor Gating Deficits
1
P50 signal in ERPs (Event-Related Potentials)
- Presented with 2 auditory stimuli (2 clicks) 500ms apart
- Healthy response - P50 wave to 2nd click is 80% diminished whereas in schizophrenic patients there is no change. Sz pp’s respond in the same way to the second click.
Sensory-Motor Gating Deficits
2
- Pre-Pulse Inhibition (PPI)
- When a weak stimulus precedes a startle stimulus by ~100ms the normal response is to inhibit the startle
- People with schizophrenia do not inhibit the startle
Oculomotor Function
Smooth pursuit - Tracking a moving stimulus
The eye movements of schizophrenic patients are not smooth compared to controls (“catchup” saccades)
Structural Differences:
What did Weinberger and Wyatt (1982) do and find?
- Weinberger and Wyatt (1982): CT scans of 80 schizophrenics and 66 healthy controls of the same mean age (29y) and measured the area of the lateral ventricles (blind study)
- The relative ventricle size of the schizophrenic patients was more than twice as big as that of normal control subjects
- Reduced brain volume (less grey matter) in temporal, frontal lobes and hippocampus
- Faulty cellular arrangement in the cortex and hippocampus
Heritability and Genetics:
- what do both adoption and twin studies show?
- so far…
- what does having a “schizophrenia gene” cause?
- Both adoption studies and twin studies indicate that schizophrenia is a heritable trait although it is not due to a single dominant or recessive gene
- So far, no single gene has been shown to cause schizophrenia. Rather, several genes are involved.
- Having a “schizophrenia gene” causes a susceptibility to develop schizophrenia which may be triggered by environmental factors.
Genetics of Schizophrenia
- what does one rare mutation involve?
- explain about this gene?
- One rare mutation involves a gene known as DISC1 (disrupted in schizophrenia 1)
– involved in the regulation of neurogenesis, neuronal migration, postsynaptic density in excitatory neurons, and mitochondria function
– Its presence appears to increase the chance of schizophrenia by a factor of 50
– Also increases the incidence of other mental health conditions, including Bipolar Disorder, and Autism Spectrum Disorder (Kim et al., 2009).
Paternal Age
- what does the effect of paternal age provide?
- who are more likely to develop schizophrenia
- most likely due to?
– what happens following puberty?
– in contrast…
- The effect of paternal age provides further evidence that genetic mutations may affect the incidence of schizophrenia (Brown et al., 2002; Sipos et al., 2004).
- The children of older fathers are more likely to develop schizophrenia.
- Most likely due to mutations in the spermatocytes, the cells that produce sperm.
- Following puberty, these cells divide every 16 days, which means that they have divided approximately 540 times by age 35
- In contrast, a woman’s oocytes divide 23 times before birth and only once after that.
Percent developing schizophrenia
Higer incidence in DZ (17%)
MZ is even higher (48%)
One one hand we have genetic contribution but on the other hand genetics cannot explain everything because we have a big percentage here that is attributed to unknown environmental factors.
Twin Studies
- MZ twins?
- when does the formation of MZ twins occur?
- what happens if this occurs before day 4?
- what happens if this occurs after day 4?
- what was the concordance rate for monochrionic MZ twins?
- MZ twins are genetically identical, but they also share the same intrauterine environment. However, the prenatal environment of monozygotic twins is not always identical
- The formation of MZ twins occurs when the blastocyst splits in two.
- If this occurs before day 4, the two organisms develop independently, each forming their own placenta – dichorionic
- If this occurs after day 4, the two organisms become monochorionic - share a single placenta.
- The concordance rate for monochorionic MZ twins was found to be 60% vs 32% in dichorionic MZ twins (Davis and Phelps, 1995)
The ‘early’ neurodevelopmental model:
- Events in early life (prenatally) cause deviations from normal neurodevelopment and these lie dormant until the brain matures sufficiently to call into operation the affected systems (Murray & Lewis, 1987)
- Early events such as infections, obstetric complications, nutritional deficiencies etc. provide evidence in support of this theory.
