Download - Schizophrenia
Biological explanations of Schizophrenia
Assumptions of biological explanations
All mental disorders have a physical cause. (micro-organisms, genetics, biochemistry or neuroanatomy)
Mental illnesses can be described in terms of clusters of symptoms.
Symptoms can be identified, leading to the diagnosis of an illness.
Diagnosis leads to appropriate physical treatments.
Schizophrenia: genetics factors
Supports a biological view as prevalence does not vary with environment
However, there are variations within broad geographical areas (e.g. Torrey 2002 – found high rates of Sz in Ireland, 4% of the population, the incidence is also high in Croatia and Scandinavian countries but low in Spain and Italy and very low in some parts of Africa)
Prevalence of schizophrenia is the same all over the world (about 1%)
How do we study the influence of genetic factors?
Twin studies
Monozygotic twins
Dizygotic twins
Share the same genes and the
same environment
Share as many genes as siblings but share the same
environment
However one is usually born bigger than the other
However they might be treated
differently
If the concordance rate is 100% in MZ twins it means
that the characteristic is genetically determined.
If it less than the 100% but higher that DZ twins What
does it mean?
Concordance rate: the proportion of pairs where both
individuals share a certain characteristic.
Adoption studies
Family studies
Children share 50% of their genes with
each of their parents. If one of
their parent is schizophrenic has
the child more chance to be
schizophrenic? If he/she is Sz, are
only genetic factors responsible?
If the adopted children have a higher
concordance rate for Sz with their biological
parents than with their adoptive
parents, does it support the influence
of genetic factors?
Twin studiesGottesman and Shields ( reviewed the
results of 5 twin studies looking for concordance rates for schizophrenia. These studies looked at 210 MZ twins and 319 DZ twins
It was found that in MZ twins there was a concordance rate of 35-58% compared with dizygotic (DZ) twin rates that ranged from 9-26%. They also found a concordance rate in MZ twins of 75-91% when the sample was restricted to the most severe form of schizophrenia.
The milder forms of schizophrenia had concordance rates of 17-33% suggesting that there may be greater genetic loading with severe forms of schizophrenia. The twin studies have all assumed that the shared environmental effects for MZ and DZ twins are equal which may be incorrect
It is a very small sample. There are very few MZ twins in the population and only 1% are Sz.
Are these diagnosis made using the same criteria?
Twins are not representative of the wider population. (gestational environment)
Adoption studies Prevalence amongst biological relatives
Prevalence among adoptive relatives
Kety et al (1968) schizophrenia only
13% 2%
Tienari et al (1994) all ‘severe’ psych. diagnoses
30% 15%
Were these diagnosis made using the same criteria?How old were children when they were adopted?Did they see their biological parents regularly?Were they adopted by members of the extended family?Could the psychiatrist making the diagnosis in the
child be influenced if he/she is aware that one of both of the parents are Sz??
The overall picture
This seems to indicate an influence of genetic factors but also the importance of environmental/ social factors
So have we found a gene responsible for Sz?
In 2006, an Edinburgh University team found people carrying a variant of a gene called neuregulin had a higher chance of developing psychotic symptoms. However since then research has shown that Sz involves a huge number of genes with each of them making only a small contribution to the development of the disorder according to Robin Murray a leading schizophrenia researcher.
Risk rises with degree of genetic relatednessSpouse – 1% (same as general
population)Child – 13%DZ twin – 17%MZ twin – 48%
Effect of shared environment?
Substantial evidence for a genetic contributionSome evidence disputed:
Shared environment issues Diagnostic criteria in adoption studiesAll the evidence also suggests
environmental triggers: Epigenetics could explain that the concordance rate is less than 100% in MZ twinsHeritability is similar with other major disorders such as breast cancer, hypertension, etc
How is schizophrenia inherited and what exactly is inherited?
DOPAMINE HYPOTHESIS
Schizophrenia: Biochemical
The dysfunction of several neurotransmitter systems Dopamine, 5-hydroxytryptamine (5-HT; Serotonin) Glutamate
are thought to play a part in schizophrenia.
We will concentrate on the Dopamine Hypothesis
Schizophrenia & dopamine
The dopamine hypothesis:Schizophrenia is caused by
excessive DA activity. This causes abnormal functioning
of DA-dependent brain systems, resulting in schizophrenic symptoms
DA can increase or decrease brain activity depending on the system you’re looking at
Lets remind ourselves how neurotransmitters work
DOPAMINE HYPOTHESIS
The Dopamine hypothesis states that the brain of schizophrenic patients produces more dopamine than normal brains.
–Evidence comes from
–studies with drugs
–post mortems
–pet scans
Normal Level of Dopamine In The
Human Brain
Elevated Level of Dopamine In The Brain of a Schizophrenic Patient
(specifically the D2 receptor)
Neurons that use the transmitter ‘dopamine’ fire too often and transmit too many messages or too often.
Certain D2 receptors are known to play a key role in guiding attention.
Lowering DA activity helps remove the symptoms of schizophrenia
Parkinson’s disease
Parkinson’s sufferers have low levels of dopamine
L-dopa raises DA activity People with Parkinson's develop
schizophrenic symptoms if they take too much L-dopa
Chlorphromazine (given to schizophrenics) reduces the symptoms by blocking D2 receptors
ROLE OF DRUGS
–Amphetamines (agonists) lead to increase in DA levels
–Large quantities lead to delusions and hallucinations
–If drugs are given to schizophrenic patients their symptoms get worse
Falkai et al 1988Autopsies have found that people
with schizophrenia have a larger than usual number of dopamine receptors.
Increase of DA in brain structures and receptor density (left amygdala and caudate nucleus putamen)
Concluded that DA production is abnormal for schizophrenia
POST MORTEM
Lindstroem et al (1999) Radioactively labelled a chemical L-
Dopa administered to 10 patients with
schizophrenia and 10 with no diagnosis
L-Dopa taken up quicker with schizophrenic patients
Suggests they were producing more DA than the control group
PET SCANS
Schizophrenia or Faulty Chemicals?
Faulty chemicals cause schizophrenia but
schizophrenia may cause faulty chemicals
The Chicken or the Egg?
Which Came First?
Drugs may influence other systems that impact on schizophrenia so cant be 100% sure about their effects
EVALUATION There is a lack of correspondence between taking the drugs and
signs of clinical effectiveness. It takes 4 weeks to see any sign that the drugs are working when they begin to block dopamine immediately. We cannot seem to explain this time difference.
It could be that the development of receptors in one part of the brain may inhibit the development in another.
Type 1 cases respond well to conventional anti-psychotic drugs. Drugs such as CHLOPROMAZINE: Only effective at relieving the Positive Symptoms of the Illness.
Not effective for negative symptoms. Therefore suggested that Type 2 is related to a different kind of abnormality such as brain structure.
PET scans have suggested that drugs did not reduce symptoms of patients diagnosed with disorder for 10 yrs or more
There may be other neurotransmitters involved.
Possible that social and environmental factors trigger the condition.
Other possible causesOther possible causes
Brain structureBrain damageViral infectionBirth complications
Brain structure
Swayze (1990) reviewed 50 studies of schizophrenics and found that many had abnormally large amounts of liquid in the cavities of the brain. Suddath, who supports this found the same enlarged cavities when using MRI scans on schizophrenic twins.
Structural abnormalities
Unusually large corpus callosum High density of white matter in the right
frontal and parietal lobe Small amount of grey matter in the temporal
lobes A change in blood flow in the cerebral
hemisphere MRI scan show unusually large ventricular
enlargement but this is also seen in non-schizophrenics
Hippocampus and the thalamus are all affected in the brains of schizophrenics
Brain Structure Evidence
Andreasen et 1990 – conducted a very well controlled CAT scan study and found significant enlargement of the ventricles in schizophrenics compared to controls.
However this was only the case for men and not for women. Therefore can’t generalise the findings to women.
Brain Structure
People with schizophrenia have abnormally large ventricles in the brain. Ventricles are fluid filled cavities. This means that the brains of schizophrenics are lighter than normal.
Enlarged ventricles due to medications?
Beng-Choon Ho (2010) in a longitudinal correlational study of 211 schizophrenics found that antipsychotic drugs have measurable influence on brain tissue loss over time. This was supported by Lewis (2009) who administered antipsychotic drugs to primates and found a brain volume loss of 10% .
However this was a correlational study so it does not show cause and effect. Lewis’s study was carried out on animals so we cannot extrapolate to humans without caution.
FurthermoreFurthermoreIf the reduction in brain volume is the cause of the schizophrenic symptoms then it cannot explain why after 30 years of the initial onset, 35% of the schizophrenics are classified as "much improved“ because the cortex does not grow back, if the structural differences were the cause then no improvement would be possible.
Brain plasticityBrain plasticity
The brain is a plastic organ which changes with the way we use it so are the differences in structure the cause or the result of schizophrenia?
Brain Damage
Decreased rate of blinkingStaringLack of the blink reflex in
response to a tap on the forehead
Poor visual pursuit movementsPoor pupil reactions to light
Viral Infection
In recent years, there has been a build up of evidence supporting the role of viral infections in the development of schizophrenia, including the poliovirus, the flu virus and a virus called encephalitis lethargica ('inflammation of the brain that makes you tired‘).
Birth Complications
Complications during pregnancy, abnormal foetal growth and complications during delivery are significant risk factors in the development of schizophrenia.
Those that play a significant role in the development of schizophrenia include: bleeding, diabetes and pre-eclampsia pregnancy complications
Birth Complications
abnormal foetal growth and development problems including conditions such as low birth weight and reduced head circumference
complications of delivery including asphyxia (lack of oxygen) and emergency Caesarean section
However, the effect of such complications is small in comparison with factors such as genetic pre-disposition to schizophrenia.