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.