Schizophrenia – biological explanations
Gottesman 1991
When the genes get more genetically similar the chances of sharing schizophrenia increases. With
third degree relatives, the chances of sharing schizophrenia are only 12.5% but when Gottesman
looked at the probability of identical twins each developing schizophrenia is one already had it, the
chance the other twin would get it was 40%. Due to identical twins sharing the same genes, there is a
greater chance that if one twin were to develop schizophrenia, the other would too.
The genetic basis of schizophrenia
It has been noted for years that schizophrenia runs in families. This is quite weak evidence for a
genetic link because family members tend to share aspects of their environment as well as genes.
However, there has been systematic investigations of the extent to which greater genetic similarity
between family members is associated with the likelihood of developing schizophrenia. For example,
we share 100% of genes with identical twins, 50% with parents and siblings and so on. There is a
strong relationship between the degree of genetic similarity and shared risk of schizophrenia.
Candidate genes. Individual genes are believed to be associated with the risk of inheritance. Due to
several genes each appear to confer a small increased risk of schizophrenia, it appears schizophrenia
is polygenic, i.e., it requires several factors to work in combination. Because different studies have
identified different candidate genes, it also appears schizophrenia is aetiologically heterogeneous, i.e.,
different combinations of factors can lead to the condition. Stephan Ripke et al (2014) carried out a
huge study combining all previous data from genome-wide studies (those looking at the whole human
genome as opposed to particular genes) of schizophrenia. The genetic make-up of 37,000 patients
were compared to that of 113,000 controls; 108 separate genetic variations were associated with the
increased risk of schizophrenia. Genes associated with this increased risk included those coding for
the functioning of several neurotransmitters including dopamine.
The Dopamine hypothesis
Dopamine is a chemical substance (neurotransmitter) manufactured in the brain that transmits
messages between neurons (brain cells).
Neurotransmitters. The brain’s chemical messages appear to work differently in the brain of the
patient with schizophrenia. Dopamine is widely believed to be involved. Dopamine is important in the
functioning of several brain systems that may be implicated in the symptoms of schizophrenia.
Hyperdopaminergia in the subcortex – The original version of the dopamine hypothesis focused on
the possible role of high levels or activity of dopamine in the subcortex i.e., the central areas of the
brain. For example, an excess of dopamine receptors in Broca’s may be associated with poverty of
speech or auditory hallucinations.
Hypodopaminergia in the cortex – More recent version of the dopamine hypothesis focusses instead
on abnormal amounts of dopamine systems in the brain’s cortex. Goldman-Rakic et al (2004) have
identified a role for low levels of dopamine in the prefrontal cortex in the negative symptoms of
schizophrenia.
It may be that both Hyper/Hypodopaminergia are correct explanations – both high and low levels of
dopamine in different areas of the brain are involved in schizophrenia.
Gottesman 1991
When the genes get more genetically similar the chances of sharing schizophrenia increases. With
third degree relatives, the chances of sharing schizophrenia are only 12.5% but when Gottesman
looked at the probability of identical twins each developing schizophrenia is one already had it, the
chance the other twin would get it was 40%. Due to identical twins sharing the same genes, there is a
greater chance that if one twin were to develop schizophrenia, the other would too.
The genetic basis of schizophrenia
It has been noted for years that schizophrenia runs in families. This is quite weak evidence for a
genetic link because family members tend to share aspects of their environment as well as genes.
However, there has been systematic investigations of the extent to which greater genetic similarity
between family members is associated with the likelihood of developing schizophrenia. For example,
we share 100% of genes with identical twins, 50% with parents and siblings and so on. There is a
strong relationship between the degree of genetic similarity and shared risk of schizophrenia.
Candidate genes. Individual genes are believed to be associated with the risk of inheritance. Due to
several genes each appear to confer a small increased risk of schizophrenia, it appears schizophrenia
is polygenic, i.e., it requires several factors to work in combination. Because different studies have
identified different candidate genes, it also appears schizophrenia is aetiologically heterogeneous, i.e.,
different combinations of factors can lead to the condition. Stephan Ripke et al (2014) carried out a
huge study combining all previous data from genome-wide studies (those looking at the whole human
genome as opposed to particular genes) of schizophrenia. The genetic make-up of 37,000 patients
were compared to that of 113,000 controls; 108 separate genetic variations were associated with the
increased risk of schizophrenia. Genes associated with this increased risk included those coding for
the functioning of several neurotransmitters including dopamine.
The Dopamine hypothesis
Dopamine is a chemical substance (neurotransmitter) manufactured in the brain that transmits
messages between neurons (brain cells).
Neurotransmitters. The brain’s chemical messages appear to work differently in the brain of the
patient with schizophrenia. Dopamine is widely believed to be involved. Dopamine is important in the
functioning of several brain systems that may be implicated in the symptoms of schizophrenia.
Hyperdopaminergia in the subcortex – The original version of the dopamine hypothesis focused on
the possible role of high levels or activity of dopamine in the subcortex i.e., the central areas of the
brain. For example, an excess of dopamine receptors in Broca’s may be associated with poverty of
speech or auditory hallucinations.
Hypodopaminergia in the cortex – More recent version of the dopamine hypothesis focusses instead
on abnormal amounts of dopamine systems in the brain’s cortex. Goldman-Rakic et al (2004) have
identified a role for low levels of dopamine in the prefrontal cortex in the negative symptoms of
schizophrenia.
It may be that both Hyper/Hypodopaminergia are correct explanations – both high and low levels of
dopamine in different areas of the brain are involved in schizophrenia.
