Black: AO1 - Description
Blue: AO2 - Evaluation - studies
Red: AO2 - Evaluation - evaluative points
The Dopamine hypothesis
This can be measured by:
- MRI scans measuring activity/density of post-synaptic dopamine receptors and levels.
- Comparison of dopamine levels between schizophrenics and a control group.
- Studies where schizophrenics are given dopamine agonists, resulting in an increase in symptom severity.
Amphetamines
Amphetamines are a class of CNS stimulant that act as agonists (increasing activity) for the neurotransmitters adrenaline and dopamine. Addicts can develop amphetamine psychosis - giving hallucinations and delusions in a similar form to those that result from schizophrenia, suggesting that heightened dopamine levels may explain some of the positive symptoms.
Homovanillic acid, produced as the body metabolises (breaks down) dopamine, is found in increased concentrations in the urine of schizophrenics. This supports the dopamine hypothesis - increased dopamine levels in schizophrenics, but correlation does not mean causation - another biological mechanism responsible for schizophrenia could also lead to these increased levels as a secondary effect.
Brain scans have found a greater density of dopamine receptors in schizophrenics - suggesting that the condition may well be a result of greater dopamine sensitivity. However, the patients studied already had schizophrenia, so cause and effect cannot be established - it may be the case that increased D2 density might be a response to either the condition itself, or the dopamine antagonists commonly prescribed as antipsychotic medication.
Some studies into the dopamine hypothesis have shown that schizophrenics who take amphetamines show increased symptom severity, but non-schizophrenics given the same dose showed no symptoms of schizophrenia, suggesting that schizophrenics have a higher sensitivity towards dopamine, rather than objectively higher levels.
The relative levels of success in the use of dopamine antagonists (reducing activity) as treatment supports the dopamine hypothesis, however, 1 in 3 schizophrenics do not respond to antagonists, suggesting that there must be other factors.
This suggests that the dopamine hypothesis is overly reductionist - factors other than neurotransmitter levels must play a role in the development of such a complex condition, as the hypothesis cannot explain all of the symptoms.
Amphetamine psychosis only explains the positive symptoms of schizophrenia - excess dopamine levels in addicts can lead to the positive symptoms, but not the negative symptoms. Dopamine antagonists are also only useful for the treatment of these positive symptoms, suggesting that the dopamine hypothesis can only really explain the symptoms such as hallucinations, delusions and thought disturbances.
Genes
There is evidence to suggest that genes can play a causal role in the development of schizophrenia, as concordance rates are higher between more genetically similar individuals. Several concordance studies support this.
Gottesman carried out a meta-analysis of 40 European studies into schizophrenia which looked at the condition's incidence rates.
- General public: 1%
- Sibling of schizophrenic: 10%
- Son or daughter of schizophrenic: 10%
- Dizygotic (non-identical) twin of schizophrenic: 17%
- Monozygotic (identical) twin of schizophrenic: 48%
These results would seem to support the concept of a genetic basis for schizophrenia, but not a purely causal relationship.
More genetically similar individuals have more environmental similarities - upbringing, how they are treated. These environmental similarities could help explain the greater incidence rates.
A methodological flaw emerges in the use of a meta-analysis. Different studies analysed used different research methods and diagnosis classifications, lowering the validity of the research. Additionally, there were large variations in concordance rates between studies.
The results suggest schizophrenia is not completely genetic, or else monozygotic twins would have an 100% concordance rate due to being genetically identical. Therefore, these results support the diathesis-stress hypothesis, the idea that schizophrenia is a result of genetic predisposition requiring an environmental trigger to cause development of the disorder.
Heston (1966) studied adoptees, seeking to eliminate the interference between genetics and upbringing in establishing a concordance rate. He studied 47 adopted children that were born to a schizophrenic mother and then adopted by non-schizophrenics. A control group was used to counter the stress of adoption potentially contributing to the development of schizophrenia.
- 5/47 of the children developed schizophrenia, just over 10%, the same as the rate of incidence in children of schizophrenics found in Gottesman's study.
This supports the concept of a definite role of genetics in the development of schizophrenia.
Even though they were adopted at birth, the children still spent 9 months in their mothers' womb during gestation - they could have been exposed to schizophrenogenic drugs, so a shared environment cannot be completely ruled out.
Heston didn't investigate the children until adulthood, so all sorts of environmental factors in childhood and adolescence could have played a role in schizophrenia development.
Sorri studied Swedish adoptees with schizophrenic biological mothers. He found that the chance of schizophrenia development depended on the quality of adoptive parenting - these children still had a greater risk of schizophrenia development, but it was upbringing-dependent. This further supports the diathesis-stress hypothesis, that schizophrenia has a genetic basis that requires environmental activation.
Gottesman and Shields compared concordance in a meta-analysis of 5 studies on severe schizophrenics, and found a concordance rate of between 75% and 91% - strongly supporting a genetic basis to at least the most severe cases of schizophrenia.
Overall, the studies into the genetic hypothesis suggests that genes can provide a biological basis, making an individual more predisposed to schizophrenia, which will then require certain environmental triggers to cause the condition's full development.
Brain anatomy
There is evidence to suggest a smaller brain size in schizophrenics - enlarged ventricles in the brain lead to an overall reduction in the volume of brain matter. The first evidence came from early autopsies of schizophrenics - meaning cause and effect could not be established, as it could be that schizophrenia caused the anatomical differences, not vice versa. Also, these patients had had a long history of antipsychotic medication, which could have affected anatomy, along with potential physical trauma or substance abuse.
Brain scans are a more contemporary method of studying neuroanatomy. Early CAT scans showed that 25% of schizophrenics had enlarged ventricles, compared to a miniscule proportion of healthy controls. However, 25% is very inconclusive - it meant that 75% had no anatomical differences to healthy individuals.
Crowe et al (1989) used Magnetic Resonance Imaging (MRI) to study schizophrenics, and found a reduction in brain matter in the hippocampus in the temporal lobe, especially on the left hand side of the brain.
Goldstein et al' (1999) used MRI to find a reduction in brain matter volume in the paralimbic cortex, a group of brain structures involved in emotion processing, goal setting, motivation and self control - all functions that the symptoms of schizophrenia impair in some way.
MRI technology is not specific enough to reliably pinpoint specific parts of the brain as being dysfunctional. It shows blood flow to regions, which, while roughly correlational, is not a direct measure of brain activity.
Enlarged ventricles are found to be a predisposing factor for many disorders, and are more likely to be an indicator of general susceptibility to psychiatric disorders than schizophrenia specifically.
The viral explanation
Research suggests that if the mother contracts the flu virus (influenza A) during the 2nd trimester of pregnancy, the child is significantly more likely to develop schizophrenia.
O'Callaghan et al (1991) looked at the 1957 influenza outbreak, and found that children in the 4th-6th month of gestation during the outbreak had a particularly incidence of schizophrenia.
Sham et al (1992) examined the relationship between flu outbreaks and reported schizophrenia incidence across several decades. They concluded that schizophrenia was more common amongst those who had been in the womb during the outbreaks. However, the majority of schizophrenics had not been exposed to influenza A in utero, alone, this hypothesis is not a complete explanation of schizophrenia.
Correlations cannot show cause and effect - a third, intervening variable that explains the correlation between antenatal influenza A exposure and schizophrenia development.
Overall evaluation of the biological explanation of schizophrenia
While biological factors such as dopamine levels, genes, neuroanatomy and viral exposure cannot fully explain the development of schizophrenia, and are reductionist in their simplification of schizophrenia to merely the result of certain biological processes, there is evidence to suggest that biology can provide a predisposition to schizophrenia, which then requires environmental circumstances to trigger the disorder's development. The diathesis-stress hypothesis is the model of schizophrenia most likely to be correct, stating that nature provides a basis to schizophrenia, which then requires environmental activation to lead to the full development of the illness.
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