WJEC A2 Psychology- Biological explanations of Schizophrenia

The Original Dopamine Hypothesis

High levels of dopamine cause SZ.

1950s Findings on the link between dopamine and Parkinsons Disease

The drug L-DOPA appeared to control symptoms of Parkinsons but also raised dopamine levels. Those given this drug demonstrated behaviours similar to SZ.

Griffiths et al. (1968)

Induced psychosis in non-SZ volunteers who were given LSD (Dextro-Amphetamine). They demonstrated abrupt onset of paranoid delusions and detatched emotional response.

The initial hypothesis was found to be too simplistic

The drugs that were being used to reduce dopamine did not reduce negative symptoms.

There are different sub-types of dopamine receptors

D1, D2, D3, D4, D5. D2 is found to be of particular importance.

Dopamine receptors are widely distributed...

Throughout the cerebral cortex and sub-cortically in the limbic region.

Seeman and Lee (1975)

Showed the impact of antipsychotic drugs on the receptors which are found mainly in the limbic region.

Revised Dopamine Hypothesis

Looks at the over-activity of the mesolimbic pathway and the mesocortical pathway dysfunction. The subcortical Limbic System is involved in many functions including memory and perception.

Mesolimbic pathway

Carries signals from the Ventral Tegmental area to the Nucleus Acumbens. Too much Dopamine (Neurons firing too often or too quickly) cause over-stimulation and cause positive SZ symptoms e.g hallucinations. Antipsychotic drugs reduce Dopamineregic Neurotransmission and reduce dopamine activity in this pathway.

Mesocortical pathway

Carries signals from the Ventral Tegmental area to the Frontal Lobe. This nerve pathway is vital in emotional responses, motivation and cognition. Involved with negative symptoms.

Davies et al. (1991)

Found low levels of dopamine hypofunction is evident in D1 receptors of the frontal lobe of many of those who have negative symptoms e.g cognitive impairment.

Evaluation- Dopamine imbalance may be caused by genes

Twin and family studies such as Gottestman et al. (1991). They found a positive correlation between genetic similarity and incidence of SZ. However, research looking for one or a few candidate genes have been disappointing. In 2014, 300 scientists from 35 countries found 108 genetic loci that are associated with SZ. If a genetic basis exists, it is complex and more than just a few abnormal genes.

Evaluation- Measuring metabolites

It is not easy to directly measure levels of neurotransmitters e.g Dopamine. In order to do this, the metabolite levels i.e what neurotransmitters are broken down into, in cerebrospinal fluid, need to be measured. Dopamine is metabolised into HVA (Homovallinic Acid) and is measured in cerebrospinal fluid obtained via a lumbar puncture. The individual's diet and drugs may affect these levels and even in controlled conditions, it is difficult to interpret with HVA levels different between individuals- affected by diet and drugs. This means that until more sensitive procedures are developed we need to be cautious in drawing conclusions from metabolite-based research.

Evaluation- Serotonin

Serotonin is implicated in SZ. Conventional antipsychotics block D2 receptor sites, and not all individuals with SZ benefit from this. Newer, atypical antipsychotics block D2 receptors and also the serotonin receptor 5-HT2A. This does not suggest that the dopamine hypothesis is wrong, but it does suggest that at best it only offers a partial explanation.

Evaluation- Dopamine, cause or effect?

It could be argued that SZ causes higher levels of dopamine as opposed to high levels of dopamine causing SZ. It is hoped that investigative techniques will become less invasive. If so, it may be possible to conduct research which will establish which comes first. PET scan research e.g by Copolov and Crook (2000) haven't yet been able to detect differences in dopamine levels in the brains of those with SZ and those without. It will, therefore, be a long time before we may establish whether dopamine imbalances cause SZ or vice versa.

Structural abnormalities

Enlarged ventricles, revered cerebral asymmetry and cortical atrophy

Enlarged ventricles

Cavities that produce and transport cerebrospinal fluid. This is important as it provides protection, buoyancy, and chemical stability to the brain and spine. Some individuals with SZ have larger ventricles than those without SZ.

4 ventricles

Left lateral, right lateral, third and fourth ventricles. The left and right lateral ventricles are in the frontal, occipital and temporal lobes. Thr third is in the left and right thalamus, and the fourth is between the pons and medulla oblongata.

Weinberger et al. (1979)

CAT scans on 58 Ps with SZ and 56 Ps without SZ. They found significantly larger ventricles in those with SZ than those without. 40% were outside the range, and 53% were 2 standard deviations bigger.

Andreasen (1988)

MRI scans of individuals with and without SZ found that those with SZ had ventricles that were 20-50% larger.

Cortical atrophy

This is the loss of neurons in the cerebral cortex. This can occur all over the brain, giving the impression it has shrunk, or it may occur in a limited area. In the latter case the atrophy affects the cognitive functions in that particular area. Atrophy results in the widening of the grooves (sulci) covering the cerebral cortex. This type of damage characterises 20-35% of people with chronic SZ.

Vita et al. (1988)

CAT scans- 124 people with SZ, 45 controls. 33% of those with SZ had atrophied. Atrophy was not found to be related to individual differences e.g age, but was more common in men, especially if they had ventricle enlargement.

Revered cerebral asymmetry

In most individuals without SZ, the left hemisphere is slightly larger than the right, known as cerebral symmetry. Some people with SZ have the reverse to be true- cerebral asymmetry. Language function is normally found in the left hemisphere. Damage or deterioration could lead to alogia- often seen in SZ.

Luchins et al. (1979)

Used CAT cans on 80 right-handed people with SZ and 57 right handed people without SZ. There was an increase in the frequency of reversals in both frontal and occipital lobes of those with SZ, but only in those who had no other form of atrophy. Those with SZ who did have evidence of atrophy had no higher level of reversals than the control group.

Evaluation- are the findings for strucutural abnormalities reliable?

McCarley at al. (1999) the presence of enlarged ventricles in people with SZ is the most reliable finding in research that uses brain scans. Flashman and Green (2004) found that structural abormalities have not always been found and reproduced in studies of individuals with SZ. McCarley suggests factors such as age, sex, and severity of symptoms can all exert a powerful influence on the prevalence and pattern of the observed symptoms. How patients are accessed are a factor. Subtle differences in the way brain structure are measured may be responsible for subtle and not so subtle differences in structural abnormalities.

Evaluation- are structural abnormalities a cause or effect of SZ?

It is not clear which one causes which. Most researchers would agree that at least some structural abnormalities cause SZ, but environmental influences can significantly impact on brain tissue. Lyon et al. (1981) reported that as doses of antipsychotic drugs increased in the sample of Ps, the density of their brain tissue decreased. This suggests that after SZ has been diagnosed and is treated with drugs, the medication is what causes some structural abnormality such as enlarged ventricles.

Evaluation- structural abnormalities are not linked only to SZ

Roy et al. (1998) noted that individuals diagnosed with bipolar disorder and schizoaffective disorder have also been found to have enlarged ventricles. Bipolar disorder and SZ have many overlapping symptoms and this may be the result of similar structural abnormalities in the brain. However, this may indicate that these disorders have a similar causation or the way these conditions are classified need to be reviewed. Perhaps as brain scanning techniques become more refined, diagnosis may actually become reliant on the scans which indicate structural and functional abnormalities rather than just the resultant behaviours.

Evaluation- neurodegenerative or neurodevelopmental?

It is unclear if abnormalities are caused by neurodevelopmental factors (e.g exposure to noxious agents, or events in early childhood which hinders healthy brain development), or if they are due to neurodegenerative cause, the result of progressive brain changes, such as the loss of cortical tissue (a process that occurs as we age). Mathalo et al. (2003) claim that structural abnormalities seen in people with SZ are the result of a combination of both neurodevelopmental and neurodegenerative factors. Neurodevelopmental factors impair cortical development, and this cortical impairment makes the individual more susceptible to neurodegenerative processes.