Schizophrenia: Biological explanation 1: Dopamine hypothesis

Question 1

What is the initial dopamine hypothesis?

Answer 1

• individuals with schizophrenia have too much neurotransmitter dopamine
• 1968, J.J Griffith et al. induced psychosis in non schizophrenic volunteers with the administration of dextro-amphetamine (a drug that increases the amount of dopamine in the brain finding that volunteers had the onset of paranoid delusions and demonstrated a cold and detached response.
• however, it was seen as too simple because administering drugs to reduce the levels of dopamine had little or no effect on those individuals who suffered mainly with the negative symptoms of schizophrenia.

Question 2

Dopamine receptor sites.

Answer 2

• the dopamine hypothesis was complicated by the discovery of several dopamine receptor sites D1-D5, which as widely distributed in the cerebral cortex and in the Limbic system.
• D2 became of particular interest, seeman and lee (1975) had shown impact of antipsychotic drugs on this specific receptor site. found in the subcortial regions

Question 3

Revision of the dopamine hypothesis

Answer 3

• the role of dopamine in the limbic system has been the main area of study more recent years.
• the limbic system consists of a variety of subcortial structures that are engaged with many functions, but most notably emotions, memory formation and arousal.
• nerve pathways leave from the limbic system to many other subcortical structures and also to the cerebral cortex; two of the main pathways associated with schizophrenia include mesolimbic pathway and mesocortical pathway.

Question 4

Revisions of dopamine hypothesis; Mesolimbic pathway.

Answer 4

• Dopamine is a major neurotransmitter in the mesolimbic pathway.
• this pathway carries signals from the ventral tegmental area to the nucleus accumens. too much dopamine, either from neurons that fire too often or too quickly, cause overstimulation and ultimately positive symptoms of schizophrenia such as hallucinations or delusions.

Question 5

Revisions of dopamine hypothesis; mesocortical pathway

Answer 5

• again dopamine is a major neurotransmitter in the mesocortical pathway.
• This pathway carries signals from the ventral tegmental area to the frontal lobe.
• this nerve pathway is vital in emotional responses, motivation and cognition.
• Kenneth davis et al. (1991). note that too little dopamine (hypofunction) is evident in D1 receptors of the frontal lobe of many individuals with the cognitive impairments and negative symptoms of schizophrenia.

Question 6

Evaluation; dopamine imbalances may be caused by genes.

Answer 6

• if dopamine imbalances are responsible for schizophrenia, the question then has to be what causes the dopamine imbalances? many researchers believe that it may be a genetic predisposition, and indeed twin and family studies indicate that there is some genetic basis for schizophrenia.
• for example, irving gottesman et al (1991) looked at incidence of schizophrenia in cousins, grandchildren, half siblings, parents, siblings, non identical and identical twins. as genetic similarity increased, so did the probability of both individuals having schizophrenia.
• however, research looking into candidate genes for schizo has been disappointing.
• in 2014, the schizo working group of the psychiatric genomics consortium (a group of 300 scientists) reported 108 genetic loci associated with schizophrenia. this shows that although there may be a genetic basis for schizophrenia, it is a complex matter, and more than just a few abnormal dopamine receptors.

Question 7

Evaluation; Measuring metabolites

Answer 7

• it is not easy to make direct measurements of neurotransmitters such as dopamine, and most of the research that supports the dopamine hypothesis is based on metabolite research.
  in order to assess neurotransmitter levels we have to measure the metabolite levels in cerebrospinal fluid.
• Dopamine becomes metabolised into HVA or homovallinic acid and this is measured in cerebrospinal fluid.
• this can only be obtained from a lumbar puncture, which is an unpleasant procedure.
• a participants diet may also skew metabolite levels.
• even when conducted under controlled conditions, the results can be difficult to interpret
• this suggests that until we have refined procedures for measuring neurotransmitters we should perhaps be cautious in the conclusions we draw from metabolite research.

Question 8

Evaluation; the role of serotonin

Answer 8

• dopamine is not the only neurotransmitter implicated in schizophrenia.
• serotonin another neurotransmitter, has also been identified as a potential influence.
• conventional antipsychotics have traditionally worked by primarily blockading the D2 receptor sites, however not all of those with schizophrenia benefit from these drugs, newer atypical antipsychotics such as clozapine, block the D2 receptor and also the serotonin receptor 5-HT2A.
• although this may not suggest that the dopamine hypothesis is completely wrong, it certainly suggests it cannot explain schizophrenia on its own. its a partial explanation to the mechanisms involved in schizophrenia.