schizophrenia - biological explanations

• dopamine hypothesis -the initial hypothesis


  proposed that individuals with schizophrenia had too much of the neurotransmitter dopamine, there demonstrated high levels of dopamine.
• the initial hypothesis - J.J Griffin et al


  the hypothesis was supported by much research, for example J.J Griffin 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 the volunteers demonstrated a cold and detached emotional response.
• problems with the initial hypothesis

  the initial dopamine hypothesis was identified as being too simple, confirmed by the fact that administering drugs that reduce the level of dopamine had little or no effect on the individuals who suffered mainly with negative symptoms of schizophrenia.
• modern dopamine hypothesis - the limbic system

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


  dopamine is a major neurotransmitter in the mesolimbic pathway. This pathway carries signals from the ventral tegmental area to the nucleus accumbens. 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.antipsychotic drugs reduce dopaminergic neurotransmission and as such reduce dopamine activity in this pathway and ultimately reduce the positive symptoms of many people with schizophrenia
• the mesocortical pathway


  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 Davies 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 the negative symptoms of schizophrenia.
• evaluation - dopamine hypothesis may be caused by genes


  many researchers believe that it may be a genetic predisposition, and indeed twin and family studies indicate that there is some genetic base for schizophrenia. Eg. the classic study Irving Gottesman et al (1991) looked at incidence of schizophrenia in cousins, grandchildren, half siblings, parents, siblings, non identical twins and identical twins. As genetic similarity increased so did the probability of both individuals having schizophrenia.
• evaluation - dopamine hypothesis may be caused by genes


  research looking for one or a few candidate genes has been disappointing in 2014, the schizophrenia working group reported that there were 108 genetic loci associated with schizophrenia. This shows that although there may be a genetic base for schizophrenia, it is a complex matter - more than just a few abnormal dopamine genes.
• evaluation - measuring metabolites


  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 the neurotransmitter levels we have to measure the metabolite levels (the neurotransmitters get broken down into) in cerebrospinal fluid.Dopamine becomes metabolised into HVA or homovallinic acid and this is measured in cerebrospinal fluid, which can only be obtained by a lumbar puncture.
• evaluation - metabolites


  the participants diet and drug use may also seriously affect metabolite levels, and, even when research is conducted under controlled conditions, the results can be difficult to interpret with HVA levels varying widely between participants. This suggests that until we have refined procedures for measuring neurotransmitters we should perhaps be cautious in the conclusions we draw from metabolite-based research.
• Serotonin


  Another neurotransmitter implicated in schizophrenia, in addition to dopamine
• Conventional antipsychotics


  • Work primarily by blocking the D2 receptor sites
  • Not all those with schizophrenia benefit from these drugs
• Newer antipsychotics (e.g. clozapine)

  • Block the D2 receptor and also the serotonin receptor 5-HT2A equally
• Dopamine hypothesis


  Cannot explain schizophrenia on its own, it is only a partial explanation
• Serotonin, another neurotransmitter, has also been identified as a potential influence in schizophrenia
• evaluation - cause or effect?

  although dopamine hypothesis proposes that dopamine imbalances cause schizophrenia, it could also legitimately be proposed that schizophrenia causes the dopamine imbalances.
• Are the dopamine discrepancies seen in some people with schizophrenia

  Just another symptom of the disease, rather than a cause of it?
• As investigative techniques become less invasive, we will be able to conduct research that will be able to establish which comes first, a dopamine imbalance or schizophrenia
• Research using PET scans (Copolov and Crook 2000) hasn't yet been able to even detect differences in the dopamine activity of the brains of individuals with schizophrenia and those without
• It may be some time before we know for certain if dopamine imbalances cause schizophrenia or if schizophrenia causes dopamine imbalances