Schizophrenia- Dopamine Hypothesis (Biological explanation)

How was the link between dopamine and schizophrenia stablished?

• 1950s

• Parkinson’s disease

• L-dopa — increased dopamine in brain (to treat tremors)

• Patients developed symptoms similar to schizophrenia

What three important things were found?

• Delay, Deniker & Harl - 1952 - discovered antipsychotic drugs

• Carlson & Lindqvist - 1963 - realised the drugs metabolised dopamine

• Amphetamine could induce symptoms and reserpine could block dopamine reuptake — Griffin et al - 1968

Dopamine receptor sites

• 1970s

• D1-D5 acknowledged

• At first, D2 was given more importance - found in a large amount of volume - most impacted by antipsychotics - (in striatum)

• Later on, D1 was also found to be important - presence in prefrontal cortex

What did the amount of D1 and D2 mean and where in the brain where they found?

Who proposes this idea? When?

• Fewer D1 (in prefrontal cortex)= negative symptoms

• Higher D2 (in striatal areas)= positive symptoms

• Proposed by Davis et al - 1991

What did Owen find?

• Excess receptor sites in left amygdala, which plays a primary role in the processing of memory and emotional reactions

What did Falkai find?

• Increased dopamine in the striatal areas such as the caudate nucleus and putamen

Mesolimbic pathway

• Carries dopamine from VTA to nucleus accumbens

• too much dopamine from neurons that fire too quickly/too often cause hyperfunction and result in positive symptoms

Mesocortical pathway

• Carries dopamine from VTA to frontal lobe

• too little dopamine in D1 receptors of the frontal lobe cause hypofunction and result in negative symptoms

What did Frankle and Laurelle do?

• 2002

• Imaging studies

• Confirmed that striatal dopamine is elevated in patients with schizophrenia

• Blocking dopamine release or blocking postsynaptic receptors leads to a reduction of the psychotic symptoms for most patients

Human Genome Project

• Successfully mapped every gene in human DNA

• Four of the the top ten genes are directly involved with dopamine activity

• Talkowski et al - 2008