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HOME > Outline of Research > Schizophrenia

Schizophrenia is a mental disorder, with the main symptoms involvinge delusion (distortions in thought context),hallucination (distortions in perception), inferential thinking (disorganized thought) and negative symptoms (restrictions in range and intensity of emotional expression, in fluency and productivity of thought and speech,and in initiation of goal-directed behaviour).

[DSM-IV] Morbidity rate is 1-1.5%, and most patients develop this disorder between their late teens and early twenties.
These symptoms are so severe that not only patients themselves but also economies of society suffer.
Regarding the cause of schizophrenia,abnormality in brain has for a long time been considered to cause these symptoms.
Yet, this has not been confirmed.
Recent research findings suggest that an imbalance of dopamine (a neurotransmitter) and its receptor cause the symptoms of schizophrenia.
Now, abnormalites in dopamine and its receptors are drawing people's attention.There are some reasons for this 'dopamine hypothesis'. First, the most widely used drugs for the treatment of schizophrenia block dopamine D2 receptors and signal transmissions by dopamine.
These drugs function as antipsychotic medications and reduce delusion and hallucination.

Figure 1

Second, by contrast,drugs such as amphetamine and cocain reinforce signal transmissions by dopamine and induce schizophrenic symptoms such as delusion and hallucination.

These dopamine transmitters are distributed as shown in Figure 1.

We measured the density of dopamineD1 receptors of 17 patients with schizophrenia by PET using [¹¹C]SCH23390. The results showed that the density of dopamine D1 receptors in patientswas significantly lower in the prefro-ntal cortex than in normal control, and that the D1 receptor binding potentialwas correlated with negative sympto-ms and the number of category achie-vement by Wisconsin Card Sorting Test.
These findings suggest that a low density of D1 receptors in the prefrontal cortex plays an important role in negative sy-mptoms and cognitive impairments in schizophrenia.(Figure 2-5)
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In our institute, we examined the changes in dopamine D2 receptorfor schizophrenia by PET using [¹¹C]FLB457. This ligand has a sel-ective and high affinity for dopamine D2 receptor.

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The results showed that the density of dop-amine D2 receptors in patients withschizophrenia was significantly lower in the anterior cingulate cortex than in normal control, and the density of dopamineD2 receptors was correlated with positivesymptoms (a patient with lower density of dopamine D2 receptors experiences strongerpositive symptoms such as delusion and hallucination) as shown in Figure 8

These findings suggests that positive symptoms (delusion and hallucination) inschizophrenia are related to abnormalityin neurotransmission through dopamine D2receptor in the anterior cingulated cortex.