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Multireceptor fingerprinting of schizophrenia Tetsuya Suhara Chiba |
The
symptoms of schizophrenia have been discussed with a functional impairment of
various
brain circuits and altered
dopaminergic transmission. Dopamine receptors are classified into five subtypes,
and selective ligands have been developed for D1 and D2 subtypes. An increasing
body of evidence favors a crucial role of extrastriatal regions in the
pathophysiology of positive symptoms, and the extrastriatal D2 receptor is
expected to be the common site of action of antipsychotics. Using [11C]FLB
457, we found reduced D2 receptor binding in the anterior cingulate cortex of
patients with schizophrenia, and a significant negative correlation was observed
between D2 receptor binding and the positive symptom score on BPRS. Subregions
of interest were defined on the thalamus using individual magnetic resonance
images (MRI). D2 receptor binding was also lower in the central medial and
posterior subregions of the thalamus in patients with schizophrenia.
Alterations in D2 receptor function in the extrastriatal region may
underlie the positive symptoms of schizophrenia. On the other hand D1 receptor
binding was found to be lower in the prefrontal cortex and a significant
negative correlation was observed between D1 receptor binding and the negative
symptom score on BPRS. Abnormality of D1 receptor function would be at the
bottom of the negative symptoms and cognitive impairment of schizophrenia.
Several lines of evidence suggested that serotonin function may also be involved
in the pathophysiology of schizophrenia. 5-HT1A receptor binding in
the patients with schizophrenia measured by [11C]WAY-100635 was lower
in the amygdala compared to the normal controls and a
significant negative correlation was observed between 5-HT1A
receptor binding in
the amygdala and the negative and depression/anxiety symptom scores. However, no
significant difference was observed in 5-HT2A receptor binding
between patients with schizophrenia and normal controls.