Dopaminergic neurotransmission in patients with schizophrenia, individuals at risk, and healthy controls

Pathomechanisms of schizophrenia comprise a wide range of neurobiological alterations including dopaminergic dysfunction. Aim of the study was to investigate dopaminergic neurotransmission in subjects with schizophrenia, individuals at risk for the development of a first episode of psychosis, and healthy controls. A dynamic IBZM SPECT protocol was used to assess endogenous dopamine release following an amphetamine challenge. Subjects underwent a SPECT study using a bolus activity of 175 MBq followed by a continuous infusion of 45 MBq/h [123I]IBZM. SPECT scans were performed two hours after bolus injection, and one hour following amphetamine challenge (0.3mg/kg i.v.). Striatal IBZM binding to dopamine D2 receptors was assessed with a region-of-interest (ROI) technique. The change in IBZM binding between pre- and post-challenge scans was used as a measure of endogenous dopamine release triggered by amphetamine. Upon amphetamine challenge mean IBZM binding decreased by about 4.9(±7.6)% in healthy subjects (n=7) as compared to a mean 13.4(±6.3)% in 6 subjects with schizophrenia (p<0.05). Preliminary observations in 'individuals at risk' revealed similar results in some of these subjects compared to patients with schizophrenia. Preliminary data are in line with a hyperdopaminergic state in patients with schizophrenia and provide evidence that IBZM SPECT and amphetamine challenge might be useful to characterise high risk subjects in terms of dopaminergic irritability.