Dopamine transporter in schizophrenia: a progressive loss with age in the cingulate cortex

The dopamine (DA) transporter (DAT) is a neuronal element that regulates dopaminergic neurotransmission by terminating the action of DA via reuptake. A defect in DAT accompanied with increased synaptic DA, may be part of the neuronal abnormalities associated with heightened dopaminergic activity in schizophrenia. This study examined the DAT in the anterior cingulate cortex obtained from postmortem brains of 18 schizophrenic and 18 control subjects. The schizophrenic subjects had a 48% reduction in the density of [3H]GBR 12935 binding sites with an apparent normal affinity. Correlations of the age at death with [3H]GBR 12935 binding constants indicated an increase in Bmax with age in the control (rS=0.68, p=0.002) and a decrease in Bmax with age in the schizophrenic group (rS= 0.48, p=0.004). Dividing the diagnostic groups according to age, the data revealed that in young schizophrenics KD was 91% higher than in the age matched controls while the Bmax was not changed. In contrast, the old schizophrenics had a 263% lower KD and a 197% lower Bmax than the old controls. Furthermore, there was a significant negative correlation between the duration of illness and the binding constants: Bmax rS0.58, p=0.03; KD rS=0.62; p=0.02. Duration of illness was directly proportional to the age at death with a correlation coefficient of 0.88, p=0.0001. Since the reduction in DAT receptors (DATR) is only present in old schizophrenics with a long duration of the disease, the data indicate that the loss of DATR is progressively related to age and the duration of the disease.