Do we still believe in the dopamine hypothesis? New data bring new evidence
Schizophrenia is characterized by positive symptoms, negative symptoms and cognitive impairment. The dopamine hypothesis of schizophrenia postulates that an excess of dopamine subcortically is associated with the positive symptoms. At the same time, the negative and cognitive symptoms of schizophrenia are thought to arise from a deficit of dopamine in the cortex. Evidence for the co-existence of subcortical dopamine excess and cortical dopamine deficit in the schizophrenic brain is presented. Neuroreceptor-imaging techniques, such as SPECT and PET, have been used to provide that evidence. After amphetamine challenge (to stimulate dopamine release), dopamine transmission was substantially increased in the brains of schizophrenic subjects compared with healthy controls. In addition, amphetamine challenge was associated with an increase in positive symptoms of schizophrenia. Furthermore, acute dopamine depletion studies indicated that there was an increased occupancy of D2 receptors by dopamine at baseline in schizophrenia in comparison with healthy controls. This is consistent with the notion of hyperstimulation of D2 receptors in schizophrenia. In the cortex, dopamine type-1 (D1) receptors were found to be up-regulated in patients with schizophrenia compared to controls; in the dorsolateral prefrontal cortex, a brain region involved in working memory, this increase correlated with a poor performance on the n-back task. The up-regulation of D1 receptors may represent a compensatory effect of the dopamine deficit in the cortex. These findings provide evidence for a cortical/subcortical imbalance in the schizophrenic brain.(Received July 27 2003)
(Reviewed September 10 2003)
(Revised October 25 2003)
(Accepted October 26 2003)
Key Words: Dopamine; hypothesis; imaging; schizophrenia.
c1 Professor A. Abi-Dargham, Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA. Tel.: +1 212 543 5066 Fax: +1 212 568 6171 E-mail: email@example.com