In reply: elevated d2 dopamine receptors in drug-naive schizophrenics.

D. F. Wong et al. (1) conclude that schizophrenia is associated with an increase in brain D2 dopamine receptor density. This interpretation is based on the application of a mathematical model (2, 3) to data obtained with and without haloperidol pretreatment. However, alternative interpretations of the same data are possible. For example, as shown below, the data in table 1 of Wong et al. under the heading "1/k3 before haloperidol" could be taken to indicate that schizophrenia may be associated with a decrease in brain D2 dopamine receptor density. The model that Wong et al. (1) apply is for (3-N-["C]methyl)spiperone ([1 C]NMSP) accumulation in the caudate nucleus, as measured by positron emission tomography (PET). The central feature of the model is the effect of the nonradioactive inhibitor haloperidol on the kinetics for [" C]NMSP accumulation. This effect is described by a parameter k3 (4), defined as konB'max/Vd, where kon is the second-order molecular association constant for ["C]NMSP binding to the receptor, B'max is the density of receptors available for the binding of ["'C]NMSP, and Vd is the water volume of ["C]NMSP in the brain [assumed to be numerically equal to 1.0 in (3)]. In the presence of a competitive inhibitor, the apparent k3 is operationally defined by the relation