On Distributions of Physiological and Anatomical Variables in Pathological Conditions: Dopamine 0 2 Receptors in Schizophrenia and their Occupancies after Drug Treatment

If a physiological, biochemical or anatomical variable has a normal distribution then the tails of such a distribution may be associated with pathological function. In certain cases this can lead to a bimodal distribution for the variable in individuals with the resultant pathology. We illustrate with a study of dopamine receptors. PET data suggest that the distribution of dopamine DA2 receptor densities in schizophrenic patients might be bimodal. A quantitative model based on the classical theory of drug action and a simple differential equation for receptor synthesis and degradation is used to estimate the effects of neuroleptics on D2 receptor occupancy. It is found that individuals in the upper tail, with higher than normal receptor densities, may eventually attain an equilibrium D2 occupancy after treatment which is in the normal range, whereas individuals with lower than normal receptor densities are predicted to have equilibrium D2 occupancies after treatment which may fall below normal values. Thus, a factor which might determine whether there is a successful outcome in the treatment of schizophrenia with classical neuroleptics is in which tail of the assumed normal distribution, a patient's D2 receptor count falls.