Catastrophe theory of dopaminergic transmission: a revised dopamine hypothesis of schizophrenia

Mathematical modeling of experimentally observed parameters of dopaminergic neuronal activity suggests the occurrence of multiple equilibrium states in neurons characterized by certain precisely defined properties of the tyrosine hydroxylating system. These equilibria may become unstable under certain conditions and transitions between multiple states are predicted. In addition, modeling of the spatial interactions of dopamine neurons within a neural net leads to domain wall soliton-like solutions of neuronal firing. In the discrete spatial case, these equations are isomorphic to those of the Ising model of phase transitions in lattice spins.The hypothesis is proposed that the occurrence of multiple stable equilibrium states rather than excessive dopaminergic transmission forms the pathophysiological basis of the schizophrenic thought disorder.The model is internally consistent with known clinical effects of drugs such as neuroleptics, reserpine and amphetamine. In agreement with postmortem and other studies, the theory predicts the lack of increased concentrations of dopamine or its major metabolite, homovanillic acid, in brain and cerebrospinal fluid of schizophrenics.The mathematical model is compatible with the theory that postulates an attention deficit as an underlying mechanism of schizophrenic psychosis and allows for a possible genetic heterogeneity of the disease.