Dopamine D3 receptor and schizophrenia: a widened scope for the immune hypothesis

Schizophrenia may be related to immunity as is suggested by many findings of altered immune parameters in schizophrenic patients. How immune alterations might be involved in the emergence of psychosis is still unclear. Clearly, however, the dopamine hypothesis has been confirmed in recent studies, which implies a crucial role for dopamine and the dopamine D2 receptor (D2R) within the pathogenesis of schizophrenia. The Dopamine D3 receptor (D3R) is considered to have autoreceptor properties modulating the synthesis and release of dopamine, thereby possibly antagonizing the dopamine D2-receptor-mediated effects of dopamine and has been found reduced in schizophrenic patients during acute psychosis and increasing in the advent of negative schizophrenic symptoms. Immune parameters apparently influence the expression of dopamine receptors by means of their capability to induce regulatory factors involved in the expression of dopamine receptor subtypes, such as the neurotrophins, associations of which with psychosis have been reported repeatedly. Here, we propose a hypothesis of immune alterations that influence the production of distinct neurotrophins such as BDNF and NGF that, as animal studies suggest, influence the expression of dopamine receptor subtypes. This mechanism could result in a decrease of D3R and a consecutive relative preponderance of D2R and thereby connect immune alterations and schizophrenia.