Changes in A_2A adenosine receptor parameters in patients affected by bipolar disorders: Correlation with antipsychotic dosage and severity of illness

Maria Letizia Trincavelli, Simona Daniele, Antonio Ciapparelli, Mario Catena Dell’Osso, Gabriele Massimetti, Donatella Marazziti, Liliana Dell’Osso, Claudia Martini

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DOI: 10.4236/ojpsych.2012.21001                

Abstract

Typical antipsychotics, potent D₂ dopamine receptor antagonists, are the most commonly used drugs in the treatment of bipolar disorders. In the central nervous system, the discovery of antagonistic interactions between A_2A adenosine receptors and D₂ dopamine receptors suggests that the adenosine system may be involved in the pathogenesis of different psychiatric disorders and in the therapeutic effectiveness of antipsychotic drugs. Previously, we have demonstrated an increase in A_2A receptor expression and agonist affinity in platelets from psychotic patients treated with haloperidol. This result suggests that there is also a structural and functional interaction between A_2A and D₂ receptors in peripheral cells. In this work, we investigated the effect of different doses of typical drugs on A_2A adenosine receptor binding and correlated these parameters with the severity of symptoms. We demonstrated, for the first time, that there was a strong correlation between A_2A receptor affinity constant values (Kd) and drug doses in psychotic patients with a moderate severity of illness and moderate psychotic symptoms. The correlation was completely lost in patients with severe illness and severe psychotic symptoms. These results demonstrated that in platelets of patients affected by psychosis, typical antipsychotics modulated A_2A receptor binding parameters; this regulation is dependent on the degree of D₂ receptor occupancy in relation to the severity of psychotic symptoms, suggesting A_2A receptors are a peripheral marker for individual therapy effectiveness.

Keywords

Bipolar Disorders; Human Platelets; A_2A Adenosine Receptors; Typical Antipsychotics; Severity Of Illness; A_2A/D₂ Functional Interaction

Conflicts of Interest

The authors declare no conflicts of interest.

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