Alterations in the Ca2+ homeostasis in lymphocytes from schizophrenic patients

Purpose: We studied whether Ca²⁺ homeostasis or NMDA/mGluR I and II mediated lymphocytic responses are altered in schizophrenia. A second focus was laid on the effect of antipsychotics on these parameters. This strategy may permit us to obtain further insight into the molecular pathomechanisms underlying schizophrenia. Methods: Peripheral lymphocytes were isolated from healthy controls (n=67) and patients (n=59). Both groups have been carefully clinically characterized. Lymphocytes were loaded with the ratiometric dye FURA-PE3/AM and stimulated with NMDA, mGluR I–II selective agents, the mitogenic PHA and thapsigargin to deplete intracellular Ca²⁺ stores. Data were kinetically acquired by microfluorometry. Quantitative measures were obtained by in situ calibration. Results: Basal Ca²⁺ levels were elevated (89.5+/-55.8 vs. 110.1+/-62.3, p=0.025). The further increment following PHA application also differed (24.7+/-15.5 vs. 38+/-28.7, p=0.003). The total intracellular Ca²⁺ capacity was not different as were the responses to NMDA, S-3,5-DHPG (target: mGlu (target: mGluR1&5) or 2R,4R-ACPD (target: mGluR2&3). While atypical neuroleptics increased baseline Ca²⁺ levels (p=0.036), typical antipsychotics attenuated the response towards PHA (p=0.023). Conclusion: We identified an altered Ca²⁺ homeostasis in lymphocytes from patients. Thus we speculate, that anomalies in the Ca²⁺ cascade or intracellular buffering systems may play a pathogenic role in schizophrenia.