Dopamine D₂ Receptor Blockade in Schizophrenia

To the Editor: We read with interest the results of a recent study making use of [¹²³I]iodobenzamide single photon emission computed tomography ([¹²³I]IBZM SPECT) with schizophrenic patients (1). The authors demonstrated a significant correlation between striatal dopamine D₂ receptor occupancy by olanzapine and risperidone in the presence of depressive symptoms, negative symptoms, and negative subjective experiences as measured by the Subjective Well-Being Under Neuroleptic Treatment Scale.

We attained similar results in a study of 18 schizophrenic patients treated with typical antipsychotics who were scanned with[123I]IBZM SPECT (2). We reanalyzed this data using three items from the Brief Psychiatric Rating Scale (BPRS) that were specific to depression (depressive mood, guilt feelings, and suicidality) as a measure of depressive symptoms that shows little overlap with measures of negative and extrapyramidal symptoms. We found a significant correlation between striatal D₂ receptor occupancy by typical antipsychotic drugs and scores on BPRS depression items (3). This association remained significant after control for total BPRS scores. There was no correlation between BPRS total scores and either BPRS depression item scores or striatal D₂ receptor occupancy (3).

The most significant association with D₂ occupancy in the study by Lieuwe de Haan, M.D., et al. was negative subjective experience. In our study, high D₂ occupancy was associated with mild rather than severe depressive symptoms. Patients frequently complain about taking antipsychotic medications, even in the absence of overt motor side effects. It is possible that this behavior reflects the emergence of the mild depressive symptoms identified in both of these studies. This phenomenon might have important implications for drug choice, dosing, and treatment-adherence strategies. Although our findings are consistent with those of Dr. de Haan et al., both are preliminary, and full elucidation is awaited in larger prospective studies.