Noradrenergic Function in Schizophrenia

Abstract

• Yohimbine, an α²-adrenergic receptor antagonist that increases noradrenergic function, was administered to 16 healthy subjects and 18 drug-free schizophrenic patients with (n =10) and without (n =8) tardive dyskinesia (TD). Outcome measures of this double-blind, placebo-controlled study included changes in behavior, plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) level, blood pressure, and heart rate. A subgroup of six patients experienced a notable dysphoric arousal reaction that occurred 60 to 90 minutes following administration of 20 mg of yohimbine, this reaction was not observed in healthy subjects. The schizophrenic group as a whole (not the subgroup) showed a statistical trend toward a greater yohimbine-induced increase in plasma MHPG level and systolic sitting blood pressure. The patients with TD did not differ from those without TD or from healthy controls in their response to yohimbine. These results do not support the hypothesis that noradrenergic dysfunction plays a strong central role in the pathogenesis of schizophrenia or TD. However, further studies of noradrenergic dysfunction in subgroups of patients with schizophrenia are indicated.