Low cerebrospinal fluid glutamate and glycine in refractory affective disorder

Background: Glutamatergic dysregulation has been documented in schizophrenia but has received less systematic study in affective illness. Methods: Cerebrospinal fluid (CSF) levels of the excitatory amino acids glutamate (Glu) and aspartate (Asp) and the N-metbyl-D-aspartate (NAIDA) receptor modulator, glycine (GLY) were measured by high performance liquid chromatography in 32 patients with refractory affective disorder (16 female/16 male, 12 bipolar 1, 12 bipolar H, and 8 unipolar) and in 14 age-matched controls. Results: There was a significant reduction in CSF glutamate and glycine in patients versus controls. A diagnosis by sex interaction was present for CSF glycine with lower levels in female patients compared to female controls. Levels of the excitatory amino acids were highly inter-correlated in patients, but not in controls. In patients studied after 6 weeks of lamotrigine, there was a trend for CSF glutamate levels to increase. Conclusions: These data suggest that in patients with refractory affective disorder, excitatory amino acids are dysregulated, as exemplified both by the decreased CSF glutamate and glycine and their high intercorrelation compared to controls. Further controlled study of glutamatergic dysregulation and its relationship to the pathophysiology of affective disorders and potential mechanism of action of mood stabilizers appears indicated.