Low Cerebrospinal Fluid Glutamate and Glycine in Refractory Affective Disorder

• Published in: Biological psychiatry (1969) 2007-01, Vol.61 (2), p.162-166
• Main Authors: Frye, Mark A, Tsai, Guochuan E, Huggins, Teresa, Coyle, Joseph T, Post, Robert M
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Anticonvulsants - therapeutic use; Antidepressive Agents - therapeutic use; Antimanic Agents - therapeutic use; Aspartic Acid - cerebrospinal fluid; Biological and medical sciences; Bipolar Disorder - cerebrospinal fluid; Chromatography, High Pressure Liquid; Depressive Disorder, Major - cerebrospinal fluid; Depressive Disorder, Major - drug therapy; Drug Resistance; Electroconvulsive Therapy; Female; Glutamic Acid - cerebrospinal fluid; Glycine - cerebrospinal fluid; Humans; Male; Medical sciences; Middle Aged; Miscellaneous; Mood disorders; N-Methylaspartate - cerebrospinal fluid; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Statistics as Topic
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.01.024

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-methyl-D-aspartate (NMDA) receptor modulator, glycine (GLY) were measured by high performance liquid chromatography in 32 patients with refractory affective disorder (16 female/16 male, 12 bipolar I, 12 bipolar II, 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.