Investigation of Cortical Glutamate–Glutamine and γ-Aminobutyric Acid in Obsessive–Compulsive Disorder by Proton Magnetic Resonance Spectroscopy

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 37; no. 12; pp. 2684 - 2692
• Main Authors: Simpson, Helen B, Shungu, Dikoma C, Bender, James, Mao, Xiangling, Xu, Xiaoyan, Slifstein, Mark, Kegeles, Lawrence S
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.11.2012
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Age of Onset; Anxiety disorders. Neuroses; Biological and medical sciences; Brain Chemistry - physiology; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Data Interpretation, Statistical; Diagnostic and Statistical Manual of Mental Disorders; Female; gamma-Aminobutyric Acid - metabolism; Glutamic Acid - metabolism; Glutamine - metabolism; Humans; Image Processing, Computer-Assisted; Indexing in process; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Medical sciences; Middle Aged; Obsessive-Compulsive Disorder - metabolism; Obsessive-Compulsive Disorder - pathology; Obsessive-Compulsive Disorder - psychology; Obsessive-compulsive disorders; Original; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Young Adult; Obsessive compulsive disorder; Central nervous system; Anxiety disorder; magnetic resonance spectroscopy; Prefrontal cortex; Glutamate; Encephalon; Dorsolateral prefrontal cortex; Medial prefrontal cortex; OCD; Glx; Cingulate cortex; Excitatory aminoacid; Neurotransmitter; GABA; anterior cingulate cortex; Glutamine
• ISSN: 0893-133X; 1740-634X; 1740-634X
• DOI: 10.1038/npp.2012.132

Glutamatergic abnormalities in corticostriatal brain circuits are thought to underlie obsessive-compulsive disorder (OCD). Whether these abnormalities exist in adults with OCD is not clear. We used proton magnetic resonance spectroscopy (¹H MRS) to test our hypothesis that unmedicated adults with OCD have reduced glutamate plus glutamine (Glx) levels in the medial prefrontal cortex (MPFC) compared with healthy controls. Levels of γ-aminobutyric acid (GABA) were also explored. Twenty-four unmedicated adults with OCD and 22 matched healthy control subjects underwent ¹H MRS scans at 3.0 T. Resonances of both Glx and GABA were obtained using the standard J-editing technique and assessed as ratios relative to voxel tissue water (W) in the MPFC (the region of interest) and the dorsolateral prefrontal cortex (DLPFC) to explore the regional specificity of any finding. In the MPFC, Glx/W did not differ by diagnostic group (p=0.98) or sex (p=0.57). However, GABA/W was decreased in OCD (2.16±0.46 × 10⁻³) compared with healthy controls (2.43±0.45 × 10⁻³, p=0.045); moreover, age of OCD onset was inversely correlated with MPFC GABA/W (r=-0.50, p=0.015). MPFC GABA/W was higher in females than in males. In the DLPFC, there were no main effects of diagnosis or gender on Glx/W or GABA/W. These data indicate that unmedicated adults with OCD do not have Glx abnormalities in a MPFC voxel that includes the pregenual anterior cingulate cortex. However, they may have decreased MPFC GABA levels. How GABA abnormalities might contribute to corticostriatal dysfunction in OCD deserves further study.