A pilot in vivo proton magnetic resonance spectroscopy study of amino acid neurotransmitter response to ketamine treatment of major depressive disorder

• Published in: Molecular psychiatry Vol. 21; no. 3; pp. 320 - 327
• Main Authors: Milak, M S, Proper, C J, Mulhern, S T, Parter, A L, Kegeles, L S, Ogden, R T, Mao, X, Rodriguez, C I, Oquendo, M A, Suckow, R F, Cooper, T B, Keilp, J G, Shungu, D C, Mann, J J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2016; Nature Publishing Group
• Subjects: 631/378; 96/95; Adult; Amino acids; Amino Acids - metabolism; Antidepressants; Antidepressive Agents - blood; Antidepressive Agents - therapeutic use; Behavioral Sciences; Biological Psychology; Brain - drug effects; Brain - metabolism; Care and treatment; Depressive Disorder, Major - drug therapy; Diagnosis; Dosage and administration; Drug dosages; Female; gamma-Aminobutyric Acid - metabolism; Glutamatergic transmission; Glutamic Acid - metabolism; Glutamic acid receptors; Glutamine; Glutamine - metabolism; Humans; Ketamine; Ketamine - blood; Ketamine - therapeutic use; Magnetic Resonance Imaging; Magnetic resonance spectroscopy; Major depressive disorder; Male; Medicine; Medicine & Public Health; Mental depression; Middle Aged; N-Methyl-D-aspartic acid receptors; Neuropathology; Neurosciences; Neurotransmitter Agents - metabolism; Neurotransmitters; Nuclear magnetic resonance spectroscopy; original-article; Patients; Pharmacotherapy; Physicians; Pilot Projects; Proton Magnetic Resonance Spectroscopy; Psychiatric Status Rating Scales; Psychiatry; Risk factors; Spectrum analysis; Suicides & suicide attempts; Surgeons; Tritium - metabolism; γ-Aminobutyric acid; New York; United States > US
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2015.83

The N-methyl-D-aspartate receptor antagonist ketamine can improve major depressive disorder (MDD) within hours. To evaluate the putative role of glutamatergic and GABAergic systems in ketamine’s antidepressant action, medial prefrontal cortical (mPFC) levels of glutamate+glutamine (Glx) and γ-aminobutyric acid (GABA) were measured before, during, and after ketamine administration using proton magnetic resonance spectroscopy. Ketamine (0.5 mg kg −1 intravenously) was administered to 11 depressed patients with MDD. Glx and GABA mPFC responses were measured as ratios relative to unsuppressed voxel tissue water (W) successfully in 8/11 patients. Ten of 11 patients remitted (50% reduction in 24-item Hamilton Depression Rating Scale and total score ⩽10) within 230 min of commencing ketamine. mPFC Glx/W and GABA/W peaked at 37.8%±7.5% and 38.0%±9.1% above baseline in ~26 min. Mean areas under the curve for Glx/W ( P =0.025) and GABA/W ( P =0.005) increased and correlated ( r =0.796; P =0.018). Clinical improvement correlated with 90-min norketamine concentration (df=6, r =−0.78, P =0.023), but no other measures.