Little is known about the acute effects of antidepressant treatments on brain glutamate and gamma-amino-butyric acid (GABA) levels, and their association with clinical response. Using proton magnetic resonance spectroscopy (1H-MRS) we examined longitudinally the effects of citalopram on glutamine/glutamate ratios and GABA levels in the pregenual anterior cingulate cortex (pgACC) of individuals with major depressive disorder (MDD). We acquired 1H-MRS scans at baseline and at days 3, 7, and 42 of citalopram treatment in nineteen unmedicated individuals with MDD. Ten age- and sex-matched non-depressed comparison individuals were scanned once. The association between 1) baseline metabolites and 2) change in metabolites from baseline to each time point and clinical response (change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 42) was assessed by longitudinal regression analysis using generalized estimating equations. Contrary to our hypotheses, no significant associations emerged between glutamate metabolites and clinical response; however, greater increases (or smaller decreases) in pgACC GABA levels from baseline to days 3 and 7 of citalopram treatment were significantly associated with clinical response. These findings suggest that an acute change in GABA levels in pgACC predicts, and possibly mediates, later clinical response to citalopram treatment in individuals with MDD.
|Number of pages||8|
|Journal||Psychiatry Research - Neuroimaging|
|State||Published - 30 Nov 2017|
Bibliographical noteFunding Information:
Dr. Brennan has received consulting fees from Rugen Therapeutics and research grant support from Eli Lilly and Transcept Pharmaceuticals. Dr. Pizzagalli has received honoraria/consulting fees from Akili Interactive Labs, Black Thorn Therapuetics, Boehringer Ingelheim, Pfizer and Posit Science for activities unrelated to this project. Dr. Hudson has received consulting fees from diaMentis, Shire, and Sunovion; and has received research grant support from Shire and Sunovion. Dr. Pope has received research grant support from Shire and Sunovion. None of the other authors report any potential conflicts of interest.
We respectfully acknowledge the singular contributions of our late friend, colleague, and collaborator, Dr. Eric Jensen, to this project and to countless prior studies performed at the McLean Imaging Center. This study was funded by grant K23-MH092397 (BPB) from the National Institute of Mental Health . DAP was partially supported by R37-MH068376 .
© 2017 Elsevier B.V.
- Magnetic resonance spectroscopy
ASJC Scopus subject areas
- Neuroscience (miscellaneous)
- Radiology Nuclear Medicine and imaging
- Psychiatry and Mental health