Acute change in anterior cingulate cortex GABA, but not glutamine/glutamate, mediates antidepressant response to citalopram

Brian P. Brennan, Roee Admon, Chris Perriello, Erin M. LaFlamme, Alison J. Athey, Diego A. Pizzagalli, James I. Hudson, Harrison G. Pope, J. Eric Jensen

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)9-16
Number of pages8
JournalPsychiatry Research - Neuroimaging
StatePublished - 30 Nov 2017

Bibliographical note

Publisher Copyright:
© 2017 Elsevier B.V.


  • Depression
  • GABA
  • Glutamate
  • MRS
  • Magnetic resonance spectroscopy
  • SSRI

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Radiology Nuclear Medicine and imaging
  • Neuroscience (miscellaneous)


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