Glutamatergic hypofunction in medication-free major depression: Secondary effects of affective diagnosis and relationship to peripheral glutaminase

Toby Wise, Matthew J. Taylor, Andres Herane-Vives, Antonella Marino Gammazza, Francesco Cappello, David J. Lythgoe, Steve CR Williams, Allan H. Young, Anthony J. Cleare, Danilo Arnone

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Background: There is uncertainty as to whether alterations in glutamatergic function in affective disorders differ between unipolar and bipolar disorders and between depressive and euthymic states. Additionally, there are currently no available blood-based markers of central glutamatergic function to support clinical diagnosis and aid brain based investigations. Methods: In this study, we measured levels of glutamate in the dorsal anterior cingulate cortex in-vivo using 1H-Magnetic Resonance Spectroscopy in medication free unipolar and bipolar patients (n = 29, 20 unipolar and 9 bipolar) experiencing a major depressive episode, in comparison with a group of matched healthy controls (n = 20). We also analysed peripheral glutaminase measured in serum to examine the relationship between central and peripheral measures. Results: Anterior cingulate glutamate levels were reduced in both unipolar and bipolar depression groups relative to healthy controls, although this only reached significance in the unipolar group. Peripheral glutaminase levels did not differentiate bipolar from unipolar depression and a positive correlation with central glutamate levels did not reach statistical significance. Limitations: The sample of bipolar disorder patients was relatively small due to the difficulties involved in finding medication-free patients experiencing a depressive episode. Conclusions: These results suggest that glutamatergic hypofunction might represent a state marker for a depressive episode irrespective of diagnosis. Peripheral glutaminase did not index central glutamate levels in this study, which could potentially reflect a small magnitude of the effect requiring larger samples for detection.

Original languageEnglish
Pages (from-to)214-219
Number of pages6
JournalJournal of Affective Disorders
Publication statusPublished - Jul 2018
Externally publishedYes


  • Bipolar disorder
  • Depression
  • Magnetic resonance
  • Mood disorders
  • Neuroimaging

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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