Relationship between depression, prefrontal creatine and grey matter volume

Paul Faulkner*, Susanna Lucini Paioni, Petya Kozhuharova, Natasza Orlov, David J. Lythgoe, Yusuf Daniju, Elenor Morgenroth, Holly Barker, Paul Allen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Background: Depression and low mood are leading contributors to disability worldwide. Research indicates that clinical depression may be associated with low creatine concentrations in the brain and low prefrontal grey matter volume. Because subclinical depression also contributes to difficulties in day-to-day life, understanding the neural mechanisms of depressive symptoms in all individuals, even at a subclinical level, may aid public health. Methods: Eighty-four young adult participants completed the Depression, Anxiety and Stress Scale (DASS) to quantify severity of depression, anxiety and stress, and underwent 1H-Magnetic Resonance Spectroscopy of the medial prefrontal cortex and structural magnetic resonance imaging (MRI) to determine whole-brain grey matter volume. Results/outcomes: DASS depression scores were negatively associated (a) with concentrations of creatine (but not other metabolites) in the prefrontal cortex and (b) with grey matter volume in the right superior medial frontal gyrus. Medial prefrontal creatine concentrations and right superior medial frontal grey matter volume were positively correlated. DASS anxiety and DASS stress scores were not related to prefrontal metabolite concentrations or whole-brain grey matter volume. Conclusions/interpretations: This study provides preliminary evidence from a representative group of individuals who exhibit a range of depression levels that prefrontal creatine and grey matter volume are negatively associated with depression. While future research is needed to fully understand this relationship, these results provide support for previous findings, which indicate that increasing creatine concentrations in the prefrontal cortex may improve mood and well-being.

Original languageEnglish
Pages (from-to)1464-1472
Number of pages9
JournalJournal of Psychopharmacology
Issue number12
Early online date26 Oct 2021
Publication statusPublished - Dec 2021


  • Creatine
  • depression
  • grey matter volume
  • neuroimaging
  • prefrontal


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