Relationship between depression, prefrontal creatine and grey matter volume.

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

doi:10.1177/02698811211050550

Abstract

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.

Highlights

Depression and low mood are leading contributors to disability worldwide and can affect more than 300 million people at any one time (Britton, 2017)
This is the first study to examine the relationship of both prefrontal creatine and grey matter volume with depression/low mood in a group of individuals who self-reported a wide range of depression severities
Our results suggest that individuals who experience subclinical depressive symptoms and low mood have lower concentrations of creatine and lower grey matter volume in the prefrontal cortex

Summary

Introduction

Depression and low mood are leading contributors to disability worldwide and can affect more than 300 million people at any one time (Britton, 2017). Kondo et al (2016) reported a weak yet significant negative relationship between depression scores and concentrations of creatine in the frontal cortex of 22 adolescent participants diagnosed with MDD (p = 0.030; actual effect size not reported), indicating that high concentrations of creatine in the prefrontal cortex may be associated with lower levels of depression Along these lines, Dechant et al (1999) report that daily administration of 20 g creatine monohydrate for 4 weeks increased total brain creatine by up to 8.7% in a small sample of nine healthy individuals (see Allen, 2012, for a review), while Lyoo et al (2012) report that daily supplementation of 5 g creatine monohydrate for 8 weeks augmented the antidepressant effects of escitalopram in 25 depressed females. On the basis of findings by Hasler et al (2007) and Auer et al (2000), who report that depressed individuals exhibit low prefrontal concentrations of glutamate and γ-aminobutyric acid (GABA) metabolites, we performed exploratory analyses to determine the relationship between depression levels and concentrations of all metabolites quantified by the 1H-MRS sequence

Methods

Participants

Results

Discussion