Relationship between depression, prefrontal creatine and grey matter volume

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.

Effects of Creatine Supplementation on Brain Function and Health

“…The critical role of creatine in the brain is well documented through creatine deficiency syndromes, which are characterized by intellectual disability, language delay, seizure disorders, autism spectrum disorder and various movement disorders, with the primary treatment being creatine monohydrate supplementation in an attempt to increase creatine content in the brain [ 108 ]. Many mental health disorders have also been characterized to have abnormalities in brain bioenergetics, with some of the more prevalent disorders, such as depression, being associated with low creatine levels in certain regions of the brain [ 109 ]. Based on such observations, there has been growing interest in the possible use of creatine monohydrate in various brain/neurological disorders, including mental/psychiatric disorders.…”

“…The authors used the National Health and Nutrition Examination Survey to demonstrate a significant negative relationship between dietary creatine and depression. Direct interventional studies using 1 H-magnetic resonance spectroscopy ( 1 H-MRS) have also demonstrated that lower creatine levels in the prefrontal cortex are associated with low mood/increased depression [ 109 ]. Even prior to these observations, many different groups have undertaken trials of creatine supplementation in both animals and humans alone and/or in combination with other pharmaceutical interventions to treat depression.…”

Creatine monohydrate supplementation changes total body water and DXA lean mass estimates in female collegiate dancers

“…Collegiate dance is unique, due to the large mental and physical demands brought about by rigorous academic schedules as well as a lack of nutrition and supplemental training resources. Previous data suggest CR supplementation augments brain CR via the blood-brain barrier, thereby eliciting an inverse relationship with depressive symptoms [ 9 , 10 ]. Furthermore, in individuals with methamphetamine dependence, 8 weeks of CR supplementation significantly decreased anxiety symptoms [ 11 ].…”

“…In addition to LM and muscle performance improvements, CR supplementation has been shown to possibly increase measures of cognitive function by increasing serotonin levels in the brain [ 8 ]. Some research suggests CR content in the pre-frontal cortex has been inversely associated with depressive symptoms, in healthy adults, due to its ability to cross the blood-brain barrier thereby augmenting brain CR with the use of CR supplementation; however, these results are mixed [ 9 , 10 ]. In addition, following 8 weeks of CR supplementation, Hellem et al [ 11 ] showed decreases in anxiety symptoms in individuals with methamphetamine dependence [ 11 ], albeit these implications in a healthy population are undetermined.…”

Repurposing psychopharmacology: A two-way street?

“…These effects may be relevant for preventing stress-induced maladaptive behaviours. Faulkner et al (2021) report on the relationship between depression, prefrontal creatine and grey matter volume. Their results provide support for previous findings which indicate that increasing creatine concentrations in the prefrontal cortex may improve mood and well-being.…”