Relationship Between Depression, Prefrontal Creatine and Gray Matter Volume

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 gray matter volume. Because sub-clinical depression also contributes to difficulties in day-to-day life, understanding the neural mechanisms of depressive symptoms in all individuals, even at a sub-clinical 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 1 H-Magnetic Resonance Spectroscopy of the medial prefrontal cortex and structural MRI to determine whole-brain gray matter volume. Results/Outcomes DASS depression scores were negatively associated with A) concentrations of creatine (but not other metabolites) in the prefrontal cortex, and B) with gray matter volume in the right superior medial frontal gyrus. Medial prefrontal creatine concentrations and right superior medial frontal gray matter volume were positively correlated. DASS anxiety and DASS stress scores were not related to prefrontal metabolite concentrations or whole-brain gray 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 gray 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 wellbeing. Declaration of Interest/Funding This research was partly funded by a British Academy/Leverhulme Trust Research Grant, awarded to PA.