Elevated hippocampal choline level is associated with altered functional connectivity in females with major depressive disorder: A pilot study

Metabolic and functional alterations in hippocampus have been associated with the pathophysiology of major depressive disorder (MDD). However, how the hippocampal biochemical disruptions lead to dysfunction of limbic-cortical circuit remains unclear. The present pilot study combined magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the hippocampal metabolic alteration and its relationship with the intrinsic functional connectivity (FC) changes in MDD. Both MRS and fMRI data were obtained from twelve women with MDD and twelve age-matched, healthy women. Bilateral hippocampi were chosen as regions of interest, in which metabolite concentrations of total choline (tCho), N-acetylaspartate and creatine were quantified. Bilateral hippocampal FC to the whole brain and its correlations with hippocampal metabolite concentrations were conducted. Females with MDD showed significantly elevated left hippocampal tCho level, and decreased anti-correlations between the left hippocampus and bilateral superior frontal gyrus (SFG), left inferior frontal gyrus, and right superior temporal gyrus. More importantly, the left hippocampal tCho level was associated with FC to the right SFG and right fusiform gyrus in healthy women, whereas it was significantly associated with FC to the right lingual gyrus in women with MDD. Our findings suggested that regional metabolic alterations in the left hippocampus might be related to the network-level dysfunction.