Study Of Female Mdd Patients’ Brain Functional Activities Using Multimodal Magnetic Resonance Imaging

Major depressive disorder,a pervasive and debilitating illness,is clinically characterized by persistent feelings of sadness and increased association of patients with negative emotion.The incidence rate of MDD in women is twofold higher than in men and somatic symptoms such as fatigue and sleep disturbance more likely appear in women.Yet,there have only been a few studies on the functional brain activity in female MDD patients and the detailed mechanisms underlying their neurobiology merit further investigations.In the present work,we used combined fMRI-MRS methods to investigate the altered intrinsic neuronal activity and its association with metabolites concentration in female MDD patients.First,we tried to explore the altered spontaneous neural activity measured with regional homogeneity(ReHo)and amplitude of low frequency fluctuation(ALFF)in female MDD patients using resting state fMRI technique.Twelve MDD females and twelve matched healthy participants were included in the study.The ReHo analysis method was used to detect regional homogeneity features across the whole brain.Increased ReHo value was found in the left anterior cingulate gyrus(ACC_L)and right fusiform gyrus,and decreased ReHo value in the right putamen,left middle frontal gyrus and left middle occipital gyrus was shown in female MDD patients compared with healthy controls.We found that the female MDD patients showed increased neuronal spontaneous activity in left medial prefrontal cortex(mPFC)and left middle frontal cortex,with decreased ALFF level in right putamen and right middle temporal cortex.Also,a significant positive correlation between patients’ReHo value and HAMA score(r=0.59,p=0.045)was found in the ACC_L.The study of spontaneous neuronal activity alteration using ReHo analysis improves our understanding about the mechanism of female depression.Through fMRI-MRS method,we investigated the relationship between ALFF and neuronal metabolites in medial prefrontal cortex(mPFC).we quantified the concentration of amino acid neurotransmitters including GABA(r-aminobutyric acid),Glu(Glutamate),and Glx(Glutamate+Glutamine)using ~1H-MRS technology.Moreover,we conducted Pearson correlation analysis between the ALFF value and neurotransmitter concentration to find out the functional-biochemical relation in mPFC area.The relationship between the metabolites concentration and MDD symptomatology was also examined through Spearman correlation analysis.The ALFF in mPFC was shown positively correlated with Glu concentration in female MDD patients(r=0.67,p=0.023).The Glu concentration in mPFC was positively correlated with patients HAMA scores(r=0.641,p=0.033).Furthermore,Metabolic and functional alterations in hippocampus have been associated with the pathophysiology of MDD.However,how the regional disruptions in hippocampus lead to dysfunction of the limbic-cortical circuit remains unclear.The combined resting state fMRI-MRS method was adopted to investigate the hippocampal metabolic levels and their relationship with the whole-brain intrinsic functional connectivity(FC)in MDD.Both MRI and fMRI data were obtained from twelve MDD women and twelve age-matched female healthy controls.MDD women showed elevated left hippocampal choline(Cho)level(t=2.20,p<0.05)reflecting abnormal membrane metabolism but no changes of N-acetyl aspartate or creatine.MDD females also exhibited decreased negative correlations between the left hippocampus and bilateral superior frontal gyrus(SFG),left inferior frontal gyrus(IFG),and right superior temporal gyrus(STG).More importantly,we further found that altered FC between the left hippocampus and the bilateral SFG and left IFG were significantly correlated with the increased left hippocampal Cho level.Our findings suggested that regional metabolic alterations in the left hippocampus might contribute to the network-level dysfunction.The combined fMRI-MRS analysis provides more insights in uncovering the pathophysiology of MDD.