Xiaoliu Zhang1, Yingying Tang2, Mirjana Maletic-Savatic3, Jianhua Sheng4, Xuanhong Zhang4, Yajing Zhu1, Tianhong Zhang2, Junjie Wang5, Shanbao Tong1, Jijun Wang6, Yao Li7. 1. School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China. 2. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Wanping Nan Road, Shanghai 200030, China; Department of EEG and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Wanping Nan Road, Shanghai 200030, China. 3. Departments of Pediatrics, Neuroscience, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston TX 77030, USA. 4. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Wanping Nan Road, Shanghai 200030, China. 5. Department of EEG and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Wanping Nan Road, Shanghai 200030, China. 6. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Wanping Nan Road, Shanghai 200030, China; Department of EEG and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Wanping Nan Road, Shanghai 200030, China. Electronic address: jijunwang27@163.com. 7. School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: yaoli118@gmail.com.
Abstract
BACKGROUND: Major depressive disorder (MDD) is twice more prevalent in females than in males. 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 neurotransmitter concentration in female MDD patients. METHODS: The whole brain amplitude of low frequency fluctuation (ALFF) analysis using resting state functional magnetic resonance imaging (fMRI) was performed to explore the alteration of intrinsic neuronal signals in MDD females (n=11) compared with female healthy controls (n=11). With a specific interest in the medial prefrontal cortex (mPFC) area, we quantified the concentration of amino acid neurotransmitters including GABA ((r-aminobutyric acid)), Glu (Glutamate), and Glx (Glutamate + Glutamine) using (1)H-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. RESULTS: 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 (p<0.01, Alphasim corrected). 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). LIMITATIONS: The relatively small sample size, metabolite information acquired only in mPFC and not all patients were unmedicated are the major limitations of our study. CONCLUSIONS: Using combined fMRI-MRS methods, we found increased spontaneous neuronal activity was correlated with Glu concentration in mPFC of female MDD patients. Other regions including left middle frontal gyrus, right putamen and middle temporal gyrus also showed altered spontaneous neuronal activities. The abnormal intrinsic neuronal activities in fronto-cortical regions shed light on the pathogenesis underlying MDD females. The multimodal resting-state neuroimaging technique served as a useful tool for functional-biochemical investigation of MDD pathophysiology.
BACKGROUND: Major depressive disorder (MDD) is twice more prevalent in females than in males. Yet, there have only been a few studies on the functional brain activity in female MDDpatients 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 neurotransmitter concentration in female MDDpatients. METHODS: The whole brain amplitude of low frequency fluctuation (ALFF) analysis using resting state functional magnetic resonance imaging (fMRI) was performed to explore the alteration of intrinsic neuronal signals in MDD females (n=11) compared with female healthy controls (n=11). With a specific interest in the medial prefrontal cortex (mPFC) area, we quantified the concentration of amino acid neurotransmitters including GABA ((r-aminobutyric acid)), Glu (Glutamate), and Glx (Glutamate + Glutamine) using (1)H-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. RESULTS: We found that the female MDDpatients 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 (p<0.01, Alphasim corrected). The ALFF in mPFC was shown positively correlated with Glu concentration in female MDDpatients (r=0.67, p=0.023). The Glu concentration in mPFC was positively correlated with patients HAMA scores (r=0.641, p=0.033). LIMITATIONS: The relatively small sample size, metabolite information acquired only in mPFC and not all patients were unmedicated are the major limitations of our study. CONCLUSIONS: Using combined fMRI-MRS methods, we found increased spontaneous neuronal activity was correlated with Glu concentration in mPFC of female MDDpatients. Other regions including left middle frontal gyrus, right putamen and middle temporal gyrus also showed altered spontaneous neuronal activities. The abnormal intrinsic neuronal activities in fronto-cortical regions shed light on the pathogenesis underlying MDD females. The multimodal resting-state neuroimaging technique served as a useful tool for functional-biochemical investigation of MDD pathophysiology.
Authors: William T Choi; Mehmet Tosun; Hyun-Hwan Jeong; Cemal Karakas; Fatih Semerci; Zhandong Liu; Mirjana Maletić-Savatić Journal: BMC Syst Biol Date: 2018-12-21
Authors: Joshua T Kantrowitz; Zhengchao Dong; Matthew S Milak; Rain Rashid; Lawrence S Kegeles; Daniel C Javitt; Jeffrey A Lieberman; J John Mann Journal: Transl Psychiatry Date: 2021-08-05 Impact factor: 6.222