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Bipolar Disord. 2016 Nov;18(7):583-590. doi: 10.1111/bdi.12445. Epub 2016 Nov 15.

Differential neurometabolite alterations in brains of medication-free individuals with bipolar disorder and those with unipolar depression: a two-dimensional proton magnetic resonance spectroscopy study.

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  • 1Mental Health Center, Shantou University Medical College, Shantou, China.
  • 2Department of Medical Imaging, The 2nd Affiliated Hospital, Shantou University Medical College, Shantou, China.
  • 3The Provincial Key Laboratory of Medical Molecular Imaging, Shantou, China.



Bipolar disorder (BD) is a mental disorder characterized by periods of elevated mood and depression. Many individuals with BD are initially misdiagnosed and treated for unipolar depression (UD). In this study, we report direct comparisons between medication-free individuals with BD and those with UD in terms of the neurometabolites in the anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), parietal cortex (PC), and posterior cingulate cortex (PCC) of the brain.


Participants included medication-free patients with BD or UD, and matched healthy controls. All patients were in the depressive state and had similar symptoms. All subjects were subjected to a multi-voxel proton magnetic resonance spectroscopy procedure with a 3.0 T GE Signa MR scanner. After post-processing, the absolute concentrations of glycerophosphocholine + phosphocholine (GPC + PC), phosphocreatine + creatine (PCr + Cr), Glx (glutamate + glutamine), myo-inositol (MI), and N-acetyl aspartate (NAA) from the above brain regions were compared across the three groups.


Patients with BD showed significantly higher levels of Glx in their ACC, lower GPC + PC, PCr + Cr, MI, and NAA in their PC, and lower NAA in their mPFC, compared to healthy controls; patients with UD presented significantly lower levels of GPC + PC, PCr + Cr, and NAA in their PCC, and lower Glx in their mPFC. All analyzed brain metabolites, except Glx, were significantly lower in the PC of patients with BD, whereas levels of GPC + PC, PCr + Cr, and NAA were significantly reduced in the PCC of patients with UD.


These results add to the evidence of brain metabolite differences in brains of patients with UD and BD which may be of help in differentiating these two mood disorders.


bipolar disorder; magnetic resonance spectroscopy; unipolar depression

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