Neurochemical abnormalities in unmedicated bipolar depression and mania: A 2D 1H MRS investigation

Abstract

The neurobiology and neurochemistry of bipolar disorder and its different phases is poorly understood. This study investigated metabolite abnormalities in both unmedicated bipolar depression as well as mania using 2D 1H Magnetic Resonance Spectroscopy Imaging (MRSI). MRSI data was obtained from 24 unmedicated Bipolar Disorder (BP) subjects (12 (hypo)manic (BPM)) and 12 depressed (BPD)), and 20 closely matched healthy controls. 2D 1H MRSI data was collected from a 15 mm axial slice placed along the AC-PC line to measure brain metabolites bilaterally in the thalamus and also the anterior and posterior cingulate cortex (ACC and PCC). Brain Lac/Cr levels were significantly increased in the BP group as a whole compared to healthy controls. Glutamate abnormalities varied across bipolar state as well as brain region: significantly increased Glx/Cr values were found in the left thalamus in BPD but BPM had decreased Glu/Cr and Glx/Cr levels in the PCC when compared to healthy controls and decreased Glu/Cr levels even when compared to the BPD subjects group. The findings of the study point to state related abnormalities of oxidative and glutamate metabolism in bipolar disorder.

Main Effects of Diagnoses, Brain Regions, and their Interaction Effects for Cerebral Metabolites in Bipolar and Unipolar Depressive Disorders

“…Therefore, in order to better understand the brain metabolism changes in the subregions of gray matter on patients with BDd and UDd, participants with un-medicated BDd patients and UDd patients were enrolled in this study. The methodology of using a ratio of one cerebral metabolism compared with other metabolite was applied in earlier studies, just like Cho/Cr ratios21330, NAA/Cr ratios26, or Glx/Cr ratios2, etc However, they could not accurately reflect the change of cerebral metabolite concentrations30. Recent results revealed that using ratio rather than absolute concentration levels of metabolites was a technical limitation23.…”

“…The methodology of using a ratio of one cerebral metabolism compared with other metabolite was applied in earlier studies, just like Cho/Cr ratios21330, NAA/Cr ratios26, or Glx/Cr ratios2, etc However, they could not accurately reflect the change of cerebral metabolite concentrations30. Recent results revealed that using ratio rather than absolute concentration levels of metabolites was a technical limitation23. Hence, we combined the 2D-MRSI (magnetic resonance spectroscopy imaging) and LCModel software2122 in gray matter areas to measure the absolute concentration.…”

“…Comparing to schizophrenia patients and healthy cohorts, lower Glu, NAA, Cr and Inositol in patients with BDd suggested that a possible location-specific abnormality was existed in the dominant hemisphere of auditory cortices in patients with BDd11. As the main excitatory transmitter in the human brain, altered Glx was found in gray matter areas of patients with BDd1213. NAA, considering close associations with the energetics of mitochondria and neuronal loss, has been found decreased in patients with BDd and UDd141516.…”

“…Most of them simply focused on independently comparing cerebral metabolites among various groups in each brain region202122. Some studies conducted an interaction analysis on between the effect of diagnosis by brain region on the Glx/Cr level or the Glu/Cr level23. However, to our knowledge, few studies have comprehensively examined the relationships of cerebral metabolites’ absolute concentration in the various subregions of gray matter among 3 cohorts.…”

Vitamin D3Supplemental Treatment for Mania in Youth with Bipolar Spectrum Disorders

“…Although one study (Xu et al 2013) found no significant difference in ACC glutamate or Glx between unmedicated adults with BD and healthy adults, two other studies (Michael et al 2003;Ongur et al 2008) reported higher Glx in the prefrontal cortex of medicated adults with BD-mania; however glutamate differences in the latter studies were not significant (Ongur et al 2008). In addition to these studies conducted with adult populations, there exist only a few studies using MRS to examine ACC glutamate and/or Glx in adolescents.…”