A Magnetic Resonance Spectroscopy Study on Polarity Subphenotypes in Bipolar Disorder

Abstract

Although magnetic resonance spectroscopy (MRS) has provided in vivo measurements of brain chemical profiles in bipolar disorder (BD), there are no data on clinically and therapeutically important onset polarity (OP) and predominant polarity (PP). We conducted a proton MRS study in BD polarity subphenotypes, focusing on emotion regulation brain regions. Forty-one euthymic BD patients stratified according to OP and PP and sixteen healthy controls (HC) were compared. 1H-MRS spectra of the anterior and posterior cingulate cortex (ACC, PCC), left and right hippocampus (LHIPPO, RHIPPO) were acquired at 3.0T to determine metabolite concentrations. We found significant main effects of OP in ACC mI, mI/tNAA, mI/tCr, mI/tCho, PCC tCho, and RHIPPO tNAA/tCho and tCho/tCr. Although PP had no significant main effects, several medium and large effect sizes emerged. Compared to HC, manic subphenotypes (i.e., manic-OP, manic-PP) showed greater differences in RHIPPO and PCC, whereas depressive suphenotypes (i.e., depressive-OP, depressive-PP) in ACC. Effect sizes were consistent between OP and PP as high intraclass correlation coefficients (ICC) were confirmed. Our findings support the utility of MRS in the study of the neurobiological underpinnings of OP and PP, highlighting that the regional specificity of metabolite changes within the emotion regulation network consistently marks both polarity subphenotypes.

Keywords: bipolar disorder; cingulate cortex; emotion regulation network; hippocampus; onset polarity; predominant polarity; proton magnetic resonance spectroscopy.

Figure 1

1H-MRS voxel position in (a) LHIPPO, (b) RHIPPO, (c) ACC, and (d) PCC (data from a healthy control). 1H-MRS = proton magnetic resonance spectroscopy; LHIPPO = left hippocampus; RHIPPO = right hippocampus; ACC = anterior cingulate cortex; PCC = posterior cingulate cortex. The voxel size for each brain region in Figure 1 was selected for visualization purposes and does not correspond to the voxel size during the MRS acquisition, which is presented in the text.

Figure 2

A representative spectrum with the fitted peaks (Tarquin software) for (a) LHIPPO, (b) RHIPPO, (c) ACC, and (d) PCC. LHIPPO = left hippocampus; RHIPPO = right hippocampus; ACC = anterior cingulate cortex; PCC = posterior cingulate cortex.

Figure 3

The pattern of the magnitude of absolute differences (absolute Cohen’s |d| effect size) (a) between HC and manic subgroups (OP-M and PP-M) and (b) between HC and depressive subgroups (OP-D and PP-D).

Figure 4

The pattern of the magnitude of differences (Cohen’s d effect size) followed up from OP to PP between-group comparisons (a) between HC and manic subgroups (OP-M and PP-M), (b) between HC and depressive subgroups (OP-D and PP-D), and (c) between manic and depressive OP and PP subgroups.