Biochemical abnormalities in basal ganglia and executive dysfunction in acute- and euthymic-episode patients with bipolar disorder: A proton magnetic resonance spectroscopy study

Background: Recent studies found abnormal biochemical metabolism and executive cognitive deficits in acute bipolar disorder (BD). However, the evidence concerning in euthymic BD is limited. Thus, a comparison between acute and euthymic BD is conductive to better understanding the association between cognition and the outcome of neuroimaging. This study sought to investigate the relationship between the executive function and the biochemical metabolism in acute- and euthymic-episode BD patients and delineate the prominent endophenotype of BD. Methods: Three groups of participants were recruited in this study: 30 BD patients with an acute depressive episode, 22 euthymic BD patients, and 31 healthy controls. All participants were interviewed using the Structured Clinical Interview for DSM-IV, and underwent two-dimensional multivoxel proton magnetic resonance spectroscopy (1H-MRS) to obtain the bilateral metabolite levels in the lenticular nucleus of basal ganglia (BG). The ratios of N-acetylaspartate (NAA)/creatine (Cr) and Choline-containing compounds (Cho)/Cr ratios were calculated. Executive function was assessed by using the Wisconsin Card Sorting Test (WCST) and Trail Making Test, Part-B(TMT-B). Results: The comparison of biochemical changes showed that the NAA/Cr ratios in bilateral lenticular nucleus in both acute and euthymic BD patients was significantly lower than that in healthy controls at a confidence level of p<0.05. In the comparison of executive function, both acute and euthymic BD patients showed significantly decreased numbers of categories completed, and increased numbers of total errors, perseverative and noperseverative errors, and TMT-B uptake compared to the healthy controls at a confidence level of p<0.05. There were no significant differences between the acute BD and euthymic BD groups in the biochemical metabolite ratios and executive function. We found that the NAA/Cr ratio in the left in BG in the acute - episode BD patients was positively correlated with the number of categories completed, whereas it was negatively correlated with the total errors and TMT-B uptake. There was no correlation between the NAA/Cr and Cho/Cr ratios in the bilateral BG and the scores of SWCT and TMT-B in euthymic-episode BD patients. Limitation: The sample size was relatively small and not all the euthymic-episode patients are the ones with an acute episode. Conclusions: Our findings suggest that biochemical abnormalities in the lenticular nucleus and the executive dysfunction may occur early in the course of BD, and persist during remission, and are the most likely markers of endophenotypes of BD. The dysfunction of the neuronal function in the lenticular nucleus may be correlated with the cold dysfunction in patients with acute BD.