Neurophysiological effects of multiple mood episodes in bipolar disorder.

OBJECTIVES: Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first- and multi-episode bipolar individuals. We hypothesized that the latter would demonstrate evidence of neurophysiological differences consistent with a model of progressive functional degradation of these networks. METHODS: First- and multi-episode manic bipolar subjects participated in functional magnetic resonance imaging (fMRI) including a continuous performance task with emotional distractors, and in single-voxel (1 H) magnetic resonance spectroscopy (MRS). A priori fMRI regions-of-interest (ROI) included structures comprising prefrontal-striatal-amygdala networks; (1 H)MRS voxels were placed within bilateral ventrolateral prefrontal (VLPFC) and anterior cingulate cortex (ACC). Both ROI and voxel-based brain activation in response to emotional stimuli, and neurochemical concentrations derived from (1 H)MRS were compared across bipolar groups. RESULTS: Multi-episode bipolar subjects showed relatively lower regional activation across prefrontal-striatal-amygdala networks, including bilateral VLPFC, orbitofrontal cortex, ACC, putamen, caudate, and amygdala. Exploratory whole-brain, voxel-based analysis suggested additional areas of lower activation extending into Brodmann area 22, posterior parietal regions, and right thalamus. Glutamate and N-acetylaspartate (NAA) concentrations were also relatively lower in the ACC of multi-episode subjects. CONCLUSIONS: Disease burden, exemplified by multiple affective episodes is associated with evidence of widespread decrements in affective network activity. Lower ACC NAA concentration is similarly consistent with a model of progressive functional deficits. These findings support the functional significance of previously observed progressive structural changes throughout these regions.

Effects of fish oil supplementation on prefrontal metabolite concentrations in adolescents with major depressive disorder: a preliminary 1H MRS study.

OBJECTIVE: To use proton magnetic resonance spectroscopy ((1)H MRS) to investigate the effects of fish oil (FO) supplementation on cortical metabolite concentrations in adolescents with major depressive disorder (MDD). METHODS: Metabolite concentrations were determined by (1)H MRS in the anterior cingulate cortex and bilateral dorsolateral prefrontal cortex (DLPFC) of adolescents with MDD before and following 10-week open-label supplementation with low (2.4 g/day, n = 7) or high (16.2 g/day, n = 7) dose FO. Depressive symptom severity scores and erythrocyte fatty acid levels were also determined. RESULTS: Baseline erythrocyte eicosapentaenoic acid (EPA) composition was positively correlated, and arachidonic acid (AA) and the AA/EPA ratio were inversely correlated, with choline (Cho) concentrations in the right DLPFC. Docosahexaenoic acid (DHA) composition was inversely correlated with myo-inositol (mI) concentrations in the left DLPFC. Erythrocyte EPA and DHA composition increased, and AA decreased, significantly following low-dose and high-dose FO supplementation. In the intent-to-treat sample, depressive symptom severity scores decreased significantly in the high-dose group (-40%, P < 0.0001) and there was a trend in the low-dose group (-20%, P = 0.06). There were no significant baseline-endpoint changes in metabolite levels in each voxel. In the low-dose group there were changes with large effect sizes, including a decrease in mI in the left DLPFC (-12%, P = 0.18, d = 0.8) and increases in glutamate + glutamine (Glx) (+12%, P = 0.19, d = 0.8) and Cho (+15%, P = 0.08, d = 1.2) in the right DLPFC. In the high-dose group, there was a trend for increases in Cho in the right DLPFC (+10%, P = 0.09, d = 1.2). DISCUSSION: These preliminary data suggest that increasing the LCn-3 fatty acid status of adolescent MDD patients is associated with subtle changes in Glx, mI, and Cho concentrations in the DLPFC that warrant further evaluation in a larger controlled trial.

Regional cerebral blood flow and magnetic resonance spectroscopic imaging findings in diaschisis from stroke.

BACKGROUND AND PURPOSE: This study evaluated blood flow and metabolite changes in cerebral diaschisis from internal capsule region infarction using regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT) and 1H magnetic resonance spectroscopic imaging (MRSI). We hypothesized that complementary measures of diaschisis effects in white matter (characterized by 1H MRSI) and gray matter (characterized by changes in rCBF) can be measured and exhibit parallel changes. METHODS: Five stroke patients and 16 normal controls underwent Tc-99m hexamethylpropyleneamine-oxime brain SPECT and 1H MRSI at 4.1 T. The metabolites N-acetyl aspartate (NAA) and creatine (Cr) were measured using 1H MRSI. The tissue content was expressed as the percent of gray or white matter in each MRSI voxel to allow comparison of the differential effects of diaschisis in gray and white matter tissue types. The blood flow and metabolite changes were evaluated at superior cerebral regions distant from the stroke to allow a measure of diaschisis relatively unconfounded by their expected changes in the infarction region. RESULTS: The rCBF SPECT data in stroke patients showed a perfusion defect, with size ranging from 1.23 cc to 10.23 cc, in the region of cortical diaschisis. 1H MRSI showed increased Cr/NAA ratios in regions of white matter diaschisis. There was a tendency for larger rCBF defect size to be associated with greater increases in Cr/NAA values in the same diaschitic cerebral hemisphere, ipsilateral to the infarction. CONCLUSION: Diaschisis ipsilateral to stroke in white matter can be characterized by 1H MRSI, and diaschisis ipsilateral to stroke in cortical gray matter regions can be characterized by changes in rCBF. The tendency for greater reductions in cortical rCBF values to be associated with increased Cr/NAA values in the same diaschitic cerebral hemisphere implies that a relationship exists between rCBF reductions in gray matter and abnormal changes in white matter subservient to it.