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4-T 7Li 3D MR spectroscopy imaging in the brains of bipolar disorder subjects.

ABSTRACT: This work demonstrates the first whole brain "high spatial resolution" (7)Li MR spectroscopy imaging in bipolar disorder subjects. The in vivo quantification is validated by a phantom containing 5 mM lithium salt using the identical radiofrequency sequence and imaging protocol. This study is the first demonstration of the (7)Li distribution in the brain of bipolar disorder patients on lithium therapy using a 3D MR spectroscopy imaging approach. The results show that brain lithium level is strongly correlated with serum lithium concentration. The brain-to-serum lithium ratios for the average brain and the local maximum were 0.39 ± 0.08 (r = 0.93) and 0.92 ± 0.16 (r = 0.90), respectively. The lithium distribution is found to be nonuniform throughout the brain for all patients, which is somewhat unexpected and highly intriguing. This uneven distribution is more evident in subjects at a higher therapeutic serum lithium level. This finding may suggest that lithium targets specific brain tissues and/or certain enzymatic and macromolecular sites that are associated with therapeutic effect. Further investigations of bipolar disorder patients on lithium therapy using 3D (7)Li MR spectroscopy imaging are warranted.

SUBMITTER: Lee JH

PROVIDER: S-EPMC3396736 | biostudies-other | 2012 Aug

REPOSITORIES: biostudies-other

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Project description:There are currently no biological tests that differentiate patients with bipolar disorder (BPD) from healthy controls. While there is evidence that peripheral gene expression differences between patients and controls can be utilized as biomarkers for psychiatric illness, it is unclear whether current use or residual effects of antipsychotic and mood stabilizer medication drives much of the differential transcription. We therefore tested whether expression changes in first-episode, never-medicated bipolar patients, can contribute to a biological classifier that is less influenced by medication and could potentially form a practicable biomarker assay for BPD. We employed microarray technology to measure global leukocyte gene expression in first-episode (n=3) and currently medicated BPD patients (n=26), and matched healthy controls (n=25). Following an initial feature selection of the microarray data, we developed a cross-validated 10-gene model that was able to correctly predict the diagnostic group of the training sample (26 medicated patients and 12 controls), with 89% sensitivity and 75% specificity (p<0.001). The 10-gene predictor was further explored via testing on an independent test cohort consisting of three pairs of monozygotic twins discordant for BPD, plus the original enrichment sample cohort (the three never-medicated BPD patients and 13 matched control subjects), and a sample of experimental replicates (n=34). 83% of the independent test sample was correctly predicted, with a sensitivity of 67% and specificity of 100% (although this result did not reach statistical significance). Additionally, 88% of sample diagnostic classes were classified correctly for both the enrichment (p=0.015) and the replicate samples (p<0.001). Peripheral blood leukocytes (PBLs) from whole blood were collected from 26 patients with bipolar disorder who had previously received medication, three patients with bipolar disorder who were experiencing their first hospitalization and had not previously received medication, and 25 matched control subjects, for RNA extraction and hybridization on Affymetrix microarrays. Immediately after blood collection, blood samples were split into two (when a sufficient volume had been collected); an "1" and replicate "2" sample (thus two separate RNA extractions, cDNA and cRNA syntheses and array hybridizations were performed).

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4-T 7Li 3D MR spectroscopy imaging in the brains of bipolar disorder subjects.

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