Xian-Feng Shi1, Lauren N Forrest2, M Danielle Kuykendall2, Andrew P Prescot3, Young-Hoon Sung4, Rebekah S Huber2, Tracy L Hellem2, Eun-Kee Jeong3, Perry F Renshaw5, Douglas G Kondo5. 1. The Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City, UT 84108, USA; Department of Psychiatry, University of Utah, School of Medicine, Salt Lake City, UT, USA. Electronic address: Xianfeng.Shi@hsc.utah.edu. 2. The Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City, UT 84108, USA. 3. Department of Radiology, University of Utah, School of Medicine, Salt Lake City, UT, USA. 4. The Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City, UT 84108, USA; Department of Psychiatry, University of Utah, School of Medicine, Salt Lake City, UT, USA. 5. The Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City, UT 84108, USA; Department of Psychiatry, University of Utah, School of Medicine, Salt Lake City, UT, USA; VISN 19 Mental Illness Research, Education and Clinical Center (MIRECC), George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA.
Abstract
BACKGROUND: Delayed diagnosis in bipolar disorder (BD) due to misdiagnosis as major depressive disorder (MDD) is a significant public health concern. Thus, identification of relevant diagnostic biomarkers is a critical unmet need, particularly early in the course of illness. The anterior cingulate cortex (ACC) is thought to play an important role in mood disorder pathophysiology. Case-control studies utilizing proton-1 magnetic resonance spectroscopy ((1)H-MRS) have found increased total choline levels in several brain regions in MDD. However, there are no published (1)H-MRS reports directly comparing adolescents with MDD and BD. We hypothesized that ACC choline levels would be increased in adolescents with unipolar versus bipolar depression. METHODS: We studied depressed adolescents with MDD (n=28; mean age 17.0±2.1 years) and BD (n=9; 17.3±3.1 years). A Siemens Verio 3-Tesla clinical MRI system was used to acquire scans, using a single-voxel PRESS sequence. The voxel (18.75 cm(3)) was positioned on the ACC in the midsagittal plane. To remove potential gender effects, only female adolescent participants were included. Data were analyzed using the ANOVA and post-hoc Tukey tests. RESULTS: A significantly increased ACC choline/creatine ratio was observed in participants with MDD (mean=0.253±0.021) compared to BD (mean=0.219±0.020) (p=0.0002). There were no significant differences in the other (1)H-MRS metabolites. LIMITATIONS: Cross sectional design, single gender sample, limited sample size. CONCLUSIONS: The present findings suggest that ACC total choline may have the potential to serve as a diagnostic biomarker in adolescent mood disorders.
BACKGROUND: Delayed diagnosis in bipolar disorder (BD) due to misdiagnosis as major depressive disorder (MDD) is a significant public health concern. Thus, identification of relevant diagnostic biomarkers is a critical unmet need, particularly early in the course of illness. The anterior cingulate cortex (ACC) is thought to play an important role in mood disorder pathophysiology. Case-control studies utilizing proton-1 magnetic resonance spectroscopy ((1)H-MRS) have found increased total choline levels in several brain regions in MDD. However, there are no published (1)H-MRS reports directly comparing adolescents with MDD and BD. We hypothesized that ACC choline levels would be increased in adolescents with unipolar versus bipolar depression. METHODS: We studied depressed adolescents with MDD (n=28; mean age 17.0±2.1 years) and BD (n=9; 17.3±3.1 years). A Siemens Verio 3-Tesla clinical MRI system was used to acquire scans, using a single-voxel PRESS sequence. The voxel (18.75 cm(3)) was positioned on the ACC in the midsagittal plane. To remove potential gender effects, only female adolescent participants were included. Data were analyzed using the ANOVA and post-hoc Tukey tests. RESULTS: A significantly increased ACC choline/creatine ratio was observed in participants with MDD (mean=0.253±0.021) compared to BD (mean=0.219±0.020) (p=0.0002). There were no significant differences in the other (1)H-MRS metabolites. LIMITATIONS: Cross sectional design, single gender sample, limited sample size. CONCLUSIONS: The present findings suggest that ACC total choline may have the potential to serve as a diagnostic biomarker in adolescent mood disorders.
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