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The Impact of Homocysteine Levels on Cognition in Euthymic Bipolar Patients: A Cross-Sectional Study

Sandra Dittmann, Ph.D.; Florian Seemüller, M.D.; Heinz C. Grunze, M.D., Ph.D.; Markus J. Schwarz, M.D., Ph.D.; Johanna Zach, B.A.; Kristina Fast, Ph.D.; Christoph Born, M.D.; Sascha Dargel, M.D.; Rolf R. Engel, Ph.D.; Britta Bernhard, Ph.D.; Hans-Jürgen Möller, M.D., Ph.D.; Michael Riedel, M.D.; and W. Emanuel Severus, M.D.


Objective: Bipolar disorder is associated with cognitive impairment. High homocysteine levels seem to have a negative impact on cognition in the elderly. The aim of the present study was to investigate the potential relationship of elevated homocysteine levels and cognitive impairment in bipolar patients.

Method: Cognitive functioning of DSM-IV bipolar disorder patients who were euthymic (Hamilton Rating Scale for Depression score <= 5 and Young Mania Rating Scale score <= 5) and healthy controls was assessed with the revised Wechsler Adult Intelligence Scale Information Subtest, the Wechsler Adult Intelligence Scale III Letter-Number Sequencing Subtest, the Trail Making Test, and the Repeatable Battery for the Assessment of Neuropsychological Status Form A to examine premorbid IQ, information processing speed, working memory, verbal learning, visuospatial/constructional abilities, delayed memory, and executive functions. Total homocysteine plasma concentration was measured by using high-performance liquid chromatography. Multivariate analyses of variance and multiple regression analyses were conducted to examine group differences and possible associations between cognitive functioning and homocysteine level. The study was conducted from 2002 through 2006.

Results: Seventy-five euthymic bipolar patients and 42 healthy controls participated in the study. Patients performed significantly worse than controls in all cognitive domains tested (Pillai Spur: F = 3.32, p = .038) except premorbid IQ (p = .068). The mean ±SD homocysteine levels were 10.2 ± 3.2 microM/L for patients and 8.9 ± 2.8 microM/L for controls (p = .036). Stepwise regression analyses revealed a significant and independent association of homocysteine levels with verbal learning (p = .002), delayed memory (p = .030), and executive function (p = .011) in the patient group. About 11% of the variance was explained by only the homocysteine level.

Conclusion: Elevated homocysteine levels may have a negative impact on verbal learning, delayed memory, and executive function in euthymic bipolar patients, but further studies are warranted.

 

(J Clin Psychiatry 2008;69:899-906. Online Ahead of Print April 8, 2008.)


Received May 30, 2007; accepted Oct. 8, 2007. From the Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.

This article was supported by the Stanley Medical Research Institute, Chevy Chase, Md.

The authors thankfully acknowledge the help from Sophia Frangou, M.D., Ph.D. (Institute of Psychiatry, King's College London, United Kingdom) in preparing the manuscript. Dr. Frangou has no conflicting financial or other interests to disclose.

Dr. Möller has been a consultant to or has served on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Organon, Pfizer, Sepracor, Servier, and Wyeth; has received grant/research support from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Eisai, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Merck, Novartis, Organon, Pfizer, Sepracor, Servier, and Wyeth; and has served on speakers bureaus for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Eisai, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Organon, Pfizer, Sanofi-Aventis, and Sepracor. Dr. Riedel has served on speakers or advisory boards for AstraZeneca, Pfizer, Eli Lilly, Janssen, Otsuka, Bristol-Myers Squibb, and Sanofi-Aventis; has been a consultant to AstraZeneca and Otsuka; and has received grant/research support from AstraZeneca, Eli Lilly, Pfizer, and Bristol-Myers Squibb. The other authors report no additional financial or other relationships relevant to the subject of this article.

Corresponding author and reprints: Sandra Dittmann, Ph.D., Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Nussbaumstr. 7, 80336 Munich, Germany (e-mail: sandra.dittmann@med.uni-muenchen.de).