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Sequence variations in CREB1 cosegregate with depressive disorders in women

Molecular Psychiatry volume 8, pages 611–618 (2003)Cite this article

Abstract

Major depressive disorder (MDD) constitutes a major public health problem worldwide and affects women twice as frequently as men. Previous linkage studies have identified a 451 kb region of 2q33–35 that exhibited significant evidence of linkage to Mood Disorders among women (but not men) from families with recurrent, early-onset MDD (RE-MDD), a severe and strongly familial subtype of MDD. This 451 kb region includes CREB1, an attractive susceptibility gene for MDD and related disorders. Sequence variations in the CREB1 promoter and intron 8 have been detected that cosegregate with Mood Disorders, or their absence, in women from these families, identifying CREB1 as a sex-limited susceptibility gene for unipolar Mood Disorders. These findings implicate the cAMP signaling pathway in the pathophysiology of Mood Disorders and related conditions.

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Acknowledgements

The previous contributions of the research staff of this project, and the families who participated, are gratefully acknowledged. This work was supported by research project Grants MH48969 and MH60866 (GSZ). Automated DNA sequencing was performed by the Genomics and Proteomics Core Laboratories of the University of Pittsburgh. Some of the results of this study were obtained using S.A.G.E., supported by US Public Health Service Resource Grant 1-P41-RR03655. GSZ was the recipient of Independent Scientist Award MH00540 from the National Institute of Mental Health.

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Authors and Affiliations

  1. Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    G S Zubenko, H B Hughes III, J S Stiffler, A Brechbiel, W N Zubenko & M L Marazita

  2. Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    B S Maher & M L Marazita

  3. Department of Biological Sciences, Mellon College of Science, Carnegie-Mellon University, Pittsburgh, PA, USA

    G S Zubenko

  4. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    M L Marazita

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  1. G S Zubenko
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Correspondence to G S Zubenko.

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Zubenko, G., Hughes, H., Stiffler, J. et al. Sequence variations in CREB1 cosegregate with depressive disorders in women. Mol Psychiatry 8, 611–618 (2003). https://doi.org/10.1038/sj.mp.4001354

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