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Molecular windows into the human brain for psychiatric disorders

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Abstract

Delineating the pathophysiology of psychiatric disorders has been extremely challenging but technological advances in recent decades have facilitated a deeper interrogation of molecular processes in the human brain. Initial candidate gene expression studies of the postmortem brain have evolved into genome wide profiling of the transcriptome and the epigenome, a critical regulator of gene expression. Here, we review the potential and challenges of direct molecular characterization of the postmortem human brain, and provide a brief overview of recent transcriptional and epigenetic studies with respect to neuropsychiatric disorders. Such information can now be leveraged and integrated with the growing number of genome-wide association databases to provide a functional context of trait-associated genetic variants linked to psychiatric illnesses and related phenotypes. While it is clear that the field is still developing and challenges remain to be surmounted, these recent advances nevertheless hold tremendous promise for delineating the neurobiological underpinnings of mental diseases and accelerating the development of novel medication strategies.

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Acknowledgements

This work was supported by NIH DA15446 (YLH), DA008227 (YLH), DA043247 (SD, YLH), MH103877 (a part of the PsychEncode consortium; SD), and VA BX001829 (SD).

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  1. Gabor Egervari

    Present address: Epigenetics Institute and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

Authors and Affiliations

  1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Gabor Egervari, Alexey Kozlenkov, Stella Dracheva & Yasmin L. Hurd

  2. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Gabor Egervari & Yasmin L. Hurd

  3. Addiction Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Gabor Egervari & Yasmin L. Hurd

  4. Friedman Brain Institute, School of Medicine at Mount Sinai, New York, NY, USA

    Gabor Egervari, Alexey Kozlenkov, Stella Dracheva & Yasmin L. Hurd

  5. James J. Peters VA Medical Center, Bronx, NY, USA

    Alexey Kozlenkov & Stella Dracheva

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  1. Gabor Egervari
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Correspondence to Yasmin L. Hurd.

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Egervari, G., Kozlenkov, A., Dracheva, S. et al. Molecular windows into the human brain for psychiatric disorders. Mol Psychiatry 24, 653–673 (2019). https://doi.org/10.1038/s41380-018-0125-2

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