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Microarray results suggest altered transport and lowered synthesis of retinoic acid in schizophrenia

Molecular Psychiatry volume 10, pages 620–621 (2005)Cite this article

SIR—A microarray study of schizophrenia in human brains reports that, among others, two proteins affecting vitamin A (retinoid) transport and function are altered. The direction of the alteration of these proteins, aldehyde dehydrogenase 1A1 and albumin, suggest that retinoic acid (RA), the final metabolic product of the retinoid cascade, is insufficient in schizophrenia. Unavailability of RA either directly or indirectly impairs transcriptional regulation of retinoid target genes, for example, DRD21 and ERBB4,2 which are candidates in schizophrenia. The identification of retinoid dysregulation as a common underlying pathway in schizophrenia suggests therapeutic interventions directed toward the development of new RA analogs.

A recent series of microarray expression analyses implicate entire pathways involving oxidative stress, energy metabolism and mitochondrial function in schizophrenia prefrontal cortex.3 Dysregulation of the synthesis of RA, which mediates oxidative stress, regulates energy expenditure and influences mitochondrial functioning and apoptosis,4 may exert a combined, cumulative influence on these pathways. Support for this suggestion can be deduced from examination of the microarray analyses referenced above: expression of the RA-synthesizing enzyme, aldehyde dehydrogenase 1A1 (ALDH1A1), a protein that is strongly expressed in dopaminergic neurons,5 is significantly decreased; albumin, a ubiquitous serum transporter of RA6 and other free fatty acids, for example, docosahexaenoic acid and arachidonic acid, which ligand the retinoid X receptors7 is highly significantly decreased. Both of these findings suggest lowered availability of retinoid receptor ligands in the schizophrenia prefrontal cortex.

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  1. The Massachusetts Mental Health Center Academic Division of Public Psychiatry in the Department of Psychiatry at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    A B Goodman

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Correspondence to A B Goodman.

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Goodman, A. Microarray results suggest altered transport and lowered synthesis of retinoic acid in schizophrenia. Mol Psychiatry 10, 620–621 (2005). https://doi.org/10.1038/sj.mp.4001668

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