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Developmental sterol biosynthesis inhibition: are prescription medications as safe as we think?

Neuropsychopharmacology volume 51, pages 368–369 (2026)Cite this article

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Cholesterol is an essential molecule for life, serving as both a key structural component of all cell membranes and a precursor for numerous homeostatic processes [1]. Notably, the brain synthesizes its own cholesterol and is the most cholesterol-rich organ in the body. The blood-brain barrier prevents cholesterol exchange between the brain and peripheral tissues [2].

The highest demand for cholesterol synthesis occurs during intrauterine development and early postnatal life [2]. Genetic disruptions in the sterol biosynthesis pathway lead to severe developmental disorders, including Smith-Lemli-Opitz syndrome (SLOS), desmosterolosis, lathosterolosis, and other complex syndromes [3]. Strikingly, up to 75% of individuals with SLOS are diagnosed with autism spectrum disorder. The pathophysiology in this genetic condition is driven by two interrelated mechanisms: a deficiency of cholesterol itself and the accumulation of 7-dehydrocholesterol (7-DHC), a highly oxidizable and toxic precursor.

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Fig. 1: Contributing factors and potential consequences of developmental sterol inhibition.

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Funding

This work was supported by NIH grant R56HD111119 to KM and ZK.

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Authors and Affiliations

  1. Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA

    Zeljka Korade

  2. Child Health Research Institute, Omaha, NE, USA

    Zeljka Korade & Karoly Mirnics

  3. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA

    Zeljka Korade & Karoly Mirnics

  4. Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA

    Karoly Mirnics

Authors
  1. Zeljka Korade
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  2. Karoly Mirnics
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ZK and KM wrote the publication.

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Correspondence to Karoly Mirnics.

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The authors declare no competing interests.

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Korade, Z., Mirnics, K. Developmental sterol biosynthesis inhibition: are prescription medications as safe as we think?. Neuropsychopharmacol. 51, 368–369 (2026). https://doi.org/10.1038/s41386-025-02171-7

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  • DOI: https://doi.org/10.1038/s41386-025-02171-7

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