Effect of psychotropic drug treatment on sterol metabolism

Zeljka Korade, Wei Liu, Emily B. Warren, Kristan Armstrong, Ned A. Porter, Christine Konradi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Cholesterol metabolism is vital for brain function. Previous work in cultured cells has shown that a number of psychotropic drugs inhibit the activity of 7-dehydrocholesterol reductase (DHCR7), an enzyme that catalyzes the final steps in cholesterol biosynthesis. This leads to the accumulation of 7-dehydrocholesterol (7DHC), a molecule that gives rise to oxysterols, vitamin D, and atypical neurosteroids. We examined levels of cholesterol and the cholesterol precursors desmosterol, lanosterol, 7DHC and its isomer 8-dehydrocholesterol (8DHC), in blood samples of 123 psychiatric patients on various antipsychotic and antidepressant drugs, and 85 healthy controls, to see if the observations in cell lines hold true for patients as well. Three drugs, aripiprazole, haloperidol and trazodone increased circulating 7DHC and 8DHC levels, while five other drugs, clozapine, escitalopram/citalopram, lamotrigine, olanzapine, and risperidone, did not. Studies in rat brain verified that haloperidol dose-dependently increased 7DHC and 8DHC levels, while clozapine had no effect. We conclude that further studies should investigate the role of 7DHC and 8DHC metabolites, such as oxysterols, vitamin D, and atypical neurosteroids, in the deleterious and therapeutic effects of psychotropic drugs. Finally, we recommend that drugs that increase 7DHC levels should not be prescribed during pregnancy, as children born with DHCR7 deficiency have multiple congenital malformations.

Original languageEnglish (US)
Pages (from-to)74-81
Number of pages8
JournalSchizophrenia Research
Volume187
DOIs
StatePublished - Sep 2017

Fingerprint

Psychotropic Drugs
Sterols
Cholesterol
Citalopram
Clozapine
Haloperidol
olanzapine
Vitamin D
Neurotransmitter Agents
Therapeutics
Desmosterol
Lanosterol
Pharmaceutical Preparations
Trazodone
Risperidone
Brain
Therapeutic Uses
Antidepressive Agents
Antipsychotic Agents
Psychiatry

Keywords

  • (6): Cholesterol
  • Aripiprazole
  • Clozapine
  • Haloperidol
  • Neurosteroids
  • Trazodone

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Korade, Z., Liu, W., Warren, E. B., Armstrong, K., Porter, N. A., & Konradi, C. (2017). Effect of psychotropic drug treatment on sterol metabolism. Schizophrenia Research, 187, 74-81. https://doi.org/10.1016/j.schres.2017.02.001

Effect of psychotropic drug treatment on sterol metabolism. / Korade, Zeljka; Liu, Wei; Warren, Emily B.; Armstrong, Kristan; Porter, Ned A.; Konradi, Christine.

In: Schizophrenia Research, Vol. 187, 09.2017, p. 74-81.

Research output: Contribution to journalArticle

Korade, Z, Liu, W, Warren, EB, Armstrong, K, Porter, NA & Konradi, C 2017, 'Effect of psychotropic drug treatment on sterol metabolism', Schizophrenia Research, vol. 187, pp. 74-81. https://doi.org/10.1016/j.schres.2017.02.001
Korade, Zeljka ; Liu, Wei ; Warren, Emily B. ; Armstrong, Kristan ; Porter, Ned A. ; Konradi, Christine. / Effect of psychotropic drug treatment on sterol metabolism. In: Schizophrenia Research. 2017 ; Vol. 187. pp. 74-81.
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