Medication effects on developmental sterol biosynthesis.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
23
11
2020
accepted:
19
03
2021
revised:
01
03
2021
pubmed:
7
4
2021
medline:
5
4
2022
entrez:
6
4
2021
Statut:
ppublish
Résumé
Cholesterol is essential for normal brain function and development. Genetic disruptions of sterol biosynthesis result in intellectual and developmental disabilities. Developing neurons synthesize their own cholesterol, and disruption of this process can occur by both genetic and chemical mechanisms. Many commonly prescribed medications interfere with sterol biosynthesis, including haloperidol, aripiprazole, cariprazine, fluoxetine, trazodone and amiodarone. When used during pregnancy, these compounds might have detrimental effects on the developing brain of the offspring. In particular, inhibition of dehydrocholesterol-reductase 7 (DHCR7), the last enzyme in the biosynthesis pathway, results in accumulation of the immediate cholesterol precursor, 7-dehydrocholesterol (7-DHC). 7-DHC is highly unstable, giving rise to toxic oxysterols; this is particularly pronounced in a mouse model when both the mother and the offspring carry the Dhcr7
Identifiants
pubmed: 33820938
doi: 10.1038/s41380-021-01074-5
pii: 10.1038/s41380-021-01074-5
pmc: PMC8490477
mid: NIHMS1685522
doi:
Substances chimiques
Aripiprazole
82VFR53I78
Cholesterol
97C5T2UQ7J
Oxidoreductases Acting on CH-CH Group Donors
EC 1.3.-
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
490-501Subventions
Organisme : NICHD NIH HHS
ID : R01 HD064727
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH067234
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES024133
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110636
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Das A, Brown MS, Anderson DD, Goldstein JL, Radhakrishnan A. Three pools of plasma membrane cholesterol and their relation to cholesterol homeostasis. Elife. 2014;3.
Dietschy JM, Turley SD. Thematic review series: brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res. 2004;45:1375–97.
pubmed: 15254070
doi: 10.1194/jlr.R400004-JLR200
Dietschy JM. Central nervous system: cholesterol turnover, brain development and neurodegeneration. Biol Chem. 2009;390:287–93.
pubmed: 19166320
pmcid: 3066069
doi: 10.1515/BC.2009.035
Tint GS, Yu H, Shang Q, Xu G, Patel SB. The use of the Dhcr7 knockout mouse to accurately determine the origin of fetal sterols. J Lipid Res. 2006;47:1535–41.
pubmed: 16651660
doi: 10.1194/jlr.M600141-JLR200
Plotz EJ, Kabara JJ, Davis ME, LeRoy GV, Gould RG. Studies on the synthesis of cholesterol in the brain of the human fetus. Am J Obstet Gynecol. 1968;101:534–8.
pubmed: 5655399
doi: 10.1016/0002-9378(68)90565-6
Quan G, Xie C, Dietschy JM, Turley SD. Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse. Brain Res Dev Brain Res. 2003;146:87–98.
pubmed: 14643015
doi: 10.1016/j.devbrainres.2003.09.015
Dietschy JM, Turley SD. Cholesterol metabolism in the brain. Curr Opin Lipidol. 2001;12:105–12.
pubmed: 11264981
doi: 10.1097/00041433-200104000-00003
Saher G, Stumpf SK. Cholesterol in myelin biogenesis and hypomyelinating disorders. Biochim Biophys Acta. 2015;1851:1083–94.
pubmed: 25724171
doi: 10.1016/j.bbalip.2015.02.010
Bjorkhem I, Meaney S. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol. 2004;24:806–15.
pubmed: 14764421
doi: 10.1161/01.ATV.0000120374.59826.1b
Lentner C. Geigy Scientific Tables. Ciba-Geigy Corp 1981.
Bjorkhem I, Lutjohann D, Diczfalusy U, Stahle L, Ahlborg G, Wahren J. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res. 1998;39:1594–600.
pubmed: 9717719
doi: 10.1016/S0022-2275(20)32188-X
Lutjohann D, Breuer O, Ahlborg G, Nennesmo I, Siden A, Diczfalusy U, et al. Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc Natl Acad Sci USA. 1996;93:9799–804.
pubmed: 8790411
pmcid: 38509
doi: 10.1073/pnas.93.18.9799
Iuliano L, Crick PJ, Zerbinati C, Tritapepe L, Abdel-Khalik J, Poirot M, et al. Cholesterol metabolites exported from human brain. Steroids. 2015;99:189–93. (Pt B)
pubmed: 25668615
pmcid: 4503873
doi: 10.1016/j.steroids.2015.01.026
Zhang Y, Appelkvist EL, Kristensson K, Dallner G. The lipid compositions of different regions of rat brain during development and aging. Neurobiol Aging. 1996;17:869–75.
pubmed: 9363798
doi: 10.1016/S0197-4580(96)00076-0
Segatto M, Trapani L, Lecis C, Pallottini V. Regulation of cholesterol biosynthetic pathway in different regions of the rat central nervous system. Acta Physiol. 2012;206:62–71.
doi: 10.1111/j.1748-1716.2012.02450.x
Soderberg M, Edlund C, Kristensson K, Dallner G. Lipid compositions of different regions of the human brain during aging. J Neurochem. 1990;54:415–23.
pubmed: 2299344
doi: 10.1111/j.1471-4159.1990.tb01889.x
Yutuc E, Angelini R, Baumert M, Mast N, Pikuleva I, Newton J, et al. Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism. Proc Natl Acad Sci USa. 2020;117:5749–60.
pubmed: 32132201
pmcid: 7084107
doi: 10.1073/pnas.1917421117
Korade Z, Kenworthy AK. Lipid rafts, cholesterol, and the brain. Neuropharmacology. 2008;55:1265–73.
pubmed: 18402986
pmcid: 2638588
doi: 10.1016/j.neuropharm.2008.02.019
Hussain G, Wang J, Rasul A, Anwar H, Imran A, Qasim M, et al. Role of cholesterol and sphingolipids in brain development and neurological diseases. Lipids Health Dis. 2019;18:26.
pubmed: 30683111
pmcid: 6347843
doi: 10.1186/s12944-019-0965-z
Cenik B, Cenik C, Snyder MP, Brown ES. Plasma sterols and depressive symptom severity in a population-based cohort. PLoS One. 2017;12:e0184382.
pubmed: 28886149
pmcid: 5590924
doi: 10.1371/journal.pone.0184382
Steegmans PH, Hoes AW, Bak AA, van der Does E, Grobbee DE. Higher prevalence of depressive symptoms in middle-aged men with low serum cholesterol levels. Psychosom Med. 2000;62:205–11.
pubmed: 10772398
doi: 10.1097/00006842-200003000-00009
Allen M, Wang X, Burgess JD, Watzlawik J, Serie DJ, Younkin CS, et al. Conserved brain myelination networks are altered in Alzheimer’s and other neurodegenerative diseases. Alzheimers Dement. 2018;14:352–66.
pubmed: 29107053
doi: 10.1016/j.jalz.2017.09.012
Misiak B, Stanczykiewicz B, Laczmanski L, Frydecka D. Lipid profile disturbances in antipsychotic-naive patients with first-episode non-affective psychosis: A systematic review and meta-analysis. Schizophr Res. 2017;190:18–27.
pubmed: 28325572
doi: 10.1016/j.schres.2017.03.031
Partonen T, Haukka J, Virtamo J, Taylor PR, Lonnqvist J. Association of low serum total cholesterol with major depression and suicide. Br J Psychiatry. 1999;175:259–62.
pubmed: 10645328
doi: 10.1192/bjp.175.3.259
Valenza M, Rigamonti D, Goffredo D, Zuccato C, Fenu S, Jamot L, et al. Dysfunction of the cholesterol biosynthetic pathway in Huntington’s disease. J Neurosci. 2005;25:9932–9.
pubmed: 16251441
pmcid: 6725556
doi: 10.1523/JNEUROSCI.3355-05.2005
Porter FD, Herman GE. Malformation syndromes caused by disorders of cholesterol synthesis. J Lipid Res. 2011;52:6–34.
pubmed: 20929975
pmcid: 2999931
doi: 10.1194/jlr.R009548
Sharpe LJ, Coates HW, Brown AJ. Post-translational control of the long and winding road to cholesterol. J Biol Chem. 2020;295:17549–59.
Lorbek G, Lewinska M, Rozman D. Cytochrome P450s in the synthesis of cholesterol and bile acids–from mouse models to human diseases. FEBS J. 2012;279:1516–33.
pubmed: 22111624
doi: 10.1111/j.1742-4658.2011.08432.x
Porter TD. Electron transfer pathways in cholesterol synthesis. Lipids. 2015;50:927–36.
pubmed: 26344922
doi: 10.1007/s11745-015-4065-1
Ridsdale A, Denis M, Gougeon PY, Ngsee JK, Presley JF, Zha X. Cholesterol is required for efficient endoplasmic reticulum-to-Golgi transport of secretory membrane proteins. Mol Biol Cell. 2006;17:1593–605.
pubmed: 16452637
pmcid: 1415298
doi: 10.1091/mbc.e05-02-0100
Jacquemyn J, Cascalho A, Goodchild RE. The ins and outs of endoplasmic reticulum-controlled lipid biosynthesis. EMBO Rep. 2017;18:1905–21.
pubmed: 29074503
pmcid: 5666603
doi: 10.15252/embr.201643426
Zhang J, Xue R, Ong WY, Chen P. Roles of cholesterol in vesicle fusion and motion. Biophys J. 2009;97:1371–80.
pubmed: 19720025
pmcid: 2749761
doi: 10.1016/j.bpj.2009.06.025
Kandutsch AA, Russell AE. Preputial gland tumor sterols. I. The occurrence of 24,25-dihydrolanosterol and a comparison with liver and the normal gland. J Biol Chem. 1959;234:2037–42.
pubmed: 13673010
doi: 10.1016/S0021-9258(18)69863-1
Kandutsch AA, Russell AE. Preputial gland tumor sterols. 3. A metabolic pathway from lanosterol to cholesterol. J Biol Chem. 1960;235:2256–61.
pubmed: 14404284
doi: 10.1016/S0021-9258(18)64608-3
Honda A, Yamashita K, Miyazaki H, Shirai M, Ikegami T, Xu G, et al. Highly sensitive analysis of sterol profiles in human serum by LC-ESI-MS/MS. J Lipid Res. 2008;49:2063–73.
pubmed: 18503032
doi: 10.1194/jlr.D800017-JLR200
Kandutsch AA, Russell AE. Preputial gland tumor sterols. 2. The identification of 4 alpha-methyl-Delta 8-cholesten-3 beta-ol. J Biol Chem. 1960;235:2253–5.
pubmed: 14404283
doi: 10.1016/S0021-9258(18)64607-1
Lutjohann D, von Bergmann K. 24S-hydroxycholesterol: a marker of brain cholesterol metabolism. Pharmacopsychiatry. 2003;36:S102–S6. Suppl 2
pubmed: 14574622
doi: 10.1055/s-2003-43053
Hughes TM, Rosano C, Evans RW, Kuller LH. Brain cholesterol metabolism, oxysterols, and dementia. J Alzheimers Dis. 2013;33:891–911.
pubmed: 23076077
pmcid: 4354887
doi: 10.3233/JAD-2012-121585
Wang HL, Wang YY, Liu XG, Kuo SH, Liu N, Song QY, et al. Cholesterol, 24-hydroxycholesterol, and 27-hydroxycholesterol as surrogate biomarkers in cerebrospinal fluid in mild cognitive impairment and Alzheimer’s disease: a meta-analysis. J Alzheimers Dis. 2016;51:45–55.
pubmed: 26836015
pmcid: 6110663
doi: 10.3233/JAD-150734
Liu W, Xu L, Lamberson C, Haas D, Korade Z, Porter NA. A highly sensitive method for analysis of 7-dehydrocholesterol for the study of Smith-Lemli-Opitz syndrome. J Lipid Res. 2014;55:329–37.
pubmed: 24259532
pmcid: 3886672
doi: 10.1194/jlr.D043877
Kim HY, Korade Z, Tallman KA, Liu W, Weaver CD, Mirnics K, et al. Inhibitors of 7-dehydrocholesterol reductase: screening of a collection of pharmacologically active compounds in Neuro2a cells. Chem Res Toxicol. 2016;29:892–900.
pubmed: 27097157
pmcid: 4868769
doi: 10.1021/acs.chemrestox.6b00054
Korade Z, Kim HY, Tallman KA, Liu W, Koczok K, Balogh I, et al. The effect of small molecules on sterol homeostasis: measuring 7-dehydrocholesterol in Dhcr7-deficient Neuro2a cells and human fibroblasts. J Med Chem. 2016;59:1102–15.
pubmed: 26789657
pmcid: 4838819
doi: 10.1021/acs.jmedchem.5b01696
Wages PA, Kim HH, Korade Z, Porter NA. Identification and characterization of prescription drugs that change levels of 7-dehydrocholesterol and desmosterol. J Lipid Res. 2018;59:1916–26.
pubmed: 30087204
pmcid: 6168312
doi: 10.1194/jlr.M086991
Tallman KA, Allen LB, Klingelsmith K, Anderson A, Genaro-Mattos TC, Mirnics K, et al. Prescription medications alter neuronal and glial cholesterol synthesis. ACS Chem Neurosci. 2021;12:735–45.
Sans M, Feider CL, Eberlin LS. Advances in mass spectrometry imaging coupled to ion mobility spectrometry for enhanced imaging of biological tissues. Curr Opin Chem Biol. 2018;42:138–46.
pubmed: 29275246
doi: 10.1016/j.cbpa.2017.12.005
Wang X, Hou Y, Hou Z, Xiong W, Huang G. Mass spectrometry imaging of brain cholesterol and metabolites with trifluoroacetic acid-enhanced desorption electrospray ionization. Anal Chem. 2019;91:2719–26.
pubmed: 30645089
doi: 10.1021/acs.analchem.8b04395
Korade Z, Mi Z, Portugal C, Schor NF. Expression and p75 neurotrophin receptor dependence of cholesterol synthetic enzymes in adult mouse brain. Neurobiol Aging. 2007;28:1522–31.
pubmed: 16887237
doi: 10.1016/j.neurobiolaging.2006.06.026
Boyles JK, Pitas RE, Wilson E, Mahley RW, Taylor JM. Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. J Clin Investig. 1985;76:1501–13.
pubmed: 3932467
pmcid: 424114
doi: 10.1172/JCI112130
Pitas RE, Boyles JK, Lee SH, Foss D, Mahley RW. Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins. Biochim Biophys Acta. 1987;917:148–61.
pubmed: 3539206
doi: 10.1016/0005-2760(87)90295-5
Genaro-Mattos TC, Anderson A, Allen LB, Korade Z, Mirnics K. Cholesterol biosynthesis and uptake in developing neurons. ACS Chem Neurosci. 2019;10:3671–81.
pubmed: 31244054
doi: 10.1021/acschemneuro.9b00248
Korade Z, Genaro-Mattos TC, Tallman KA, Liu W, Garbett KA, Koczok K, et al. Vulnerability of DHCR7(+/-) mutation carriers to aripiprazole and trazodone exposure. J Lipid Res. 2017;58:2139–46.
pubmed: 28972118
pmcid: 5665669
doi: 10.1194/jlr.M079475
Mitsche MA, McDonald JG, Hobbs HH, Cohen JC. Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways. Elife. 2015;4:e07999.
pubmed: 26114596
pmcid: 4501332
doi: 10.7554/eLife.07999
Funfschilling U, Jockusch WJ, Sivakumar N, Mobius W, Corthals K, Li S, et al. Critical time window of neuronal cholesterol synthesis during neurite outgrowth. J Neurosci. 2012;32:7632–45.
pubmed: 22649242
pmcid: 6703588
doi: 10.1523/JNEUROSCI.1352-11.2012
Berghoff SA, Spieth L, Sun T, Hosang L, Schlaphoff L, Depp C, et al. Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis. Nat Neurosci. 2021;24:47–60.
pubmed: 33349711
doi: 10.1038/s41593-020-00757-6
Hubler Z, Allimuthu D, Bederman I, Elitt MS, Madhavan M, Allan KC, et al. Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination. Nature. 2018;560:372–6.
pubmed: 30046109
pmcid: 6423962
doi: 10.1038/s41586-018-0360-3
Nakai M, Kawamata T, Taniguchi T, Maeda K, Tanaka C. Expression of apolipoprotein E mRNA in rat microglia. Neurosci Lett. 1996;211:41–4.
pubmed: 8809843
doi: 10.1016/0304-3940(96)12716-6
Fitzky BU, Witsch-Baumgartner M, Erdel M, Lee JN, Paik YK, Glossmann H, et al. Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome. Proc Natl Acad Sci USA. 1998;95:8181–6.
pubmed: 9653161
pmcid: 20950
doi: 10.1073/pnas.95.14.8181
Bissig C, Gruenberg J. Lipid sorting and multivesicular endosome biogenesis. Cold Spring Harb Perspect Biol. 2013;5:a016816.
pubmed: 24086044
pmcid: 3783046
doi: 10.1101/cshperspect.a016816
Xu L, Davis TA, Porter NA. Rate constants for peroxidation of polyunsaturated fatty acids and sterols in solution and in liposomes. J Am Chem Soc. 2009;131:13037–44.
pubmed: 19705847
doi: 10.1021/ja9029076
Xu L, Porter NA. Free radical oxidation of cholesterol and its precursors: implications in cholesterol biosynthesis disorders. Free Radic Res. 2015;49:835–49.
pubmed: 25381800
doi: 10.3109/10715762.2014.985219
Yin H, Xu L, Porter NA. Free radical lipid peroxidation: mechanisms and analysis. Chem Rev. 2011;111:5944–72.
pubmed: 21861450
doi: 10.1021/cr200084z
Xu L, Korade Z, Porter NA. Oxysterols from free radical chain oxidation of 7-dehydrocholesterol: product and mechanistic studies. J Am Chem Soc. 2010;132:2222–32.
pubmed: 20121089
pmcid: 2839323
doi: 10.1021/ja9080265
Goyal S, Xiao Y, Porter NA, Xu L, Guengerich FP. Oxidation of 7-dehydrocholesterol and desmosterol by human cytochrome P450 46A1. J Lipid Res. 2014;55:1933–43.
pubmed: 25017465
pmcid: 4617353
doi: 10.1194/jlr.M051508
Korade Z, Xu L, Shelton R, Porter NA. Biological activities of 7-dehydrocholesterol-derived oxysterols: implications for Smith-Lemli-Opitz syndrome. J Lipid Res. 2010;51:3259–69.
pubmed: 20702862
pmcid: 2952566
doi: 10.1194/jlr.M009365
Xu L, Mirnics K, Bowman AB, Liu W, Da J, Porter NA, et al. DHCEO accumulation is a critical mediator of pathophysiology in a Smith-Lemli-Opitz syndrome model. Neurobiol Dis. 2012;45:923–9.
pubmed: 22182693
doi: 10.1016/j.nbd.2011.12.011
Sever N, Mann RK, Xu L, Snell WJ, Hernandez-Lara CI, Porter NA, et al. Endogenous B-ring oxysterols inhibit the Hedgehog component Smoothened in a manner distinct from cyclopamine or side-chain oxysterols. Proc Natl Acad Sci USA. 2016;113.
Keller RK, Arnold TP, Fliesler SJ. Formation of 7-dehydrocholesterol-containing membrane rafts in vitro and in vivo, with relevance to the Smith-Lemli-Opitz syndrome. J Lipid Res. 2004;45:347–55.
pubmed: 14594996
doi: 10.1194/jlr.M300232-JLR200
Liu Y, Chipot C, Shao X, Cai W. The effects of 7-dehydrocholesterol on the structural properties of membranes. Phys Biol. 2011;8:056005.
pubmed: 21865621
doi: 10.1088/1478-3975/8/5/056005
Griffiths WJ, Wang Y. Oxysterols as lipid mediators: their biosynthetic genes, enzymes and metabolites. Prostaglandins Other Lipid Mediat. 2020;147:106381.
pubmed: 31698146
pmcid: 7081179
doi: 10.1016/j.prostaglandins.2019.106381
Brown AJ, Sharpe LJ, Rogers MJ. Oxysterols: From physiological tuners to pharmacological opportunities. Br J Pharmacol 2020;1–15. https://doi.org/10.1111/bph.15073 .
Olkkonen VM, Beaslas O, Nissila E. Oxysterols and their cellular effectors. Biomolecules 2012;2:76–103.
pubmed: 24970128
pmcid: 4030866
doi: 10.3390/biom2010076
Wang Y, Kumar N, Crumbley C, Griffin PR, Burris TP. A second class of nuclear receptors for oxysterols: regulation of RORalpha and RORgamma activity by 24S-hydroxycholesterol (cerebrosterol). Biochim Biophys Acta. 2010;1801:917–23.
pubmed: 20211758
pmcid: 2886165
doi: 10.1016/j.bbalip.2010.02.012
Bjorkhem I. Rediscovery of cerebrosterol. Lipids. 2007;42:5–14.
pubmed: 17393206
doi: 10.1007/s11745-006-1003-2
Emnett CM, Eisenman LN, Mohan J, Taylor AA, Doherty JJ, Paul SM, et al. Interaction between positive allosteric modulators and trapping blockers of the NMDA receptor channel. Br J Pharmacol. 2015;172:1333–47.
pubmed: 25377730
pmcid: 4337705
doi: 10.1111/bph.13007
Linsenbardt AJ, Taylor A, Emnett CM, Doherty JJ, Krishnan K, Covey DF, et al. Different oxysterols have opposing actions at N-methyl-D-aspartate receptors. Neuropharmacology. 2014;85:232–42.
pubmed: 24878244
pmcid: 4107067
doi: 10.1016/j.neuropharm.2014.05.027
Wang Y, Yutuc E, Griffiths WJ. Neuro-oxysterols and neuro-sterols as ligands to nuclear receptors, GPCRs, ligand-gated ion channels and other protein receptors. Br J Pharmacol. 2020;1–18. https://doi.org/10.1111/bph.15191 .
Jira P. Cholesterol metabolism deficiency. Handb Clin Neurol. 2013;113:1845–50.
pubmed: 23622407
doi: 10.1016/B978-0-444-59565-2.00054-X
Porter FD. RSH/Smith-Lemli-Opitz syndrome: a multiple congenital anomaly/mental retardation syndrome due to an inborn error of cholesterol biosynthesis. Mol Genet Metab. 2000;71:163–74.
pubmed: 11001807
doi: 10.1006/mgme.2000.3069
Waterham HR, Koster J, Romeijn GJ, Hennekam RC, Vreken P, Andersson HC, et al. Mutations in the 3beta-hydroxysterol Delta24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis. Am J Hum Genet. 2001;69:685–94.
pubmed: 11519011
pmcid: 1226055
doi: 10.1086/323473
Ikegawa S, Ohashi H, Ogata T, Honda A, Tsukahara M, Kubo T, et al. Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata. Am J Med Genet. 2000;94:300–5.
pubmed: 11038443
doi: 10.1002/1096-8628(20001002)94:4<300::AID-AJMG7>3.0.CO;2-3
Brunetti-Pierri N, Corso G, Rossi M, Ferrari P, Balli F, Rivasi F, et al. Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5-desaturase. Am J Hum Genet. 2002;71:952–8.
pubmed: 12189593
pmcid: 378549
doi: 10.1086/342668
Krakowiak PA, Wassif CA, Kratz L, Cozma D, Kovarova M, Harris G, et al. Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5-desaturase deficiency. Hum Mol Genet. 2003;12:1631–41.
pubmed: 12812989
doi: 10.1093/hmg/ddg172
Konig A, Happle R, Bornholdt D, Engel H, Grzeschik KH. Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome. Am J Med Genet. 2000;90:339–46.
pubmed: 10710235
doi: 10.1002/(SICI)1096-8628(20000214)90:4<339::AID-AJMG15>3.0.CO;2-5
Cross JL, Iben J, Simpson CL, Thurm A, Swedo S, Tierney E, et al. Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by analysis of massively parallel sequencing data sets. Clin Genet. 2015;87:570–5.
pubmed: 24813812
doi: 10.1111/cge.12425
Bianconi SE, Cross JL, Wassif CA, Porter FD. Pathogenesis, epidemiology, diagnosis and clinical aspects of Smith-Lemli-Opitz syndrome. Expert Opin Orphan Drugs. 2015;3:267–80.
pubmed: 25734025
pmcid: 4343216
doi: 10.1517/21678707.2015.1014472
Wassif CA, Maslen C, Kachilele-Linjewile S, Lin D, Linck LM, Connor WE, et al. Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome. Am J Hum Genet. 1998;63:55–62.
pubmed: 9634533
pmcid: 1377256
doi: 10.1086/301936
Liu W, Xu L, Lamberson CR, Merkens LS, Steiner RD, Elias ER, et al. Assays of plasma dehydrocholesteryl esters and oxysterols from Smith-Lemli-Opitz syndrome patients. J Lipid Res. 2013;54:244–53.
pubmed: 23072947
pmcid: 3520531
doi: 10.1194/jlr.M031732
Porter FD. Smith-Lemli-Opitz syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet. 2008;16:535–41.
pubmed: 18285838
doi: 10.1038/ejhg.2008.10
Wassif CA, Krakowiak PA, Wright BS, Gewandter JS, Sterner AL, Javitt N, et al. Residual cholesterol synthesis and simvastatin induction of cholesterol synthesis in Smith-Lemli-Opitz syndrome fibroblasts. Mol Genet Metab. 2005;85:96–107.
pubmed: 15896653
doi: 10.1016/j.ymgme.2004.12.009
Griffiths WJ, Abdel-Khalik J, Crick PJ, Ogundare M, Shackleton CH, Tuschl K, et al. Sterols and oxysterols in plasma from Smith-Lemli-Opitz syndrome patients. J Steroid Biochem Mol Biol 2017;169:77–87.
pubmed: 26976653
doi: 10.1016/j.jsbmb.2016.03.018
Tint GS, Irons M, Elias ER, Batta AK, Frieden R, Chen TS, et al. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med. 1994;330:107–13.
pubmed: 8259166
doi: 10.1056/NEJM199401133300205
Porter FD. Human malformation syndromes due to inborn errors of cholesterol synthesis. Curr Opin Pediatr. 2003;15:607–13.
pubmed: 14631207
doi: 10.1097/00008480-200312000-00011
Tint GS, Salen G, Batta AK, Shefer S, Irons M, Elias ER, et al. Correlation of severity and outcome with plasma sterol levels in variants of the Smith-Lemli-Opitz syndrome. J Pediatr. 1995;127:82–7.
pubmed: 7608816
doi: 10.1016/S0022-3476(95)70261-X
Koo G, Conley SK, Wassif CA, Porter FD. Discordant phenotype and sterol biochemistry in Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2010;152A:2094–8.
pubmed: 20635399
pmcid: 3027211
doi: 10.1002/ajmg.a.33540
Olah AV, Szabo GP, Varga J, Balogh L, Csabi G, Csakvary V, et al. Relation between biomarkers and clinical severity in patients with Smith-Lemli-Opitz syndrome. Eur J Pediatr. 2013;172:623–30.
pubmed: 23319240
doi: 10.1007/s00431-012-1925-z
Lee RW, Conley SK, Gropman A, Porter FD, Baker EH. Brain magnetic resonance imaging findings in Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2013;161A:2407–19.
pubmed: 23918729
Sikora DM, Ruggiero M, Petit-Kekel K, Merkens LS, Connor WE, Steiner RD. Cholesterol supplementation does not improve developmental progress in Smith-Lemli-Opitz syndrome. J Pediatr. 2004;144:783–91.
pubmed: 15192627
Linck LM, Lin DS, Flavell D, Connor WE, Steiner RD. Cholesterol supplementation with egg yolk increases plasma cholesterol and decreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome. Am J Med Genet. 2000;93:360–5.
pubmed: 10951458
doi: 10.1002/1096-8628(20000828)93:5<360::AID-AJMG4>3.0.CO;2-P
Starck L, Lovgren-Sandblom A, Bjorkhem I. Cholesterol treatment forever? The first Scandinavian trial of cholesterol supplementation in the cholesterol-synthesis defect Smith-Lemli-Opitz syndrome. J Intern Med. 2002;252:314–21.
pubmed: 12366604
doi: 10.1046/j.1365-2796.2002.01037.x
Tierney E, Conley SK, Goodwin H, Porter FD. Analysis of short-term behavioral effects of dietary cholesterol supplementation in Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2010;152A:91–5.
pubmed: 20014133
pmcid: 2799534
doi: 10.1002/ajmg.a.33148
Korade Z, Xu L, Harrison FE, Ahsen R, Hart SE, Folkes OM, et al. Antioxidant supplementation ameliorates molecular deficits in Smith-Lemli-Opitz syndrome. Biol Psychiatry. 2014;75:215–22.
pubmed: 23896203
doi: 10.1016/j.biopsych.2013.06.013
Pfeffer BA, Xu L, Porter NA, Rao SR, Fliesler SJ. Differential cytotoxic effects of 7-dehydrocholesterol-derived oxysterols on cultured retina-derived cells: Dependence on sterol structure, cell type, and density. Exp Eye Res. 2016;145:297–316.
pubmed: 26854824
pmcid: 5024725
doi: 10.1016/j.exer.2016.01.016
Fliesler SJ, Vaughan DK, Jenewein EC, Richards MJ, Nagel BA, Peachey NS. Partial rescue of retinal function and sterol steady-state in a rat model of Smith-Lemli-Opitz syndrome. Pediatr Res. 2007;61:273–8.
pubmed: 17314682
pmcid: 2072818
doi: 10.1203/pdr.0b013e318030d1cf
Lazarin GA, Haque IS, Evans EA, Goldberg JD. Smith-Lemli-Opitz syndrome carrier frequency and estimates of in utero mortality rates. Prenat Diagn. 2017;37:350–5.
pubmed: 28166604
pmcid: 5413855
doi: 10.1002/pd.5018
Boland MR, Tatonetti NP. Investigation of 7-dehydrocholesterol reductase pathway to elucidate off-target prenatal effects of pharmaceuticals: a systematic review. Pharmacogenomics J. 2016;16:411–29.
pubmed: 27401223
pmcid: 5028238
doi: 10.1038/tpj.2016.48
Shefer S, Salen G, Honda A, Batta A, Hauser S, Tint GS, et al. Rapid identification of Smith-Lemli-Opitz syndrome homozygotes and heterozygotes (carriers) by measurement of deficient 7-dehydrocholesterol-delta 7-reductase activity in fibroblasts. Metabolism. 1997;46:844–50.
pubmed: 9225842
doi: 10.1016/S0026-0495(97)90133-5
Korade Z, Folkes OM, Harrison FE. Behavioral and serotonergic response changes in the Dhcr7-HET mouse model of Smith-Lemli-Opitz syndrome. Pharm Biochem Behav. 2013;106:101–8.
doi: 10.1016/j.pbb.2013.03.007
Sharif NF, Korade Z, Porter NA, Harrison FE. Oxidative stress, serotonergic changes and decreased ultrasonic vocalizations in a mouse model of Smith-Lemli-Opitz syndrome. Genes Brain Behav. 2017;16:619–26.
pubmed: 28220990
pmcid: 5495606
doi: 10.1111/gbb.12376
Hall P, Michels V, Gavrilov D, Matern D, Oglesbee D, Raymond K, et al. Aripiprazole and trazodone cause elevations of 7-dehydrocholesterol in the absence of Smith-Lemli-Opitz Syndrome. Mol Genet Metab. 2013;110:176–8.
pubmed: 23628460
doi: 10.1016/j.ymgme.2013.04.004
Genaro-Mattos TC, Allen LB, Anderson A, Tallman KA, Porter NA, Korade Z, et al. Maternal aripiprazole exposure interacts with 7-dehydrocholesterol reductase mutations and alters embryonic neurodevelopment. Mol Psychiatry. 2019;24:491–500.
pubmed: 30742019
pmcid: 6477890
doi: 10.1038/s41380-019-0368-6
Genaro-Mattos TC, Anderson A, Allen LB, Tallman KA, Porter NA, Korade Z, et al. Maternal cariprazine exposure inhibits embryonic and postnatal brain cholesterol biosynthesis. Mol Psychiatry. 2020;25:2685–94.
pubmed: 32504050
pmcid: 7577905
doi: 10.1038/s41380-020-0801-x
Korade Z, Liu W, Warren EB, Armstrong K, Porter NA, Konradi C. Effect of psychotropic drug treatment on sterol metabolism. Schizophr Res 2017;187:74–81.
pubmed: 28202290
pmcid: 5554466
doi: 10.1016/j.schres.2017.02.001
Korade Z, Allen LB, Anderson A, Tallman KA, Genaro-Mattos TC, Porter NA et al. Trazodone effects on developing brain. Transl Psychiatry 2021;11:85. https://doi.org/10.1038/s41398-021-01217-w .
Wages PA, Joshi P, Tallman KA, Kim HH, Bowman AB, Porter NA. Screening ToxCast for chemicals that affect cholesterol biosynthesis: studies in cell culture and human induced pluripotent stem cell-derived neuroprogenitors. Environ Health Perspect. 2020;128:17014.
pubmed: 31985273
doi: 10.1289/EHP5053
Gray SL, Marcum ZA, Schmader KE, Hanlon JT. Update on medication use quality and safety in older adults, 2017. J Am Geriatr Soc. 2018;66:2254–8.
pubmed: 30423194
pmcid: 6421859
doi: 10.1111/jgs.15665
Dawson AL, Ailes EC, Gilboa SM, Simeone RM, Lind JN, Farr SL, et al. Antidepressant prescription claims among reproductive-aged women with private employer-sponsored insurance—United States 2008-2013. MMWR Morb Mortal Wkly Rep. 2016;65:41–6.
pubmed: 26821271
doi: 10.15585/mmwr.mm6503a1
Lynch MM, Squiers LB, Kosa KM, Dolina S, Read JG, Broussard CS, et al. Making decisions about medication use during pregnancy: implications for communication strategies. Matern Child Health.2018;22:92–100.
doi: 10.1007/s10995-017-2358-0
Mitchell AA, Gilboa SM, Werler MM, Kelley KE, Louik C, Hernandez-Diaz S, et al. Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. Am J Obstet Gynecol. 2011;205:51 e1–8.
doi: 10.1016/j.ajog.2011.02.029
Thorpe PG, Gilboa SM, Hernandez-Diaz S, Lind J, Cragan JD, Briggs G, et al. Medications in the first trimester of pregnancy: most common exposures and critical gaps in understanding fetal risk. Pharmacoepidemiol Drug Saf. 2013;22:1013–8.
pubmed: 23893932
pmcid: 3996804
doi: 10.1002/pds.3495
Werler MM, Mitchell AA, Hernandez-Diaz S, Honein MA. Use of over-the-counter medications during pregnancy. Am J Obstet Gynecol. 2005;193:771–7.
pubmed: 16150273
doi: 10.1016/j.ajog.2005.02.100
Sparks SE, Wassif CA, Goodwin H, Conley SK, Lanham DC, Kratz LE, et al. Decreased cerebral spinal fluid neurotransmitter levels in Smith-Lemli-Opitz syndrome. J Inherit Metab Dis. 2014;37:415–20.
pubmed: 24500076
pmcid: 4166510
doi: 10.1007/s10545-013-9672-5
Waage-Baudet H, Lauder JM, Dehart DB, Kluckman K, Hiller S, Tint GS, et al. Abnormal serotonergic development in a mouse model for the Smith-Lemli-Opitz syndrome: implications for autism. Int J Dev Neurosci. 2003;21:451–9.
pubmed: 14659996
doi: 10.1016/j.ijdevneu.2003.09.002
Lanoue L, Dehart DB, Hinsdale ME, Maeda N, Tint GS, Sulik KK. Limb, genital, CNS, and facial malformations result from gene/environment-induced cholesterol deficiency: further evidence for a link to sonic hedgehog. Am J Med Genet. 1997;73:24–31.
pubmed: 9375918
doi: 10.1002/(SICI)1096-8628(19971128)73:1<24::AID-AJMG6>3.0.CO;2-P
Kelley RL, Roessler E, Hennekam RC, Feldman GL, Kosaki K, Jones MC, et al. Holoprosencephaly in RSH/Smith-Lemli-Opitz syndrome: does abnormal cholesterol metabolism affect the function of Sonic Hedgehog? Am J Med Genet. 1996;66:478–84.
pubmed: 8989473
doi: 10.1002/(SICI)1096-8628(19961230)66:4<478::AID-AJMG22>3.0.CO;2-Q
Xu Q, Guo L, Moore H, Waclaw RR, Campbell K, Anderson SA. Sonic hedgehog signaling confers ventral telencephalic progenitors with distinct cortical interneuron fates. Neuron. 2010;65:328–40.
pubmed: 20159447
pmcid: 2868511
doi: 10.1016/j.neuron.2010.01.004
Xu Q, Wonders CP, Anderson SA. Sonic hedgehog maintains the identity of cortical interneuron progenitors in the ventral telencephalon. Development. 2005;132:4987–98.
pubmed: 16221724
doi: 10.1242/dev.02090