Effect of psychotropic drug treatment on sterol metabolism

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

doi:10.1016/j.schres.2017.02.001

Cited by 36 publications

(50 citation statements)

References 68 publications

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“…Several psychotropic medications have been shown to alter 7-DHC levels and metabolism. Most relevant to our findings, Korade et al, recently reported that the use of aripiprazole, haloperidol and trazodone in psychiatric patients and controls is correlated with increased 7-DHC levels in plasma [ 45 ]. Aripiprazole is a second generation antipsychotic that is sometimes used as an augmentation agent in depression resistant to first line therapies.…”

Section: Discussionsupporting

confidence: 77%

Plasma sterols and depressive symptom severity in a population-based cohort

Cenik

Snyder

et al. 2017

PLoS ONE

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Convergent evidence strongly suggests major depressive disorder is heterogeneous in its etiology and clinical characteristics. Depression biomarkers hold potential for identifying etiological subtypes, improving diagnostic accuracy, predicting treatment response, and personalization of treatment. Human plasma contains numerous sterols that have not been systematically studied. Changes in cholesterol concentrations have been implicated in suicide and depression, suggesting plasma sterols may be depression biomarkers. Here, we investigated associations between plasma levels of 34 sterols (measured by mass spectrometry) and scores on the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16) scale in 3117 adult participants in the Dallas Heart Study, an ethnically diverse, population-based cohort. We built a random forest model using feature selection from a pool of 43 variables including demographics, general health indicators, and sterol concentrations. This model comprised 19 variables, 13 of which were sterol concentrations, and explained 15.5% of the variation in depressive symptoms. Desmosterol concentrations below the fifth percentile (1.9 ng/mL, OR 1.9, 95% CI 1.2–2.9) were significantly associated with depressive symptoms of at least moderate severity (QIDS-SR16 score ≥10.5). This is the first study reporting a novel association between plasma concentrations cholesterol precursors and depressive symptom severity.

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Section: Discussionsupporting

confidence: 77%

Plasma sterols and depressive symptom severity in a population-based cohort

Cenik

Snyder

et al. 2017

PLoS ONE

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“…Evidence has showed that aripiprazole could inhibit the activity of 7-dehydrocholesterol reductase, thus leading to the accumulation of 7dehydrocholesterol, while olanzapine and paliperidone could not. 16 As a result, the rising vitamin D in schizophrenic patients treated with aripiprazole may be ascribed to the elevated concentration of its precursor 7-dehydrocholesterol (as shown in Figure 4). Aripiprazole, an atypical antipsychotic drug, performed its beneficial functions to improve schizophrenic symptom via partial agonist activity at D 2 receptors to normalize both hyperdopaminergic and hypodopaminergic states.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence showed that aripiprazole could increase circulating 7-dehydrocholesterol concentrations. 16,17 As a precursor of vitamin D, it could be postulated that the increased 7-dehydrocholesterol might have a potential positive effect on vitamin concentrations. However, there was a paucity of systematic research demonstrating the effects of atypical antipsychotics on vitamins.…”

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confidence: 99%

Effects of Atypical Antipsychotics on Neuroactive Vitamins in Patients With Schizophrenia

Yuan

Wang

et al. 2020

The Journal of Clinical Pharma

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In schizophrenia, neuroactive vitamins A/D/E play vital neuroprotective roles in its pathophysiological processes. During medical treatment, atypical antipsychotics, including aripiprazole, amisulpride, olanzapine, and paliperidone, were widely used at present. However, their impact on vitamin metabolism in vivo remained unclear. In this study, we conducted a case‐control research to investigate the impacts of antipsychotics on vitamin metabolism. Schizophrenic patients (n = 163), who were divided into 5 groups (aripiprazole group, amisulpride group, olanzapine group, paliperidone group, nonmedication group) according to their different medication patterns, and healthy controls (n = 75) were involved. The concentrations of vitamin A/D/E and antipsychotics were measured using liquid chromatography–tandem mass spectrometry methods. Compared with healthy controls, significantly lower vitamin D and E concentrations were found in the nonmedication group after covariance analysis adjusting for age, sex, albumin, bilirubin, triglyceride, and cholesterol. We found that aripiprazole could affect vitamin D concentrations in vivo, and a positive correlation between aripiprazole concentrations and vitamin D concentrations (r = 0.319, P = 0.025) was observed in aripiprazole group. Such result revealed the very first observation for the influence of atypical antipsychotics medication toward vitamin status in vivo. Our study showed that low concentrations of vitamin D and E in vivo could be associated with schizophrenia, suggesting that hypovitaminosis may lead to a vulnerability to schizophrenia. More importantly, aripiprazole may potentially benefit the patients through improving their vitamin D status in vivo.

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“…Nine compounds in the library were very potent, increasing levels of 7-DHC with a Z score greater than 100. Of these nine drugs, haloperidol, aripiprazole, and domiphen had previously been reported to affect 7-DHC levels in cell culture studies and/or in vivo (30). Six of the compounds (nebivolol, rotigotine, iloperidone, ziprasidone, dyclonine, and penfluridol) had not been previously linked to elevated 7-DHC.…”

Section: Fda Drugs Elevate 7-dhc Levelsmentioning

confidence: 99%

“…Perturbing DHCR7 activity has been a known human health risk since the 1960s when the DHCR7 inhibitor, AY-9944, was demonstrated to be teratogenic in rodent models (17). Since that time, a number of other chemicals have been identified as DHCR7 inhibitors and, similarly, their use is cautioned and/or altogether discontinued during pregnancy (30). In addition to increased risk of birth defects and perturbed fetal development, there is also the potential for DHCR7 inhibitors to pose increased health risks for adult patients as well.…”

Section: The Potential Risks Of Elevated Levels Of 7-dhcmentioning

confidence: 99%

Identification and characterization of prescription drugs that change levels of 7-dehydrocholesterol and desmosterol

Wages

Kim

Korade

et al. 2018

Journal of Lipid Research

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Regulating blood cholesterol (Chol) levels by pharmacotherapy has successfully improved cardiovascular health. There is growing interest in the role of Chol precursors in the treatment of diseases. One sterol precursor, desmosterol (Des), is a potential pharmacological target for inflammatory and neurodegenerative disorders. However, elevating levels of the precursor 7-dehydrocholesterol (7-DHC) by inhibiting the enzyme 7-dehydrocholesterol reductase is linked to teratogenic outcomes. Thus, altering the sterol profile may either increase risk toward an adverse outcome or confer therapeutic benefit depending on the metabolite affected by the pharmacophore. In order to characterize any unknown activity of drugs on Chol biosynthesis, a chemical library of Food and Drug Administration-approved drugs was screened for the potential to modulate 7-DHC or Des levels in a neural cell line. Over 20% of the collection was shown to impact Chol biosynthesis, including 75 compounds that alter 7-DHC levels and 49 that modulate Des levels. Evidence is provided that three tyrosine kinase inhibitors, imatinib, ponatinib, and masitinib, elevate Des levels as well as other substrates of 24-dehydrocholesterol reductase, the enzyme responsible for converting Des to Chol. Additionally, the mechanism of action for ponatinib and masitinib was explored, demonstrating that protein levels are decreased as a result of treatment with these drugs.

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Effect of psychotropic drug treatment on sterol metabolism

Cited by 36 publications

References 68 publications

Plasma sterols and depressive symptom severity in a population-based cohort

Plasma sterols and depressive symptom severity in a population-based cohort

Effects of Atypical Antipsychotics on Neuroactive Vitamins in Patients With Schizophrenia

Identification and characterization of prescription drugs that change levels of 7-dehydrocholesterol and desmosterol

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