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<p>Psychotic disorders, particularly schizophrenia, are characterized by significant cognitive and social impairments, with early identification being crucial for effective intervention. Cholesterol plays a vital role in brain function and is primarily synthesized within the central nervous system. We analyzed plasma levels of total cholesterol and specific oxysterols, including 24-hydroxycholesterol, 27-hydroxycholesterol, and others, in a cohort of 61 ultra-high risk individuals and 44 healthy controls. Our findings indicate no difference in total cholesterol levels between groups; however, ultra-high risk individuals exhibited significantly increased levels of all measured oxysterols, suggesting dysregulation of cholesterol metabolism. Furthermore, a weak correlation was found between 27-hydroxycholesterol levels and positive psychotic symptoms. These results highlight the potential role of altered cholesterol metabolism in the early stages of psychotic disorders, proposing that specific oxysterols may serve as biomarkers for early detection and intervention strategies. This study contributes to the understanding of the biochemical underpinnings of psychosis and emphasizes the need for further investigation related to lipid metabolism and psychotic disorders.</p> Graphical Abstract <p>Disturbances of brain cholesterol metabolism in individuals at ultra-high risk for psychosis. Abbreviation: HC, Healthy control; UHR, Ultra High Risk for psychosis; BBB, Blood brain barrier; CYP46A1, Cholesterol 24-hydroxylase; 24-OHC, 24-hydroxycholesterol; 25-OHC, 25-hydroxycholesterol; 27-OHC, 27- hydroxycholesterol; 7-KC, 7-ketocholesterol; 7α-OHC, 7α-hydroxycholesterol; 7β-OHC, 7β-hydroxycholesterol; d7-24-OHC, 24-Hydroxycholesterol-d7. The figure was Created in BioRender. <a href="https://BioRender.com/b79v764">https://BioRender.com/b79v764</a>.</p> <p></p>

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Cholesterol metabolism and its implications in psychotic disorders: a comparative study of individuals at ultra high risk and control groups

  • 期刊论文

  • 发表日期：

    2025年2月13日

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  • Mislene Bispo Teixeira Moreno,
  • Monique Patricio Singulani,
  • Martinus Theodorus van de Bilt,
  • Alexandre Andrade Loch,
  • Wagner Farid Gattaz,
  • Leda Leme Talib

摘要

Psychotic disorders, particularly schizophrenia, are characterized by significant cognitive and social impairments, with early identification being crucial for effective intervention. Cholesterol plays a vital role in brain function and is primarily synthesized within the central nervous system. We analyzed plasma levels of total cholesterol and specific oxysterols, including 24-hydroxycholesterol, 27-hydroxycholesterol, and others, in a cohort of 61 ultra-high risk individuals and 44 healthy controls. Our findings indicate no difference in total cholesterol levels between groups; however, ultra-high risk individuals exhibited significantly increased levels of all measured oxysterols, suggesting dysregulation of cholesterol metabolism. Furthermore, a weak correlation was found between 27-hydroxycholesterol levels and positive psychotic symptoms. These results highlight the potential role of altered cholesterol metabolism in the early stages of psychotic disorders, proposing that specific oxysterols may serve as biomarkers for early detection and intervention strategies. This study contributes to the understanding of the biochemical underpinnings of psychosis and emphasizes the need for further investigation related to lipid metabolism and psychotic disorders.

Graphical Abstract

Disturbances of brain cholesterol metabolism in individuals at ultra-high risk for psychosis. Abbreviation: HC, Healthy control; UHR, Ultra High Risk for psychosis; BBB, Blood brain barrier; CYP46A1, Cholesterol 24-hydroxylase; 24-OHC, 24-hydroxycholesterol; 25-OHC, 25-hydroxycholesterol; 27-OHC, 27- hydroxycholesterol; 7-KC, 7-ketocholesterol; 7α-OHC, 7α-hydroxycholesterol; 7β-OHC, 7β-hydroxycholesterol; d7-24-OHC, 24-Hydroxycholesterol-d7. The figure was Created in BioRender. https://BioRender.com/b79v764.