International Journal of Molecular Sciences

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Steroids and Neuropsychiatric Disorders

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Dear Colleagues,

Already more than 80 years ago, Selye described the rapid neuroinhibitory effect of allopregnanolone. Since then, many articles have been published on the role of bioactive steroids in the pathophysiology of neuropsychiatric diseases. Nevertheless, there remains a vast scope to study the relationship between steroids and these pathologies regarding steroid biosynthesis and metabolism, including steroid effects and the diagnosis of these diseases based on steroidomic changes. Therefore, this special edition aims to gain further insights and expand the existing horizon. We welcome both original and review papers focusing on the relationship between steroids and epilepsy, Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, schizophrenia, panic disorder, bipolar disorder, anxiety, attention deficit disorder, autism, premenstrual syndrome, peripartum depression and anxiety, hyperactivity disorder, personality disorder, sleep disorders, etc., in terms of their effects, the steroidomic changes accompanying these diseases and the effects of psychotropic drugs on the steroidome.

Dr. Martin Hill
Guest Editor

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Research

38 pages, 4797 KiB

Open AccessArticle

Steroidomics in Men with Schizophrenia

by Martin Hill, Marta Velíková, Tereza Hovorková, Josef Bulant, Katarína Janšáková and Karel Valeš

Int. J. Mol. Sci. 2024, 25(16), 8729; https://doi.org/10.3390/ijms25168729 - 10 Aug 2024

Viewed by 802

Abstract

Schizophrenia is associated with numerous abnormalities, including imbalances in all hormonal axes, among which steroids play a major role. Steroidomic studies therefore represent a promising tool for early diagnosis and appropriate treatment of schizophrenia. A total of 51 adult male schizophrenics aged 27 (22, 34) years (shown as median with quartiles) and 16 healthy controls (HCs) aged 28 (25, 32) years were enrolled into this study. Our results showed the effective differentiation of men with schizophrenia from controls based on steroidomic profiles. We also found an altered metabolic pathway from pregnenolone and its sulfate (PREG/S) to cortisol in schizophrenics with several metabolic bottlenecks such as lower PREG levels due to increased PREG sulfation and/or suppressed PREGS desulfation and attenuated conversion of 17-hydroxy-PREG to 17-hydroxy-progesterone, as well as the results suggestive of suppressed CYP11B1 activity. In contrast, steroid molar ratios suggested two counterregulatory steps involving increased conversion of PREG/S to 17-hydroxy-PREG/S and decreased conversion of cortisol to cortisone, which may maintain unchanged basal cortisol levels but may not ensure a sufficient cortisol response to stress. Our data also indicated a trend to higher 7α-, 7β-, and 16α-hydroxylation that may counteract the autoimmune complications and proinflammatory processes accompanying schizophrenia. Finally, a possible suppression of HSD17B3 activity was suggested, resulting in decreased circulating testosterone levels with increased androstenedione levels. Full article

(This article belongs to the Special Issue Steroids and Neuropsychiatric Disorders)

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28 pages, 1032 KiB

Open AccessArticle

Association between Disgust Sensitivity during Pregnancy and Endogenous Steroids: A Longitudinal Study

by Šárka Kaňková, Daniela Dlouhá, Jana Ullmann, Marta Velíková, Josef Včelák and Martin Hill

Int. J. Mol. Sci. 2024, 25(13), 6857; https://doi.org/10.3390/ijms25136857 - 22 Jun 2024

Cited by 2 | Viewed by 732

Abstract

The emotion of disgust protects individuals against pathogens, and it has been found to be elevated during pregnancy. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. This study aimed to assess the association between steroids and disgust sensitivity in pregnancy. Using a prospective longitudinal design, we analyzed blood serum steroid concentrations and measured disgust sensitivity via text-based questionnaires in a sample of 179 pregnant women during their first and third trimesters. We found positive correlations between disgust sensitivity and the levels of C19 steroids (including testosterone) and its precursors in the Δ⁵ pathway (androstenediol, DHEA, and their sulfates) and the Δ⁴ pathway (androstenedione). Additionally, positive correlations were observed with 5α/β-reduced C19 steroid metabolites in both trimesters. In the first trimester, disgust sensitivity was positively associated with 17-hydroxypregnanolone and with some estrogens. In the third trimester, positive associations were observed with cortisol and immunoprotective Δ⁵ C19 7α/β-hydroxy-steroids. Our findings show that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, with steroids which may be related to potential maternal-anxiety-related symptoms. This study highlights the complex relationship between hormonal changes and disgust sensitivity during pregnancy. Full article

(This article belongs to the Special Issue Steroids and Neuropsychiatric Disorders)

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