Psychotropic Drug Effects on Steroid Stress Hormone Release and Possible Mechanisms Involved

• Published in: International journal of molecular sciences Vol. 23; no. 2; p. 908
• Main Authors: Romanova, Zuzana, Hlavacova, Natasa, Jezova, Daniela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.01.2022; MDPI
• Subjects: Adrenal Cortex Hormones - biosynthesis; Animals; Antipsychotic Agents - pharmacology; Brain-derived neurotrophic factor; CLOCK Proteins - genetics; CLOCK Proteins - metabolism; Cytokines; Cytokines - metabolism; Dopamine; Drugs; Epigenesis, Genetic; Gene Expression Regulation; Gene Expression Regulation, Enzymologic; Hormones; Humans; Hydrocortisone - biosynthesis; Hypothalamo-Hypophyseal System - metabolism; Kinases; Mental disorders; Mental Disorders - drug therapy; Mental Disorders - etiology; Mental Disorders - metabolism; Metabolic Networks and Pathways - drug effects; Neurogenesis; Neurogenesis - drug effects; Neurotransmitter Agents - metabolism; Plasma; Proteins; Psychotropic drugs; Psychotropic Drugs - pharmacology; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Receptors, Neurotransmitter - metabolism; Review; Signal Transduction - drug effects; Steroids; Stress, Physiological - drug effects; Stress, Physiological - genetics; cortisol; lithium; molecular pathways; aldosterone; neurotransmitters; antipsychotic drugs
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23020908

There is no doubt that chronic stress accompanied by adrenocortical stress hormone release affects the development and treatment outcome of several mental disorders. Less attention has been paid to the effects of psychotropic drugs on adrenocortical steroids, particularly in clinical studies. This review focuses on the knowledge related to the possible modulation of cortisol and aldosterone secretion under non-stress and stress conditions by antipsychotic drugs, which are being used in the treatment of several psychotic and affective disorders. The molecular mechanisms by which antipsychotic drugs may influence steroid stress hormones include the modulation of central and/or adrenocortical dopamine and serotonin receptors, modulation of inflammatory cytokines, influence on regulatory mechanisms in the central part of the hypothalamic-pituitary axis, inhibition of corticotropin-releasing hormone gene promoters, influencing glucocorticoid receptor-mediated gene transcription, indirect effects via prolactin release, alteration of signaling pathways of glucocorticoid and mineralocorticoid actions. Clinical studies performed in healthy subjects, patients with psychosis, and patients with bipolar disorder suggest that single and repeated antipsychotic treatments either reduce cortisol concentrations or do not affect its secretion. A single and potentially long-term treatment with dopamine receptor antagonists, including antipsychotics, has a stimulatory action on aldosterone release.